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BMC Gastroenterology Jun 2022There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients.
METHODS
We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis.
RESULTS
We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications.
CONCLUSIONS
Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.
Topics: Adult; Antibodies, Monoclonal, Humanized; Colitis, Ulcerative; Crohn Disease; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Infliximab
PubMed: 35676620
DOI: 10.1186/s12876-022-02347-1 -
Blood Advances Jun 2020Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer... (Meta-Analysis)
Meta-Analysis
Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer TKIs requires the definition of the optimal first-line TKI for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic-phase (CP) CML. This systematic review of randomized controlled trials (RCTs) compares the efficacy and safety of imatinib vs second-generation (dasatinib, nilotinib, bosutinib) and third-generation TKIs (ponatinib) in adults with newly diagnosed Ph+ CP CML, concentrating on OS, progression-free survival (PFS), and hematological and nonhematological adverse events. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Seven RCTs published between 1990 and 2019 (involving 3262 participants) satisfied the eligibility criteria. Two RCTs (imatinib vs nilotinib and imatinib vs dasatinib) found no difference in 5-year OS or PFS. Second- and third-generation TKIs improved 3-month major molecular responses (relative risk [RR], 4.28; 95% confidence interval [CI], 2.20-8.32) and other efficacy outcomes, decreased accelerated/blastic-phase transformations (RR, 0.44; 95% CI, 0.26-0.74), but were associated with more cases of thrombocytopenia (RR, 1.57; 95% CI, 1.20-2.05), cardiovascular events (RR, 2.54; 95% CI, 1.49-4.33), and pancreatic (RR, 2.29; 95% CI, 1.32-3.96) and hepatic effects (RR, 3.51; 95% CI 1.55-7.92). GRADE showed that the certainty of the evidence ranged from high to moderate. This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities.
Topics: Adult; Antineoplastic Agents; Dasatinib; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
PubMed: 32559295
DOI: 10.1182/bloodadvances.2019001329 -
The Cochrane Database of Systematic... Jan 2018Endoscopic assessment of mucosal disease activity is routinely used to determine eligibility and response to therapy in clinical trials of ulcerative colitis. The... (Review)
Review
BACKGROUND
Endoscopic assessment of mucosal disease activity is routinely used to determine eligibility and response to therapy in clinical trials of ulcerative colitis. The operating properties of the existing endoscopic scoring indices are unclear.
OBJECTIVES
A systematic review was undertaken to evaluate the development and operating characteristics of endoscopic scoring indices for the evaluation of ulcerative colitis.
SEARCH METHODS
We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2016. We also searched references and conference proceedings (Digestive Disease Week, United European Gastroenterology Week, European Crohn's and Colitis Organization).
SELECTION CRITERIA
Any study design (e.g. randomized controlled trials, cohort studies, case series) that evaluated endoscopic indices for evaluation of ulcerative colitis disease activity were considered for inclusion. Eligible participants were adult patients (> 16 years), diagnosed with ulcerative colitis using conventional clinical, radiologic and endoscopic criteria.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed the studies identified from the literature search. These authors also independently extracted and recorded data on the number of patients enrolled; number of patients per treatment arm; patient characteristics including age and gender distribution; endoscopic index; and outcomes such as reliability (intra-rater and inter-rater), validity (content, construct, criterion), responsiveness and feasibility. Any disagreements regarding study inclusion or data extraction were resolved by discussion and consensus with a third author. Risk of bias was assessed by determining whether assessors were blinded to clinical information and whether assessors scored the endoscopic index independently. We also assessed the methodological quality of the validation studies using the COSMIN checklist MAIN RESULTS: A total of 23 reports of 20 studies met the pre-defined inclusion criteria and were included in the review. Of the 20 included validation studies, 19 endoscopic scoring indices were assessed, including the Azzolini Classification, Baron Score, Blackstone Endoscopic Interpretation, Chinese Grading System of Ulcerative Colitis, Endoscopic Activty Index, Jeroen Score, Magnifying Colonoscopy Grade, Matts Score, Mayo Clinic Endoscopic Subscore, Modified