The impact of RAGE inhibition in animal models of bacterial sepsis: a systematic review and meta-analysis

Objective To evaluate the impact of inhibition of the receptor for advanced glycation end products (RAGE) on the outcome of bacterial sepsis in animal models. Methods Relevant publications were identified by systematic searches of PubMed, ISI Web of Science and Elsevier-Scopus databases. Results A total of Eleven studies with moderate quality were selected for analysis. A meta-analysis of survival rates revealed a significant advantage of RAGE inhibition in comparison with controls (HR 0.67, 95% CI 0.52–0.86). This effect was most pronounced in polymicrobial infection (HR 0.28, 95% CI 0.14–0.55), followed by Gram positive (G+) bacterial infection (HR 0.70, 95% CI 0.50–0.97) and Gram negative (G−) bacterial infection (HR 0.89, 95% CI 0.58–1.38). For G+ bacterial infection, RAGE inhibition decreased bacterial outgrowth and dissemination, inflammatory cell influx, plasma cytokine levels, and pulmonary injury. Conclusions RAGE inhibition appears to have a beneficial impact on the outcome of sepsis in animal models, although there are discrepancies between different types of infection.

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The impact of antibiotics on the metabolic status of obese adults without bacterial infection: a systematic review and meta-analysis

Annals of Translational Medicine ◽

10.21037/atm-20-1007a ◽

2020 ◽

Vol 8 (17) ◽

pp. 1059-1059

Author(s):

Naofumi Yoshida ◽

Yoshihiro Saito ◽

Yasushi Tsujimoto ◽

Shunsuke Taito ◽

Masahiro Banno ◽

...

Keyword(s):

Systematic Review ◽

Bacterial Infection ◽

Meta Analysis ◽

Metabolic Status ◽

Obese Adults ◽

The Impact

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The Potential Role of Previous Physical Exercise Program to Reduce Seizure Susceptibility: A Systematic Review and Meta-Analysis of Animal Studies

Frontiers in Neurology ◽

10.3389/fneur.2021.771123 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ricardo Mario Arida ◽

Adrielle Andrade Passos ◽

Alexandre Lebedev Graciani ◽

João Angelo Ferres Brogin ◽

Mayara de Almeida Lima Ribeiro ◽

...

Keyword(s):

Systematic Review ◽

Animal Models ◽

Physical Exercise ◽

Random Effects ◽

Meta Analysis ◽

Risk Of Bias ◽

Seizure Susceptibility ◽

Seizure Onset ◽

Exercise Programs ◽

The Impact

Background: Clinical and pre-clinical studies indicate a reduction in seizure frequency as well as a decrease in susceptibility to subsequently evoked seizures after physical exercise programs. In contrast to the influence of exercise after epilepsy previously established, various studies have been conducted attempting to investigate whether physical activity reduces brain susceptibility to seizures or prevents epilepsy. We report a systematic review and meta-analysis of different animal models that addressed the impact of previous physical exercise programs to reduce seizure susceptibility.Methods: We included animal model (rats and mice) studies before brain insult that reported physical exercise programs compared with other interventions (sham, control, or naïve). We excluded studies that investigated animal models after brain insult, associated with supplement nutrition or drugs, that did not address epilepsy or seizure susceptibility, ex vivo studies, in vitro studies, studies in humans, or in silico studies. Electronic searches were performed in the MEDLINE (PubMed), Web of Science (WOS), Scopus, PsycINFO, Scientific Electronic Library Online (SciELO) databases, and gray literature, without restrictions to the year or language of publication. We used SYRCLE's risk of bias tool and CAMARADES checklist for study quality. We performed a synthesis of results for different types of exercise and susceptibility to seizures by random-effects meta-analysis.Results: Fifteen studies were included in the final analysis (543 animals), 13 of them used male animals, and Wistar rats were the most commonly studied species used in the studies (355 animals). The chemoconvulsants used in the selected studies were pentylenetetrazol, penicillin, kainic acid, pilocarpine, and homocysteine. We assessed the impact of study design characteristics and the reporting of mitigations to reduce the risk of bias. We calculated a standardized mean difference effect size for each comparison and performed a random-effects meta-analysis. The meta-analysis included behavioral analysis (latency to seizure onset, n = 6 and intensity of motor signals, n = 3) and electrophysiological analysis (spikes/min, n = 4, and amplitude, n = 6). The overall effect size observed in physical exercise compared to controls for latency to seizure onset was −130.98 [95% CI: −203.47, −58.49] (seconds) and the intensity of motor signals was −0.40 [95% CI: −1.19, 0.40] (on a scale from 0 to 5). The largest effects were observed in electrophysiological analysis for spikes/min with −26.96 [95% CI: −39.56, −14.36], and for spike amplitude (μV) with −282.64 [95% CI: −466.81, −98.47].Discussion:Limitations of evidence. A higher number of animal models should be employed for analyzing the influence of exerciseon seizure susceptibility. The high heterogeneity in our meta-analysis is attributable to various factors, including the number of animals used in each study and the limited number of similar studies. Interpretation. Studies selected in this systematic review and meta-analysis suggest that previous physical exercise programs can reduce some of the main features related to seizure susceptibility [latency seizure onset, spikes/min, and spike amplitude (μV)] induced by the administration of different chemoconvulsants.Systematic Review Registration: PROSPERO, identifier CRD42021251949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251949.

