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The Lancet. Rheumatology Dec 2023Sex-related differences in clinical manifestations and disease outcomes exist in psoriatic arthritis, however, there is limited information on sex-related differences in... (Meta-Analysis)
Meta-Analysis
Sex-related differences in patient characteristics, and efficacy and safety of advanced therapies in randomised clinical trials in psoriatic arthritis: a systematic literature review and meta-analysis.
BACKGROUND
Sex-related differences in clinical manifestations and disease outcomes exist in psoriatic arthritis, however, there is limited information on sex-related differences in randomised controlled trials of psoriatic arthritis. We aimed to compare patient characteristics and efficacy and safety of advanced therapies (including biological and targeted synthetic therapies) between male and female patients with psoriatic arthritis participating in randomised controlled trials.
METHODS
In this systematic review and meta-analysis, we searched Medline, Embase, and Central databases, and conference abstract archives, from their inception to June 10, 2022, for randomised controlled trials that assessed the efficacy of advanced therapies in psoriatic arthritis. Two reviewers extracted information on participants' characteristics and rates of American College of Rheumatology (ACR) 20 and ACR50 response and minimal disease activity (MDA) by sex. Random-effects models were used to calculate pooled effects of ACR20, ACR50, and MDA in male versus female patients by drug class.
FINDINGS
We included 54 trials (11 514 [50·9%] of 22 621 participants were female and 11 107 [49·1%] were male). Sex-disaggregated results were reported in a minority of studies (nine [17%] of 54 reported baseline characteristics by sex, 18 [33%] reported efficacy by sex, and two [4%] reported safety endpoints by sex). At baseline, male patients had lower baseline tender joint count (mean difference -3·01 [95% CI -3·83 to -2·18], health assessment questionnaire scores (-0·28 [-0·33 to -0·24]), pain scores (-4·58 [-6·86 to -2·30]), patient global assessment (-3·22 [-5·27 to -1·17]), and physician global assessment (-1·34 [-2·08 to -0·08]) than did female patients. Male patients had higher baseline psoriasis area and severity index scores (mean difference 1·95 [95% CI 0·78 to 3·11]) and C-reactive protein concentrations (2·57 [0·40 to 4·74]) than did female patients. ACR20 response by sex varied across drug classes, with higher rates in males than females with interleukin (IL)-17 inhibitors (odds ratio [OR] 1·70 [95% CI 1·38-2·11]), IL-23 inhibitor (1·46 [1·20-1·78]), IL-12 and IL-23 inhibitor (2·67 [1·39-5·09]), and tumour necrosis factor (TNF) inhibitors (1·55 [1·11-2·18]), but no difference with JAK and TYK2 inhibitors (1·10 [0·87-1·38]). Similarly, ACR50 response rates were higher in male patients versus female patients in all drug classes, with exception of JAK and TYK2 inhibitors (TNF inhibitors, OR 2·17 [95% CI 1·62-2·90]; IL-17 inhibitors, 1·93 [1·56-2·38]; IL-23 inhibitor, 1·71 [1·25-2·34]; IL-12 and 23 inhibitor, 2·43 [1·14-5·20]; and JAK and TYK2 inhibitors, 1·09 [0·73-1·62]). Male patients were more likely to reach MDA with most drug classes, including IL-17 inhibitors (OR 1·99 [95% CI 1·50-2·63]), IL-23 inhibitors (1·79 [1·29-2·50]), TNF inhibitors (2·62 [1·54-4·44]), and JAK and TYK2 inhibitors (1·77 [1·15-2·73]). Risk of bias was low for most studies.
INTERPRETATION
Biological sex of patients with psoriatic arthritis influences their response to advanced therapies, but the effect varies by drug class. Selective reporting might have influenced these results. Future trials should report baseline characteristics and endpoint results by sex.
FUNDING
Canadian Rheumatology Association.