Baron Score, Modified Mayo Clinic Endoscopic Subscore, Osada Score, Rachmilewtiz Endoscopic Score, St. Mark's Index, Ulcerative Colitis Colonoscopic Index of Serverity (UCCIS), endoscopic component of the Ulcerative Colitis Disease Activity Index (UCDAI), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Witts Sigmoidoscopic Score and Watson Grade. The individuals who performed the endoscopic scoring were blinded to clinical and/or histologic information in ten of the included studies, not blinded to clinical and/or histologic information in one of the included studies, and it was unclear whether blinding occurred in the remaining nine included studies. Independent observation was confirmed in four of the included studies, unclear in five of the included studies, and non-applicable (since inter-rater reliability was not assessed) in the remaining eleven included studies. The methodological quality (COSMIN checklist) of most of the included studies was rated as 'good' or 'excellent'. One study that assessed responsiveness was rated as 'fair'. The inter-rater reliability of nine endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Endoscopic Activity Index, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS, UCEIS, Watson Grade was assessed in seven studies, with estimates of correlation, ƙ, ranging from 0.44 to 0.97. The iIntra-rater reliability of seven endoscopic scoring indices including the Baron Score, Blackstone Endoscopic Interpretation, Matts Score, Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS and UCEIS was assessed in three studies, with estimates of correlation, ƙ, ranging from 0.41 to 0.86. No studies assessed content validity. Three studies evaluated the criterion validity of three endoscopic scoring indices including the Rachmilewitz Endoscopic Score, Magnifying Colonoscopy Grade and the UCCIS. These indices were correlated with objective markers of disease activity including albumin, blood leukocytes, C-reactive protein, fecal calprotectin, hemoglobin, mucosal interleukin-8 concentration and platelet count. Correlation estimates ranged from r = -0.19 to 0.83. Thirteen endoscopic scoring indices were tested for construct validity in 13 studies. Estimates of correlation between the endoscopic scoring indices and other measures of disease activity ranged from r = 0.27 to 0.93. Two studies explored the responsiveness of four endoscopic scoring indices including the Mayo Endoscopic Subscore, Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS. One study concluded that the Modified Baron Score, Modified Mayo Endoscopic Subscore and UCEIS had similar responsiveness for detecting disease change in ulcerative colitis. The other included study concluded that the UCEIS may be the most accurate endoscopic scoring tool. None of the included studies formally assessed feasibility.
AUTHORS' CONCLUSIONS
While the UCEIS, UCCIS and Mayo Clinic Endoscopic Subscore have undergone extensive validation, none of these instruments have been fully validated and only two studies assessed responsiveness. Further research on the operating properties of these indices is needed given the lack of a fully-validated endoscopic scoring instrument for the evaluation of disease activity in ulcerative colitis.
Topics: Colitis, Ulcerative; Colonoscopy; Humans; Reproducibility of Results; Severity of Illness Index; Sigmoidoscopy
PubMed: 29338066
DOI: 10.1002/14651858.CD011450.pub2 -
Advances in Medical Sciences Mar 2023Multimodal treatment is the standard of care in patients with locally advanced gastric cancer. Unfortunately, the response rate after neoadjuvant treatment remains... (Meta-Analysis)
Meta-Analysis Review
Pre-therapeutic molecular biomarkers of pathological response to neoadjuvant chemotherapy in gastric and esophago-gastric junction adenocarcinoma: A systematic review and meta-analysis.
PURPOSE
Multimodal treatment is the standard of care in patients with locally advanced gastric cancer. Unfortunately, the response rate after neoadjuvant treatment remains limited. The ability to predict the response has a potential to improve patient outcomes by promoting a more individualized approach. We sought to describe the current state of research in pre-treatment molecular biomarkers of response to neoadjuvant therapy in gastric adenocarcinoma available for testing before the initiation of treatment and to perform a systematic review and meta-analysis in order to summarize and evaluate the potential methods.
METHODS
A systematic MEDLINE, EMBASE and CENTRAL literature search was conducted to extract articles on potentially predictive molecular biomarkers of pathological response to neoadjuvant therapy in patients with gastric- and esophago-gastric junction adenocarcinoma. Fixed and random effects models were used to undertake the meta-analysis when appropriate.
