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Pancreatology : Official Journal of the... Nov 2023Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts.
METHODS
We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC.
RESULTS
Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts.
CONCLUSIONS
Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts.
Topics: Humans; Cyst Fluid; Pancreatic Neoplasms; Carcinoembryonic Antigen; Carcinoma, Pancreatic Ductal; Pancreatic Cyst; DNA; Biomarkers, Tumor
PubMed: 37230894
DOI: 10.1016/j.pan.2023.05.005 -
Reviews in Medical Virology Jan 2023Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic... (Meta-Analysis)
Meta-Analysis Review
Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic virus, has been proposed as marker of functional immunity: higher loads correspond to over-immunosuppression, and lower loads to under-immunosuppression. This review offers an overview of the current evidence of the association between TTV-load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer-reviewed articles were assessed investigating the association between TTV-load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)-tool was used to assess the risk of bias. Meta-analysis with random-effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV-load was measured longitudinally, within the first 2 years post-transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV-load and infections, whereas 13 out of 15 reported an association between low TTV-load and rejection. Meta-analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03-1.32; HR: 1.05, 95% CI: 0.97-1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87-0.94; HR: 0.74, 95% CI: 0.71-0.76) per 1 log TTV-load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta-analysis indicates that blood TTV-load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT.
Topics: Humans; Torque teno virus; Retrospective Studies; Prospective Studies; Organ Transplantation; Immunosuppression Therapy; Viral Load; DNA, Viral
PubMed: 36056751
DOI: 10.1002/rmv.2393 -
Otolaryngology--head and Neck Surgery :... Nov 2015Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma is increasing in incidence and appears to exhibit improved response to treatment and better... (Review)
Review
OBJECTIVE
Human papillomavirus-positive (HPV+) head and neck squamous cell carcinoma is increasing in incidence and appears to exhibit improved response to treatment and better survival than that of HPV- head and neck squamous cell carcinoma. The purpose of this systematic review was to examine the current literature regarding treatment and prognosis of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) and identify whether type of treatment (primarily surgery vs primarily radiation) significantly affects survival rates.
DATA SOURCES
PubMed and Cochrane Library databases.
REVIEW METHODS
A computerized search of the PubMed and Cochrane Library databases was performed to identify English-language articles published between January 1, 2000, and October 21, 2014. Studies were included only if they were prospective or retrospective observational series of OPSCC patients that reported HPV status, treatment regimen, and survival outcomes. Outcomes were determined for HPV+ and HPV- OPSCC patients, with subanalyses according to the type of treatment received.
RESULTS
Fifty-six articles were eligible for this review. In the HPV+ analysis, the unadjusted hazard rate ratio (HR) for surgery vs radiation treatment was 1.33 (P = .114). Nine confounders were considered, and HRs were adjusted for each covariate. While HRs were almost all >1 for all covariates, none of the HRs was statistically significant at P < .05. The HR for HPV- OPSCC was higher for radiation than surgery.
CONCLUSIONS
HPV+ OPSCC has an improved prognosis and lower rates of adverse events when compared with HPV- OPSCC. HPV- OPSCC had significantly worse outcomes when treated with primary radiation as compared with primary surgery. There was no statistically significant difference in HRs for HPV+ OPSCC with primary radiation vs primary surgery treatment.
Topics: Carcinoma, Squamous Cell; Combined Modality Therapy; DNA, Viral; Global Health; Humans; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Registries; Survival Rate
PubMed: 26124261
DOI: 10.1177/0194599815592157 -
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 -
Microbial Pathogenesis Jan 2018Hepatitis B is one of the most common infectious diseases worldwide. In patients undergoing immunosuppressive therapy such as rheumatic diseases, reactivation of... (Review)
Review
BACKGROUND
Hepatitis B is one of the most common infectious diseases worldwide. In patients undergoing immunosuppressive therapy such as rheumatic diseases, reactivation of hepatitis B virus (HBV) is considered clinically important. This systematic review and meta-analysis were performed to determine the prevalence rate of HBV reactivation in rheumatic patients from different parts of the world.
METHODS
The authors performed a systematic literature review from several reliable databases including Scopus, ISI Web of Science and PubMed. Furthermore, the keywords of this research were "Hepatitis B virus", "Rheumatic diseases", "HBV reactivation", "Anti-TNF", "DMARDs" and "Biologic agents".