Topics: Humans; Female; Male; Arthritis, Psoriatic; Interleukin-17; Tumor Necrosis Factor Inhibitors; Canada; Interleukin-12; Interleukin Inhibitors; Interleukin-23; Randomized Controlled Trials as Topic
PubMed: 38251562
DOI: 10.1016/S2665-9913(23)00264-3 -
Sleep Medicine Reviews Aug 2023Alzheimer's disease (AD) is the most common type of dementia and is characterized by the aggregation of extracellular amyloid-beta and intracellular hyperphosphorylation... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's disease (AD) is the most common type of dementia and is characterized by the aggregation of extracellular amyloid-beta and intracellular hyperphosphorylation of tau proteins. Obstructive Sleep Apnea (OSA) is associated with increased AD risk. We hypothesize that OSA is associated with higher levels of AD biomarkers. The study aims to conduct a systematic review and meta-analysis of the association between OSA and levels of blood and cerebrospinal fluid biomarkers of AD. Two authors independently searched PubMed, Embase, and Cochrane Library for studies comparing blood and cerebrospinal fluid levels of dementia biomarkers between patients with OSA and healthy controls. Meta-analyses of the standardized mean difference were conducted using random-effects models. From 18 studies with 2804 patients, meta-analysis found that cerebrospinal fluid amyloid beta-40 (SMD:-1.13, 95%CI:-1.65 to -0.60), blood total amyloid beta (SMD:0.68, 95%CI: 0.40 to 0.96), blood amyloid beta-40 (SMD:0.60, 95%CI: 0.35 to 0.85), blood amyloid beta-42 (SMD:0.80, 95%CI: 0.38 to 1.23) and blood total-tau (SMD: 0.664, 95% CI: 0.257 to 1.072, I = 82, p<0.01, 7 studies) were significantly higher in OSA patients compared with healthy controls. These findings suggest that OSA is associated with an elevation of some biomarkers of AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; tau Proteins; Sleep Apnea, Obstructive; Biomarkers
PubMed: 37245474
DOI: 10.1016/j.smrv.2023.101790 -
The Journal of Nutrition Dec 2023The indicator amino acid oxidation (IAAO) method has been accepted as an approach to evaluate habitual protein requirements under free-living conditions.
BACKGROUND
The indicator amino acid oxidation (IAAO) method has been accepted as an approach to evaluate habitual protein requirements under free-living conditions.
OBJECTIVES
This scoping review reports on literature that evaluated protein requirements in humans using the IAAO methods.
METHODS
Three databases (PubMed/Medline, Web of Science, and ProQuest) were systematically searched to identify studies that evaluated protein requirements using the IAAO method published in English until 5 June, 2023. We evaluated the study quality using previously developed criteria. We extracted the characteristics of the study design and the results of protein requirements. Two reviewers conducted both reviews and quality assessments independently; any differences among them were resolved by consensus or agreement of all team members.
RESULTS
We extracted 16 articles targeting children, young adults (including pregnant women, resistance training athletes, endurance-training athletes, and team sports), and older adults. In quality assessment, 14 studies were evaluated "strong," but the remaining 2 were "moderate." These studies were conducted in only 3 countries and did not include all sexes or life stages. The range of the estimated average protein requirements of each life stage was 1.30 g/kg body weight/d for children, 0.87 to 2.10 (0.87-0.93 for general young adults, 1.22-1.52 for pregnant women, 1.49-2.00 for resistance-trained athletes, 1.65-2.10 for endurance athletes, and 1.20-1.41 for team sports athletes) g/kg body weight/d for young adults, and 0.85 to 0.96 g/kg body weight/d for older adults.
CONCLUSIONS
Protein requirements in 14 studies were higher than the current reference for each sex, life stage, and physical activity that are related to protein requirements. In the future, protein requirements of various populations including sex and life stage could be assessed using the IAAO methods worldwide.
