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Cureus Aug 2022Rheumatoid arthritis (RA) is associated with both local and systemic inflammatory processes via the aberrant regulation of inflammatory pathways and imbalances in... (Review)
Review
A Systematic Review of Nutritional Interventions on Key Cytokine Pathways in Rheumatoid Arthritis and Its Implications for Comorbid Depression: Is a More Comprehensive Approach Required?
Rheumatoid arthritis (RA) is associated with both local and systemic inflammatory processes via the aberrant regulation of inflammatory pathways and imbalances in several mediators of inflammation. Cytokines, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1B, IL-6, IL-17, IL-18, rheumatoid factor, anti-cyclic citrullinated protein, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) have been used in diagnosing and tracking the progression of RA. The primary objective of this review is to identify and summarize which specific dietary patterns and nutritional interventions go beyond symptom management to improve the response to known inflammatory cytokines and possibly decrease markers of inflammation in the RA disease process. Analysis of the 41 identified publications demonstrated that certain dietary patterns, the consumption of specific macronutrients, and supplementation with herbals or other compounds have shown some effect on improving cytokine profiles in patients with RA. This review illustrates the importance of proper patient education on the anti-inflammatory and potential protective impacts substantial dietary change may have on the disease progression and symptoms of RA. Identifying nutritional interventions and dietary patterns that improve the inflammatory cytokine profile, and therefore disease progression and inflammatory comorbidities of RA will help further focus research on treatments that may provide a better overall improvement in quality of life for RA patients by focusing on the root cause inflammatory processes that affect not only joint destruction but also depression-rated disability. This review further notes that while depression is commonly found in patients who suffer from chronic illnesses, it is especially prevalent in the RA population. The pathology of depression is associated with systemic inflammation, which is a known outcome of RA and may explain this strong association. Cytokines IL-6, IL-1, and TNF-α, known mediators involved in the progression of RA, are strongly associated with stress-related disorders including depression and anxiety. The presence of these cytokines is also correlated with the severity and duration of depression. This may signal a potential use of cytokines in diagnosing and following the progression of depression not only in patients with RA but also others. Given the statistics presented on depression and suicide in patients with RA, and the shared inflammatory pathway between the two diseases, depression and suicide screening scales should be included along with analysis of inflammatory markers and disease activity scores (DAS) in any future RA study.
PubMed: 35990558
DOI: 10.7759/cureus.28031 -
Frontiers in Nutrition 2022Physical training can improve several health variables in patients with type 2 diabetes mellitus (T2DM). A growing body of studies also finds a positive influence of...
INTRODUCTION
Physical training can improve several health variables in patients with type 2 diabetes mellitus (T2DM). A growing body of studies also finds a positive influence of dietary supplement (DS) intake. The aim of this review is to shed light on the possible effects of training interventions combined with DS intake in T2DM patients.
METHODS
A systematic search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and BISp Surf databases. Inclusion criteria were defined using the Patient-Intervention-Comparison-Outcome (PICO) scheme. The Physiotherapy Evidence Database (PEDro) scale was used for quality assessment and risk of bias analysis.
RESULTS
Ten controlled interventional studies with a total number of 643 subjects met the inclusion criteria. These studies investigated the effects of (a) vitamin D (VD), (b) VD + whey protein, (c) polyphenol containing antioxidant capsules, (d) creatine, (e) L-arginine, (f) leucine-rich amino acids, and (g) broccoli sprouts powder. Eight studies investigated effects on one or more of the following health outcomes: body mass index, fat mass, insulin resistance, glycemic control, lipid profile, oxidative stress/antioxidative capacity and/or inflammatory markers/molecules. Five of the studies show clear superior effects of physical training combined with DS intake (supplements a, b, c, e) on some of these variables compared with training only. However, one study indicates that VD intake might attenuate the training effects on triglyceride levels. Another study found that training + VD + whey protein intake increased tumor necrosis factor-α levels in T2DM patients. The effects of training combined with DS intake on renal function (supplement d) or incretin metabolism (supplement a) were investigated in two further studies. These studies do not show any additional effects of DS intake. The quality of the majority of the studies was high.
CONCLUSION
DS intake can potentially increase the benefits of physical training for specific health outcomes in T2DM patients. However, negative effects can also be observed. Possible cellular and molecular mechanisms behind potential synergistic or divergent effects of exercise training and DS use in T2DM should be explored in detail in future studies for the development of safe recommendations.
