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Urologic Oncology Jan 2021To evaluate the predictive value of molecular subtypes on oncological outcomes and response to cancer treatment in patients with urothelial bladder carcinoma (UBC). (Meta-Analysis)
Meta-Analysis
The value and limitations of urothelial bladder carcinoma molecular classifications to predict oncological outcomes and cancer treatment response: A systematic review and meta-analysis.
AIM
To evaluate the predictive value of molecular subtypes on oncological outcomes and response to cancer treatment in patients with urothelial bladder carcinoma (UBC).
MATERIALS AND METHODS
A literature search using PubMed, Scopus, and Cochrane Library was conducted on April 2020 to identify relevant studies according to the preferred reporting items for systematic review and meta-analysis guidelines. The pooled overall survival (OS), cancer-specific survival (CSS), and progression-free survival were calculated using a fixed or random effects model.
RESULTS
We identified 66 studies (including 21,447 molecular subtype records) evaluating the impact of molecular classification on oncologic outcomes in patients with UBC. We found significant association of different molecular subtypes with OS, CSS, progression-free survival, recurrence-free survival, and response to treatment. Totally, 11 studies were included in the meta-analysis. Basal group and NE-like subtypes were associated with worse OS (pooled HR: 1.78, 95%CI: 1.49-2.12, and pooled HR: 2.67, 95%CI: 1.08-6.60, respectively) in patients with muscle invasive bladder cancer. Luminal group was also associated with worse CSS (pooled HR of 3.67, 95%CI: 2.19-6.14).
CONCLUSIONS
Based on these data, UBC molecular classifications are significant predictors of oncological outcomes and identify patients who are most likely to benefit from intensified or different therapies. The optimal consensus on molecular classification remains to be verified in well-designed prospective studies to allow precise prognostic and predictive value assessment.
Topics: Carcinoma, Transitional Cell; Humans; Predictive Value of Tests; Survival Rate; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 32900624
DOI: 10.1016/j.urolonc.2020.08.023 -
Journal of Sport Rehabilitation Nov 2012Systematic literature review. (Review)
Review
STUDY DESIGN
Systematic literature review.
OBJECTIVE
To assess the efficacy of deep friction massage (DFM) in the treatment of tendinopathy.
CONTEXT
Anecdotal evidence supports the efficacy of DFM for the treatment of tendinopathy. An advanced understanding of the etiopathogenesis of tendinopathy and the resultant paradigm shift away from an active inflammatory model has taken place since the popularization of the DFM technique by Cyriax for the treatment of "tendinitis." However, increasing mechanical load to the tendinopathic tissue, as well as reducing molecular cross-linking during the healing process via transverse massage, offers a plausible explanation for observed responses in light of the contemporary understanding of tendinopathy.
EVIDENCE ACQUISITION
The authors surveyed research articles in all languages by searching PubMed, Scopus, Pedro, CINAHL, PsycINFO, and the Cochrane Library using the terms deep friction massage, deep tissue massage, deep transverse massage, Cyriax, soft tissue mobilization, soft tissue mobilisation, cross friction massage, and transverse friction massage. They included 4 randomized comparison trials, 3 at the extensor carpi radialis brevis (ECRB) and 1 supraspinatus outlet tendinopathy; 2 nonrandomized comparison trials, both receiving DFM at the ECRB; and 3 prospective noncomparison trials-supraspinatus, ECRB, and Achilles tendons. Articles meeting inclusion criteria were assessed based on PEDro and Centre for Evidence-Based Medicine rating scales.
RESULTS
Nine studies met the inclusion criteria.
EVIDENCE SYNTHESIS
The heterogeneity of dependent measures did not allow for meta-analysis.
CONCLUSION
The varied locations, study designs, etiopathogenesis, and outcome tools used to examine the efficacy of DFM make a unified conclusion tenuous. There is some evidence of benefit at the elbow in combination with a Mills manipulation, as well as for supraspinatus tendinopathy in the presence of outlet impingement and along with joint mobilization. The examination of DFM as a single modality of treatment in comparison with other methods and control has not been undertaken, so its isolated efficacy has not been established. Excellent anecdotal evidence remains along with a rationale for its use that fits the current understanding of tendinopathy.
