scholarly journals Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens: Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis

2014 ◽  
Vol 32 (10) ◽  
pp. 1031-1039 ◽  
Author(s):  
Dan Rosmarin ◽  
Claire Palles ◽  
David Church ◽  
Enric Domingo ◽  
Angela Jones ◽  
...  

Purpose Fluourouracil (FU) is a mainstay of chemotherapy, although toxicities are common. Genetic biomarkers have been used to predict these adverse events, but their utility is uncertain. Patients and Methods We tested candidate polymorphisms identified from a systematic literature search for associations with capecitabine toxicity in 927 patients with colorectal cancer in the Quick and Simple and Reliable trial (QUASAR2). We then performed meta-analysis of QUASAR2 and 16 published studies (n = 4,855 patients) to examine the polymorphisms in various FU monotherapy and combination therapy regimens. Results Global capecitabine toxicity (grades 0/1/2 v grades 3/4/5) was associated with the rare, functional DPYD alleles 2846T>A and *2A (combined odds ratio, 5.51; P = .0013) and with the common TYMS polymorphisms 5′VNTR2R/3R and 3′UTR 6bp ins-del (combined odds ratio, 1.31; P = 9.4 × 10−6). There was weaker evidence that these polymorphisms predict toxicity from bolus and infusional FU monotherapy. No good evidence of association with toxicity was found for the remaining polymorphisms, including several currently included in predictive kits. No polymorphisms were associated with toxicity in combination regimens. Conclusion A panel of genetic biomarkers for capecitabine monotherapy toxicity would currently comprise only the four DPYD and TYMS variants above. We estimate this test could provide 26% sensitivity, 86% specificity, and 49% positive predictive value—better than most available commercial kits, but suboptimal for clinical use. The test panel might be extended to include additional, rare DPYD variants functionally equivalent to *2A and 2846A, though insufficient evidence supports its use in bolus, infusional, or combination FU. There remains a need to identify further markers of FU toxicity for all regimens.

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Hee Joong Lee ◽  
Tae Chul Park ◽  
Jae Hoon Kim ◽  
Errol Norwitz ◽  
Banghyun Lee

Objective. To conduct systematic analyses to evaluate the efficacy of progesterone therapy for the prevention of miscarriages in pregnant women experiencing threatened abortion. Methods. In November 2016, we performed a systematic literature search and identified 51 articles in PubMed, Embase, and Cochrane databases. We identified nine randomized trials that included 913 pregnant women (including 322 treated with oral dydrogesterone, 213 treated with vaginal progesterone, and 378 control subjects) who met the selection criteria. Results. The incidence of miscarriage was significantly lower in the total progesterone group than in the control group (13.0% versus 21.7%; odds ratio, 0.53; 95% confidence interval (CI), 0.36 to 0.78; P=0.001; I2, 0%). Moreover, the incidence of miscarriage was significantly lower in the oral dydrogesterone group than in the control group (11.7% versus 22.6%; odds ratio, 0.43; 95% CI, 0.26 to 0.71; P=0.001; I2, 0%) and was lower in the vaginal progesterone group than in the control group, although this difference was nonsignificant (15.4% versus 20.3%; odds ratio, 0.72; 95% CI, 0.39 to 1.34; P=0.30; I2, 0%). However, the incidence of miscarriage was not different between the oral dydrogesterone and vaginal progesterone groups. Conclusion. Progesterone therapy, especially oral dydrogesterone, can effectively prevent miscarriage in pregnant women experiencing threatened abortion.


2021 ◽  
pp. 027112142110327
Author(s):  
Esther R. Lindström ◽  
Jason C. Chow ◽  
Kathleen N. Zimmerman ◽  
Hongyang Zhao ◽  
Elise Settanni ◽  
...  

Engagement in early childhood has been linked with later achievement, but the relation between these variables and how they are measured in early childhood requires examination. We estimated the overall association between academic engagement and achievement in children prior to kindergarten entry. Our systematic literature search yielded 13,521 reports for structured eligibility screening; from this pool of studies, we identified 21 unique data sets, with 199 effect sizes for analysis. We coded eligible studies, extracted effect sizes, accounted for effect size dependency, and used random-effects models to synthesize findings. The overall correlation between academic engagement and achievement was r = .24 (range: −.08 to −.71), and moderator analyses did not significantly predict the relation between the two constructs. This study aligns with previous research on this topic and examines issues related to these measures, their constraints, and applications as they pertain to early childhood research.


