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The Cochrane Database of Systematic... May 2016About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis. Although other reviews have assessed the ability of blood tests to diagnose endometriosis, this is the first review to use Cochrane methods, providing an update on the rapidly expanding literature in this field.
OBJECTIVES
To evaluate blood biomarkers as replacement tests for diagnostic surgery and as triage tests to inform decisions on surgery for endometriosis. Specific objectives include:1. To provide summary estimates of the diagnostic accuracy of blood biomarkers for the diagnosis of peritoneal, ovarian and deep infiltrating pelvic endometriosis, compared to surgical diagnosis as a reference standard.2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses.
SEARCH METHODS
We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as these databases to 20 April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.
SELECTION CRITERIA
We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more blood biomarkers with the findings of surgical visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS
Two authors independently collected and performed a quality assessment of data from each study. For each diagnostic test, we classified the data as positive or negative for the surgical detection of endometriosis, and we calculated sensitivity and specificity estimates. We used the bivariate model to obtain pooled estimates of sensitivity and specificity whenever sufficient datasets were available. The predetermined criteria for a clinically useful blood test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of ≥ 0.95 and a specificity of ≥ 0.50, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of ≥ 0.50 and a specificity of ≥ 0.95, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).
MAIN RESULTS
We included 141 studies that involved 15,141 participants and evaluated 122 blood biomarkers. All the studies were of poor methodological quality. Studies evaluated the blood biomarkers either in a specific phase of the menstrual cycle or irrespective of the cycle phase, and they tested for them in serum, plasma or whole blood. Included women were a selected population with a high frequency of endometriosis (10% to 85%), in which surgery was indicated for endometriosis, infertility work-up or ovarian mass. Seventy studies evaluated the diagnostic performance of 47 blood biomarkers for endometriosis (44 single-marker tests and 30 combined tests of two to six blood biomarkers). These were angiogenesis/growth factors, apoptosis markers, cell adhesion molecules, high-throughput markers, hormonal markers, immune system/inflammatory markers, oxidative stress markers, microRNAs, tumour markers and other proteins. Most of these biomarkers were assessed in small individual studies, often using different cut-off thresholds, and we could only perform meta-analyses on the data sets for anti-endometrial antibodies, interleukin-6 (IL-6), cancer antigen-19.9 (CA-19.9) and CA-125. Diagnostic estimates varied significantly between studies for each of these biomarkers, and CA-125 was the only marker with sufficient data to reliably assess sources of heterogeneity.The mean sensitivities and specificities of anti-endometrial antibodies (4 studies, 759 women) were 0.81 (95% confidence interval (CI) 0.76 to 0.87) and 0.75 (95% CI 0.46 to 1.00). For IL-6, with a cut-off value of > 1.90 to 2.00 pg/ml (3 studies, 309 women), sensitivity was 0.63 (95% CI 0.52 to 0.75) and specificity was 0.69 (95% CI 0.57 to 0.82). For CA-19.9, with a cut-off value of > 37.0 IU/ml (3 studies, 330 women), sensitivity was 0.36 (95% CI 0.26 to 0.45) and specificity was 0.87 (95% CI 0.75 to 0.99).Studies assessed CA-125 at different thresholds, demonstrating the following mean sensitivities and specificities: for cut-off > 10.0 to 14.7 U/ml: 0.70 (95% CI 0.63 to 0.77) and 0.64 (95% CI 0.47 to 0.82); for cut-off > 16.0 to 17.6 U/ml: 0.56 (95% CI 0.24, 0.88) and 0.91 (95% CI 0.75, 1.00); for cut-off > 20.0 U/ml: 0.67 (95% CI 0.50 to 0.85) and 0.69 (95% CI 0.58 to 0.80); for cut-off > 25.0 to 26.0 U/ml: 0.73 (95% CI 0.67 to 0.79) and 0.70 (95% CI 0.63 to 0.77); for cut-off > 30.0 to 33.0 U/ml: 0.62 (95% CI 0.45 to 0.79) and 0.76 (95% CI 0.53 to 1.00); and for cut-off > 35.0 to 36.0 U/ml: 0.40 (95% CI 0.32 to 0.49) and 0.91 (95% CI 0.88 to 0.94).We could not statistically evaluate other biomarkers meaningfully, including biomarkers that were assessed for their ability to differentiate endometrioma from other benign ovarian cysts.Eighty-two studies evaluated 97 biomarkers that did not differentiate women with endometriosis from disease-free controls. Of these, 22 biomarkers demonstrated conflicting results, with some studies showing differential expression and others no evidence of a difference between the endometriosis and control groups.