Topics: Evidence-Based Medicine; Friction; Humans; Joint Diseases; Massage; Randomized Controlled Trials as Topic; Tendinopathy
PubMed: 22234925
DOI: 10.1123/jsr.21.4.343 -
International Journal of Molecular... Apr 2024Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal... (Review)
Review
Preeclampsia, a serious complication of pregnancy, involves intricate molecular and cellular mechanisms. Fetal microchimerism, where fetal cells persist within maternal tissues and in circulation, acts as a mechanistic link between placental dysfunction and maternal complications in the two-stage model of preeclampsia. Hormones, complements, and cytokines play pivotal roles in the pathophysiology, influencing immune responses, arterial remodeling, and endothelial function. Also, soluble HLA-G, involved in maternal-fetal immune tolerance, is reduced in preeclampsia. Hypoxia-inducible factor 1-alpha (Hif-α) dysregulation leads to placental abnormalities and preeclampsia-like symptoms. Alterations in matrix metalloproteinases (MMPs), endothelins (ETs), chemokines, and cytokines contribute to defective trophoblast invasion, endothelial dysfunction, and inflammation. Preeclampsia's genetic complexity includes circRNAs, miRNAs, and lncRNAs. CircRNA_06354 is linked to early-onset preeclampsia by influencing trophoblast invasion via the hsa-miR-92a-3p/VEGF-A pathway. The dysregulation of C19MC, especially miR-519d and miR-517-5p, affects trophoblast function. Additionally, lncRNAs like IGFBP1 and EGFR-AS1, along with protein-coding genes, impact trophoblast regulation and angiogenesis, influencing both preeclampsia and fetal growth. Besides aberrations in CD31+ cells, other potential biomarkers such as MMPs, soluble HLA-G, and hCG hold promise for predicting preeclampsia and its complications. Therapeutic interventions targeting factors such as peroxisome PPAR-γ and endothelin receptors show potential in mitigating preeclampsia-related complications. In conclusion, preeclampsia is a complex disorder with a multifactorial etiology and pathogenesis. Fetal microchimerism, hormones, complements, and cytokines contribute to placental and endothelial dysfunction with inflammation. Identifying novel biomarkers and therapeutic targets offers promise for early diagnosis and effective management, ultimately reducing maternal and fetal morbidity and mortality. However, further research is warranted to translate these findings into clinical practice and enhance outcomes for at-risk women.
Topics: Female; Humans; Pregnancy; Biomarkers; Hormones; MicroRNAs; Placenta; Pre-Eclampsia; Trophoblasts
PubMed: 38674114
DOI: 10.3390/ijms25084532 -
European Journal of Clinical Nutrition Mar 2023To determine the minimum amount of oat β-glucan (OBG) required to reduce glycaemic responses (MinDose), we conducted a systematic review and meta-regression analysis of... (Review)
Review
The importance of molecular weight in determining the minimum dose of oat β-glucan required to reduce the glycaemic response in healthy subjects without diabetes: a systematic review and meta-regression analysis.
