-
Annals of the American Thoracic Society Jan 2024The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic... (Meta-Analysis)
Meta-Analysis
The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with cyclophosphamide. A literature search was conducted across the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using cyclophosphamide to treat patients with SSc-ILD. Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group method was used to assess the quality of evidence. Five studies were included; two randomized controlled trials compared cyclophosphamide versus placebo, and one randomized controlled trial and two retrospective case-control studies compared cyclophosphamide versus mycophenolate. Compared with placebo, there was a 2.83% reduction in the decline at 12 months for forced vital capacity (FVC) % predicted using cyclophosphamide (95% confidence interval [CI], 0.80-4.87; low evidence). There were improvements in breathlessness (Transition Dyspnea Index mean difference [MD], 2.90; 95% CI, 1.94-3.86; minimum clinically important difference, 1; moderate evidence) and disability (Health Assessment Questionnaire-Disability Index MD, -0.16; 95% CI, -0.28 to -0.04; minimum clinically important difference, -0.14; moderate evidence). There were increased risks of leukopenia and constitutional symptoms using cyclophosphamide, but no difference in mortality. When cyclophosphamide was compared with mycophenolate, there were differences in diffusing capacity of the lung for carbon monoxide % predicted favoring mycophenolate at 6 months (MD, -3.67%; 95% CI, -6.3% to -1.1% unadjusted; MD, -4.88%; 95% CI, -7.3% to -2.5% adjusted for alveolar volume; moderate evidence), 12 months (MD, -5.90%; 95% CI, -8.4% to -3.4% adjusted for alveolar volume; moderate evidence), and 18 months (MD, -3.26%; 95% CI, -6.1% to -0.4%; moderate evidence), but not at 24 months. There were no differences in FVC % predicted, mortality, or quality-of-life outcomes, but participants were more likely to prematurely discontinue cyclophosphamide compared with mycophenolate (relative risk, 1.70; 95% CI, 1.10-2.63; high-certainty evidence). A review of the published evidence shows that cyclophosphamide is effective in SSc-ILD compared with placebo, with an increased risk of side effects. However, mycophenolate may be equivocal or better than cyclophosphamide. Clinicians and patients should weigh the potential benefits and risks with respect to individual patient circumstances and preferences.
Topics: Humans; Retrospective Studies; Quality of Life; Cyclophosphamide; Immunosuppressive Agents; Lung Diseases, Interstitial; Dyspnea; Scleroderma, Systemic
PubMed: 37772975
DOI: 10.1513/AnnalsATS.202301-053OC -
BMC Nephrology Sep 2023Rituximab (RTX) and cyclophosphamide (CYC) based treatments are both recommended as first-line therapies in idiopathic membranous nephropathy (IMN) by KDIGO 2021... (Meta-Analysis)
Meta-Analysis
Rituximab (RTX) and cyclophosphamide (CYC) based treatments are both recommended as first-line therapies in idiopathic membranous nephropathy (IMN) by KDIGO 2021 guideline. However, the efficacy of RTX vs. CYC-based treatments in IMN is still controversial. We performed this systemic review and meta-analysis registered in PROSPERO (CRD 42,022,355,717) by pooling data from randomized controlled trials or cohort studies in IMN patients using the EMBASE, PubMed, and Cochrane libraries (till Orc 1, 2022). The primary outcomes were the complete remission (CR) rate + partial remission (PR) rate. CR rate, immunologic response rate, relapse rate, and the risk of serious adverse events (SAE) were secondary outcomes. Eight studies involving 600 adult patients with IMN were included with a median follow-up duration of 12 to 60 months. RTX induced a similar overall remission rate compared with CYC (RR 0.88, 95% CI: 0.71, 1.09, P = 0.23). At the follow-up time of 6 months, RTX was associated with a lower CR + PR rate compared with CYC (RR 0.67, 95% CI: 0.52, 0.88, P = 0.003). Moreover, RTX might be less effective in inducing CR + PR than CYC treatment in IMN patients with high antiPLA2R antibody levels (RR 0.67, 95% CI: 0.48, 0.94, P = 0.02). The occurrences of CRs, relapse rates, immunologic response rates, and SAE were not significantly different between RTX and CYC, respectively. In conclusion, although the long-term efficacy and safety of CYC compared to RTX were comparable, CYC might respond faster and be more advantageous in IMN patients with high antiPLA2R antibody titers.