2020 ◽  
Author(s):  
Xueyan Li ◽  
DI LIU ◽  
Sun Yang ◽  
Jingyun Yang ◽  
Youcheng Yu

Previous studies have reported the association between multiple genetic variants in enamel formation-related genes and the risk of dental caries with inconsistent results. We performed a systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases for studies published before March 21, 2020 and conducted meta-, gene-based and gene-cluster analysis on the association between genetic variants in enamel- formation-related genes and the risk of dental caries. Our systematic literature search identified 21 relevant publications including a total of 24 studies for analysis. The genetic variant rs17878486 in AMELX was significantly associated with dental caries risk (OR=1.40, 95% CI: 1.02-1.93, P=0.037). We found no significant association between the risk of dental caries with rs12640848 in ENAM (OR=1.15, 95% CI: 0.88-1.52, P=0.310), rs1784418 in MMP20 (OR=1.07, 95% CI: 0.76-1.49, P=0.702) and rs3796704 in ENAM (OR=1.06, 95% CI: 0.96-1.17, P=0.228). Gene-based analysis indicated that multiple genetic variants in AMELX showed joint association with the risk of dental caries (6 variants; P<10-5), so did genetic variants in MMP13 (3 variants; P=0.004), MMP2 (3 variants; P<10-5), MMP20 (2 variants; P<10-5) and MMP3 (2 variants; P<10-5). The gene-cluster analysis indicated a significant association between the genetic variants in this enamel-formation gene cluster and the risk of dental caries (P<10-5). The present meta-analysis revealed that genetic variant rs17878486 in AMELX were associated with dental caries, and multiple genetic variants in enamel-formation-related genes jointly contribute to the risk of dental caries, supporting the role of genetic variants in the enamel-formation genes in the etiology of dental caries.


2020 ◽  
Vol 27 (2) ◽  
pp. 221-230
Author(s):  
Jojo Hoi-Ching Lai ◽  
Samuel KK Ling ◽  
Patrick Cacho ◽  
SW Mok ◽  
Patrick SH Yung

Background: Our aim was to conduct a review to summarize the existing information regarding the effects of shoe collar height in altering ankle sprain mechanics in athletes. Methods: A systematic literature search of PubMed, Embase, MEDLINE, and SPORTDiscus was conducted in September 2019. Results: There were 10 studies published from 1993 to 2019 that were included. Most studies showed high-top shoes limited ankle sprain kinematics and increased resistance to inversion moment in static but not dynamic testing. High-top shoes were associated with delayed pre-landing ankle evertor muscle activation and smaller electromyography amplitudes. Conclusions: There is currently weak evidence to support that high-top shoes can limit ankle sprain kinematics in dynamic testing. Further studies with more consistent study interventions and outcome variables are needed to definitively establish the effects of shoe collar height on ankle sprain mechanics in athletes. The Translational Potential of this Article: Multiple studies on the effects of shoe collar height and ankle sprain mechanics have been performed but there is a lack of consistency in terms of study design, intervention, and outcome measures. A formal systematic review and meta-analysis were not applicable due to the heterogeneity of studies, and mixed results from these studies can be confusing to interpret, making further research on this topic difficult as a result of lack of future direction. We summarized the existing literature on this topic to provide a clearer picture and guide future research on this controversial matter.


2018 ◽  
Vol 157 (04) ◽  
pp. 392-399
Author(s):  
Sebastian Scheidt ◽  
Patrick Vavken ◽  
Cornelius Jacobs ◽  
Sebastian Koob ◽  
Davide Cucchi ◽  
...  

