Immune capacity determines outcome following surgery or trauma: a systematic review and meta-analysis

Abstract Purpose Immunological functions are altered following physical injury. The magnitude of the immunological response is dependent on the initial injury. However, variability in the immune response exists within and between patients where only some patients are at risk of developing complications such as systemic inflammatory response syndrome after injury. This systematic review and meta-analysis assessed whether lipopolysaccharide (LPS) induced cytokine production capacity of leucocytes can be used as a functional test to predict the risk of developing complications after injury. Methods Medline, Embase and Web of Science were systematically searched to identify articles that investigated the association between LPS induced cytokine production capacity in leucocytes and any clinical outcome after surgery or trauma. Where sufficient information was supplied, a meta-analysis was performed to determine the overall clinical outcomes. Results A total of 25 articles out of 6765 abstracts identified through the literature search were included in this review. Most articles described a positive association between cytokine production capacity and the development of inflammatory complications (n = 15/25). Coincidingly, the meta-analysis demonstrated that TNFα (Hedges g: 0.63, 95% CI 0.23, 1.03), IL-6 (Hedges g: 0.76, 95% CI 0.41, 1.11) and IL-8 (Hedges g: 0.93, 95% CI 0.46, 1.39) production capacity was significantly higher, one day after injury, in patients who developed inflammatory complications compared to patients who did not following trauma or surgical intervention. No significant difference was observed for IL-1β. Conclusion The associations of elevated LPS-induced cytokine production capacity with the risk of developing inflammatory complications are consistent with previous theories that proposed excessive inflammation is accompanied by anti-inflammatory mechanisms that results in a period of immunosuppression and increased risk of secondary complications. However, immunological biomarkers for risk stratification is still a developing field of research where further investigations and validations are required.

Download Full-text

Abstract 13315: Long-term Risk of Cardiovascular Events Following Hospitalization for Sepsis: A Systematic Review and Meta-analysis

Circulation ◽

10.1161/circ.142.suppl_3.13315 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Leah B Kosyakovsky ◽

Federico Angriman ◽

Emma Katz ◽

Neill Adhikari ◽

Lucas C Godoy ◽

...

Keyword(s):

Systematic Review ◽

Cumulative Incidence ◽

Meta Analysis ◽

Hazard Ratios ◽

Increased Risk ◽

Significant Difference ◽

Sepsis Survivors ◽

Risk Ratios

Introduction: Sepsis results in dysregulated inflammation, coagulation, and metabolism, which may contribute to increased cardiovascular disease (CVD) risk. We conducted a systematic review and meta-analysis to determine the association between sepsis and subsequent long-term CVD events. Methods: MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception to May 2020 to identify observational studies of adult sepsis survivors (defined by diagnostic codes or consensus definitions) measuring long-term CV outcomes. The primary outcome was a composite of myocardial infarction, CV death, and stroke. Random-effects models estimated the pooled cumulative incidence and adjusted hazard ratios of CV events relative to hospital or population controls. Odds ratios were included as risk ratios assuming <10% incidence in non-septic controls, and risk ratios were taken as hazard ratios (HR) assuming no censoring. Outcomes were analyzed at maximum follow-up (primary analysis) and stratified by time (<1 year, 1-2 years, and >2 years) since sepsis. Results: Of 11,235 abstracts screened, 25 studies (22 cohort studies, 2 case-crossover studies, and 1 case-control) involving 1,949,793 sepsis survivors were included. The pooled cumulative incidence of CVD events was 9% (95% CI; 5-14%). Sepsis was associated with an increased risk (HR 1.59, 95% CI 1.37-1.86) of CVD events at maximum follow-up ( Figure ); between-study heterogeneity was substantial (I 2 =97.3%). There was no significant difference when comparing studies using population and hospital controls. Significantly elevated risk was observed up to 5 years following sepsis. Conclusions: Sepsis survivors experience an approximately 50% increased risk of CVD events, which may persist for years following the index episode. These results highlight a potential unmet need for early cardiac risk stratification and optimization in sepsis survivors.