Topics: Adult; Humans; Glomerulonephritis, Membranous; Rituximab; Cyclophosphamide; Patients
PubMed: 37740193
DOI: 10.1186/s12882-023-03307-x -
Epigenetics Dec 2024Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health.... (Review)
Review
Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 ( = 15) and studies ( = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation ( = 9), (2) genome-wide analyses ( = 4), and (3) gene specific ( = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including , , and ; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.
Topics: Female; Humans; Pregnancy; DNA Methylation; Placenta; Genome-Wide Association Study; Folic Acid; S-Adenosylmethionine; Choline; Carbon
PubMed: 38484284
DOI: 10.1080/15592294.2024.2318516 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Briefings in Bioinformatics Sep 2023DNA methylation is a fundamental epigenetic modification involved in various biological processes and diseases. Analysis of DNA methylation data at a genome-wide and...
DNA methylation is a fundamental epigenetic modification involved in various biological processes and diseases. Analysis of DNA methylation data at a genome-wide and high-throughput level can provide insights into diseases influenced by epigenetics, such as cancer. Recent technological advances have led to the development of high-throughput approaches, such as genome-scale profiling, that allow for computational analysis of epigenetics. Deep learning (DL) methods are essential in facilitating computational studies in epigenetics for DNA methylation analysis. In this systematic review, we assessed the various applications of DL applied to DNA methylation data or multi-omics data to discover cancer biomarkers, perform classification, imputation and survival analysis. The review first introduces state-of-the-art DL architectures and highlights their usefulness in addressing challenges related to cancer epigenetics. Finally, the review discusses potential limitations and future research directions in this field.
Topics: Humans; DNA Methylation; Deep Learning; Epigenesis, Genetic; Genome; Neoplasms
PubMed: 37985455
DOI: 10.1093/bib/bbad411 -
Epigenetics Dec 2023Research has recently begun to examine the potential intergenerational impacts of trauma on obesity. This scoping review examines the literature on the interactions... (Review)
Review
Research has recently begun to examine the potential intergenerational impacts of trauma on obesity. This scoping review examines the literature on the interactions between intergenerational trauma, epigenetics, and obesity in Indigenous populations. The review was conducted to identify what is known from the literature about how intergenerational trauma may epigenetically influence obesity in Indigenous populations. Following the PRISMA-ScR guidelines for scoping reviews, online databases were used to identify studies that included discussion of the four focus topics: trauma, epigenetics, obesity, and Indigeneity. The review resulted in six studies that examined those themes. The focus and findings of the selected studies varied from cultural to biological mechanisms and from discussion regarding trauma, epigenetics, obesity, or Indigeneity, but they support three broad statements. First, they support that obesity has genetic and epigenetic factors. Second, intergenerational trauma is prevalent in Indigenous communities. Finally, intergenerational trauma has cultural and biological influences on obesity. Current literature illustrates that intergenerational trauma has behavioural and epigenetic influences that can lead to increased obesity. This scoping review provides a preliminary map of the current literature and understandings of these topics. This review calls for continued studies regarding the connection between trauma, obesity, and epigenetics in Indigenous communities. Future research is vital for practice and policy surrounding individual and communal healing.
Topics: Humans; Historical Trauma; DNA Methylation; Indigenous Peoples; Obesity; Epigenesis, Genetic; Canada
PubMed: 37752750
DOI: 10.1080/15592294.2023.2260218 -
Gynecologic and Obstetric Investigation 2024This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer (CC) and its precancerous lesions.
METHODS
CNKI, Wanfang, Cochrane Library, PubMed, and Ovid databases were searched using a combination of subject headings and free words. Pertinent data were retrieved after screening for inclusion and exclusion criteria, and the quality of the included studies was evaluated using QUADAS-2 criteria. The appropriate software was used for heterogeneity analysis and combined effect size calculation. Additionally, sensitivity analysis was used to evaluate the robustness of the combined results, and meta-regression and subgroup analysis were conducted to investigate the origins of heterogeneity.
RESULTS
This meta-analysis included six studies, including 525 healthy individuals, 182 cervical intraepithelial neoplasia 1 (CIN1) samples, 182 CIN2 samples, 281 CIN3 samples, and 226 CC samples. EPB41L3 methylation detection for CIN2 and above lesions demonstrated combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve of the comprehensive receiver operating characteristic curve of 0.67, 0.76, 3.19, 0.41, 7.60, and 0.80, respectively; CIN3 and above lesions demonstrated these evaluations at 0.73, 0.84, 4.35, 0.33, 23.94, and 0.90, respectively. Meta-regression analysis revealed that the population, time, sample type, detection method, literature quality, and sample size were not significant sources of heterogeneity affecting the combined diagnostic efficacy of CIN2 and above lesions (p > 0.05). Subgroup analysis revealed higher combined diagnostic values of CIN2 and above lesions in retrospective studies, tissue samples, and Chinese populations, with DORs of 41.03, 14.59, and 13.70, respectively.