Topics: Young Adult; Child; Humans; Female; Pregnancy; Aged; Amino Acids; Nutritional Requirements; Dietary Proteins; Oxidation-Reduction; Body Weight
PubMed: 37573015
DOI: 10.1016/j.tjnut.2023.07.015 -
Physiological Reports Aug 2023Dietary protein ingestion augments post (resistance) exercise muscle protein synthesis (MPS) rates. It is thought that the dose of leucine ingested within the protein... (Review)
Review
BACKGROUND
Dietary protein ingestion augments post (resistance) exercise muscle protein synthesis (MPS) rates. It is thought that the dose of leucine ingested within the protein (leucine threshold hypothesis) and the subsequent plasma leucine variables (leucine trigger hypothesis; peak magnitude, rate of rise, and total availability) determine the magnitude of the postprandial postexercise MPS response.
METHODS
A quantitative systematic review was performed extracting data from studies that recruited healthy adults, applied a bout of resistance exercise, ingested a bolus of protein within an hour of exercise, and measured plasma leucine concentrations and MPS rates (delta change from basal).
RESULTS
Ingested leucine dose was associated with the magnitude of the MPS response in older, but not younger, adults over acute (0-2 h, r = 0.64, p = 0.02) and the entire postprandial (>2 h, r = 0.18, p = 0.01) period. However, no single plasma leucine variable possessed substantial predictive capacity over the magnitude of MPS rates in younger or older adults.
CONCLUSION
Our data provide support that leucine dose provides predictive capacity over postprandial postexercise MPS responses in older adults. However, no threshold in older adults and no plasma leucine variable was correlated with the magnitude of the postexercise anabolic response.
Topics: Humans; Aged; Leucine; Muscle Proteins; Diet; Muscle, Skeletal; Dietary Proteins; Postprandial Period
PubMed: 37537134
DOI: 10.14814/phy2.15775 -
Cancer Investigation Sep 2023RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered... (Review)
Review
RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS, and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60-89%, 0-11%, and 55-89%, respectively, with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects. Hence, selpercatinib and pralsetinib were effective and well tolerated by most of the patients with RET-altered tumors.
Topics: Humans; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Hypertension; Neutropenia; Protein Kinase Inhibitors; Lung Neoplasms; Proto-Oncogene Proteins c-ret
PubMed: 37782113
DOI: 10.1080/07357907.2023.2255655 -
Nutrition Journal Oct 2023The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines,... (Meta-Analysis)
Meta-Analysis Review
The effects of conjugated linoleic acid supplementation on glycemic control, adipokines, cytokines, malondialdehyde and liver function enzymes in patients at risk of cardiovascular disease: a GRADE-assessed systematic review and dose-response meta-analysis.
BACKGROUND
The present systematic review and meta-analysis sought to evaluate the effects of conjugated linoleic acid (CLA) supplementation on glycemic control, adipokines, cytokines, malondialdehyde (MDA) and liver function enzymes in patients at risk of cardiovascular disease.
METHODS
Relevant studies were obtained by searching the PubMed, SCOPUS and Web of Science databases (from inception to January 2023). Weighted mean differences (WMD) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity, sensitivity analysis, and publication bias were reported using standard methods.
RESULTS
A pooled analysis of 13 randomized controlled trials (RCTs) revealed that CLA supplementation led to a significant increment in fasting blood glucose (FBG) (WMD: 4.49 mg/dL; 95%CI: 2.39 to 6.59; P < 0.001), and aspartate aminotransferase (AST) (WMD: 2.54 IU/L; 95%CI: 0.06 to 5.01; P = 0.044). Moreover, CLA supplementation decreased leptin (WMD: -1.69 ng/ml; 95% CI: -1.80 to -1.58; P < 0.001), and interleukin 6 (IL-6) (WMD: -0.44 pg/ml; 95%CI: -0.86 to -0.02; P = 0.037). However, there was no effect on hemoglobin A1c (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and alanine aminotransferase (ALT) adiponectin compared to the control group.
