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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 -
Advances in Nutrition (Bethesda, Md.) Dec 2022Reported breast milk lipid concentrations may vary with geographical region, postnatal age, and year of sample collection. In this review, we summarized data on the... (Meta-Analysis)
Meta-Analysis
Reported breast milk lipid concentrations may vary with geographical region, postnatal age, and year of sample collection. In this review, we summarized data on the concentrations of total fat, total phospholipids, cholesterol, and fatty acids in human milk worldwide and their variation according to lactation stage, study area, and sample collection year. A systematic literature search was performed using the PubMed, Embase, Web of Science, and Medline databases for English-language papers and Wanfang and China National Knowledge Infrastructure databases for Chinese-language papers. A total of 186 studies evaluating the human milk lipid profiles were included. According to random-effects models based on worldwide data, the summarized means (95% CIs) as percentages of total fat were 42.2% (41.1%, 43.3%) for SFAs, 36.6% (35.6%, 37.5%) for MUFAs, and 21.0% (19.3%, 22.7%) for PUFAs. However, the study heterogeneity was high for most types of fatty acids (I2 > 99%). Human milk from Western countries had higher concentrations of MUFAs and 18:1n-9 (ω-9), but lower concentrations of PUFAs, 18:2n-6, 20:4n-6, 18:3n-3, 20:5n-3, 22:6n-3, and total n-6 PUFA compared with those from non-Western countries (P < 0.001-0.011). Significant lactation stage differences were observed for total fat and some individual fatty acids. The concentrations of SFAs and 16:0 were significantly negatively correlated with sampling year (P < 0.001-0.028). In contrast, a significant positive correlation between the concentrations of 18:2n-6 and 18:3n-3 and sampling year was observed (P < 0.001-0.035). Our results suggest that the pooling of data on human milk lipid profiles in different studies should be done with caution due to the high between-study heterogeneity. The concentration of lipids, including total fat, cholesterol, and specific fatty acids, differs in human milk according to lactation stage, geographical region, and year of sample collection.
Topics: Female; Humans; Milk, Human; Fatty Acids; Fatty Acids, Unsaturated; Lactation; Breast Feeding
PubMed: 36083999
DOI: 10.1093/advances/nmac097 -
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 -
PloS One 2022A systematic review and meta-analysis was conducted comparing the presence of anti-phospholipid (anti-PL) antibodies between women of reproductive age, without diagnosis... (Meta-Analysis)
Meta-Analysis
Presence of antiphospholipid antibodies is associated with increased implantation failure following in vitro fertilization technique and embryo transfer: A systematic review and meta-analysis.
PURPOSE
A systematic review and meta-analysis was conducted comparing the presence of anti-phospholipid (anti-PL) antibodies between women of reproductive age, without diagnosis of antiphospholipid syndrome, who experienced at least two implantation failures following in vitro fertilization and embryo transfer (IVF-ET), and either women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET.
METHODS
Systematic search of the literature and meta-analysis of the relevant studies studying presence of antiphospholipid antibodies in women experiencing at least two implantation failures in IVF-ET as compared to either women who had a successful implantation after IVF-ET or/and women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET. Six hundred ninety-four published reports were retrieved; 17 of them fulfilled the inclusion criteria set.
RESULTS
Presence of either any type of anti-phospholipid or anticardiolipin antibodies or lupus-anticoagulant in women experiencing at least two implantation failures in IVF-ET was associated with increased implantation failure compared to women who had a successful implantation after IVF-ET (relative risk, RR: 3.06, 5.06 and 5.81, respectively). Presence of either anticardiolipin or lupus-anticoagulant or anti-beta2 glycoprotein-I or anti-phosphatidylserine antibodies in women experiencing at least two implantation failures in IVF-EΤ was associated with increased implantation failure compared to unselected healthy fertile women with no history of IVF-ET (RR:13.92, 6.37, 15.04 and 164.58, respectively).