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Impact of Multidisciplinary Team Management on the Survival Rate of Head and Neck Cancer Patients: A Cohort Study Meta-analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.630906 ◽

2021 ◽

Vol 11 ◽

Author(s):

Changyi Shang ◽

Linfei Feng ◽

Ying Gu ◽

Houlin Hong ◽

Lilin Hong ◽

...

Keyword(s):

Head And Neck Cancer ◽

Survival Rate ◽

Cohort Studies ◽

Head And Neck ◽

Neck Cancer ◽

Multidisciplinary Team ◽

Meta Analysis ◽

Survival Rates ◽

Team Management ◽

The Impact

Background: Head and neck cancer (HNC) is one of the more common malignant tumors that threaten human health worldwide. Multidisciplinary team management (MDTM) in HNC treatment has been introduced in the past several decades to improve patient survival rates. This study reviewed the impact of MDTM on survival rates in patients with HNC compared to conventional treatment methods.Methods: Only cohort studies were identified for this meta-analysis that included an exposure group that utilized MDTM and a control group. Heterogeneity and sensitivity also were assessed. Survival rate data for HNC patients were analyzed using RevMan 5.2 software.Results: Five cohort studies (n = 39,070) that examined survival rates among HNC patients were included. Hazard ratios (HR) were calculated using the random effect model. The results revealed that exposure groups treated using MDTM exhibited a higher survival rate [HR = 0.84, 95% CI (0.76–0.92), P = 0.0004] with moderate heterogeneity (I2 = 68%, p = 0.01). For two studies that examined the effect of MDTM on the survival rate for patients specifically with stage IV HNC, MDTM did not produce any statistically significant improvement in survival rates [HR = 0.81, 95% CI (0.59–1.10), p = 0.18].Conclusions: The application of MDTM based on conventional surgery, radiotherapy, and chemotherapy improved the overall survival rate of patients with HNC. Future research should examine the efficacy of MDTM in patients with cancer at different stages.

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Animal models of chemotherapy-induced peripheral neuropathy: a machine-assisted systematic review and meta-analysis

10.1101/293480 ◽

2018 ◽

Cited By ~ 2

Author(s):

Gillian L. Currie ◽

Helena N. Angel-Scott ◽

Lesley Colvin ◽

Fala Cramond ◽

Kaitlyn Hair ◽

...

Keyword(s):

Systematic Review ◽

Peripheral Neuropathy ◽

Experimental Design ◽

Animal Models ◽

Study Design ◽

Outcome Measure ◽

Meta Analysis ◽

Risk Of Bias ◽

Behavioural Tests ◽

The Impact

AbstractBackground and aimsChemotherapy-induced peripheral neuropathy (CIPN) can be a severely disabling side-effect of commonly used cancer chemotherapeutics, requiring cessation or dose reduction, impacting on survival and quality of life. Our aim was to conduct a systematic review and meta-analysis of research using animal models of CIPN to inform robust experimental design.MethodsWe systematically searched 5 online databases (PubMed, Web of Science, Citation Index, Biosis Previews and Embase (September 2012) to identify publications reporting in vivo CIPN modelling. Due to the number of publications and high accrual rate of new studies, we ran an updated search November 2015, using machine-learning and text mining to identify relevant studies.All data were abstracted by two independent reviewers. For each comparison we calculated a standardised mean difference effect size then combined effects in a random effects meta- analysis. The impact of study design factors and reporting of measures to reduce the risk of bias was assessed. We ran power analysis for the most commonly reported behavioural tests.Results341 publications were included. The majority (84%) of studies reported using male animals to model CIPN; the most commonly reported strain was Sprague Dawley rat. In modelling experiments, Vincristine was associated with the greatest increase in pain-related behaviour (−3.22 SD [−3.88; −2.56], n=152, p=0). The most commonly reported outcome measure was evoked limb withdrawal to mechanical monofilaments. Pain-related complex behaviours were rarely reported. The number of animals required to obtain 80% power with a significance level of 0.05 varied substantially across behavioural tests. Overall, studies were at moderate risk of bias, with modest reporting of measures to reduce the risk of bias.ConclusionsHere we provide a comprehensive summary of the field of animal models of CIPN and inform robust experimental design by highlighting measures to increase the internal and external validity of studies using animal models of CIPN. Power calculations and other factors, such as clinical relevance, should inform the choice of outcome measure in study design.