AUTHORS' CONCLUSIONS
Of the biomarkers that were subjected to meta-analysis, none consistently met the criteria for a replacement or triage diagnostic test. A subset of blood biomarkers could prove useful either for detecting pelvic endometriosis or for differentiating ovarian endometrioma from other benign ovarian masses, but there was insufficient evidence to draw meaningful conclusions. Overall, none of the biomarkers displayed enough accuracy to be used clinically outside a research setting. We also identified blood biomarkers that demonstrated no diagnostic value in endometriosis and recommend focusing research resources on evaluating other more clinically useful biomarkers.
Topics: Adult; Autoantibodies; Biomarkers; CA-125 Antigen; CA-19-9 Antigen; Endometriosis; Endometrium; Female; Humans; Interleukin-6; Ovarian Diseases; Pelvis; Peritoneal Diseases; Randomized Controlled Trials as Topic
PubMed: 27132058
DOI: 10.1002/14651858.CD012179 -
Biomedicine & Pharmacotherapy =... Jan 2021Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines...
Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines (TCMs) have shown considerable effects in the treatment of metabolic disorders by regulating the gut microbiota. However, the underlying mechanisms are unclear. Studies have shown that TCMs significantly affect glucose and lipid metabolism by modulating the gut microbiota, particularly mucin-degrading bacteria, bacteria with anti-inflammatory properties, lipopolysaccharide- and short-chain fatty acid (SCFA)-producing bacteria, and bacteria with bile-salt hydrolase activity. In this review, we explored potential mechanisms by which TCM improved metabolic disorders via regulating gut microbiota composition and functional structure. In particular, we focused on the protection of the intestinal barrier function, modulation of metabolic endotoxemia and inflammatory responses, regulation of the effects of SCFAs, modulation of the gut-brain axis, and regulation of bile acid metabolism and tryptophan metabolism as therapeutic mechanisms of TCMs in metabolic diseases.
Topics: Animals; Bacteria; Blood Glucose; Drugs, Chinese Herbal; Dysbiosis; Energy Metabolism; Gastrointestinal Microbiome; Humans; Intestines; Lipid Metabolism; Medicine, Chinese Traditional; Metabolic Diseases; Treatment Outcome
PubMed: 33197760
DOI: 10.1016/j.biopha.2020.110857 -
Journal of Clinical Oncology : Official... Apr 2020To provide recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer based on available evidence and expert consensus. (Meta-Analysis)
Meta-Analysis
PURPOSE
To provide recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer based on available evidence and expert consensus.
METHODS
A literature search and prospectively defined study selection criteria sought systematic reviews, meta-analyses, randomized controlled trials (RCTs), and comparative observational studies published from 2007 through 2019. Guideline recommendations were based on the review of the evidence.
RESULTS
The systematic review identified 19 eligible studies. The evidence consisted of systematic reviews of observational data, consensus guidelines, and RCTs.
RECOMMENDATIONS
All women diagnosed with epithelial ovarian cancer should have germline genetic testing for and other ovarian cancer susceptibility genes. In women who do not carry a germline pathogenic or likely pathogenic variant, somatic tumor testing for pathogenic or likely pathogenic variants should be performed. Women with identified germline or somatic pathogenic or likely pathogenic variants in genes should be offered treatments that are US Food and Drug Administration (FDA) approved in the upfront and the recurrent setting. Women diagnosed with clear cell, endometrioid, or mucinous ovarian cancer should be offered somatic tumor testing for mismatch repair deficiency (dMMR). Women with identified dMMR should be offered FDA-approved treatment based on these results. Genetic evaluations should be conducted in conjunction with health care providers familiar with the diagnosis and management of hereditary cancer. First- or second-degree blood relatives of a patient with ovarian cancer with a known germline pathogenic cancer susceptibility gene variant should be offered individualized genetic risk evaluation, counseling, and genetic testing. Clinical decision making should not be made based on a variant of uncertain significance. Women with epithelial ovarian cancer should have testing at the time of diagnosis.