CONCLUSION
Our findings showed the overall favorable effect of CLA supplementation on the adipokines and cytokines including serum IL-6, and leptin, while increasing FBG and AST. It should be noted that the mentioned metabolic effects of CLA consumption were small and may not reach clinical importance.
PROSPERO REGISTERATION COD
CRD42023426374.
Topics: Humans; Dietary Supplements; Leptin; Cytokines; Linoleic Acids, Conjugated; Interleukin-6; Adipokines; Cardiovascular Diseases; Glycemic Control; Malondialdehyde; Liver; Blood Glucose
PubMed: 37794481
DOI: 10.1186/s12937-023-00876-3 -
European Journal of Neurology Jul 2024This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A), a rare but severe neuroinflammatory disorder, to facilitate early diagnosis and appropriate treatment.
METHODS
A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis)-conforming systematic review and meta-analysis was performed on all available data from January 2016 to June 2023. Clinical and neuroimaging phenotypes were extracted for both adult and paediatric forms.
RESULTS
A total of 93 studies with 681 cases (55% males; median age = 46, range = 1-103 years) were included. Of these, 13 studies with a total of 535 cases were eligible for the meta-analysis. Clinically, GFAP-A was often preceded by a viral prodromal state (45% of cases) and manifested as meningitis, encephalitis, and/or myelitis. The most common symptoms were headache, fever, and movement disturbances. Coexisting autoantibodies (45%) and neoplasms (18%) were relatively frequent. Corticosteroid treatment resulted in partial/complete remission in a majority of cases (83%). Neuroimaging often revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities (74%) as well as perivascular (45%) and/or leptomeningeal (30%) enhancement. Spinal cord abnormalities were also frequent (49%), most commonly manifesting as longitudinally extensive myelitis. There were 88 paediatric cases; they had less prominent neuroimaging findings with lower frequencies of both T2/FLAIR hyperintensities (38%) and contrast enhancement (19%).
CONCLUSIONS
This systematic review and meta-analysis provide high-level evidence for clinical and imaging phenotypes of GFAP-A, which will benefit the identification and clinical workup of suspected cases. Differential diagnostic cues to distinguish GFAP-A from common clinical and imaging mimics are provided as well as suitable magnetic resonance imaging protocol recommendations.
Topics: Humans; Astrocytes; Autoantibodies; Autoimmune Diseases of the Nervous System; Glial Fibrillary Acidic Protein; Neuroimaging; Neuroinflammatory Diseases; Phenotype
PubMed: 38506182
DOI: 10.1111/ene.16284 -
Clinical Biochemistry Nov 2023This study aimed to quantitatively estimate the correlation between systemic inflammation with cognitive function, as well as glycemic and lipid profiles in patients... (Meta-Analysis)
Meta-Analysis Review
Correlation between inflammatory biomarkers, cognitive function and glycemic and lipid profiles in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.
This study aimed to quantitatively estimate the correlation between systemic inflammation with cognitive function, as well as glycemic and lipid profiles in patients with type 2 diabetes mellitus (T2DM). The PubMed, Web of Science, EMBASE, SCOPUS, CNKI, Wanfang, VIP, and CBM databases were searched from its inception until June 2023 (PROSPERO registration: CRD42022356889). We analyzed data extracted from observational studies to quantify the correlations (r) as the pooled effect size and further performed subgroup analyses and sensitivity analyses. A total of 32 studies involving 7,483 patients with T2DM were included. The findings revealed a significant moderate negative correlation between interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) levels with Montreal Cognitive Assessment scores. TNF-α levels also had moderate negative correlation with Mini-Mental State Examination scores. For glycemic and lipid profiles, there was a significant moderate positive correlation between CRP and TNF-α levels and glycated hemoglobin (HbA1c), and TNF-α levels were also found to be lowly positively correlated with fasting blood glucose (FBG). CRP levels were found to have a low positive correlation with total cholesterol (TC), and IL-6 levels were found to be lowly positively correlated with triglycerides. The results indicate that elevated levels of IL-6, CRP, and TNF-α are significantly associated with cognitive impairment in patients with T2DM and may serve as inflammatory markers for T2DM with mild cognitive impairment. The CRP and TNF-α levels were more strongly correlated with HbA1c than with FBG and TC. Further research is needed to determine the clinical value of these inflammatory biomarkers and to investigate potential causal mechanisms underlying this association.