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The Janus Face of Neutrophil Specific Antigen CD177 in Bacterial Infection: Focal Disease Versus Systemic Disease

Blood ◽

10.1182/blood.v118.21.1108.1108 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1108-1108

Author(s):

Behnaz Bayat ◽

Vanessa Santoso ◽

Beate Kehrel ◽

Ulrich J Sachs ◽

Sentot Santoso

Keyword(s):

Bacterial Infection ◽

Conflicts Of Interest ◽

Systemic Disease ◽

Specific Antigen ◽

Favourable Effect ◽

Bacterial Sepsis ◽

Migration Ability ◽

Significant Difference ◽

The Impact

Abstract Abstract 1108 CD177, also known as NB1 (or HNA-2) is a GPI-linked glycoprotein, which is exclusively expressed on neutrophils. Approximately 3 to 5% of healthy individuals do not express this antigen on their neutrophils (NBnull). Recent data demonstrated a strong upregulation of NB1 on neutrophils in patients with bacterial, but not viral infections. The mechanism underlying this phenomenon, however, is unknown. Our previous studies showed that NB1 functions as a partner of endothelial PECAM-1 and therefore plays a role on neutrophil diapedesis. Consequently, neutrophils carrying NB1 (NB1plus) migrate faster through endothelial cells than NBnull neutrophils. However, several studies have documented an abrogation of neutrophil migratory abilities in sepsis conditions. In this study, we aim to clarify the impact of neutrophil NB1 expression in bacterial sepsis. To mimic this condition in vitro, we first compared the transendothelial migration ability of NB1 phenotyped neutrophils after stimulation with the bacterial peptide fMLP in a transwell system. Lower transmigration ability (75% vs. 40%) was observed in fMLP-treated NB1plus neutrophils (n = 5) in comparison to untreated neutrophils. In contrast, no significant difference in the migration ability was observed between fMLP-treated and untreated NB1null neutrophils (n = 3). Expression analysis by flow cytometry showed a dose-dependent upregulation of NB1 after stimulation with fMLP (10−6 to 10−8 μM) in NB1plus neutrophils. Interestingly, down regulation of PECAM-1 expression was observed in these treated cells. Contrary, no PECAM-1 downregulation was detected in NBnull fMLP-treated neutrophils. These results could be confirmed by immunoblotting analysis using specific antibodies directed against different epitopes on NB1 (mabs 7D8, MEM166) and against different PECAM-1 Ig domains (mabs PECAM1.1, 1.2 and 1.3). Analysis of the supernatants of fMLP-treated neutrophils demonstrated the shedding of PECAM-1 from NB1plus, but not from NB1null neutrophils. These results indicate that shedding of PECAM-1 from neutrophils during bacterial infections depends on NB1 expression. Recent studies showed that a single nucleotide polymorphism (42C>G) located in NB1 promoter region is associated with the regulation of NB1 expression. Individuals homozygous for C allele express high NB1 surface density in comparison to individuals homozygous for G allele. Our association study showed higher frequency of C allele in patients with bacterial sepsis (n=98) compared with healthy cohort (n = 132) (8.16% vs. 12.88%; P<0.03). This observation indicates the role of C42 allele (or high NB1 expression) as genetic risk factor for bacterial sepsis. All together, these data demonstrate a reverse role of NB1 expression in focal and systemic infection, indicating favourable effect of low NB1 in systemic bacterial infection. This phenomenon may be caused by reduction of neutrophil directionality and motility due to NB1-mediated PECAM-1 shedding. Disclosures: No relevant conflicts of interest to declare.

