scholarly journals Optimizing Livers for Transplantation Using Machine Perfusion versus Cold Storage in Large Animal Studies and Human Studies: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xinan Jiang ◽  
Lei Feng ◽  
Mingxin Pan ◽  
Yi Gao
Keyword(s):  
Hyaluronic Acid ◽  
Cold Storage ◽  
Animal Studies ◽  
Meta Analysis ◽  
Human Studies ◽  
Large Animal ◽  
Machine Perfusion ◽  
Early Graft ◽  
Meta Analyses ◽  
Early Graft Dysfunction

Background. Liver allograft preservation frequently involves static cold storage (CS) and machine perfusion (MP). With its increasing popularity, we investigated whether MP was superior to CS in terms of beneficial outcomes. Methods. Human studies and large animal studies that optimized livers for transplantation using MP versus CS were assessed (PubMed/Medline/EMBASE). Meta-analyses were conducted for comparisons. Study quality was assessed according to the Newcastle-Ottawa quality assessment scale and SYRCLE’s risk of bias tool. Results. Nineteen studies were included. Among the large animal studies, lower levels of lactate dehydrogenase (SMD -3.16, 95% CI -5.14 to -1.18), alanine transferase (SMD -2.46, 95% CI -4.03 to -0.90), and hyaluronic acid (SMD -2.48, 95% CI -4.21 to -0.74) were observed in SNMP-preserved compared to CS-preserved livers. NMP-preserved livers showing lower level of hyaluronic acid (SMD -3.97, 95% CI -5.46 to -2.47) compared to CS-preserved livers. Biliary complications (RR 0.45, 95% CI 0.28 to 0.73) and early graft dysfunction (RR 0.56, 95% CI 0.34 to 0.92) also significantly reduced with HMP preservation in human studies. No evidence of publication bias was found. Conclusions. MP preservation could improve short-term outcomes after transplantation compared to CS preservation. Additional randomized controlled trials (RCTs) are needed to develop clinical applications of MP preservation.

scholarly journals Normothermic Ex Vivo Machine Perfusion for Liver Grafts Recovered from Donors after Circulatory Death: A Systematic Review and Meta-Analysis

HPB Surgery ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jordan J. Nostedt ◽  
Daniel T. Skubleny ◽  
A. M. James Shapiro ◽  
Sandra Campbell ◽  
Darren H. Freed ◽  
...  
Keyword(s):  
Cold Storage ◽  
Meta Analysis ◽  
Mean Difference ◽  
Large Animal ◽  
Machine Perfusion ◽  
Donation After Circulatory Death ◽  
Economic Implications ◽  
Normothermic Perfusion ◽  
Normothermic Machine Perfusion ◽  
Circulatory Death

As a result of donation after circulatory death liver grafts’ poor tolerance to cold storage, there has been increasing research interest in normothermic machine perfusion. This study aims to systematically review the current literature comparing normothermic perfusion to cold storage in donation after circulatory death liver grafts and complete a meta-analysis of published large animal and human studies. A total of nine porcine studies comparing cold storage to normothermic machine perfusion for donation after circulatory death grafts were included for analysis. There was a significant reduction in AST (mean difference −2291 U/L, CI (−3019, −1563); P ≤ 0.00001) and ALT (mean difference −175 U/L, CI (−266, −85); P=0.0001), for normothermic perfusion relative to static cold storage, with moderate (I2 = 61%) and high (I2 = 96%) heterogeneity, respectively. Total bile production was also significantly higher (mean difference = 174 ml, CI (155, 193); P≤0.00001). Further research focusing on standardization, performance of this technology following periods of cold storage, economic implications, and clinical trial data focused on donation after circulatory death grafts will be helpful to advance this technology toward routine clinical utilization for these grafts.

scholarly journals Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kei Hayashida ◽  
Ryosuke Takegawa ◽  
Muhammad Shoaib ◽  
Tomoaki Aoki ◽  
Rishabh C. Choudhary ◽  
...  
Keyword(s):  
Systematic Review ◽  
Reperfusion Injury ◽  
Animal Studies ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Human Studies ◽  
Cochrane Library

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

Similar effect of autologous and allogeneic cell therapy for ischemic heart disease: results from a meta-analysis of large animal studies