Download Full-text

Effect of Early Intravenous Immunoglobulin Therapy in Kawasaki Disease: A Systematic Review and Meta-Analysis

Frontiers in Pediatrics ◽

10.3389/fped.2020.593435 ◽

2020 ◽

Vol 8 ◽

Author(s):

Fan Yan ◽

Huayong Zhang ◽

Ruihua Xiong ◽

Xingfeng Cheng ◽

Yang Chen ◽

...

Keyword(s):

Systematic Review ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Meta Analysis ◽

The United States ◽

Cochrane Library ◽

Ivig Treatment ◽

Intravenous Immunoglobulin Therapy ◽

Increased Risk ◽

Significant Difference

Background: In the latest 2017 American Heart Association guidelines for Kawasaki disease (KD), there are no recommendations regarding the early administration of intravenous immunoglobulin (IVIG). Therefore, the purpose of this systematic review and meta-analysis was to investigate the effects of early IVIG therapy on KD.Methods: We searched databases including the PubMed, Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2019.Results: Fourteen studies involving a total of 70,396 patients were included. Early treatment with IVIG can lead to an increased risk of IVIG unresponsiveness [OR 2.24; 95% CI (1.76, 2.84); P = 0.000]. In contrast to the studies performed in Japan [OR 1.27; 95% CI (0.98, 1.64); P = 0.074] that found no significant difference in coronary artery lesions (CAL) development, studies conducted in China [OR 0.73; 95% CI (0.66, 0.80); P = 0.000] and the United States [OR 0.50; 95% CI (0.38, 0.66); P = 0.000] showed a reduced risk in the occurrence of CAL with early IVIG treatment.Conclusions: At present, the evidence does not support the treatment with IVIG in the early stage of the onset of KD. But, early IVIG treatment could be a protective factor against the development of CAL, which needs to be further clarified.

Download Full-text

Impact of depression on clinical outcomes following percutaneous coronary intervention: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-026445 ◽

2019 ◽

Vol 9 (8) ◽

pp. e026445 ◽

Cited By ~ 1

Author(s):

Wen Yi Zhang ◽

Nan Nan ◽

Xian Tao Song ◽

Jin Fan Tian ◽

Xue Yao Yang

Keyword(s):

Systematic Review ◽

Percutaneous Coronary Intervention ◽

Meta Analysis ◽

Positive Association ◽

Coronary Intervention ◽

Adverse Outcomes ◽

Increased Risk ◽

Percutaneous Coronary ◽

Assessment Time

ObjectivesThe objective of this meta-analysis was to assess whether depression in percutaneous coronary intervention (PCI) patients is associated with higher risk of adverse outcomes.DesignSystematic review and meta-analysis.MethodsEMBASE, PubMed, CINAHL and PsycINFO were searched as data sources. We selected prospective cohort studies evaluating the relationship between depression and any adverse medical outcome, including all-cause mortality, cardiac mortality and non-fatal events, from inception to 28 February 2019. Two reviewers independently extracted information and calculated the risk of cardiovascular events in patients with preoperative or postoperative depression compared with non-depressed patients.ResultsEight studies (n=3297) met our inclusion criteria. Most studies found a positive association between depression and adverse cardiovascular outcomes. Meta-analysis yielded an aggregate risk ratio of 1.57 (95% CI 1.28 to 1.92, p<0.0001) for the magnitude of the relation between depression and adverse outcomes.ConclusionsOur systematic review and meta-analysis suggests that depression is associated with an increased risk of worse clinical outcome or mortality in patients undergoing PCI. Assessment time and length of follow-up do not have a significant effect on this conclusion.

Download Full-text

New-onset glucose disorders in peritoneal dialysis patients: a meta-analysis and systematic review

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz116 ◽

2019 ◽

Vol 35 (8) ◽

pp. 1412-1419 ◽

Cited By ~ 1

Author(s):

Cheng Xue ◽

Yan-Yan Gu ◽

Cheng-Ji Cui ◽

Chen-Chen Zhou ◽

Xian-Dong Wang ◽

...

Keyword(s):

Systematic Review ◽

Peritoneal Dialysis ◽

Glucose Tolerance ◽

Meta Analysis ◽

Incidence Rates ◽

Cochrane Library ◽

Sample Sizes ◽

Increased Risk ◽

Significant Difference ◽

New Onset

Abstract Background Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. Methods We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. Results We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4–12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3–31; I2 = 97%) and 32% (95% CI 27–37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69–1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01–1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. Conclusions Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.