RESULTS
Data on predictive biomarkers was reported in 38 studies. These articles described 47 biomarkers showing statistical significance. After evaluation of all reported biomarkers, 3 of them met the inclusion criteria for meta-analysis. The meta-analysis results indicate that >5 ng/mL pre-therapeutic serum concentration of carcinoembryonic antigen (CEA; norm <5 ng/mL) is significantly associated with tumor response (RR = 5.13, 95% CI 2.53-10.43, P = 0.026).
CONCLUSION
Previous studies describe a large number of candidate biomarkers. Our meta-analysis indicated pre-therapeutic serum concentration of CEA >5 ng/mL as a potential and easy-accessible biomarker available for use before initiation of treatment. However, it could be only an additional tool for complex qualification for neoadjuvant therapy.
Topics: Humans; Neoadjuvant Therapy; Stomach Neoplasms; Carcinoembryonic Antigen; Esophageal Neoplasms; Adenocarcinoma
PubMed: 36944288
DOI: 10.1016/j.advms.2023.02.005 -
BMJ Open Jun 2022Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and modified RECIST (mRECIST) are commonly used to assess tumour response. Which one is better to... (Meta-Analysis)
Meta-Analysis
RECIST 1.1 versus mRECIST for assessment of tumour response to molecular targeted therapies and disease outcomes in patients with hepatocellular carcinoma: a systematic review and meta-analysis.
OBJECTIVES
Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) and modified RECIST (mRECIST) are commonly used to assess tumour response. Which one is better to evaluate efficacy after molecular targeted therapies in hepatocellular carcinoma (HCC) patients is still controversial. A systemic review was performed to compare the objective response rate (ORR) and disease control rate (DCR) and a meta-analysis was conducted to compare the correlation between objective response and overall survival (OS).
DESIGN
Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation approach.
DATA SOURCES
EMBASE, PubMed, Web of Science and Cochrane Library were searched through 31 December 2021.
ELIGIBILITY CRITERIA
We included studies assessing the efficacy of molecular targeted therapy for HCC according to both RECIST 1.1 and mRECIST.
DATA EXTRACTION AND SYNTHESIS
Two investigators extracted data independently. The consistency between RECIST 1.1 vs mRECIST is measured by the k coefficient. HRs with corresponding 95% CIs were used for meta-analysis.
RESULTS
23 studies comprising 2574 patients were included in systematic review. The ORR according to mRECIST is higher than RECIST1.1 (15.9% vs 7.8%, p<0.001). The DCR is similar (68.4% vs 67.2%, p=0.5). The agreement of tumour response is moderate for objective response (k=0.499) and perfect for progressive disease (k=0.901), calculated from 8 studies including 372 patients. OS was significantly longer in response group than non-response group according to mRECIST (HR 0.56, 95% CI 0.41 to 0.78, p0.0004) calculated from 7 studies including 566 patients, however, the RECIST1.1 could not distinguish the OS well (HR 0.68, 95% CI 0.44 to 1.05, p=0.08). Subgroup analusis by type of treatment was conducted.
CONCLUSIONS
mRECIST may be more accurate than RECIST 1.1 in assessing ORR after molecular targeted therapies in HCC patients and can better assess the prognosis. However, the performance of both criteria in assessing disease progression is identical.
PROSPERO REGISTRATION NUMBER
CRD42020200895.
ETHICS APPROVAL
Ethics approval is not required in this meta-analysis.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Molecular Targeted Therapy; Prognosis; Response Evaluation Criteria in Solid Tumors
PubMed: 35649603
DOI: 10.1136/bmjopen-2021-052294 -
Nutrients Apr 2023Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of... (Review)
Review
BACKGROUND
Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) as the underlying molecular mechanisms for the anticancer properties of tocotrienol.
METHOD
A comprehensive literature search was performed in March 2023 using the PubMed, Scopus, Web of Science, and EMBASE databases. In vitro, in vivo, and human studies were considered.