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P1462-P1462
Author(s):  
S. J. Jansen Of Lorkeers ◽  
J. E. C. Eding ◽  
T. I. G. Van Der Spoel ◽  
H. M. Vesterinen ◽  
S. Koudstaal ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cell Therapy ◽  
Ischemic Heart Disease ◽  
Animal Studies ◽  
Meta Analysis ◽  
Ischemic Heart ◽  
Large Animal ◽  
Allogeneic Cell ◽  
Allogeneic Cell Therapy

scholarly journals The Impact of Consumption of Dairy Products on Phospholipid Metabolism: A Systematic Review

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1261-1261
Author(s):  
Emad Yuzbashian ◽  
Catherine B Chan
Keyword(s):  
Dairy Products ◽  
Animal Studies ◽  
Meta Analysis ◽  
Phospholipid Metabolism ◽  
Human Studies ◽  
Resistance Risk ◽  
Human Trials ◽  
Beneficial Effects ◽  
Funding Sources ◽  
The Impact

Abstract Objectives Metabolomics approach indicates that circulating phospholipid (PL) and some PL species are associated with a lower insulin resistance risk. Evidence suggests that dairy products' health beneficial effects may pertain to their regulatory influence on PL metabolism. Therefore, we aimed to systematically review the existing literature of animal and human trials to unravel the impact of dairy products on the concentration of PL and its metabolism. Methods Three online databases, including PubMed, Scopus, and Web of Science, were searched to find relevant studies published in peer-reviewed journals between January 2000 and July 2020. Included studies were interventional trials (animal and human) that investigated the effect of dairy or its subtypes on the circulating or liver content of PL and its species. The risk of bias (RoB) in trials in humans and animals was assessed using the revised Cochrane's and SYRCLE's RoB assessment, respectively. Since there was marked methodological heterogeneity, a meta-analysis did not perform. Results In this review, 2427 articles were identified and screened after removing duplicate articles. Following evaluation of the titles and abstracts and then full-text assessment, 17 studies were identified that met the inclusion criteria. Studies were classified according to their type, resulting in nine human trials and eight animal studies. For human studies, the RoB assessment indicated that more than 55% of studies had high RoB. None animal studies receive low RoB because of the lack of methodological information. Findings from human studies revealed that plasma/serum concentration of PL did not change after intervention with dairy products. PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL; however, certain PC or LPC species were increased by interventions. These findings were also confirmed in animal studies. The interesting point in animal studies was that high fat diet-induced elevation of PL tends to be normalized after intervention with dairy products enriched with milk-PL. Furthermore, in mice, intervention with yogurt or cheese did not impact serum or liver content of PL or PC. Conclusions Dairy products can influence the blood concentration of PC and LPC species in both rodents and humans without alteration of total PL and PC. Funding Sources Alberta Diabetes Institute.

scholarly journals Immunogenicity and safety of adenovirus-based vector vaccines for COVID-19: a systematic review and meta-analysis

2021 ◽  
Vol 30 (4) ◽  
pp. 264-78
Author(s):  
Ayers Gilberth Ivano Kalaij ◽  
Valerie Josephine Dirjayanto ◽  
Syarif Maulana Yusuf ◽  
Erni Juwita Nelwan
Keyword(s):  
Systematic Review ◽  
Animal Studies ◽  
Vaccine Development ◽  
Meta Analysis ◽  
Fixed Effect Model ◽  
Effective Vaccine ◽  
Forest Plot ◽  
Vector Vaccine ◽  
Effect Model ◽  
Meta Analyses