Download Full-text

The role of obesity and adipokines in coronary microvascular dysfunction: a systematic review and meta-analysis

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.383 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

M Spezia ◽

A Bonato ◽

G De Fortunato ◽

A Bossi ◽

M Glauber

Keyword(s):

Systematic Review ◽

Blood Flow ◽

Coronary Flow ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Flow Reserve ◽

Increased Risk ◽

Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with obesity present structural and functional changes in the heart and in the coronary circulation, which ultimately leads to an increased risk of cardiovascular disease. Obesity is associated with a low chronic state of inflammation which seems to be linked to a compromised coronary vasoreactivity, which is shown to be a forerunner and a long-term predictor of clinically relevant cardiovascular events. Methods A systematic review was performed by searching PubMed, Embase and Cochrane Library database. Selection criteria were applied leading to the inclusion of studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results. Relative data were extracted and critically analysed. PRISMA guidelines were applied and risk of bias was assessed, as well as the methodological quality of the included studies. After this assessment, we excluded all the articles with serious risk of bias and/or low quality. Meta-analysis was conducted on the data collected regarding coronary blood flow (CFR) and hyperemic myocardial blood flow (MBF), while for the other parameters a descriptive analysis was performed. Results After applying the described criteria, we included 15 articles on human and animal literature assessed as medium or high quality. The data of 1399 patients were examined, 456 of which with obesity (BMI ≥ 30). A pooled effect size analysis shows that coronary flow reserve (CFR) is significantly reduced in patients with obesity [Random Effect (RE): -47.7%, 95% confidence interval (CI) -80.2% – -15.2%; n = 422]. Increased BMI is associated with reduced CFR. The same trend is found evaluating pharmacological induced stress MBF, which was reduced in patients with obesity [RE: -47.8%, 95% CI -73.7% – -21.8%; n = 409]. Nevertheless, MBF at rest did not show a significant difference in patients with obesity from our analysis [RE: 15%, 95% CI -24% - 53%; n = 409]. Pro-inflammatory adipokines secretion, as leptin and CRP, seems to correlate with a significant decrease of stress-induced MBF and reduced CFR. Conclusions Obesity is associated with a significant higher risk of coronary microvascular disfunction, which is reflected by diminished CFR and stress MBF. Systemic inflammation and the imbalance of adipokines related to obesity has been closely linked to a blunt coronary flow. CMD is a pre-clinical heart conditions that often remains undiagnosed. Further evidence is required to clear out the role of Obesity from a molecular point of view on the coronary endothelium.

Download Full-text

Current understanding of bleeding with ibrutinib use: a systematic review and meta-analysis

Blood Advances ◽

10.1182/bloodadvances.2016001883 ◽

2017 ◽

Vol 1 (12) ◽

pp. 772-778 ◽

Cited By ~ 33

Author(s):

François Caron ◽

Darryl P. Leong ◽

Christopher Hillis ◽

Graeme Fraser ◽

Deborah Siegal

Keyword(s):

Systematic Review ◽

Relative Risk ◽

Confidence Interval ◽

Major Bleeding ◽

Meta Analysis ◽

Allocation Concealment ◽

Risk Of Bleeding ◽

Increased Risk ◽

Significant Difference ◽

Event Rates

Abstract Ibrutinib therapy was associated with an increased risk of bleeding in previous trials. In this systematic review and meta-analysis of published trials including patients treated with ibrutinib, the relative risk (95% confidence interval [CI]) of overall bleeding was significantly higher in ibrutinib recipients (2.72 [1.62-6.58]), but major bleeding did not show a significant difference (1.66 [0.96-2.85]). The incidences (95% CI) of major bleeding and any bleeding were 3.0 (2.3-3.7) and 20.8 (19.1-22.1) per 100 patient-years, respectively. This analysis is limited by reporting bias from variable ascertainment of bleeding and lack of allocation concealment in some studies and differing exposures between groups, leading to potential overestimation of event rates in the ibrutinib group.

