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Cancer Medicine Feb 2023Cutaneous adverse effects (AEs) are common following the phosphoinositide-3-kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K... (Meta-Analysis)
Meta-Analysis Review
Risk of cutaneous adverse events in cancer patients treated with phosphatidylinositol-3-kinase inhibitors: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Cutaneous adverse effects (AEs) are common following the phosphoinositide-3-kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K inhibitor-related cutaneous AEs.
METHODS
The protocol was submitted to the PROSPERO registry. We searched ClinicalTrials.gov and international databases up to July 29, 2022. Meta-analysis was conducted by using risk ratios (RRs) with 95% confidence intervals (CIs).
RESULTS
Fourteen randomized controlled trials (RCTs) comprising 3877 patients were analyzed in this study. Compared with control arms, PI3K inhibitors showed a significant increase in the risk of all-grade rash, high-grade rash, and serious rash events (RR 2.29, 95% CI 1.58-3.31, p < 0.00001; RR 9.34, 95% CI 4.21-20.69, p < 0.00001; RR 5.11, 95% CI 2.11-12.36, p = 0.0003). The overall incidences of all-grade rash and high-grade rash were 26.2% (592/2257) and 4.4% (66/1487). Subgroup analyses of all-grade rash according to cancer types and PI3K inhibitor assignations identified the significant associations. PI3K inhibitors also significantly increased the risk of pruritus and dry skin (RR 1.63, 95% CI 1.14-2.33, p = 0.007; RR 3.34, 95% CI 2.30-4.85, p < 0.00001), with incidences of 13.4% (284/2115) and 9.8% (141/1436) in the treatment group.
CONCLUSION
There is a significantly increased risk of some cutaneous AEs in patients using PI3K inhibitors. Advance intervention is recommended in case of severe and life-threatening events. Further research is required to investigate the risk factors and pathogenesis.
Topics: Humans; Randomized Controlled Trials as Topic; Neoplasms; Phosphoinositide-3 Kinase Inhibitors; Exanthema; Phosphatidylinositol 3-Kinases; Phosphatidylinositols
PubMed: 35986570
DOI: 10.1002/cam4.5153 -
Advances in Medical Sciences Sep 2018Anaphylaxis is defined as severe, life-threatening, systemic or general, immediate reaction of hypersensitivity, with repeatable symptoms caused by the dose of stimulus...
Anaphylaxis is defined as severe, life-threatening, systemic or general, immediate reaction of hypersensitivity, with repeatable symptoms caused by the dose of stimulus which is well tolerated by healthy persons. The proper diagnosis, immediate treatment and differential diagnosis are crucial for saving patient's life. However, anaphylaxis is relatively frequently misdiagnosed or confused with other clinical entities. Thus, there is a continuous need for identifying detectable markers improving the proper diagnosis of anaphylaxis. Here we presented currently known markers of anaphylaxis and discussed in more detail the most clinically valuable ones: tryptase, platelet activacting factor (PAF), PAF-acethylhydrolase, histamine and its metabolites.
Topics: Anaphylaxis; Biomarkers; Histamine; Humans; Platelet Activating Factor; Tryptases
PubMed: 29486376
DOI: 10.1016/j.advms.2017.12.003 -
Talanta Feb 2021Stimulated by the increased recognition of phosphatidylethanol (PEth) as sensitive direct marker of alcohol intake, the Ghent University's Laboratory of Toxicology and...
BACKGROUND
Stimulated by the increased recognition of phosphatidylethanol (PEth) as sensitive direct marker of alcohol intake, the Ghent University's Laboratory of Toxicology and the National Institute of Criminalistics and Criminology combined their efforts to develop a quantitative method. To facilitate implementation the focus was on the use of a sampling technique which allows quick and easy blood collection, without the need of dedicated personnel at any place/any time. In the meantime the cooperation of the two labs should also allow to initiate a Belgian network of laboratories capable of quantifying PEth.
METHODS
Dried blood microsamples were collected via volumetric absorptive microsampling (VAMS). PEth 16:0/18:1 was quantified after liquid-liquid extraction using two independent isotope dilution - liquid chromatography - tandem mass spectrometry methods. A systematic review of the entire process at both sites was performed before the final method comparison using samples from 59 routine toxicology cases collected within a one-year time interval.
RESULTS
Initial differences between both laboratories were solved by focusing on important methodological aspects: (i) trueness verification of the calibration protocol focusing on the primary material, preparation of the stock solutions and adequate equilibration of calibrators and QCs, and (ii) verification of comparability of results obtained with different m/z transitions. Several of these aspects could only be verified by critically assessing spiked and native samples. After a final validation good average comparability of the two methods was observed. The average bias was -0.4%, with 85% of the differences within 20%. Moreover, the methods proved to be reproducible and robust within a one-year time interval.