AbstractThe rising number of medical publications makes it difficult to keep up-to-date on scientific knowledge. In recent years, reviews in the form of narrative or systematic publications and meta-analyses have increased. These can only be interpreted and evaluated if the reader understands the techniques used. This review article describes the differences between narrative and systematic reviews, together with the characteristics of meta-analysis, and discusses their interpretation. The concept of systematic reviews and meta-analysis includes a systematic literature search and summary, together with an appraisal of the quality of the publications. Systematic reviews are often considered to be original studies due to their structure and ability to reduce bias.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Andreas Pregernig ◽  
Mattia Müller ◽  
Ulrike Held ◽  
Beatrice Beck-Schimmer

Abstract Background Angiopoietin-1 (Ang-1) and 2 (Ang-2), high mobility group box 1 (HMGB1), soluble receptor for advanced glycation endproducts (sRAGE), soluble triggering receptor expressed on myeloid cells 1 (sTREM1), and soluble urokinase-type plasminogen activator receptor (suPAR) have shown promising results for predicting all-cause mortality in critical care patients. The aim of our systematic review and meta-analysis was to assess the prognostic value of these biomarkers for mortality in adult patients with sepsis. Methods A systematic literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases, for articles in English published from 01.01.1990 onwards, was conducted. The systematic review focused exclusively on observational studies of adult patients with sepsis, any randomized trials were excluded. For the meta-analysis, only studies which provide biomarker concentrations within 24 h of admission in sepsis survivors and nonsurvivors were included. Results are presented as pooled mean differences (MD) between nonsurvivors and survivors with 95% confidence interval for each of the six biomarkers. Studies not included in the quantitative analysis were narratively summarized. The risk of bias was assessed in all included studies using the Quality in Prognosis Studies (QUIPS) tool. Results The systematic literature search retrieved 2285 articles. In total, we included 44 studies in the qualitative analysis, of which 28 were included in the meta-analysis. The pooled mean differences in biomarker concentration (nonsurvivors − survivors), measured at onset of sepsis, are listed as follows: (1) Ang-1: − 2.9 ng/ml (95% CI − 4.1 to − 1.7, p < 0.01); (2) Ang-2: 4.9 ng/ml (95% CI 2.6 to 7.1, p < 0.01); (3) HMGB1: 1.2 ng/ml (95% CI 0.0 to 2.4, p = 0.05); (4) sRAGE: 1003 pg/ml (95% CI 628 to 1377, p < 0.01); (5) sTREM-1: 87 pg/ml (95% CI 2 to 171, p = 0.04); (6) suPAR: 5.2 ng/ml (95% CI 4.5 to 6.0, p < 0.01). Conclusions Ang-1, Ang-2, and suPAR provide beneficial prognostic information about mortality in adult patients with sepsis. The further development of standardized assays and the assessment of their performance when included in panels with other biomarkers may be recommended. Trial registration This study was recorded on PROSPERO, prospective register of systematic reviews, under the registration ID: CRD42018081226


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ruokun Yi ◽  
Fang Tan ◽  
Huayi Suo ◽  
Wenfeng Li ◽  
Xianrong Zhou ◽  
...  

In the present research, the effects of Lactobacillus plantarum YS4 (LP-YS4) on colitis were tested in an oxazolone-induced mouse model. BALB/c mice were induced by oxazolone and then treated with LP-YS4. The serum levels of mice were analyzed using commercial kits and the protein and mRNA expression levels of mouse colon tissue were detected by Western blotting and qPCR assay, respectively. The results demonstrated that LP-YS4 significantly (P<0.05) increased the colon length and ratio of colon weight/length in mice with colitis and attenuated the negative effects of colitis. The results also showed that treatment with LP-YS4 significantly reduced the serum concentrations of ET-1, SP, and IL-10 while significantly increasing those of SS, VIP, and IL-2 in colitis mice (P<0.05). In addition, LP-YS4 significantly increased the activities of GSH and SOD while decreasing those of MPO and MDA in the colon tissue of colitis mice (P<0.05). LP-YS4 also significantly upregulated the mRNA and protein expression of c-Kit, eNOS, nNOSe, and SCF in colitis mice while significantly downregulating the relative expression of iNOS. In summary, LP-YS4 could reduce the negative effects of colitis, and such effects were better than those of the common probiotic Lactobacillus bulgaricus.