Download Full-text

Association of diabetes with atrial fibrillation types: a systematic review and meta-analysis

Cardiovascular Diabetology ◽

10.1186/s12933-021-01423-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Fadi Alijla ◽

Chepkoech Buttia ◽

Tobias Reichlin ◽

Salman Razvi ◽

Beatrice Minder ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Meta Analysis ◽

Population Sample ◽

Positive Association ◽

Cross Sectional ◽

Random Effects Models ◽

Increased Risk ◽

Patients With Diabetes ◽

The Impact

Abstract Background Atrial fibrillation (AF) is a common arrhythmia classified as paroxysmal and non-paroxysmal. Non-paroxysmal AF is associated with an increased risk of complications. Diabetes contributes to AF initiation, yet its role in AF maintenance is unclear. We conducted a systematic review and meta-analysis to summarize the evidence regarding the association of diabetes with AF types. Methods We searched 5 databases for observational studies investigating the association of diabetes with the likelihood of an AF type (vs another type) in humans. Study quality was evaluated using the Newcastle–Ottawa Scale. Studies classifying AF types as paroxysmal (reference) and non-paroxysmal were pooled in a meta-analysis using random effects models. Results Of 1997 articles we identified, 20 were included in our systematic review. The population sample size ranged from 64 to 9816 participants with mean age ranging from 40 to 75 years and percentage of women from 24.8 to 100%. The quality of studies varied from poor (60%) to fair (5%) to good (35%). In the systematic review, 8 studies among patients with AF investigated the cross-sectional association of diabetes with non-paroxysmal AF (vs paroxysmal) of which 6 showed a positive association and 2 showed no association. Fourteen studies investigated the longitudinal association of diabetes with “more sustained” AF types (vs “less sustained”) of which 2 showed a positive association and 12 showed no association. In the meta-analysis of cross-sectional studies, patients with AF and diabetes were 1.31-times more likely to have non-paroxysmal AF than those without diabetes [8 studies; pooled OR (95% CI), 1.31 (1.13–1.51), I2 = 82.6%]. The meta-analysis of longitudinal studies showed that for patients with paroxysmal AF, diabetes is associated with 1.32-times increased likelihood of progression to non-paroxysmal AF [five studies; pooled OR (95% CI), 1.32 (1.07–1.62); I2 = 0%]. Conclusions Our findings suggest that diabetes is associated with an increased likelihood of non-paroxysmal AF rather than paroxysmal AF. However, further high quality studies are needed to replicate these findings, adjust for potential confounders, elucidate mechanisms linking diabetes to non-paroxysmal AF, and assess the impact of antidiabetic medications on AF types. These strategies could eventually help decrease the risk of non-paroxysmal AF among patients with diabetes.

Download Full-text

Enough with the madness: a systematic review and meta-analysis of hydroxychloroquine for COVID-19

Jornal Brasileiro de Economia da Saúde ◽

10.21115/jbes.v13.n2.p186-220 ◽

2021 ◽

Vol 13 (2) ◽

pp. 186-220

Author(s):

André Santos ◽

◽

Érica Gonçalves ◽

Ananda Oliveira ◽

Douglas Lima ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Meta Analysis ◽

Standard Of Care ◽

P Value ◽

Serious Adverse Events ◽

Risk Of Death ◽

Increased Risk ◽

Significant Difference

Objective: Because of preliminary results from in vitro studies, hydroxychloroquine (HCQ) and chloroquine (CQ) have been proposed as possible treatments for COVID-19, but the clinical evidence is discordant. This study aims to evaluate the safety and efficacy of CQ and HCQ for the treatment of COVID-19. Methods: A systematic review with meta-analysis was performed. An electronic search was conducted in four databases for randomized controlled trials that compared HCQ or CQ with standard-of-care. A complementary search was performed. A quantitative synthesis of clinical outcomes was performed using the inverse variance method adjusting for a random-effects model. Results: In total, 16 studies were included. The meta-analysis found no significant difference between intervention and control groups in terms of mortality at the most extended follow-up (RR = 1.09, CI95% = 0.99-1.19, p-value = 0.08), patients with negative PCR results (RR = 0.99, CI95% = 0.89-1.10, p-value = 0.86), or serious adverse events (RR = 2.21, CI95% = 0.89-5.47, p-value = 0.09). HCQ was associated with an increased risk of adverse events (RR = 2.28, CI95% = 1.36-2.83, p-value < 0.01). The quality of evidence varied from very low to high. Conclusion: There is no evidence that HCQ reduces the risk of death or improves cure rates in patients with COVID-19, but it might be associated with an increased risk of adverse events