CONCLUSION
This study is the first to develop a quantitative volumetric absorptive microsampling based method for PEth measurements, in addition it is the first to perform a systematic comparison of PEth measurements between two laboratories. From the discussion on the encountered pitfalls it is clear that also on a global scale, more efforts are needed to improve interlaboratory agreement.
Topics: Chromatography, Liquid; Dried Blood Spot Testing; Glycerophospholipids; Humans; Tandem Mass Spectrometry
PubMed: 33303146
DOI: 10.1016/j.talanta.2020.121694 -
Critical Care (London, England) Feb 2019With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in pulmonary disease diagnosis. We aimed to review and summarize lung fluid biomarkers associated with acute respiratory distress syndrome diagnosis and mortality.
METHODS
After searching PubMed, Embase, Web of Science, and the Cochrane Library for articles published prior to January 11, 2018, we performed a meta-analysis on biomarkers for acute respiratory distress syndrome diagnosis in at-risk patients and those related to disease mortality. From the included studies, we then extracted the mean and standard deviation of the biomarker concentrations measured in the lung fluid, acute respiratory distress syndrome etiologies, sample size, demographic variables, diagnostic criteria, mortality, and protocol for obtaining the lung fluid. The effect size was measured by the ratio of means, which was then synthesized by the inverse-variance method using its natural logarithm form and transformed to obtain a pooled ratio and 95% confidence interval.
RESULTS
In total, 1156 articles were identified, and 49 studies were included. Increases in total phospholipases A2 activity, total protein, albumin, plasminogen activator inhibitor-1, soluble receptor for advanced glycation end products, and platelet activating factor-acetyl choline were most strongly associated with acute respiratory distress syndrome diagnosis. As for biomarkers associated with acute respiratory distress syndrome mortality, interleukin-1β, interleukin-6, interleukin-8, Kerbs von Lungren-6, and plasminogen activator inhibitor-1 were significantly increased in the lung fluid of patients who died. Decreased levels of Club cell protein and matrix metalloproteinases-9 were associated with increased odds for acute respiratory distress syndrome diagnosis, whereas decreased levels of Club cell protein and interleukin-2 were associated with increased odds for acute respiratory distress syndrome mortality.
CONCLUSIONS
This meta-analysis provides a ranking system for lung fluid biomarkers, according to their association with diagnosis or mortality of acute respiratory distress syndrome. The performance of biomarkers among studies shown in this article may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.
Topics: Antigens, Human Platelet; Biomarkers; Bronchoalveolar Lavage Fluid; Hepatocyte Growth Factor; Humans; Interleukin-8; Lung; Plasminogen Activator Inhibitor 1; Platelet Activating Factor; Receptor for Advanced Glycation End Products; Respiratory Distress Syndrome
PubMed: 30755248
DOI: 10.1186/s13054-019-2336-6 -
JBI Database of Systematic Reviews and... Aug 2017Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade... (Review)
Review
BACKGROUND
Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade non-metastatic and metastatic and/or relapsed osteosarcoma involves neoadjuvant multiagent conventional chemotherapy, followed by surgical resection of macroscopically detected tumor and postoperative adjuvant chemotherapy. However, residual micrometastatic deposits that develop following surgery have shown resistance to postoperative/adjuvant chemotherapy. Therefore, there is a critical need for more effective and innovative therapeutic approaches such as immune stimulatory agents. The most extensively studied immune stimulatory agent in the treatment of osteosarcoma is mifamurtide. The aim of this systematic review was to identify and synthesize the evidence on the effectiveness of mifamurtide in addition to standard chemotherapy on survival outcomes.
OBJECTIVES
To present the best available evidence on the treatment of high-grade non-metastatic and metastatic osteosarcoma with mifamurtide in addition to standard chemotherapy.
INCLUSION CRITERIA TYPES OF PARTICIPANTS
All populations of patients regardless of age, gender or ethnicity with high-grade, resectable, non-metastatic and metastatic osteosarcoma based on histological diagnosis.
TYPES OF INTERVENTIONS AND COMPARATORS
This review focused on intravenous infusion of either of the pharmaceutical formulations of mifamurtide (MTP-PE or L-MTP-PE) in addition to standard chemotherapy, and the comparator was chemotherapy alone.
TYPES OF STUDIES
This review considered any experimental study design including randomized controlled trials, non-randomized trials and quasi-experimental studies.
OUTCOMES
The primary outcomes of interest were event-free survival, overall survival and recurrence of osteosarcoma. Secondary outcomes that were considered included health-related quality of life and any mifamurtide-related adverse events.