CONCLUSION
The prevalence of antiphospholipid antibodies, particularly that of anti-beta2 glycoprotein-I and anti-phosphatidylserine antibodies, in women experiencing at least two implantation failures in IVF-ET without diagnosis of antiphospholipid syndrome is significantly greater than either in women who had a successful implantation after IVF-ET or women with at least one successful spontaneous pregnancy or unselected healthy fertile women with no history of IVF-ET.
TRIAL REGISTRATION NUMBER
PROSPERO ID: CRD42018081458.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Embryo Implantation; Embryo Transfer; Female; Fertilization in Vitro; Humans; Lupus Coagulation Inhibitor; Pregnancy; beta 2-Glycoprotein I
PubMed: 35895635
DOI: 10.1371/journal.pone.0260759 -
Medicina (Kaunas, Lithuania) Jul 2022: The prevalence of cachexia has increased across all of the cancer types and accounts for up to 20% of cancer-related deaths. This paper is a systematic review of... (Review)
Review
: The prevalence of cachexia has increased across all of the cancer types and accounts for up to 20% of cancer-related deaths. This paper is a systematic review of nutritional interventions aiming to improve cachexia outcomes in cancer, focusing on weight gain. : A search in Medline and Elsevier databases for articles up until the 23 January 2022, was conducted. : Out of 5732 screened records, 26 publications were included in the final analysis. Four randomized clinical trials showed a significant body weight (BW) increase in patients treated with eicosapentaenoic acid (EPA), β-hydroxy-beta-methyl butyrate (β-HMB), arginine, and glutamine or marine phospholipids (MPL). An upward BW trend was observed in patients treated with L-carnitine, an Ethanwell/Ethanzyme (EE) regimen enriched with ω-3 fatty acids, micronutrients, probiotics, fish oil, a leucine-rich supplement, or total parental nutrition (TPN) with a high dose of a branched-chain amino acid (BCAA). : Although clinical trials relating to large numbers of nutritional supplements present promising data, many trials provided negative results. Further studies investigating the underlying mechanisms of action of these nutritional supplements in cancer cachexia are needed. Early screening for cancer cachexia risk and nutritional intervention in cancer patients before aggravating weight loss may stabilize their weight, preventing cachexia syndrome. According to the GRADE methodology, no positive recommendation for these nutritional supplements may be expressed.
Topics: Cachexia; Dietary Supplements; Eicosapentaenoic Acid; Humans; Micronutrients; Neoplasms
PubMed: 35888685
DOI: 10.3390/medicina58070966 -
Obesity Science & Practice Jun 2022Inositol is a sugar-alcohol and recognized as a key component of cell membrane phospholipids. It has crucial role in the cell signaling pathways and contribute to... (Review)
Review
BACKGROUND
Inositol is a sugar-alcohol and recognized as a key component of cell membrane phospholipids. It has crucial role in the cell signaling pathways and contribute to improving glycemic responses. Although some earlier studies have revealed the effect of inositol mediating glucose uptake by improving insulin sensitivity, the benefit of inositol supplementation in patients with overweight and obesity is not completely understood. This study aimed to assess the impact of inositol supplementation on body mass index (BMI) through a systematic review and meta-analysis of controlled clinical trials.
METHODS
A systematic search was performed to August 2021 in the following databases: PubMed-Medline, Embase, Web of Science and Scopus. Fifteen controlled clinical trials investigating the effect of inositol on adult's BMI were finally included in the study. A random-effects model was employed to estimate the effect size. Subgroup analysis was performed by dose, duration, age, type of inositol. Meta-regression was used to investigate presence of any linear relationship. Begg's and Egger's tests were carried out to detect small study effect.
RESULTS
The results of pooled analysis showed that inositol supplementation significantly decreased BMI scores (WMD = -0.41 kg/m; 95% CI: -0.78, -0.04; = 0.028). Subgroup analysis was performed to identify the source of heterogeneity among studies ( = 73.9%, < 0.001), demonstrating supplementation duration, baseline BMI, mean age of participants, type of inositol and dosage were potential sources of heterogeneity. The effect of intervention was more clinically significant in participants with polycystic ovary syndrome (PCOS) and overweight/obesity. Inositol in the form of myo-inositol (MI) had stronger effect on BMI reduction.