PubMed: 35356737
DOI: 10.3389/fnut.2022.817724 -
Critical Care (London, England) Jan 2022Sepsis, the dysregulated host response to infection, triggers abnormal pro-coagulant and pro-inflammatory host responses. Limitations in early disease intervention... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis, the dysregulated host response to infection, triggers abnormal pro-coagulant and pro-inflammatory host responses. Limitations in early disease intervention highlight the need for effective diagnostic and prognostic biomarkers. Protein C's role as an anticoagulant and anti-inflammatory molecule makes it an appealing target for sepsis biomarker studies. This meta-analysis aims to assess the diagnostic and prognostic value of protein C (PC) as a biomarker for adult sepsis.
METHODS
We searched MEDLINE, PubMed, EMBASE, CINAHL and Cochrane Library from database inception to September 12, 2021. We included prospective observational studies of (1) adult patients (> 17) with sepsis or suspicion of sepsis that; (2) measured PC levels with 24 h of study admission with; and (3) the goal of examining PC as a diagnostic or prognostic biomarker. Two authors screened articles and conducted risk of bias (RoB) assessment, using the Quality in Prognosis Studies (QUIPS) and the Quality Assessment in Diagnostic Studies-2 (QUADAS-2) tools. If sufficient data were available, meta-analysis was conducted to estimate the standardized mean difference (SMD) between patient populations.
RESULTS
Twelve studies were included, and 8 were synthesized for meta-analysis. Pooled analysis demonstrated moderate certainty of evidence that PC levels were less reduced in sepsis survivors compared to non-survivors (6 studies, 741 patients, SMD = 0.52, 95% CI 0.24-0.81, p = 0.0003, I = 55%), and low certainty of evidence that PC levels were less reduced in septic patients without disseminated intravascular coagulation (DIC) compared to those with DIC (3 studies, 644 patients, SMD = 0.97, 95% CI 0.62-1.32, p < 0.00001, I = 67%). PC could not be evaluated as a diagnostic tool due to heterogeneous control populations between studies.
CONCLUSION AND RELEVANCE
Our review demonstrates that PC levels were significantly higher in sepsis survivors compared to non-survivors and patients with sepsis but not disseminated intravascular coagulation (DIC). Our evaluation is limited by high RoB in included studies and poor reporting of the sensitivity and specificity of PC as a sepsis biomarker. Future studies are needed to determine the sensitivity and specificity of PC to identify its clinical significance as a biomarker for early sepsis recognition. Trial Registration PROSPERO registration number: CRD42021229786. The study protocol was published in BMJ Open.
Topics: Adult; Biomarkers; Disseminated Intravascular Coagulation; Humans; Observational Studies as Topic; Prognosis; Protein C; Sepsis
PubMed: 35031071
DOI: 10.1186/s13054-022-03889-2 -
Archives of Gerontology and Geriatrics 2021Biomarkers for delirium could increase diagnostic accuracy and may help to identify pathological pathways. Until now study findings concerning cytokine levels have been... (Meta-Analysis)
Meta-Analysis Review
Consistent patterns in the inconsistent associations of Insulin-like growth factor 1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin 6 (IL-6) levels with delirium in surgical populations. A systematic review and meta-analysis.
BACKGROUND
Biomarkers for delirium could increase diagnostic accuracy and may help to identify pathological pathways. Until now study findings concerning cytokine levels have been inconsistent.
AIMS
Systematic review and meta-analysis investigating the association between peripheral levels of Insulin-like Growth Factor-1 (IGF-1), C-Reactive Protein (C-RP) and Interleukin-6 (IL-6) and delirium in surgical patients, and to explore if there are distinct/specific patterns that may potentially explain inconsistent results.
METHODS
PubMed, Scopus, CINAHL, Cochrane, and EMBASE databases were searched. Inclusion criteria were: prospective studies, surgical populations excluding preoperative delirium, available data. The following were collected: type of operation (orthopaedic, abdominal, etc), the timing of operation (acute, elective, both), demographics, number of participants with delirium, time of preoperative blood withdrawal, and preoperative levels of each biomarker.
RESULTS
Low levels of IGF-1 (n = 7 studies) are significantly associated with post-operative delirium in abdominal surgical samples. High levels of C-RP (n = 9) are associated with delirium in acute orthopaedic and elective abdominal operations. IL-6 (n = 14) is a significant predictor of post-operative delirium in a variety of surgical conditions (elective or acute).