SEARCH STRATEGY
A search for published and unpublished literature in English was undertaken (seven published literature databases, four unpublished literature databases, and three government agency and organizational websites were searched). Studies published between 1990 to June 2016 were considered. A three-step strategy was developed using MeSH terminology and keywords to ensure that all relevant studies were included related to this review.
METHODOLOGICAL QUALITY
The methodological quality of included studies was assessed by two reviewers, who appraised each study independently, using a standardized Joanna Briggs Institute (JBI) critical appraisal tool.
DATA EXTRACTION
Data was extracted from the studies that were identified as meeting the criteria for methodological quality using the standard JBI data extraction tool.
DATA SYNTHESIS
Due to the heterogeneity of populations and interventions in available studies, meta-analysis was not possible and results are presented in narrative form.
RESULTS
Three papers outlining two studies involving 802 patients evaluated the effectiveness of mifamurtide in addition of chemotherapy. Results indicated no significant difference in event-free survival between the addition of mifamurtide to standard chemotherapy regimen and chemotherapy alone, both in non-metastatic and metastatic osteosarcoma patients. There was a significant difference in progression-free survival favoring the addition of mifamurtide in pulmonary metastatic and/or relapsed osteosarcoma. There was no significant difference in overall survival between the addition of mifamurtide and chemotherapy alone in metastatic osteosarcoma; however there was a significant difference favoring the addition of mifamurtide in non-metastatic osteosarcoma patients. The addition of mifamurtide resulted in a significant difference in survival after relapse in pulmonary metastatic and/or relapsed osteosarcoma patients. Both studies reported on mifamurtide-related adverse events - the first was reported as toxicity which included haematological, hepatic, renal, gastrointestinal disorders, cardiac, rhythm and nervous system disorders, ear disorders and others (infection, fever; and performance status) in metastatic osteosarcoma patients. Results were similar across all combined treatment regimens. Although no statistical analysis was undertaken, the figures suggest there were no significant differences between the treatment regimens. In the other study, mifamurtide-related adverse events were reported as clinical toxic effects of mifamurtide in relapsed osteosarcoma, which included chills, fever and headache for the initial dose of mifamurtide, while for the subsequent doses of mifamurtide all patients reported toxicity as delayed fatigue.
CONCLUSIONS
The available evidence on the effectiveness of mifamurtide in addition to a standard chemotherapy regimen for the treatment of high-grade osteosarcoma is limited and therefore no definitive conclusions can be made.
Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Drug Therapy; Humans; Osteosarcoma; Phosphatidylethanolamines
PubMed: 28800058
DOI: 10.11124/JBISRIR-2016-003105 -
Scientific Reports Jan 2019An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested... (Meta-Analysis)
Meta-Analysis
An unmet but urgent medical need is the development of myelin repair promoting therapies for Multiple Sclerosis (MS). Many such therapies have been pre-clinically tested using different models of toxic demyelination such as cuprizone, ethidium bromide, or lysolecithin and some of the therapies already entered clinical trials. However, keeping track on all these possible new therapies and their efficacy has become difficult with the increasing number of studies. In this study, we aimed at summarizing the current evidence on such therapies through a systematic review and at providing an estimate of the effects of tested interventions by a meta-analysis. We show that 88 different therapies have been pre-clinically tested for remyelination. 25 of them (28%) entered clinical trials. Our meta-analysis also identifies 16 promising therapies which did not enter a clinical trial for MS so far, among them Pigment epithelium-derived factor, Plateled derived growth factor, and Tocopherol derivate TFA-12.We also show that failure in bench to bedside translation from certain therapies may in part be attributable to poor study quality. By addressing these problems, clinical translation might be smoother and possibly animal numbers could be reduced.
Topics: Animals; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Ethidium; Eye Proteins; Lysophosphatidylcholines; Mice; Multiple Sclerosis; Myelin Sheath; Nerve Growth Factors; Oligodendrocyte Precursor Cells; Oligodendroglia; Platelet-Derived Growth Factor; Remyelination; Serpins; Tocopherols
PubMed: 30696832
DOI: 10.1038/s41598-018-35734-4 -
BMC Cancer Sep 2022Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC. METHODS: Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies.
RESULTS
The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I = 35%) and shorter median OS (-8.4 [-13.4, -3.5], I = 58%, N = 1,545). Findings were similar for PFS rates at 6 months (odds ratio [95% CI]: 0.74 [0.59, 0.94], I = 42%, N = 3,160) and 12 months (0.76 [0.59, 0.99], I = 42%, N = 2,468) and directionally consistent but not statistically significant at 18 months (N = 1,726).