BACKGROUND Despite various research on vaccine development, severe acute respiratory syndrome coronavirus 2 infection continues to spread. Thus, developing a more effective vaccine for production and clinical efficacy is still in high demand. This review aimed to assess the immunogenicity and safety of adenovirus-based vector vaccine (Ad-vaccines) including Ad5-vectored, ChAdOx1 nCoV-19, rAd26-S or rAd5-S, and Ad26.COV2.S as the promising solutions for COVID-19. METHODS We conducted a systematic review and meta analysis of clinical trials based on the preferred reporting items for systematic reviews and meta-analyses guidelines through PubMed, Scopus, Cochrane, and EBSCOhost until August 17, 2021. We implemented inclusion and exclusion criteria and assessed the studies using OHAT risk of bias rating tool for human and animal studies. Pooled estimates of odds ratio (OR) were analyzed using fixed-effect model. RESULTS This systematic review yielded 12 clinical studies with a total of 75,105 subjects. Although the studies were heterogeneous, this meta-analysis showed that Ad-vaccine significantly increased protection and immune response against COVID-19 with a pooled efficacy of 84.68% compared to placebo (p<0.00001). Forest plot also indicated that Ad-vaccine conferred protection against moderate to severe COVID-19 with a pooled OR of 0.26 (p<0.00001). Ad-vaccine had also shown a good safety profile with local site pain and fever as the most common side effects. CONCLUSIONS Ad-vaccine had shown a good immunogenicity for COVID-19 with a good pooled efficacy and was proven safe for COVID-19 patients.

scholarly journals Effect of Bone Marrow Mesenchymal Stromal Cell Therapies in Rodent Models of Sepsis: A Meta-Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Lite Ge ◽  
Jing Zhao ◽  
Huiyin Deng ◽  
Chunli Chen ◽  
Zhiping Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Fixed Effects ◽  
Animal Studies ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Large Animal ◽  
Significant Heterogeneity ◽  
Rodent Models ◽  
Inclusion Criteria ◽  
Knowledge Gaps

BackgroundMultiple preclinical studies have demonstrated that bone‐marrow derived mesenchymal stromal (stem) cells [MSC(M)] positively influence the severity of sepsis symptoms and mortality in rodent models. However, this remains an inconclusive finding.ObjectiveTo review the effect of naïve MSC(M) in rodent models of sepsis.MethodsThe PubMed, EMBASE, and Web of Science databases were searched up to August 31, 2021. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified MSC(M); (3) comparison: not specified; (4) primary outcome: the effects of MSC(M) cell therapy on the mortality of rodent models of sepsis and endotoxemia; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis.The inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs).Resultstwenty-four animal studies met the inclusion criteria. Our results revealed an overall OR difference between animals treated with naïve MSC(M) and controls for mortality rate was 0.34(95% confidence interval: 0.27-0.44; P &lt; 0.0001). Significant heterogeneity among studies was observed.ConclusionsThe findings of this meta-analysis suggest that naïve MSC(M) therapy decreased mortality in rodent models of sepsis. Additionally, we identified several key knowledge gaps, including the lack of large animal studies and uncertainty regarding the optimal dose of MSC(M) transplantation in sepsis. Before MSC(M) treatment can advance to clinical trials, these knowledge gaps must be addressed.

scholarly journals Vitamin C can reduce mortality in sepsis: a systematic review and meta-analysis of animal and human evidence

2020 ◽  
Author(s):  
Cong-Cong Zhao ◽  
Li-Nan Han ◽  
Gui-Jun Zhu ◽  
Zhi-Qiang Li ◽  
Zhen-Jie Hu
Keyword(s):  
Systematic Review ◽  
Mean Arterial Pressure ◽  
Vitamin C ◽  
Animal Studies ◽  
Meta Analysis ◽  
Capillary Density ◽  
Human Studies ◽  
Pooled Data ◽  
Intravenous Vitamin