Topics: Humans; Diabetes Mellitus, Type 2; Interleukin-6; Tumor Necrosis Factor-alpha; Glycated Hemoglobin; C-Reactive Protein; Biomarkers; Cognition; Triglycerides; Blood Glucose
PubMed: 37939987
DOI: 10.1016/j.clinbiochem.2023.110683 -
RMD Open Aug 2023The first biomarker associated with the rheumatoid arthritis is rheumatoid factor (RF) and since the earliest reports a role has been proposed in the diagnosis and in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The first biomarker associated with the rheumatoid arthritis is rheumatoid factor (RF) and since the earliest reports a role has been proposed in the diagnosis and in the prediction of clinical features and outcome. The study of RF isotypes has further attempted to improve diagnostic accuracy and identify specific subgroups of patients. The main objective of this study is to provide an analysis of the literature on the role of RF isotypes in the diagnosis and prognosis of rheumatoid arthritis (RA).
METHODS
We performed a systematic literature review and meta-analysis on the role of RF isotypes in RA (only in English, from PubMed, search terms: "rheumatoid factor isotypes", "diagnosis", "prognosis" and "rheumatoid arthritis", last search 31 July 2022, two independent assessment of quality and biases, results included in tables and in the meta-analysis).
RESULTS
Thirty-six articles were examined (7517 patients). Testing all RF isotypes with latex test or nephelometry allows for the highest sensitivity (68.6%, 95% CI 66.2% to 71.0%); nonetheless, the determination of IgA isotype provides the highest specificity (91.4%, 95% CI 90.8% to 92.0%) and the highest positive likelihood ratio (7.7, 95% CI 5.7 to 10.4). When testing IgM isotype the highest diagnostic OR (21.7, 95% CI 16.1 to 29.3) is reached. When analysing anti-citrullinated protein antibodies, RF isotype determination increases diagnostic accuracy. On the other hand, these do not provide relevant prognostic information, as results are conflicting.
CONCLUSIONS
Testing RF allows the highest sensitivity, while IgA isotype the highest specificity and positive likelihood ratio for RA diagnosis. On the other hand, determination of RF isotypes dose not allow prognostic information, as data are limited and heterogeneous.
Topics: Humans; Rheumatoid Factor; Arthritis, Rheumatoid; Immunoglobulin Isotypes; Anti-Citrullinated Protein Antibodies; Immunoglobulin A
PubMed: 37541740
DOI: 10.1136/rmdopen-2022-002817 -
BMC Cancer Nov 2023RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial.
METHODS
We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups.
RESULTS
Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47-5.73) and 2.69 (1.82-3.98)] and OS [HRs = 2.66 (1.95-3.65) and 2.45 (1.55-3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (P < 0.01 for PFS). Patients with tumors with any mutation in the KRAS/NRAS/BRAF/PIK3CA gene also showed similar results compared with all wild-type tumors (P for PFS, OS, and ORR were < 0.01, < 0.01 and 0.01, respectively). While low miR-31-3p expression could predict PFS (P = 0.01) and OS (P = 0.04) benefit. The prognostic and predictive value regarding PIK3CA mutations, PTEN mutations or deletions, EGFR, EREG/AREG, HER2, HER3, and HER4 expression remains uncertain.
CONCLUSIONS
In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.
Topics: Humans; Prognosis; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); ErbB Receptors; Antibodies, Monoclonal; Colonic Neoplasms; Rectal Neoplasms; Biomarkers; Class I Phosphatidylinositol 3-Kinases; Mutation; MicroRNAs; Biomarkers, Tumor
PubMed: 37974093
DOI: 10.1186/s12885-023-11600-z