RESULT
A total of 840 articles were retrieved during the initial search, and 11 articles that fit the selection criteria were included for qualitative analysis. The current mechanistic findings are based solely on in vitro studies. Tocotrienol induces cancer cell growth arrest, autophagy, and cell death primarily through apoptosis but also through paraptosis-like cell death. Tocotrienol-rich fractions, including α-, γ- and δ-tocotrienols, induce ERS, as evidenced by upregulation of UPR markers and/or ERS-related apoptosis markers. Early endoplasmic reticulum calcium ion release, increased ceramide level, proteasomal inhibition, and upregulation of microRNA-190b were suggested to be essential in modulating tocotrienol-mediated ERS/UPR transduction. Nevertheless, the upstream molecular mechanism of tocotrienol-induced ERS is largely unknown.
CONCLUSION
ERS and UPR are essential in modulating tocotrienol-mediated anti-cancer effects. Further investigation is needed to elucidate the upstream molecular mechanism of tocotrienol-mediated ERS.
Topics: Humans; Tocotrienols; Endoplasmic Reticulum Stress; Unfolded Protein Response; Apoptosis; Cell Death
PubMed: 37111076
DOI: 10.3390/nu15081854 -
European Journal of Surgical Oncology :... Jun 2017This study aimed to evaluate whether the response rate of chemotherapy with molecular target agents correlates with the conversion rate, R0 resection rate, and survival... (Review)
Review
Does response rate of chemotherapy with molecular target agents correlate with the conversion rate and survival in patients with unresectable colorectal liver metastases?: A systematic review.
PURPOSE
This study aimed to evaluate whether the response rate of chemotherapy with molecular target agents correlates with the conversion rate, R0 resection rate, and survival in patients with initially unresectable colorectal liver metastases (CRLM).
METHODS
We reviewed the literature of prospective, controlled trials of systemic chemotherapy for patients with unresectable liver-only CRLM, including resectable extrahepatic metastases. Pearson's correlation coefficients were calculated.
RESULTS
A total of 26 patient groups from 18 studies were reviewed. The response rate was significantly correlated with the conversion rate (r = 0.66) and R0 resection rate (r = 0.43) in overall patients. In subgroup analysis, only the conversion rate in patients with chemotherapy only (r = 0.75) and anti-EGFR therapy (r = 0.78) were significantly strongly correlated with the response rate. A non-significant strong trend toward correlation between response and conversion rates was observed in patients with bevacizumab (r = 0.73, p = 0.10). The regression line in the scatter plot of patients using bevacizumab showed a less steep slope. This indicated that conversion rates were relatively less affected by response rates under anti-VEGF therapy compared with the other patient groups. The response rate in chemotherapy-only patients was significantly correlated with median progression-free survival (r = 0.61) and overall survival (r = 0.66).
CONCLUSIONS
Chemotherapy without molecular target agents and with anti-EGFR agents shows similar results of correlation between response and conversion/R0 resection rates. Under anti-VEGF therapy, conversion would be expected, even with a relatively lower response rate.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antineoplastic Agents; Bevacizumab; Carcinoma; Cetuximab; Colorectal Neoplasms; Disease-Free Survival; ErbB Receptors; Hepatectomy; Humans; Liver Neoplasms; Metastasectomy; Molecular Targeted Therapy; Panitumumab; Survival Rate; Vascular Endothelial Growth Factor A
PubMed: 27624917
DOI: 10.1016/j.ejso.2016.08.019 -
Acta Oncologica (Stockholm, Sweden) 2016The choice of a specific tyrosine kinase inhibitor (TKI) as first line treatment in chronic myeloid leukemia (CML) is complex and influenced by multiple factors. We... (Meta-Analysis)
Meta-Analysis Review
First line treatment with newer tyrosine kinase inhibitors in chronic myeloid leukemia associated with deep and durable molecular response - systematic review and meta-analysis.
BACKGROUND
The choice of a specific tyrosine kinase inhibitor (TKI) as first line treatment in chronic myeloid leukemia (CML) is complex and influenced by multiple factors. We published a meta-analysis examining the role of newer TKIs as first line treatment in chronic phase CML. In view of the recently published data, we decided to update it.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials comparing first line treatment with imatinib to the newer TKIs (nilotinib, dasatinib, bosutinib and ponatinib). We searched MEDLINE, conference proceedings and databases of ongoing trials up to August 2015.