Abstract Background: The effect of vitamin C on outcomes in sepsis is unclear. This systematic review and meta-analysis included animal and human studies to evaluate the value of intravenous vitamin C as a monotherapy in sepsis. Methods: We searched MEDLINE via PubMed, EMBASE, CENTRAL and CBM for animal studies, randomized controlled trials (RCTs), and quasi-RCTs dated up to August 10, 2020. The included studies compared the effect of intravenous vitamin C and control on outcomes in sepsis. No language restrictions were applied. Two authors independently assessed the eligibility and quality of the trials and extracted data. Results: A total of 7 animal studies and 5 RCTs were included. Four animal studies (n=176) and all 5 RCTs (n=472) reported mortality, the primary outcome of this meta-analysis. The mortality of the vitamin C group was lower than that of the control group (odds ratio (OR) 0.22, 95% CI 0.06 to 0.81, P = 0.02; I2 =60% in animal studies, and OR 0.48, 95% CI 0.33 to 0.71, P < 0.001; I2 =0% in human studies). The GRADE assessment showed that the outcome was downgraded from high- to moderate-quality evidence due to imprecision. With regard to the secondary outcomes, the pooled data from animal studies showed that vitamin C had a beneficial effect on mean arterial pressure (std. mean difference (SMD) 1.36, 95% CI 0.32 to 2.41, P = 0.01; I2 =78%) and capillary density (SMD 1.97, 95% CI 0.89 to 3.04, P=0.69; I2 =0%) but had no effect on the level of lactate. The pooled data from human studies showed that vitamin C was associated with a reduction in vasopressor duration (MD -18.85, 95% CI -24.61 to -11.55, P < 0.001; I2 =0%) but could not shorten the length of ICU stay or duration of mechanical ventilation. No adverse effects were reported.Conclusions: Evidence from animal and human studies suggests that intravenous vitamin C monotherapy can reduce mortality in sepsis, with a moderate quality of evidence. We also found that vitamin C had a beneficial effect on mean arterial pressure, capillary density, and reduction of vasopressor duration in sepsis.

scholarly journals The Impact of Steatosis on the Outcome of Liver Transplantation: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Qiong-Yue Zhang ◽  
Qiong-Fang Zhang ◽  
Da-Zhi Zhang
Keyword(s):  
Liver Transplantation ◽  
Survival Rate ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Graft Dysfunction ◽  
Outcome Indicators ◽  
Significant Difference ◽  
Early Graft ◽  
The Impact ◽  
Early Graft Dysfunction

Background and Aims. Liver transplantation is one of the most effective treatments for end-stage liver disease as well as for cases of acute liver failure. Facing organ donor shortage, liver transplant teams had to use marginal organs. Thus, increasing availability is a key concern of donor liver grafts including steatotic livers. However, the use of steatotic liver is still controversial. The aim of this systematic review and meta-analysis was to analyze the impact of steatosis on the outcome of liver transplantation. Methods. We searched PubMed, Cochrane Library, Embase, Web of knowledge, and so on for studies published through May 31, 2018, in which patients experienced liver transplantation using fatty liver. All studies extracted outcome indicators, and we draw conclusions by contrasting outcome indicators in different groups of steatosis. Odds ratios and 95% confidence intervals were calculated. P<0.05 was considered as statistically significant difference. Results. 19 publications were included. There was no significant difference between the group of no steatosis and mild group in primary nonfunction rate (P=0.605) or early graft dysfunction rate (P=0.44). The PNF rate was significantly higher in moderate group (P=0.003) and severe group (P <0.001) compared with that in no steatosis group. The same results were seen in early graft dysfunction rate. However, graft survival rate and patient survival rate did not differ between groups. Conclusions. Livers with mild steatosis, even with moderate or severe steatosis, could be suitable donor under strict control of transplant conditions.

scholarly journals The effect of analgesics on stimulus evoked pain-like behaviour in animal models for chemotherapy induced peripheral neuropathy- a meta-analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Carlijn R. Hooijmans ◽  
Derk Draper ◽  
Mehmet Ergün ◽  
Gert Jan Scheffer
Keyword(s):  
Clinical Trials ◽  
Peripheral Neuropathy ◽  
Animal Models ◽  
Animal Studies ◽  
Pain Threshold ◽  
Meta Analysis ◽  
Scientific Basis ◽  
Chemotherapeutic Agents ◽  
Comprehensive Search ◽  
Meta Analyses

AbstractChemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and animal studies, there is no sufficiently effective pharmacological treatment for CIPN. Although reducing pain is often a focus of CIPN treatment, remarkably few analgesics have been tested for this indication in clinical trials. We conducted a systematic review and meta-analyses regarding the effects of analgesics on stimulus evoked pain-like behaviour during CIPN in animal models. This will form a scientific basis for the development of prospective human clinical trials. A comprehensive search identified forty-six studies. Risk of bias (RoB) analyses revealed that the design and conduct of the included experiments were poorly reported, and therefore RoB was unclear in most studies. Meta-analyses showed that administration of analgesics significantly increases pain threshold for mechanical (SMD: 1.68 [1.41; 1.82]) and cold (SMD: 1. 41 [0.99; 1.83]) evoked pain. Subgroup analyses revealed that dexmedetomidine, celecoxib, fentanyl, morphine, oxycodone and tramadol increased the pain threshold for mechanically evoked pain, and lidocaine and morphine for cold evoked pain. Altogether, this meta-analysis shows that there is ground to investigate the use of morphine in clinical trials. Lidocaine, dexmedetomidine, celecoxib, fentanyl, oxycodone and tramadol might be good alternatives, but more animal-based research is necessary.