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The Impact of Extramural Venous Invasion in Colorectal Cancer: A Detailed Analysis Based on Tumor Location and Evaluation Methods

International Journal of Surgical Pathology ◽

10.1177/1066896919874493 ◽

2019 ◽

Vol 28 (2) ◽

pp. 120-127

Author(s):

Young-Min Shin ◽

Jung-Soo Pyo ◽

Mee Ja Park

Keyword(s):

Colorectal Cancer ◽

Subgroup Analysis ◽

Meta Analysis ◽

Survival Rates ◽

Venous Invasion ◽

Tumor Location ◽

Evaluation Methods ◽

Hazard Ratio ◽

Significant Difference ◽

The Impact

This study aimed to elucidate the prognostic implications of extramural venous invasion (EMVI) in colorectal cancer (CRC) through a meta-analysis. Eighteen eligible studies were included in this meta-analysis. Data on the prevalence of EMVI and the correlation between EMVI and survival were collected from these studies. In addition, a subgroup analysis was conducted based on tumor location and evaluation methods. The estimated prevalence of EMVI was 28.3% (95% confidence interval [CI] = 23.1% to 34.0%) in patients with CRC. The estimated prevalence of EMVI in patients with colon cancer and rectal cancer was 23.0% (95% CI = 17.6% to 29.6%) and 35.7% (95% CI = 22.3% to 51.6%), respectively. Based on the evaluation method, the estimated prevalence of EMVI were 28.3% (95% CI = 23.2% to 34.1%) and 27.3% (95% CI = 8.4% to 60.6%) in pathologic and radiologic examinations, respectively. The correlation of EMVI with worse overall and disease-free survival rates was significant (hazard ratio = 1.773, 95% CI = 1.483-2.120, and hazard ratio = 2.059, 95% CI = 1.683-2.520, respectively). However, in the subgroup analysis with radiologic examination, there was no significant difference in survival rates between patients with and without EMVI. Our study showed that EMVI was frequently detected in 28.3% of patients with CRC and was correlated to worse survival. The detection of EMVI can be useful for predicting the prognosis of patients with CRC.

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Esophageal Atresia: Future Directions for Research on the Digestive Tract

European Journal of Pediatric Surgery ◽

10.1055/s-0036-1587330 ◽

2016 ◽

Vol 27 (04) ◽

pp. 306-312 ◽

Cited By ~ 2

Author(s):

Nathalie Rommel ◽

Jan Tack ◽

Jan Deprest ◽

Karel Allegaert ◽

Maissa Rayyan

Keyword(s):

Animal Models ◽

Esophageal Atresia ◽

Survival Rates ◽

Short Term ◽

Future Directions ◽

Experimental Animal Models ◽

The Impact ◽

Medical Morbidity ◽

Function Assessment

AbstractEsophageal atresia (EA) is a congenital malformation defined by the discontinuity of the esophagus occurring in 2.4 in 10,000 births. As survival rates are high, the significant medical morbidity became more relevant. Short-term and long-term morbidities involve the respiratory and gastrointestinal system in the majority of the patients. The impact of this morbidity seems large enough to inspire researchers to develop experimental animal models that may help understanding the pathogenesis and pathophysiology. These models can also be used to explore potential surgical therapies. We reviewed the clinical and experimental literature focusing on esophageal morbidity in EA. Although the consequences of esophageal motility disorders are very relevant in the clinical setting, research remains largely underexplored. Consequently, we suggest integrating motility function assessment in the existing research models.

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Early versus late initiation of renal replacement therapy impacts mortality in septic patients with acute kidney injury: a meta-analysis

10.21203/rs.3.rs-16023/v1 ◽

2020 ◽

Author(s):

Chenglong Ge ◽

Yuan Jiang ◽

Qianyi Peng ◽

Yuhang Ai

Keyword(s):

Acute Kidney Injury ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Meta Analysis ◽

Kidney Injury ◽

Cochrane Library ◽

Optimal Time ◽

Late Initiation ◽

Beneficial Impact ◽

The Impact

Abstract Background: Acute kidney injury (AKI) is a frequent complication in septic patients and increases in-hospital mortality. Our aim was to evaluate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in septic patients with acute kidney injury (AKI). Methods: Systematic review and meta-analysis were used in this study. We searched PubMed, EMBASE, MEDLINE and Cochrane Library. Results: Nine studies (two randomized controlled trials (RCTs) and seven retrospective cohorts) including 1694 patients were identified for detailed evaluation. This meta-analysis suggested that early RRT initiation within 48 hours (OR 0.30; 95% CI 0.20 to 0.45; I 2 0%) in septic patients with AKI reduced 28-day mortality (odds ratio (OR) 0.56; 95% confidence interval (CI) 0.37 to 0.86; I 2 73%), but intensive care unit (ICU) length of stay (LOS) (mean difference (MD) -1.49; 95% CI -3.65 to -0.67; I 2 53%), hospital LOS (MD -3.18; 95% CI -7.35 to 0.99; I 2 41%), the duration of RRT (MD -2.05; 95%CI -6.86 to 2.76; I 2 83%) and the duration of ventilation (MD 1.99; 95%CI -2.76 to 6.75; I 2 85%) were not influenced by the timing of RRT initiation. Conclusions: Early initiation of RRT within 48 hours in septic patients with AKI may have a beneficial impact on survival. However, this conclusion is based on heterogeneous trials of different quality and only two RCTs. Conclusive therapeutic recommendations regarding the optimal time to initiate RRT remain uncertain.