CONCLUSIONS
Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; Disease-Free Survival; Female; Humans; Mutation; Phosphatidylinositol 3-Kinases; Phosphatidylinositols; Receptor, ErbB-2
PubMed: 36131248
DOI: 10.1186/s12885-022-10078-5 -
International Journal of Gynecological... Jan 2015This study aimed to assess the diagnostic value of lysophosphatidic acid (LPA) in ovarian cancer. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to assess the diagnostic value of lysophosphatidic acid (LPA) in ovarian cancer.
METHODS
A systematic review of related studies was performed; sensitivity, specificity, and other measures about the accuracy of serum LPA in the diagnosis of ovarian cancer were pooled using random-effects models. Summary receiver operating characteristic curve analysis was used to summarize the overall test performance.
RESULTS
Six studies involving 363 patients with ovarian cancer and 273 healthy control women met the inclusion criteria. The summary estimates for LPA in diagnosing ovarian cancer in the included studies were as follows: sensitivity, 0.94 [95% confidence interval (CI), 0.91-0.96]; specificity, 0.88 (95% CI, 0.83-0.91); and diagnostic odds ratio, 141.59 (95% CI, 52.1-384.63). The area under the curve and Q value for summary receiver operating characteristic curves were 0.97 and 0.92, respectively.
CONCLUSIONS
The LPA assay showed high accuracy and sensitivity for the diagnosis of ovarian cancer. The present study was limited by the small number of available studies and sample size; therefore, additional studies with a better design and larger samples are needed to further assess the diagnostic accuracy of LPA.
Topics: Biomarkers, Tumor; Case-Control Studies; Female; Humans; Lysophospholipids; Ovarian Neoplasms; Prognosis; ROC Curve
PubMed: 25398018
DOI: 10.1097/IGC.0000000000000319 -
Frontiers in Endocrinology 2023Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that...
Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that present mainly as hyperglycemia. Here, we present two case reports of diabetes mellitus caused by the use of tremelimumab and apalutamide, respectively, in cancer treatment, and a comprehensive, comparative review of the literature on these forms of diabetes. Case 1 presented with diabetic ketoacidosis and was diagnosed with ICI-related diabetes mellitus and treated with insulin. Case 2 was diagnosed with PI3Ki-related diabetes mellitus, and her blood glucose level returned to normal with the use of metformin and dapagliflozin. We systematically searched the PubMed database for articles on ICI- and PI3Ki-related diabetes mellitus and characterized the differences in clinical features and treatment between these two forms of diabetes.
Topics: Female; Humans; Antineoplastic Agents; Diabetes Mellitus; Diabetic Ketoacidosis; Hyperglycemia; Immune Checkpoint Inhibitors; Phosphatidylinositols
PubMed: 37732122
DOI: 10.3389/fendo.2023.1236946 -
International Journal of Molecular... May 2021Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of...
Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of obesity because it negatively modulates the hypothalamic control of food intake due to metaflammation and lipotoxicity. The use of animal models, such as rodents, in conjunction with in vitro models of hypothalamic cells, can enhance the understanding of hypothalamic functions related to the control of energy balance, thereby providing knowledge about the impact of diet on the hypothalamus, in addition to targets for the development of new drugs that can be used in humans to decrease body weight. Recently, sphingolipids were described as having a lipotoxic effect in peripheral tissues and the central nervous system. Specifically, lipid overload, mainly from long-chain saturated fatty acids, such as palmitate, leads to excessive ceramide levels that can be sensed by the hypothalamus, triggering the dysregulation of energy balance control. However, no systematic review has been undertaken regarding studies of sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), the hypothalamus, and obesity. This review confirms that ceramides are associated with hypothalamic dysfunction in response to metaflammation, endoplasmic reticulum (ER) stress, and lipotoxicity, leading to insulin/leptin resistance. However, in contrast to ceramide, S1P appears to be a central satiety factor in the hypothalamus. Thus, our work describes current evidence related to sphingolipids and their role in hypothalamic energy balance control. Hypothetically, the manipulation of sphingolipid levels could be useful in enabling clinicians to treat obesity, particularly by decreasing ceramide levels and the inflammation/endoplasmic reticulum stress induced in response to overfeeding with saturated fatty acids.
Topics: Animals; Ceramides; Diet, High-Fat; Endoplasmic Reticulum Stress; Energy Metabolism; Fatty Acids; Humans; Hypothalamus; Insulin Resistance; Leptin; Lysophospholipids; Obesity; Signal Transduction; Sphingolipids; Sphingosine
PubMed: 34069652
DOI: 10.3390/ijms22105357