To determine the minimum amount of oat β-glucan (OBG) required to reduce glycaemic responses (MinDose), we conducted a systematic review and meta-regression analysis of acute, crossover, single-meal feeding trials that examined the effects of adding OBG or oat bran to a carbohydrate-containing test-meal versus a control test-meal containing an equivalent amount of available-carbohydrate (avCHO) from the same or similar source. Medline, Embase, and Cochrane Library were searched up to 18 August 2021. The primary outcome was glucose incremental-area-under-the-curve (iAUC). Secondary outcomes included insulin iAUC, and glucose and insulin incremental peak-rise (iPeak). Two independent reviewers extracted data. Results were expressed as ratio-of-means (RoM) with 95% confidence intervals (CIs). Linear associations were assessed by random effects meta-regression. MinDose was defined as the dose at which the upper 95% CI of the regression line cut the line of no effect (i.e., RoM = 1). Fifty-nine comparisons (n = 340) were included; 57 in healthy subjects without diabetes and two in subjects with diabetes; 24 high-MW (>1000 kg/mol), 22 medium-MW (300-1,000 kg/mol), and 13 low-MW (<300 kg/mol). In healthy subjects without diabetes the associations between OBG dose and glucose iAUC and iPeak were linear (non-linear p value >0.05). MinDoses for glucose iAUC for high-MW, medium-MW and low-MW OBG, respectively, were estimated to be 0.2 g, 2.2 g and 3.2 g per 30 g avCHO; MinDoses for glucose iPeak were less than those for iAUC. Insufficient data were available to assess MinDose for insulin, however, there was no evidence of a disproportionate increase in insulin. More high-quality trials are needed to establish MinDose in individuals with diabetes.
Topics: Humans; Blood Glucose; Molecular Weight; Healthy Volunteers; Avena; Diabetes Mellitus; Insulin; Regression Analysis; Glucose
PubMed: 35768556
DOI: 10.1038/s41430-022-01176-5 -
The Journal of Orthopaedic and Sports... Apr 2023To summarize the effectiveness of management strategies and rehabilitation approaches for knee joint structural and molecular biomarker outcomes following anterior... (Review)
Review
The Effects of Different Management Strategies or Rehabilitation Approaches on Knee Joint Structural and Molecular Biomarkers Following Traumatic Knee Injury: A Systematic Review of Randomized Controlled Trials for the OPTIKNEE Consensus.
To summarize the effectiveness of management strategies and rehabilitation approaches for knee joint structural and molecular biomarker outcomes following anterior cruciate ligament (ACL) and/or meniscal tear. Intervention systematic review. We searched the MEDLINE, Embase, CINAHL, CENTRAL, and SPORTDiscus databases from their inception up to November 3, 2021. We included randomized controlled trials (RCTs) investigating the effectiveness of management strategies or rehabilitation approaches for structural/molecular biomarkers of knee joint health following ACL and/or meniscal tear. We included 5 RCTs (9 papers) with primary ACL tear (n = 365). Two RCTs compared initial management strategies (rehabilitation plus early vs optional delayed ACL surgery), reporting on structural biomarkers (radiographic osteoarthritis, cartilage thickness, meniscal damage) in 5 papers and molecular biomarkers (inflammation, cartilage turnover) in 1 paper. Three RCTs compared different post-ACL reconstruction (ACLR) rehabilitation approaches (high vs low intensity plyometric exercises, accelerated vs nonaccelerated rehabilitation, continuous passive vs active motion), reporting on structural biomarkers (joint space narrowing) in 1 paper and molecular biomarkers (inflammation, cartilage turnover) in 2 papers. There were no differences in structural or molecular biomarkers between post-ACLR rehabilitation approaches. One RCT comparing initial management strategies demonstrated that rehabilitation plus early ACLR was associated with greater patellofemoral cartilage thinning, elevated inflammatory cytokine response, and reduced incidence of medial meniscal damage over 5 years compared to rehabilitation with no/delayed ACLR. Very low-certainty evidence suggests that different initial management strategies (rehabilitation plus early vs optional delayed ACL surgery) but not postoperative rehabilitation approaches may influence the incidence of meniscal damage, patellofemoral cartilage loss and cytokine concentrations over 5 years post-ACL tear. .
Topics: Humans; Anterior Cruciate Ligament Injuries; Consensus; Inflammation; Knee Injuries; Knee Joint; Randomized Controlled Trials as Topic
PubMed: 36802814
DOI: 10.2519/jospt.2023.11576 -
Value in Health : the Journal of the... 2013In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic... (Meta-Analysis)
Meta-Analysis Review
Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: a case study for technology appraisal on the basis of surrogate outcomes evidence.