Topics: Carcinoma, Ovarian Epithelial; Female; Genes, BRCA1; Genes, BRCA2; Genetic Counseling; Genetic Testing; Germ-Line Mutation; Health Status Disparities; Humans; Ovarian Neoplasms; Practice Guidelines as Topic; Randomized Controlled Trials as Topic
PubMed: 31986064
DOI: 10.1200/JCO.19.02960 -
World Journal of Gastroenterology Aug 2015To investigate the relationship between Helicobacter pylori (H. pylori) and mucin expression in gastric mucosa. (Meta-Analysis)
Meta-Analysis Review
AIM
To investigate the relationship between Helicobacter pylori (H. pylori) and mucin expression in gastric mucosa.
METHODS
English Medical literature searches were conducted for gastric mucin expression in H. pylori infected people vs uninfected people. Searches were performed up to December 31(th) 2014, using MEDLINE, PubMed, EMBASE, Scopus, and CENTRAL. Studies comparing mucin expression in the gastric mucosa in patients positive and negative for H. pylori infection, were included. Meta-analysis was performed by using Comprehensive meta-analysis software (Version 3, Biostat Inc., Englewood, NJ, United States). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated compared mucin expression in individual studies by using the random effects model. Heterogeneity between studies was evaluated using the Cochran Q-test, and it was considered to be present if the Q-test P value was less than 0.10. I(2) statistic was used to measure the proportion of inconsistency in individual studies, with I(2) > 50% representing substantial heterogeneity. We also calculated a potential publication bias.
RESULTS
Eleven studies, which represent 53 sub-studies of 15 different kinds of mucin expression, were selected according to the inclusion criteria. Every kind of mucin has been considered as one study. When a specific mucin has been studied in more than one paper, we combined the results in a nested meta-analysis of this particular mucin: MUC2, MUC6, STn, Paradoxical con A, Tn, T, Type 1 chain mucin, LeA, SLeA, LeB, AB-PAS, MUC1, and MUC5AC. The odds ratio of mucin expression in random analysis was 2.33, 95%CI: 1.230-4.411, P = 0.009, higher expression in H. pylori infected patients. Odds ratio for mucin expression in H. pylori positive patients was higher for MUC6 (9.244, 95%CI: 1.567-54.515, P = 0.014), and significantly lower for MUC5AC (0.447, 95%CI: 0.211-0.949, P = 0.036). Thus, H. pylori infection may increase MUC6 expression and decrease MUC5AC expression by 924% and 52%, respectively.
CONCLUSION
H. pylori inhibits MUC5AC expression in the gastric epithelium, and facilitates colonization. In contrast, increased MUC6 expression may help inhibiting colonization, using MUC6 antibiotics properties.
Topics: Gastric Mucins; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Host-Pathogen Interactions; Humans; Mucin 5AC; Mucin-6; Odds Ratio
PubMed: 26309370
DOI: 10.3748/wjg.v21.i31.9430 -
Cureus Oct 2023Muco-obstructive lung disease is a new classification under the diseases of respiratory tract. A lot of discussion is still going on regarding this new group of... (Review)
Review
Muco-obstructive lung disease is a new classification under the diseases of respiratory tract. A lot of discussion is still going on regarding this new group of diseases. It is characterised by obstruction of the respiratory tract with a thick mucin layer. Usually in normal individuals, the mucus is swept out of the respiratory system while coughing in the form of sputum or phlegm, but if the consistency of the mucus is thick, or the amount is heavy or there is a certain defect in the ciliary function of the respiratory tract, the mucus is not cleared and it gets accumulated in the lungs alveoli, therefore blocking it. The mucus trapped in the distal airways cannot be cleared by coughing therefore forming a layer in the alveoli and bronchioles. Long-standing condition causes inflammation and infection. This new group of diseases specifically includes chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and non-cystic fibrosis bronchiectasis (NCFB). Asthma, although an obstructive disease of the lung, is not particularly included under muco-obstructive lung disease. The major symptoms with which these diseases present are sputum production, chronic cough and acute exacerbations of the condition. The mucus adheres to the lung parenchyma causing airway obstruction and hyperinflation. In this article, we will see how muco-obstructive lung diseases affect the normal physiology of the respiratory system and how is it different from other obstructive and restrictive lung diseases. We will individually look into all the four conditions that come under the category of muco-obstructive lung diseases.