CONCLUSION
EPB41L3 methylation demonstrated a relatively low diagnostic performance in CC and precancerous lesions. However, it merits further investigation as a potential biomarker. Integrating it with multiple gene detection, human papillomavirus testing, and ThinPrep liquid-based cytology test examination is recommended to explore improved diagnostic strategies for CC and its precancerous lesions.
Topics: Female; Humans; Uterine Cervical Neoplasms; Retrospective Studies; DNA Methylation; Uterine Cervical Dysplasia; Precancerous Conditions; Papillomavirus Infections; Early Detection of Cancer; Microfilament Proteins
PubMed: 38081153
DOI: 10.1159/000535563 -
Prevention Science : the Official... Oct 2023Biological age, measured via epigenetic clocks, offers a unique and useful tool for prevention scientists to explore the short- and long-term implications of age... (Review)
Review
Biological age, measured via epigenetic clocks, offers a unique and useful tool for prevention scientists to explore the short- and long-term implications of age deviations for health, development, and behavior. The use of epigenetic clocks in pediatric research is rapidly increasing, and there is a need to review the landscape of this work to understand the utility of these clocks for prevention scientists. We summarize the current state of the literature on the use of specific epigenetic clocks in childhood. Using systematic review methods, we identified studies published through February 2023 that used one of three epigenetic clocks as a measure of biological aging. These epigenetic clocks could either be used as a predictor of health outcomes or as a health outcome of interest. The database search identified 982 records, 908 of which were included in a title and abstract review. After full-text screening, 68 studies were eligible for inclusion. While findings were somewhat mixed, a majority of included studies found significant associations between the epigenetic clock used and the health outcome of interest or between an exposure and the epigenetic clock used. From these results, we propose the use of epigenetic clocks as a tool to understand how exposures impact biologic aging pathways and development in early life, as well as to monitor the effectiveness of preventive interventions that aim to reduce exposure and associated adverse health outcomes.
Topics: Child; Humans; Epigenesis, Genetic; DNA Methylation; Aging; Databases, Factual
PubMed: 37477807
DOI: 10.1007/s11121-023-01576-4 -
Neurosurgical Review Apr 2024Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after... (Review)
Review
Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.
Topics: Humans; Subarachnoid Hemorrhage; DNA Methylation; Cerebral Infarction; Brain Ischemia; Biomarkers; Vasospasm, Intracranial; Cadherin Related Proteins
PubMed: 38594575
DOI: 10.1007/s10143-024-02381-5 -
Archives of Gynecology and Obstetrics Feb 2024Polycystic ovary syndrome (PCOS) is an endocrine metabolic disease that affects women of reproductive age and is one of the main causes of anovulatory infertility.... (Review)
Review
PURPOSE
Polycystic ovary syndrome (PCOS) is an endocrine metabolic disease that affects women of reproductive age and is one of the main causes of anovulatory infertility. However, the cause of PCOS is yet fully understood, and genetic factors play an important role in its etiology. In this study, we reviewed the main genes involved in the etiology of PCOS and the influence of DNA methylation, aiming to answer the study´s guiding question: 'What is the influence of DNA methylation on the main genes involved in PCOS?'.
METHODS
We used the MEDLINE database, and inclusion criteria (primary and original articles, written in English, found through our entry terms) and exclusion criteria (literature reviews and articles that used animals to perform the experiments and that focused in other epigenetics mechanism without being DNA methylation) were applied.
RESULTS
Twenty-three scientific articles, from a total of 43 articles read in full, were chosen for this study. Eighteen studies confirmed DNA methylation associated with PCOS.
CONCLUSION
The most relevant genes related to PCOS were INSR, LHCGR, and RAB5B, which may be epigenetically altered in DNA, with the first two genes hypomethylated and the last hypermethylated. The epigenetic changes presented in the genes related to PCOS or their promoters were only at the CpG sites.
Topics: Animals; Female; Humans; DNA Methylation; Polycystic Ovary Syndrome; Epigenesis, Genetic; Reproduction
PubMed: 37119419
DOI: 10.1007/s00404-023-07025-5