OBJECTIVES
In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence's recommendation on the public funding of these first-line treatments for CML.
METHODS
We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR.
RESULTS
Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21-23 years) following first-line treatment with imatinib, dasatinib, or nilotinib.
CONCLUSIONS
This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cytogenetic Analysis; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Organizational Case Studies; Outcome Assessment, Health Care; Survival Analysis; Technology Assessment, Biomedical; Young Adult
PubMed: 24041359
DOI: 10.1016/j.jval.2013.07.004 -
Journal of Endodontics Nov 2015Signaling molecules and responding dental pulp stem cells are the 2 main control keys of dentin regeneration/dentinogenesis. The aim of this study was to present a... (Review)
Review
INTRODUCTION
Signaling molecules and responding dental pulp stem cells are the 2 main control keys of dentin regeneration/dentinogenesis. The aim of this study was to present a systematic review investigating the gene expression of various dental pulp cells in response to different variants of tricalcium silicate cements.
METHODS
A systematic search of the literature was performed by 2 independent reviewers followed by article selection and data extraction. Studies analyzing all sorts of dental pulp cells (DPCs) and any variant of tricalcium silicate cement either as the experimental or as the control group were included.
RESULTS
A total of 39 articles were included in the review. Among the included studies, ProRoot MTA (Dentsply, Tulsa Dental, OK) was the most commonly used tricalcium silicate cement variant. The extracellular signal regulated kinase/mitogen-activated protein kinase pathway was the most commonly activated pathway to be identified, and similarly, dentin sialophosphoprotein osteocalcin dentin matrix acidic phosphoprotein 1, alkaline phosphatase, bone sialoprotein, osteopontin, type I collagen, and Runx2 were the most commonly expressed genes in that order of frequency.
CONCLUSIONS
Biodentine (Septodont Ltd, Saint Maur des Faussés, France), Bioaggregate (Innovative Bioceramix, Vancouver, BC, Canada), and mineral trioxide aggregate stimulate the osteogenic/odontogenic capacity of DPCs by proliferation, angiogenesis, and biomineralization through the activation of the extracellular signal regulated kinase ½, nuclear factor E2 related factor 2, p38, c-Jun N-terminal kinase mitogen-activated protein kinase, p42/p44 mitogen-activated protein kinase, nuclear factor kappa B, and fibroblast growth factor receptor pathways. When DPCs are placed into direct contact with tricalcium silicate cements, they show higher levels of gene activation, which in turn could translate into more effective pulpal repair and faster and more predictable formation of reparative dentin.
Topics: Calcium Compounds; Cell Proliferation; Cytokines; Dental Materials; Dental Pulp; Gene Expression Profiling; Humans; Osteogenesis; Silicates
PubMed: 26381895
DOI: 10.1016/j.joen.2015.07.015 -
Journal of Endodontics Dec 2016The aim of this study was to present a systematic review investigating the gene expression of various cells (other than dental pulp cells) in response to different... (Review)
Review
INTRODUCTION
The aim of this study was to present a systematic review investigating the gene expression of various cells (other than dental pulp cells) in response to different variants of tricalcium silicate cements (TSCs).
METHODS
A systematic search of the literature was performed by 2 independent reviewers followed by article selection and data extraction. Studies analyzing any cell type except dental pulp stem cells and any variant of tricalcium silicate cement either as the experimental or as the control group were included.
RESULTS
A total of 41 relevant articles were included in this review. Among the included studies, ProRoot MTA (Dentsply, Tulsa, OK) was the most commonly studied (69.1%) TSC variant, and 11 cell types were identified, with 13 articles investigating gene expression in osteoblasts. A total of 39 different genes/molecules expressed were found in the selected studies. The experimental group (irrespective of the TSC variant) was identified to express significantly increased gene expression compared with the control group (untreated) in all included studies. Recent studies have provided useful insight into the gene expression and molecular signaling of various cells in response to TSCs, and new elements have been supplied on the pathways activated in this process.