PubMed: 37954759
DOI: 10.7759/cureus.46866 -
International Journal of Medical... 2023The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5,... (Review)
Review
The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5, 6, 7) and δ (TMED 10), with a total of nine members, which are important regulators of intracellular protein transport and are involved in normal embryonic development, as well as in the pathogenic processes of many human diseases. Here we systematically review the composition, structure and function of TMED family members, and describe the progress of TMED family in human diseases, including malignancies (head and neck tumors, lung cancer, breast cancer, ovarian cancer, endometrial cancer, gastrointestinal tumors, urological tumors, osteosarcomas, etc.), immune responses, diabetes, neurodegenerative diseases, and nonalcoholic fatty liver disease, dilated cardiomyopathy, mucin 1 nephropathy (MKD), and desiccation syndrome (SS). Finally, we discuss and prospect the potential of TMED for disease prognosis prediction and therapeutic targeting, with a view to laying the foundation for therapeutic research based on TMED family causative genes.
Topics: Pregnancy; Female; Humans; Membrane Proteins; Protein Transport; Non-alcoholic Fatty Liver Disease; Vesicular Transport Proteins
PubMed: 37928880
DOI: 10.7150/ijms.87272 -
The Journal of Dermatological Treatment Jun 2022Endocrine mucin-producing sweat gland carcinoma is a rare, under-reported cutaneous adnexal tumor that is often misdiagnosed and has an unknown incidence of metastasis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endocrine mucin-producing sweat gland carcinoma is a rare, under-reported cutaneous adnexal tumor that is often misdiagnosed and has an unknown incidence of metastasis.
OBJECTIVE
To determine the incidence of metastasis and tumor recurrence, as well as diagnostic accuracy and current trends in treatment modality.
METHODS
A search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Tumor pathology and clinical data concerning demographics, presentation, diagnosis, treatment and follow-up were assessed.
RESULTS
A total of 36 publications with 110 cases were identified. Initial pathological diagnosis was incorrect in 45.5% of cases. One case of metastatic disease was reported. The incidence of locoregional recurrence was 10.6% over a mean follow-up period of 21.3 months. Of cases with known methods of resection, 34.6% were resected by excisional biopsy, 42.8% were resected by wide surgical excision, and 31.3% were cleared by Mohs micrographic surgery.
LIMITATIONS
The low reported incidence and level of evidence was suboptimal with only case reports and retrospective case studies being reported.
CONCLUSION
Reported cases of this pathology demonstrate poor diagnostic accuracy. High rates of misdiagnosis and inadequate definitive treatment suggest the need for more comprehensive work-up and management of lesions suspicious for this pathology.
Topics: Adenocarcinoma, Mucinous; Eyelid Neoplasms; Humans; Mucins; Neoplasm Recurrence, Local; Retrospective Studies; Sweat Gland Neoplasms; Sweat Glands
PubMed: 34057875
DOI: 10.1080/09546634.2021.1937479 -
Critical Reviews in Food Science and... Jul 2023Carotenoids have anti-inflammatory and antioxidant properties, being a potential bioactive compound for gut health. The objective of this systematic review was to... (Review)
Review
Carotenoids have anti-inflammatory and antioxidant properties, being a potential bioactive compound for gut health. The objective of this systematic review was to investigate the effects of carotenoids on gut microbiota, gut barrier, and inflammation in healthy animals. The systematic search from PubMed, Scopus, and Lilacs databases were performed up to March 2023. The final screening included thirty studies, with different animal models (mice, rats, pigs, chicks, drosophila, fish, and shrimp), and different carotenoid sources (β-carotene, lycopene, astaxanthin, zeaxanthin, lutein, and fucoxanthin). The results suggested that carotenoids seem to act on gut microbiota by promoting beneficial effects on intestinal bacteria related to both inflammation and SCFA production; increase tight junction proteins expression, important for reducing intestinal permeability; increase the mucins expression, important in protecting against pathogens and toxins; improve morphological parameters important for digestion and absorption of nutrients; and reduce pro-inflammatory and increase anti-inflammatory cytokines. However, different carotenoids had distinct effects on gut health. In addition, there was heterogeneity between studies regarding animal model, duration of intervention, and doses used. This is the first systematic review to address the effects of carotenoids on gut health. Further studies are needed to better understand the effects of carotenoids on gut health.