2021 ◽  
Author(s):  
Jeff Clements ◽  
Matthew N. George

1. Many bivalve molluscs settle and attach to surfaces using adhesive byssal threads – proteinaceous fibers that together form a network known as the byssus. Since these bivalves rely on byssus for survival, strong byssal attachment promotes a myriad of broad ecological services, including water filtration, nutrient extraction, sediment stabilization, and enhancing biodiversity through habitat creation.2. Numerous studies have documented weakened byssal attachment strength under ocean acidification (OA); however, a comparable number report no effect, even within the same species. Consequently, whether elevated CO2 levels expected under near-future OA will affect byssal attachment strength in nature remains hotly contested.3. We used a systematic literature search and meta-analysis to explore factors that could potentially explain observed effect size variation in byssal attachment strength following OA exposure. 4. A systematic literature search uncovered 20 studies experimentally testing the impact of OA on byssal attachment strength (or some proxy thereof). Meta-analysis revealed that body size (mean shell length) was the strongest predictor of effect size variation, with no significant effect of climate, species, year, study temperature, study location, exposure time, food amount, and pH offset. Functionally, a negative linear relationship was observed between body size and effect size.5. Our finding that the byssal strength of larger bivalves is more susceptible to negative OA effects runs counter to prevailing wisdom that larger, older animals of a given species are more robust to OA than earlier life history stages. 6. This highlights that body size and age may be important factors that determine OA sensitivity in adult calcifiers. In addition to body size, a critical review of each study revealed commonly neglected factors that could influence byssal thread attachment strength which we highlight to provide suggestions for future research in this area.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012436
Author(s):  
Chetan Bettegowda ◽  
Meena Upadhayaya ◽  
D Gareth Evans ◽  
AeRang Kim ◽  
Dimitrios Mathios ◽  
...  

Objective:As clinically validated biomarkers for neurofibromatosis 1 (NF1) and neurofibromatosis 2 (NF2), have not been identified to date, we wanted to determine whether genotype-phenotype correlations are usefull in clinical trials in Neurofibromatosis 1 and 2Methods:The biomarker group first performed a systematic literature search and reviewed existing data on genetic biomarkers in NF1 and NF2 and in in malignant peripheral nerve sheath tumours (MPNST). The group then met during a series of consensus meetings to develop a joint report.Results:We found that In NF2 the genetic severity score is clearly of potential clinical use. In NF1 despite over 3000 constitutional variants having been described in the NF1 gene, only four actionable genotype phenotype correlations currently exist. The diagnosis and treatment decision of these tumours should ideally include histopathology and compilation of some of the genetic markersConclusion:We summarized emerging clinical use of genotype-phenotype correlations in Neurofibromatosis.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Yan Zhao ◽  
Erjiang Zhao ◽  
Junhui Zhang ◽  
Yuanyuan Chen ◽  
Junli Ma ◽  
...  

Purpose. Associations between XRCC1, XRCC3, and ERCC2 gene polymorphism and prognosis have been investigated in several cancers. The aim of this meta-analysis was to assess the prognostic value of XRCC1, XRCC3, and ERCC2 gene polymorphism in hepatocellular carcinoma (HCC). Methods. A systematic literature search was performed to identify relevant studies in PubMed, Embase, and the Cochrane library up to December 2018. The prognostic values of XRCC1, XRCC3, and ERCC2 polymorphisms in HCC were estimated using crude HRs with 95% CIs. Results. Ten studies involving 2687 patients were included in the quantitative analysis. There were no statistically significant associations between XRCC1 rs1799782 C>T, XRCC1 rs25487 G>A, and ERCC2 rs1799793 G>A polymorphisms and overall survival (OS). OS was significantly longer for the ERCC2 rs13181 CC genotype than for AA (CC vs. AA: HR = 0.33, 95% CI = 0.15–0.72). A significantly lower OS was observed for patients with the CT genotype compared with the CC genotype at XRCC3 rs861539 (CT vs. CC: HR = 1.64, 95% CI = 1.11–2.42). Conclusion. The ERCC2 rs13181 A>C polymorphism and XRCC3 rs861539 C>T polymorphism may be predictive markers for prognosis in patients with HCC. Well-designed studies with larger sample sizes are needed to verify our findings.


Sign in / Sign up

Export Citation Format

Share Document