CONCLUSIONS
TSCs are capable of eliciting a favorable cellular response in periapical regeneration.
Topics: Calcium Compounds; Cell Line; Cell Proliferation; Cytokines; Dental Cements; Dental Cementum; Dental Materials; Dental Pulp; Fibroblasts; Gene Expression; Gene Expression Profiling; Humans; Materials Testing; Odontoblasts; Osteoblasts; Osteoclasts; Signal Transduction; Silicate Cement; Silicates; Stem Cells
PubMed: 27776883
DOI: 10.1016/j.joen.2016.08.027 -
Frontiers in Oncology 2019A new goal in treatment of chronic myeloid leukemia (CML) in patients with stable deep molecular response (DMR) is maintaining durable treatment-free remission (TFR)...
Discontinuation of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia With Losing Major Molecular Response as a Definition for Molecular Relapse: A Systematic Review and Meta-Analysis.
A new goal in treatment of chronic myeloid leukemia (CML) in patients with stable deep molecular response (DMR) is maintaining durable treatment-free remission (TFR) after discontinuing tyrosine kinase inhibitor (TKI) treatment. We conducted a systematic review and meta-analysis focusing on the efficacy and safety of TKI discontinuation but also exploring the factors contributing to successful TFR. The search yielded 10 trials including 1,601 patients. For patients who discontinued TKIs, the estimated weighted mean incidence of major molecular relapse was 16% (95%CI: 11-21), 34% (95%CI: 29-38), 39% (95%CI: 35-43) and 41% (95%CI: 36-47) at 3, 6, 12, and 24 months, respectively. Of these, 39, 82, and 95% of molecular losses occurred within the first 3, 6, and 12 months. In safety analysis, among patients without TFR, 98% (95% CI: 96-100) were sensitive to TKI retreatment. No new safety issues were identified except TKI withdrawal syndrome, which appeared during the early TFR phase, with a weighted mean incidence of 27% (95%CI: 19-35). Our subgroup analysis suggested better TFR associated with interferon therapy ( = 0.007), depth of molecular response ( = 0.018) and duration of DMR ( < 0.001). TFR as an extension of an approach to optimize management of CML is clinically feasible in approximately 59% of patients with sufficient TKI response. In the remaining 41% of patients with molecular relapse, discontinuing TKIs had no negative impact on clinical outcomes. Given the high heterogeneity among studies, the role of these predictors for successful TFR still requires further investigation.
PubMed: 31139566
DOI: 10.3389/fonc.2019.00372 -
Critical Reviews in Microbiology Jul 2023The formation of bacterial biofilms in the human body and on medical devices is a serious human health concern. Infections related to bacterial biofilms are often... (Review)
Review
The formation of bacterial biofilms in the human body and on medical devices is a serious human health concern. Infections related to bacterial biofilms are often chronic and difficult to treat. Detailed information on biofilm formation and composition over time is essential for a fundamental understanding of the underlying mechanisms of biofilm formation and its response to anti-biofilm therapy. However, information on the chemical composition, structural components of biofilms, and molecular interactions regarding metabolism- and communication pathways within the biofilm, such as uptake of administered drugs or inter-bacteria communication, remains elusive. Imaging these molecules and their distribution in the biofilm increases insight into biofilm development, growth, and response to environmental factors or drugs. This systematic review provides an overview of molecular imaging techniques used for bacterial biofilm imaging. The techniques included mass spectrometry-based techniques, fluorescence-labelling techniques, spectroscopic techniques, nuclear magnetic resonance spectroscopy (NMR), micro-computed tomography (µCT), and several multimodal approaches. Many molecules were imaged, such as proteins, lipids, metabolites, and quorum-sensing (QS) molecules, which are crucial in intercellular communication pathways. Advantages and disadvantages of each technique, including multimodal approaches, to study molecular processes in bacterial biofilms are discussed, and recommendations on which technique best suits specific research aims are provided.
PubMed: 37452571
DOI: 10.1080/1040841X.2023.2223704