Download Full-text

Dioxins Exposure and the Risk of Breast Cancer: A Systematic Review and Meta-Analysis

Jundishapur Journal of Health Sciences ◽

10.5812/jjhs.116516 ◽

2021 ◽

Vol 13 (2) ◽

Author(s):

Nematollah Jaafarzadeh Haghighi ◽

Amal Saki Malehi ◽

Zeinab Ghaedrahmat

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

English Language ◽

Meta Analysis ◽

Breast Cancer Mortality ◽

Positive Association ◽

Great Distance ◽

Organic Chemical ◽

Significant Positive Association ◽

Increased Risk

Context: Dioxins and dioxin-like chemicals composed of 419 compounds are a large group of compounds, including polychlorinated di-benzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs). Dioxins are extremely persistent in the environment and disperse in a great distance from the emission source, and bioaccumulation in the food chain is one of their critical properties. The incidence of breast cancer among Iranian women is about 30 to 35 per 100,000 cases. The present study is a systematic review of published studies in English language to discover the relationship between exposure to dioxin compounds and breast cancer. Methods: We conducted a comprehensive literature review utilizing PubMed, Embase, Scopus, and ISI web of science databases. The MeSH-based keywords used included Organic Chemical (MeSH) OR Dioxins (MeSH) AND cancer (MeSH) OR Breast cancer (MeSH) AND Breast disease (MeSH). Results: The review of the literature indicated a significant positive association between dioxins exposure and the risk of breast cancer. Only in one study, breast cancer mortality rate was reported in terms of exposure to dioxins, and standardized mortality rates (SMRs) were determined. Conclusions: Although there were limitations in this study, statistical analyses in various epidemiological studies demonstrated that dioxins exposure is linked to an increased risk of breast cancer.

Download Full-text

Bone Mineral Density, Osteoporosis, and Fracture Risk in Adult Patients with Psoriasis or Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Observational Studies

Journal of Clinical Medicine ◽

10.3390/jcm9113712 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3712

Author(s):

Tai-Li Chen ◽

Jing-Wun Lu ◽

Yu-Wen Huang ◽

Jen-Hung Wang ◽

Kuei-Ying Su

Keyword(s):

Bone Mineral Density ◽

Systematic Review ◽

Psoriatic Arthritis ◽

Bone Mineral ◽

Observational Studies ◽

Meta Analysis ◽

Mineral Density ◽

Psoriatic Disease ◽

Increased Risk ◽

Significant Difference

Introduction: Awareness of psoriasis-related comorbidities has been established in the current guidelines; however, evidence regarding the association of bone density or bone fragility with psoriatic disease remains inconclusive. Methods: We conducted a systematic review and meta-analysis to assess bone mineral density and the risk of osteoporosis and fractures in patients with psoriatic disease, including those with cutaneous psoriasis and psoriatic arthritis. We searched electronic databases for published observational studies. A meta-analysis was performed using the random-effect model. Pooled estimates and their confidence intervals (CIs) were calculated. Small-study effects were examined using the Doi plot and Luis Furuya–Kanamori index. Results: The analysis of the standardized mean difference in the absolute value of bone mineral density at different measuring sites (lumbar spine, femoral neck, and total hip) revealed no significant difference between patients with psoriatic disease and non-psoriatic controls. The pooled results of the adjusted odds ratios (ORs) demonstrated no increased risk of osteoporosis in patients with psoriatic disease. Notably, patients with psoriatic disease had a higher OR of developing bone fractures (adjusted OR: 1.09; 95% CI: 1.06 to 1.12; I2: 0%). Conclusion: Patients with psoriatic disease may be more likely to develop fractures compared with non-psoriatic controls. This higher risk for fracture may not necessarily be associated with lower bone mineral density nor a higher risk for osteoporosis.

Download Full-text