DISCUSSION
A common pattern exists in the otherwise conflicting reported findings. This similarity may reflect different underling mechanisms and predisposing factors like cachexia and catabolic stages. It seems that delirium in abdominal surgery is triggered by IGF-1 disturbances, while in other surgeries by an inflammatory reaction.
CONCLUSIONS
Despite the contradictory results concerning the association of IGF-1, C-RP and IL-6 with postoperative delirium, the present meta-analysis shows that there are certain patterns. IL-6 seems a consistent predictor for delirium in surgical samples.
Topics: C-Reactive Protein; Delirium; Humans; Insulin-Like Growth Factor I; Interleukin-6; Prospective Studies
PubMed: 34536657
DOI: 10.1016/j.archger.2021.104518 -
Food & Function Sep 2021Diabetic nephropathy (DN) is a microvascular complication that is becoming a worldwide public health concern. The aim of this study was to assess the effects of dietary... (Meta-Analysis)
Meta-Analysis
Diabetic nephropathy (DN) is a microvascular complication that is becoming a worldwide public health concern. The aim of this study was to assess the effects of dietary soy isoflavone intervention on renal function and metabolic syndrome markers in DN patients. Seven databases including Medline, the Cochrane Central Register of Controlled Trials, Science Direct, Web of Science, Embase, China National Knowledge Infrastructure, and WanFang were searched for controlled trials that assessed the effects of soy isoflavone treatment in DN patients. Finally, a total of 141 patients from 7 randomized controlled trials were included. The meta-analysis showed that dietary soy isoflavones significantly decreased 24-hour urine protein, C-reactive protein (CRP), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG) in DN patients. The standard mean difference was -2.58 (95% CI: -3.94, -1.22; P = 0.0002) for 24-hour urine protein, -0.67 (95% CI: -0.94, -0.41; P < 0.00001) for BUN, -6.16 (95% CI: -9.02, -3.31; P < 0.0001) for CRP, -0.58 (95% CI: -0.83, -0.33; P < 0.00001) for TC, -0.41 (95% CI: -0.66, -0.16; P < 0.00001) for TG, -0.68 (95% CI: -0.94, -0.42; P < 0.00001) for LDL-C, and -0.39 (95% CI: -0.68, -0.10; P = 0.008) for FBG. Therefore, soy isoflavones may ameliorate DN by significantly decreasing 24-hour urine protein, BUN, CRP, TC, TG, LDL-C, and FBG.
Topics: Adult; Aged; Blood Glucose; C-Reactive Protein; Cholesterol, LDL; Diabetic Nephropathies; Dietary Supplements; Female; Humans; Isoflavones; Male; Middle Aged; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 34236368
DOI: 10.1039/d1fo01175h -
Human Reproduction (Oxford, England) Apr 2021Is there an association between hereditary thrombophilia in pregnant women and risk of recurrent pregnancy loss (RPL)? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
Is there an association between hereditary thrombophilia in pregnant women and risk of recurrent pregnancy loss (RPL)?
SUMMARY ANSWER
Pregnant women with hereditary thrombophilia have an increased risk of RPL, especially for pregnant women with the G1691A mutation of the factor V Leiden (FVL) gene, the G20210A mutation of the prothrombin gene (PGM), and deficiency of protein S (PS).
WHAT IS KNOWN ALREADY
Prior studies have suggested that pregnant women with hereditary thrombophilia have a higher risk of RPL, however, the results are inconsistent; furthermore, a complete overview is missing. This lack of information is an obstacle to the risk assessment of RPL in pregnant women with hereditary thrombophilia. A comprehensive meta-analysis on the relation between hereditary thrombophilia and the risk of RPL is needed.