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Fever worsens outcomes in animal models of ischaemic stroke: A systematic review and meta-analysis

European Stroke Journal ◽

10.1177/2396987318776421 ◽

2018 ◽

Vol 4 (1) ◽

pp. 29-38 ◽

Cited By ~ 3

Author(s):

Jeroen C de Jonge ◽

Justin Wallet ◽

H. Bart van der Worp

Keyword(s):

Systematic Review ◽

Animal Models ◽

Infarct Size ◽

Ischaemic Stroke ◽

Meta Analysis ◽

Animal Experiments ◽

Primary Outcome Measure ◽

Artery Occlusion ◽

Poor Outcome ◽

The Impact

Background Subfebrile temperatures and fever in the first days after stroke are associated with a greater risk of a poor outcome. If this relation is causal, prevention of hyperthermia may improve outcome. Causality can be tested in animal models. We therefore assessed the effects of hyperthermia on outcomes in animal models of ischaemic stroke and explored under which conditions prevention of hyperthermia could be most effective. Methods We performed a systematic review and meta-analysis of data from animal experiments testing the effect of spontaneous or induced hyperthermia on outcome after focal cerebral ischaemia. Our primary outcome measure was infarct size. Normalised mean differences were combined using the random effects model and stratified meta-analysis was used to explore the impact of study characteristics. Results We included 19 publications, reporting on 49 comparisons involving 603 animals. Overall, hyperthermia increased infarct size by 43.4% (95% confidence interval, 29.8–56.9%) and worsened neurobehavioral outcomes by 48.5% (17.2–79.8%). The increase in infarct size was larger with higher temperatures. Hyperthermia was most harmful if present for more than 2 h and when started at the time of artery occlusion rather than later. Conclusion Hyperthermia substantially increased infarct size in animal models of ischaemic stroke, suggesting that the relation between fever and poor outcome observed in patients is at least in part causal. These data provide support to trials testing the effect of the prevention of fever with antipyretic drugs in patients with acute stroke.

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The impact of low advanced glycation end products diet on obesity and related hormones: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-020-79216-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Mohammad Hassan Sohouli ◽

Elham Sharifi-Zahabi ◽

Abolfazl Lari ◽

Somaye Fatahi ◽

Farzad Shidfar

Keyword(s):

Systematic Review ◽

Systematic Reviews ◽

Advanced Glycation End Products ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

High Age ◽

The Impact

AbstractSeveral randomized clinical trials (RCTs) have investigated the effect of dietary advanced glycation end products (AGE) on obesity factors and related hormones in adults; results were conflicting. Therefore, a study was performed to assess the effect of low advanced glycation end products diet on obesity and related hormones. A comprehensive literature search without any limitation on language was conducted using the following bibliographical databases: Web of Science, Scopus, Ovid MEDLINE, Cochrane, and Embase up to October, 2019. From the eligible trials, 13 articles were selected for the systematic review and meta-analysis. Our systematic reviews and meta-analyses have shown a significant decrease in BMI (WMD: − 0.3 kg/m2; 95% CI: − 0.52, − 0.09, p = 0.005; I2 = 55.8%), weight (WMD: − 0.83 kg; 95% CI: − 1.55, − 0.10, p = 0.026; I2 = 67.0%), and leptin (WMD: − 19.85 ng/ml; 95% CI: − 29.88, − 9.82, p < 0.001; I2 = 81.8%) and an increase in adiponectin (WMD: 5.50 µg/ml; 95% CI: 1.33, 9.67, p = 0.010; I2 = 90.6%) levels after consumption of the low AGE diets compared to the high AGE diets. Also, the effect of intake of low AGE compared to high AGE diets was more pronounced in subgroup with duration > 8 weeks for the BMI and weight. Overall, according to our results, although low AGE diets appeared to be statistically significant in reducing the prevalence of obesity and chronic diseases compared to high consumption of dietary AGEs. But, no clinical significance was observed. Therefore, to confirm these results clinically, further prospective studies should be conducted in this regard. The study protocol was registered in the in International prospective register of systematic reviews (PROSPERO) database as CRD42020203734.

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