RESULTS
The authors selected 30 studies out of 983 for the present review. The overall estimation of the prevalence of HBV reactivation was 1.4 (95% confidence interval (CI): 1.3-1.6). Also, the heterogeneity in estimating the pooled prevalence among the studies was shown; Cochran Q test, P < 0.001, I = 99.9%. It should be noted that max and min reactivation rate of HBV were in Italy and France respectively.
CONCLUSIONS
Rheumatic disease patients with resolved hepatitis B should be tightly monitored for possible HBV reactivation by elevation of liver enzymes and HBV DNA levels.
Topics: Antirheumatic Agents; DNA, Viral; Databases, Factual; Hepatitis B; Hepatitis B virus; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Liver; Meta-Analysis as Topic; Rheumatic Diseases; Tumor Necrosis Factor-alpha; Virus Activation
PubMed: 29223453
DOI: 10.1016/j.micpath.2017.12.014 -
Cancer Epidemiology, Biomarkers &... Feb 2016The ability to undertake molecular analysis to inform on prognosis and predictors of response to therapy is limited by accessibility of tissue. Measurement of total... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The ability to undertake molecular analysis to inform on prognosis and predictors of response to therapy is limited by accessibility of tissue. Measurement of total circulating free DNA (cfDNA) or circulating tumor DNA (ctDNA) in peripheral blood may allow easier access to tumor material and help to predict clinical outcomes.
METHODS
A systematic review of electronic databases identified publications exploring the association between cfDNA or ctDNA and overall survival (OS) in solid tumors. HRs for OS were extracted from multivariable analyses and included in a meta-analysis. Pooled HRs were computed and weighted using generic inverse variance and random-effect modeling. For studies not reporting multivariable analyses, univariable ORs were estimated from Kaplan-Meier curves for OS at 1 and 3 years.
RESULTS
Thirty-nine studies comprising 4,052 patients were included in the analysis. Detection of ctDNA was associated with a significantly worse OS in multivariable analyses [HR, 2.70; 95% confidence interval (CI), 2.02-3.61; P < 0.001). Similar results were observed in the univariable analyses at 3 and 1 year (OR, 4.83; 95% CI, 3.20-7.28; P < 0.001).There was also a statistically significant association between high total cfDNA and worse OS for studies reporting multivariable and univariate data at 3 years (HR, 1.91; 95% CI, 1.59-2.29; P < 0.001 and OR, 2.82; 95% CI, 1.93-4.13; P < 0.001, respectively).
CONCLUSIONS
High levels of total cfDNA and presence of ctDNA are associated with worse survival in solid tumors.
IMPACT
Circulating DNA is associated with worse outcome in solid tumors.
Topics: DNA; Humans; Neoplasms; Prognosis
PubMed: 26604269
DOI: 10.1158/1055-9965.EPI-15-0893 -
International Journal of Molecular... Dec 2022Collection and interpretation of "touch DNA" from crime scenes represent crucial steps during criminal investigations, with clear consequences in courtrooms. Although... (Review)
Review
Collection and interpretation of "touch DNA" from crime scenes represent crucial steps during criminal investigations, with clear consequences in courtrooms. Although the main aspects of this type of evidence have been extensively studied, some controversial issues remain. For instance, there is no conclusive evidence indicating which sampling method results in the highest rate of biological material recovery. Thus, this study aimed to describe the actual considerations on touch DNA and to compare three different sampling procedures, which were "single-swab", "double-swab", and "other methods" (i.e., cutting out, adhesive tape, FTA paper scraping), based on the experimental results published in the recent literature. The data analysis performed shows the higher efficiency of the single-swab method in DNA recovery in a wide variety of experimental settings. On the contrary, the double-swab technique and other methods do not seem to improve recovery rates. Despite the apparent discrepancy with previous research, these results underline certain limitations inherent to the sampling procedures investigated. The application of this information to forensic investigations and laboratories could improve operative standard procedures and enhance this almost fundamental investigative tool's probative value.
Topics: Touch; DNA Fingerprinting; DNA; Specimen Handling
PubMed: 36555182
DOI: 10.3390/ijms232415541 -
Scientific Reports Aug 2016Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus... (Review)
Review
Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease.