STUDY DESIGN, SIZE, DURATION
A systematic review and meta-analysis was performed using observational studies published in English before 1 April 2020 to evaluate the relation between hereditary thrombophilia and risk of RPL.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Relevant studies were identified from PubMed, Web of Science, and EMBASE searches and complemented with perusal of bibliographies of retrieved articles. The exposure of interest was hereditary thrombophilia, including FVL mutation, PGM, deficiency of antithrombin (AT), deficiency of protein C (PC), and deficiency of PS. The overall risk estimates were pooled using random effects models. Subgroup and sensitivity analyses were carried out to explore possible sources of heterogeneity and assess the robustness of the results.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 89 studies involving 30 254 individuals were included. Results showed that women with FVL mutation (odds ratio (OR): 2.44, 95% CI: 1.96-3.03), PGM (OR: 2.08, 95% CI: 1.61-2.68), or deficiency of PS (OR: 3.45, 95% CI: 1.15-10.35) had higher risks of developing RPL. Compared with the reference group, there was no observed relation between a deficiency in AT or PC and RPL (all P > 0.05). Heterogeneity in the risk estimates of RPL was partially explained by geographic region, definitions of RPL, types of RPL, and controlled confounders. Sensitivity analyses validated the robustness of the findings.
LIMITATIONS, REASONS FOR CAUTION
Only 39 of the included studies controlled for one or more confounders, and the heterogeneity across all included studies was high. Based on the data available, we cannot determine whether this association is confounded by other potential risk factors of RPL.
WIDER IMPLICATIONS OF THE FINDINGS
This systematic review and meta-analysis show a possible association between hereditary thrombophilia and an increased risk of RPL, suggesting that testing for hereditary thrombophilia should be considered in individuals with RPL.
STUDY FUNDING/COMPETING INTEREST(S)
The study was funded by the Hunan Provincial Key Research and Development Program (Grant number: 2018SK2062) and National Natural Science Foundation Program (Grant number: 81973137). There are no conflicts of interest.
REGISTRATION NUMBER
N/A.
Topics: Abortion, Habitual; Female; Humans; Mutation; Odds Ratio; Pregnancy; Risk Factors; Thrombophilia
PubMed: 33575779
DOI: 10.1093/humrep/deab010 -
Viral Immunology 2021We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic...
We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic paralysis/myelopathy related to human T cell lymphotropic virus type 1. The databases accessed were PubMed, Scopus, Science Direct, and Web of Science. Neither the time of publishing nor the language of the articles was limited. The descriptors used for this systematic literature review were: Tropical Paraparesis, Proto-Oncogenic Protein C, Bcl-2, Bcl-X Protein, Bax protein, Fas ligand (FasL) protein, Fas receptor, TNF-related apoptosis-inducing ligand and Fas-associated protein with death domain (FADD)-like apoptosis regulating. The search resulted in 546 articles from which 9 articles were selected for analysis; ranging from serum levels of Bcl-2, Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) measured by enzyme-linked immunosorbent assay and the levels of cellular expression of Bcl-2 and Bcl-xL the TCD4+ lymphocytes accessed by western blot. Most studies accessed either gene expression or polymorphism of Fas, FasL, and TRAIL in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas one study used flow cytometry and fluorescence to determine Fas expression. Increased Bcl-xL expression inhibited T lymphocyte apoptosis, whereas Bcl-2, serum levels, and cellular expression did not influence T lymphocyte apoptosis and serum levels of Fas were significantly higher and associated with markers of leukocyte activation in patients with HAM/TSP. In addition, Fas polymorphism (FAS-670AA) was associated with higher proviral load. There is a need for additional research on this issue since the number of patients was small and the studies presented higher heterogeneity.
Topics: Apoptosis; Human T-lymphotropic virus 1; Humans; Paraparesis, Tropical Spastic
PubMed: 33470891
DOI: 10.1089/vim.2020.0131 -
Frontiers in Pharmacology 2020Acute coronary syndrome, that is a common and serious cardiovascular disease, imposes a huge economic burden on global public health. And Danshen class injections are...
BACKGROUND
Acute coronary syndrome, that is a common and serious cardiovascular disease, imposes a huge economic burden on global public health. And Danshen class injections are commonly used in the treatment of acute coronary syndrome in China. Thus, the Bayesian network meta-analysis was devised to investigate the efficacy of different Danshen class injections against acute coronary syndrome.
METHODS
Eligible inclusion and exclusion criteria were established in advance. Then, a systematic literature search was performed in several databases from inception to February 2020. Further, the included randomized controlled trials data were adopted to calculation, prepare graphs and multidimensional cluster analysis by WinBUGS 1.4.3, Stata V.13.0 and R 3.6.1 software, respectively.