PubMed: 37450500
DOI: 10.1080/10408398.2023.2234025 -
Journal of Clinical Medicine Apr 2021Mucins are a family of glycosylated proteins which are the primary constituents of mucus and play a dynamic role in the regulation of the protective mucosal barriers... (Review)
Review
Mucins are a family of glycosylated proteins which are the primary constituents of mucus and play a dynamic role in the regulation of the protective mucosal barriers throughout the human body. Ulcerative colitis (UC) is an Inflammatory Bowel Disease (IBD) characterised by continuous inflammation of the inner layer of the large intestine, and in this systematic review we analyse currently available data to determine whether alterations exist in mucin activity in the colonic mucosa of UC patients. Database searches were conducted to identify studies published between 1990 and 2020 that assess the role of mucins in cohorts of UC patients, where biopsy specimens were resected for analysis and control groups were included for comparison. 5497 articles were initially identified and of these 14 studies were systematically selected for analysis, a further 2 articles were identified through citation chaining. Therefore, 16 studies were critically reviewed. 13 of these studies assessed the role of MUC2 in UC and the majority of articles indicated that alterations in MUC2 structure or synthesis had an impact on the colonic mucosa, although conflicting results were presented regarding MUC2 expression. This review highlights the importance of further research to enhance our understanding of mucin regulation in UC and summarises data that may inform future studies.
PubMed: 33946184
DOI: 10.3390/jcm10091935 -
JAMA Network Open Jun 2023Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Randomized clinical trials examining the effectiveness of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer predominantly included patients with high-grade serous carcinomas. The use and outcomes of NACT in less common epithelial carcinomas are understudied.
OBJECTIVE
To investigate the uptake and survival outcomes in treatment with NACT for less common histologic subtypes of epithelial ovarian cancer.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study and systematic literature review with meta-analysis was conducted using the National Cancer Database from 2006 to 2017 and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2006 to 2019. Data analysis was performed from July 2022 to April 2023. The evaluation included patients with stage III to IV ovarian cancer with clear cell, mucinous, or low-grade serous histologic subtypes who received multimodal treatment with surgery and chemotherapy.
EXPOSURES
Exposure assignment per the sequence of treatment: primary debulking surgery (PDS) followed by chemotherapy (PDS group) or NACT followed by interval surgery (NACT group).
MAIN OUTCOMES AND MEASURES
Temporal trends and characteristics of NACT use were assessed using multivariable analysis, and overall survival (OS) was assessed with the inverse probability of treatment weighting propensity score.
RESULTS
A total of 3880 patients were examined in the National Cancer Database including 1829 women (median age, 56 [IQR, 49-63] years) with clear cell, 1156 women (median age, 53 [IQR, 42-64] years) with low-grade serous, and 895 women (median age, 57 [IQR, 48-66] years) with mucinous carcinomas. NACT use increased in patients with clear cell (from 10.2% to 16.2%, 58.8% relative increase; P < .001 for trend) or low-grade serous (from 7.7% to 14.2%, 84.4% relative increase; P = .007 for trend) carcinoma during the study period. This association remained consistent in multivariable analysis. NACT use also increased, but nonsignificantly, in mucinous carcinomas (from 8.6% to 13.9%, 61.6% relative increase; P = .07 for trend). Across the 3 histologic subtypes, older age and stage IV disease were independently associated with NACT use. In a propensity score-weighted model, the NACT and PDS groups had comparable OS for clear cell (4-year rates, 31.4% vs 37.7%; hazard ratio [HR], 1.12; 95% CI, 0.95-1.33) and mucinous (27.0% vs 26.7%; HR, 0.90; 95% CI, 0.68-1.19) carcinomas. For patients with low-grade serous carcinoma, NACT was associated with decreased OS compared with PDS (4-year rates, 56.4% vs 81.0%; HR, 2.12; 95% CI, 1.55-2.90). Increasing NACT use and histologic subtype-specific survival association were also found in the Surveillance, Epidemiology, and End Results Program cohort (n = 1447). A meta-analysis of 4 studies, including the current study, observed similar OS associations for clear cell (HR, 1.13; 95% CI, 0.96-1.34; 2 studies), mucinous (HR, 0.93; 95% CI, 0.71-1.21; 2 studies), and low-grade serous (HR, 2.11; 95% CI, 1.63-2.74; 3 studies) carcinomas.
CONCLUSIONS AND RELEVANCE
Despite the lack of data on outcomes of NACT among patients with less common carcinomas, this study noted that NACT use for advanced disease has gradually increased in the US. Primary chemotherapy for advanced-stage, low-grade serous ovarian cancer may be associated with worse survival compared with PDS.
Topics: Female; Humans; Middle Aged; Adenocarcinoma, Mucinous; Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Cystadenocarcinoma, Serous; Neoadjuvant Therapy; Neoplasm Staging; Ovarian Neoplasms; Peritoneal Neoplasms; Retrospective Studies; Adult; Aged
PubMed: 37326992
DOI: 10.1001/jamanetworkopen.2023.18602