CONCLUSION
The meta-analysis suggests that oral inositol supplementation has positive effect on BMI reduction. Inositol supplementation could be considered as an adjunct treatment to improve body mass index.
PubMed: 35664247
DOI: 10.1002/osp4.569 -
International Journal of Molecular... Apr 2022(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a... (Review)
Review
(1) Objective: Considering that current knowledge of mechanisms involved in the molecular pathogenesis of Social Anxiety Disorder (SAD) is limited, we conducted a systematic review to evaluate cumulative data obtained by Proton Magnetic Resonance Spectroscopic (H MRS) studies. (2) Methods: A computer-based literature search of Medline, EMBASE, PsycInfo, and ProQuest was performed. Only cross-sectional studies using H MRS techniques in participants with SAD and healthy controls (HCs) were selected. (3) Results: The search generated eight studies. The results indicated regional abnormalities in the 'fear neurocircuitry' in patients with SAD. The implicated regions included the anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), dorsolateral prefrontal cortex (dlPFC), insula, occipital cortex (OC), as well as the subcortical regions, including the thalamus, caudate, and the putamen. (4) Conclusions: The evidence derived from eight studies suggests that possible pathophysiological mechanisms of SAD include impairments in the integrity and function of neurons and glial cells, including disturbances in energy metabolism, maintenance of phospholipid membranes, dysregulations of second messenger systems, and excitatory/inhibitory neurocircuitry. Conducting more cross-sectional studies with larger sample sizes is warranted given the limited evidence in this area of research.
Topics: Brain; Cross-Sectional Studies; Humans; Magnetic Resonance Imaging; Phobia, Social; Proton Magnetic Resonance Spectroscopy; Protons
PubMed: 35563145
DOI: 10.3390/ijms23094754 -
Frontiers in Immunology 2022Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages...
Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages are effector cells and accumulate to the damaged and inflamed sites of arteries to internalize native and chemically modified lipoproteins to transform them into cholesterol-loaded foam cells. Foam cell formation is determined by the capacity of phagocytosis, migration, scavenging, and the features of phenotypes. Macrophages are diverse, and the subsets and functions are controlled by their surrounding microenvironment. Generally, macrophages are divided into classically activated (M1) and alternatively activated (M2). Recently, intraplaque macrophage phenotypes are recognized by the stimulation of CXCL4 (M4), oxidized phospholipids (Mox), hemoglobin/haptoglobin complexes [HA-mac/M(Hb)], and heme (Mhem). The pro-atherogenic or anti-atherosclerotic phenotypes of macrophages decide the progression of AS. Besides, apoptosis, necrosis, ferroptosis, autophagy and pyrotopsis determine plaque formation and cardiovascular vulnerability, which may be associated with macrophage polarization phenotypes. In this review, we first summarize the three most popular hypotheses for AS and find the common key factors for further discussion. Secondly, we discuss the factors affecting macrophage polarization and five types of macrophage death in AS progression, especially ferroptosis. A comprehensive understanding of the cellular and molecular mechanisms of plaque formation is conducive to disentangling the candidate targets of macrophage-targeting therapies for clinical intervention at various stages of AS.