Treatment of heroin dependence with ibogaine

2016 ◽  
Vol 33 (S1) ◽  
pp. S10-S11
Author(s):  
A. Schellekens ◽  
T. Oosteren ◽  
T. Knuijver ◽  
R.J. verkes ◽  
M. Belgers
Keyword(s):  
Systematic Review ◽  
Substance Use ◽  
Animal Studies ◽  
Meta Analysis ◽  
Human Studies ◽  
Opiate Withdrawal ◽  
Close Monitoring ◽  
Qtc Prolongation ◽  
Self Administration ◽  
Number Of Patients

BackgroundThe use of the hallucinogen ibogaine as an anti-addiction agent has been described in several case reports, dating back to the eighties. The anti-addiction properties of ibogaine have been confirmed in a large body of animal work. Ibogaine has been shown to be effective in reducing withdrawal severity and substance use for a variety of substances, including cocaine and opiates. Animal studies also show some potentially dangerous adverse reactions, including cerebellar toxicity and potential cardiac effects. While pharmacological treatment options for opiate and cocaine dependence are still limited, ibogaine assisted treatment might be a promising new option. Therefore more systematic studies on its toxicity and efficacy are warranted. In our studies we address these two research questions: is ibogaine treatment for opiate dependence safe and effective for treating opiate withdrawal and relapse prevention? A secondary objective is to explore the pharmacokinetic properties of ibogaine.MethodsAnimal work: first we performed a systematic review and meta-analysis of animal studies on ibogaine. Thirty studies were included in the systematic review, of which 27 could be analyzed in meta-analysis. Human studies: fifteen opiate dependent patients will be treated with ibogaine (10 mg/kg), on top of treatment as usual. Ibogaine toxicity will be assessed through close monitoring with electrocardiography, with QTc prolongation as main outcome measure, repeated assessments of ataxia using the (SARA) and observation of psychotic symptoms by using the Delirium Observations Scale (DOS). Ibogaine efficacy will be measured, using repeated evaluations of opiate withdrawal severity (Subjective Opiate Withdrawal Scale: SOWS; Objective Opiate Withdrawal Scale: OOWS), craving intensity (using a Visual Analogue Scale) and substance use, with a six-month follow-up. Clinical observations in ibogaine treated individuals will be compared with a cohort of opiate dependent patients treated with a rapid detoxification procedure. Both acute and long-term effects will be linked with serum ibogaine and noribogaine levels.ResultsAnimal work: overall, ibogaine reduced drug self-administration, particularly during the first 24 hours after administration. Ibogaine had no effect on drug-induced conditioned place preference. Ibogaine administration resulted in motor impairment in the first 24 hours after supplementation, and cerebral cell loss even weeks after administration. Data on ibogaines effect on cardiac rhythm as well as on its neuropharmacological working mechanisms are limited. Human studies: human data are still being collected. Treatment of the first patients confirmed strong effects of ibogaine on heart rhythm (QTc prolongation) and ataxia, while the opiate withdrawal symptoms were relatively mild. The first observations on the clinical effect of ibogaine on craving and substance use will also be shared.ConclusionsBased on our meta-analysis of animal data, there is strong evidence that ibogaine is effective in reducing drug self-administration in animals. This warrants further studies into the clinical efficacy of ibogaine in substance dependent patients in reducing craving and substance use. Our first clinical experiences in a limited number of patients confirm that ibogaine treatment may be effective in reducing opiate withdrawal, but can potentially have transient cardiac and cerebellar toxicity.Disclosure of interestThe authors have not supplied his declaration of competing interest.

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