RESULTS
Our search yielded eight trials including 3554 patients. Treatment with the newer TKIs significantly improved major molecular response (MMR) at all time points and increased the rate of complete molecular response (CMR) at 12 and 24 months [relative risk (RR) 2.58, 95% CI 1.98-3.37, six trials and RR 2.05, 95% CI 1.63-2.58, three trials, respectively]. Early molecular response at three months was better with the newer TKIs (RR 1.33, 95% CI 1.26-1.40, six trials). Importantly, progression rate to accelerated or blastic phase was significantly lower with the newer TKIs at 12, 24 months and 5 years. Yet, there was no difference in all-cause mortality. The risk of adverse events requiring treatment discontinuation increased with the newer TKIs.
CONCLUSIONS
With a longer follow-up, the newer TKIs remain more potent than imatinib, yet with no significant effect on survival. As CMR is a prerequisite for treatment discontinuation and cure, the newer TKIs favor treatment cessation.
Topics: Antineoplastic Agents; Dasatinib; Disease Progression; Humans; Imatinib Mesylate; Imidazoles; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Pyridazines; Pyrimidines; Randomized Controlled Trials as Topic; Withholding Treatment
PubMed: 27560448
DOI: 10.1080/0284186X.2016.1201214 -
Journal of Receptor and Signal... Apr 2017Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption,... (Review)
Review
CONTEXT
Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption, particularly in the skin, eyes and lungs, systemic spread of the agent also has detrimental effects on gonads, bone marrow and nervous system. Moreover, chronic exposure of SM to respiratory system causes death. Inducing oxidative stress, and disturbing DNA and tissue repair systems, inflammation and cell death signaling pathways have been introduced as molecular mechanisms of the injury.
METHODS
In this systematic review, more than 1200 (2000-2014) articles focusing on gross or molecular pathological reports in the acute phase of the respiratory injury after SM exposure were reviewed, followed by two different layers of gross and molecular pathological data (clinic and laboratory) integrated together in a spatio-temporal order. Role of epithelial, neutrophil and macrophage cells and three signaling pathways of inflammation, oxidative stress and cell death are covered in details.
RESULTS AND CONCLUSION
Our results propose a critical role of interleukin-17 producing cells in acute and chronic inflammatory responses.
Topics: Cell Death; Chemical Warfare Agents; DNA Damage; DNA Repair; Inflammation; Interleukin-17; Mustard Gas; Oxidative Stress; Signal Transduction
PubMed: 27485024
DOI: 10.1080/10799893.2016.1212374 -
Clinical and Experimental Rheumatology Oct 2023The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the... (Review)
Review
The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the microbiome and immunity in BD. A systematic search for relevant articles was made on PubMed and the Cochrane Library database using the following terms: "microbiota AND Behçet's disease" or "microbiome AND Behçet's disease". Sixteen articles were included in a qualitative synthesis. This systematic review on the microbiome and Behçet's disease underlines the presence of gut dysbiosis in BD patients. This dysbiosis is marked by (i) a decrease in butyrate-producing bacteria, which could affect T cell differentiation and epigenetic regulation of immune-related genes, (ii) a modification of tryptophan-metabolising bacteria, which could be linked to dysregulated IL-22 secretion, and (iii) a decrease in bacteria known to have anti-inflammatory properties. Regarding oral microbiota, this review underlines the possible role of Streptococcus sanguinis through molecular mimicry and NETosis. Clinical studies of BD have shown that (i) need for dentistry is associated with a more severe course in BD, and (ii) antibiotic-supplemented mouthwash reduces pain and ulcers. Fecal transplantation of BD patients' microbiota into mouse models led to decreased SCFA production, neutrophil activation, and Th1/Th17 responses.Recipient mice showed exacerbated experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). In Herpes Virus Simplex-1 (HSV-1) infected mice mimicking BD, administration of butyrateproducing bacteria improved symptoms and immune variables. The microbiome may thus be involved in BD through immunity regulation and epigenetic modifications.
Topics: Humans; Animals; Mice; Behcet Syndrome; Dysbiosis; Epigenesis, Genetic; Uveitis; Microbiota; Bacteria
PubMed: 37382445
DOI: 10.55563/clinexprheumatol/zbt4gx