Topics: Atherosclerosis; Foam Cells; Humans; Macrophage Activation; Macrophages; Plaque, Atherosclerotic
PubMed: 35432323
DOI: 10.3389/fimmu.2022.843712 -
Reproduction & Fertility Jul 2021Controversy exists regarding the benefits of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Controversy exists regarding the benefits of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no evidence to support the effectiveness, utility or safety for this treatment. While individual studies may be perceived as weak, a systematic review and meta-analysis were performed to determine if there is any advantage to patients. PubMed, Embase and Scopus searches were performed with the target populations being either recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF) undergoing assisted reproductive technology (ART) and receiving intralipid infusions. These cohorts were compared with either placebo, no intervention or alternative treatments. The most relevant outcome measures were considered to be clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate (IR) and miscarriage rate (MR). Twelve studies encompassing 2676 participants met the criteria for selection and were included and reviewed. Treatment of the target population with intralipid led to an improvement in IR (Odds Ratio (OR): 2.97, 2.05-4.29), pregnancy rate (OR: 1.64, 1.31-2.04), and LBR (OR: 2.36, 1.75-3.17), with a reduction in MR (OR: 0.2, 0.14-0.30). Although intravenous intralipid is not recommended as a routine treatment for recurrent miscarriage or implantation failure, there is enough data to suggest consideration in selected patients where routine testing is unremarkable, standard treatments have failed and immunological risk factors are present. The presence of abnormal uterine natural killer (uNK) cells needs more study as a target marker to determine those who could benefit.
LAY SUMMARY
There is controversy regarding the benefits and efficacy of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no credible evidence to support their use. A situation we frequently face as medical professionals is patients asking us to consider immune therapy (such as intralipid) for reproductive failure where good quality embryos have been used. Intralipid infusions have been reported to improve pregnancy rates with IVF, and reduce the miscarriage risk in selected patient groups, but study results are not universally accepted. We have performed a detailed review and analysis of the literature to determine if there is any benefit to this immune treatment in specific patient groups. Our paper identified and analyzed 12 studies, finding that treatment with intravenous intralipid leads to an improvement in implantation, pregnancy and live birth rates, with a decrease in miscarriage rate. This study shows that there is evidence to suggest consideration of intralipid in certain patients where standard treatments have failed.
Topics: Abortion, Habitual; Emulsions; Female; Humans; Live Birth; Phospholipids; Pregnancy; Pregnancy Rate; Soybean Oil
PubMed: 35118388
DOI: 10.1530/RAF-20-0052 -
Frontiers in Immunology 2021Psoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of autoimmune diseases. However, there is currently a lack of comprehensive evidence of the effectiveness of S1P on psoriasis.
OBJECTIVE
To assess the efficacy and possible mechanism of S1P and its signal modulators in the treatment of psoriasis-like dermatitis.
METHODS
Six databases were searched through May 8, 2021, for studies reporting S1P and its signal modulators. Two reviewers independently extracted information from the enrolled studies. Methodological quality was assessed using SYRCLE's risk of bias tool. RevMan 5.3 software was used to analyze the data. For clinical studies, the Psoriasis Area and Severity Index score were the main outcomes. For preclinical studies, we clarified the role of S1P and its regulators in psoriasis in terms of phenotype and mechanism.
RESULTS
One randomized double-blind placebo-controlled trial and nine animal studies were included in this study. The pooled results showed that compared with control treatment, S1P receptor agonists [mean difference (MD): -6.80; 95% confidence interval (CI): -8.23 to -5.38; p<0.00001], and sphingosine kinase 2 inhibitors (MD: -0.95; 95% CI: -1.26 to -0.65; p<0.00001) alleviated psoriasis-like dermatitis in mice. The mechanism of S1P receptor agonists in treating psoriasis might be related to a decrease in the number of white blood cells, topical lymph node weight, interleukin-23 mRNA levels, and percentage of CD3 T cells (p<0.05). Sphingosine kinase 2 inhibitors ameliorated psoriasis in mice, possibly by reducing spleen weight and cell numbers (p<0.05).
CONCLUSIONS
S1P receptor agonists and sphingosine kinase 2 inhibitors could be potential methods for treating psoriasis by decreasing immune responses and inflammatory factors.
Topics: Animals; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Lysophospholipids; Mice; Phosphotransferases (Alcohol Group Acceptor); Psoriasis; Randomized Controlled Trials as Topic; Receptors, Lysosphingolipid; Software; Sphingosine
PubMed: 34992595
DOI: 10.3389/fimmu.2021.759276