Topics: Aged; Biopsy; DNA, Mitochondrial; Female; Humans; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Middle Aged; Mitochondria, Muscle; Mitochondrial Myopathies; Muscle, Skeletal; Mutation; Young Adult
PubMed: 27506553
DOI: 10.1038/srep30610 -
PLoS Neglected Tropical Diseases Mar 2021We were tasked by the World Health Organization (WHO) to address the following question: What techniques should be used to diagnose Schistosoma infections in snails and...
BACKGROUND
We were tasked by the World Health Organization (WHO) to address the following question: What techniques should be used to diagnose Schistosoma infections in snails and in the water in potential transmission sites? Our goal was to review and evaluate the available literature and provide recommendations and insights for the development of WHO's Guidelines Development Group for schistosomiasis control and elimination.
METHODOLOGY
We searched several databases using strings of search terms, searched bibliographies of pertinent papers, and contacted investigators who have made contributions to this field. Our search covered from 1970 to Sept 2020. All papers were considered in a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework, and retained papers were grouped by technique and subjected to our GRADE (Grading of Recommendations, Assessment, Development and Evaluations) evidence assessment profile determined in consultation with WHO. We also considered issues of sensitivity, specificity, coverage, cost, robustness, support needs, schistosome species discrimination, and relevant detection limits.
PRINCIPAL FINDINGS
Our PRISMA process began with the perusal of 949 articles, of which 158 were retained for data extraction and evaluation. We identified 25 different techniques and for each applied a GRADE assessment considering limitations, inconsistency, imprecision, indirectness, and publication bias. We also provide advantages and disadvantages for each category of techniques.
CONCLUSIONS
Our GRADE analysis returned an assessment of moderate quality of evidence for environmental DNA (eDNA), qPCR and LAMP (Loop-mediated isothermal amplification). No single ideal diagnostic approach has yet been developed, but considerable recent progress has been made. We note a growing trend to use eDNA techniques to permit more efficient and replicable sampling. qPCR-based protocols for follow-up detection offer a versatile, mature, sensitive, and specific platform for diagnosis though centralized facilities will be required to favor standardization. Droplet digital PCR (ddPCR) can play a complementary role if inhibitors are a concern, or more sensitivity or quantification is needed. Snail collection, followed by shedding, is encouraged to provide specimens for sequence verifications of snails or schistosomes. LAMP or other isothermal detection techniques offer the prospect of less expensive and more distributed network of analysis but may face standardization and verification challenges related to actual sequences amplified. Ability to detect schistosome infections in snails or in the water is needed if control and elimination programs hope to succeed. Any diagnostic techniques used need to be regularly verified by the acquisition of DNA sequences to confirm that the detected targets are of the expected species. Further improvements may be necessary to identify the ideal schistosome or snail sequences to target for amplification. More field testing and standardization will be essential for long-term success.
Topics: Animals; DNA, Environmental; DNA, Helminth; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Real-Time Polymerase Chain Reaction; Schistosoma; Schistosomiasis; Snails; Water
PubMed: 33760814
DOI: 10.1371/journal.pntd.0009175 -
Sensors (Basel, Switzerland) Jan 2023This systematic review describes and discusses three commercially available integrated systems for forensic DNA analysis, i.e., ParaDNA, RapidHIT, and ANDE. A variety of... (Review)
Review
This systematic review describes and discusses three commercially available integrated systems for forensic DNA analysis, i.e., ParaDNA, RapidHIT, and ANDE. A variety of aspects, such as performance, time-to-result, ease-of-use, portability, and costs (per analysis run) of these three (modified) rapid DNA analysis systems, are considered. Despite their advantages and developmental progress, major steps still have to be made before rapid systems can be broadly applied at crime scenes for full DNA profiling. Aspects in particular that need (further) improvement are portability, performance, the possibility to analyze a (wider) variety of (complex) forensic samples, and (cartridge) costs. Moreover, steps forward regarding ease-of-use and time-to-result will benefit the broader use of commercial rapid DNA systems. In fact, it would be a profit if rapid DNA systems could be used for full DNA profile generation as well as indicative analyses that can give direction to forensic investigators which will speed up investigations.
Topics: Forensic Genetics; Microsatellite Repeats; Polymerase Chain Reaction; DNA Fingerprinting; DNA
PubMed: 36772114
DOI: 10.3390/s23031075