RESULTS
A total of 53 eligible randomized controlled trial studies with 6401 patients were obtained that evaluated the clinical effectiveness rate, the level of hypersensitive C-reactive protein, C-reactive protein, interleukin-6, fibrinogen, and adverse reactions after the application of Danshen class injections plus western medicine. Compared with western medicine alone, Danshen class injections combined with western medicine therapy were associated with significantly improved the therapeutic effect. In addition, the results of the multidimensional cluster analysis demonstrated that Danhong injection + western medicine and Danshen injection + western medicine had better therapeutic effects. However, since most eligible randomized controlled trial studies did not focus on the monitoring of adverse reactions, the safety of these Chinese herbal injections needs to be further explored.
CONCLUSION
Based on this Bayesian network meta-analysis results, Danhong injection + western medicine and Danshen injection + western medicine might have a better impact on acute coronary syndrome patients. Nevertheless, more large samples, high-quality clinical and multicenter randomized controlled trial studies should be tested and verified in the future.
PubMed: 32982726
DOI: 10.3389/fphar.2020.01260 -
Journal of Thrombosis and Haemostasis :... Dec 2020Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear.
OBJECTIVES
This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature.
PATIENTS/METHODS
PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated.
RESULTS
Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in <2%. The MTHFR C677T and PAI 4G homozygous polymorphism were observed in 13% (95% CI: 10-17) and 23% (95% CI: 16-31) of RVO, respectively; 8% presented APL antibodies. Similar findings were observed in individuals with RAO.
CONCLUSIONS
Compared with healthy subjects, patients with retinal vascular occlusion showed similar prevalences of inherited and acquired thrombophilias. These findings do not support routine thrombophilia screening in individuals with RAO or RVO.
Topics: Adult; Factor V; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Prothrombin; Retinal Vein Occlusion; Risk Factors; Thrombophilia
PubMed: 32805772
DOI: 10.1111/jth.15068 -
Cureus Apr 2020Cerebral venous sinus thrombosis (CVST) is a rare condition characterized by elevated intracranial pressure due to impaired cerebral venous drainage, potentially... (Review)
Review
Cerebral venous sinus thrombosis (CVST) is a rare condition characterized by elevated intracranial pressure due to impaired cerebral venous drainage, potentially leading to life-threatening consequences. We searched the PubMed electronic database for 'cerebral venous sinus thrombosis' and 'prothrombotic' cases reported in adults (19+ years) and conducted a systematic review for the published literature in the English language pooled with a case from our institution. Data were analyzed regarding patient demographics, risk factors, clinical features, treatment modalities, and outcomes when available. Thirty cases of CVST were identified (29 case reports, of whom two were described in a case series, and the one case from our institution). The patients' mean age was 39 years (range: 19 - 65). The male: female ratio was 1.14:1. The majority (73.3%) had at least one preexisting risk factor, with prescription drug use being the most common risk factor (33.3%) shared among all patients. Most patients (83.3%) presented with at least two symptoms. The most common presenting symptoms were headache (70%), gastrointestinal disturbance (50%), and seizures (40%). Focal deficits (36.7%), vision disturbances (30%), and altered consciousness (20%) were the remaining presenting complaints. Twelve cases (40%) commented on papilledema, with 10 (83.3%) having papilledema present. Anticoagulation abnormalities were examined in 26 cases (86.7%), out of which four cases (15.4%) had isolated protein S (PS) deficiency, three cases (11.5%) had isolated antithrombin III (ATIII) deficiency, and one case (3.8%) had isolated protein C (PC) deficiency. The most common initial imaging modality (22 cases, 73.3%), and most commonly used overall (23 cases, 76.7%), was computed tomography (CT). Magnetic resonance imaging (MRI) was the second most common imaging modality for initial use (five cases, 16.7%), diagnosis or confirmation of CVST (eight cases, 26.7%), and overall (21 cases, 70%). Heparin treatment was involved in the treatment of 18 cases (60%), and warfarin treatment was used in 10 cases (33.3%). Heparin-warfarin combination treatment was utilized in eight cases (26.7%). Most patients survived (28 cases, 93.3%), while the two remaining patients died secondary to brain death from the CVST (6.7%). The findings from this study highlight the clinical characteristics of CVST. Therefore, this study aims to increase awareness of this rare entity. Physicians should maintain a high index of suspicion in order to diagnose patients presenting in the proper clinical context, given this case shares various forms of presentations with other common clinical conditions but requires long-term anticoagulation.
PubMed: 32411555
DOI: 10.7759/cureus.7654