The sources of the replenishment and hydrogeochemical evolution of acid mine drainage (AMD) from abandoned mines are issues of public concern around the world. To reveal the sources of groundwater replenishment and the nature of the hydrogeochemical processes that control the evolution of water quality in the multi-aquifer system of the abandoned Dashu pyrite mine in southwest China, the main control mechanisms of groundwater evolution are examined, based on hydrogeochemical analysis methods in combination with environmental isotope tracing methods, which in turn clarify the hydrogeochemical causes of groundwater pollution. According to the hydrogeochemical and stable and unstable isotope analyses, the diversity of groundwater hydrochemical types in the study area reflects the complexity of the groundwater hydrogeochemical environment, where groundwater is formed after the mixing of atmospheric precipitation and groundwater over multiple periods. The analysis of 2H, 18O, and T is used to identify the main sources of hydraulic connection between aquifers, groundwater, and mine water. The results show that there are close hydraulic connections between aquifers. Mine water and groundwater mainly come from the groundwater in the Quaternary accumulation platform. The results of the ion analysis and sulfur isotope tracing show that the main ions in the groundwater are derived from mineral dissolution/precipitation, cation exchange, pyrite oxidation, and other water-rock interaction processes. The sulfur in the groundwater mainly comes from the dissolution of gypsum, while the main source of sulfur in the mine water is the oxidation of pyrite, indicating that pyrite oxidation and cation exchange are the dominant processes in the mine water. The key hydrogeochemical processes were simulated using the reverse hydrogeochemical simulation method. The results show that the mining activities changed the water levels and flow conditions, strengthened the interaction between groundwater and aquifer lithology, which in turn affected the accompanying hydrogeochemical processes. After all of the mine was abandoned, it saw the cross-contamination between the aquifer and mine water. These results provide theoretical guidance for the identification of sources and key hydrogeochemical processes affecting groundwater and pollutants in the abandoned Dashu pyrite mines and similar abandoned mines with multiple aquifers, and can, therefore, provide technical support for the preparation of source prevention and control plans.

Background: Cardiac injury has been described in children with both acute COVID-19 and the multisystem inflammatory syndrome in children (MIS-C). Strain has been shown to be a sensitive measure of systolic function and can be used for detecting subclinical left ventricular (LV) dysfunction. We sought to describe strain findings in both groups on initial presentation and outpatient follow up. Methods: A retrospective study analyzing echocardiograms of all patients presenting with acute COVID-19 infection and MIS-C at our institution between March 2020 and December 2020 was performed. TOMTEC software was used for strain analysis in both study groups (COVID-19 and MIS-C) and age matched healthy controls. Regional strain was obtained and comparison amongst groups was performed using the Mann-Whitney U test. Strain was compared against LV ejection fraction (EF) as measured by 5/6 area length method. Results: 45 patients (34 MIS-C and 11 COVID-19) met inclusion criteria. There was a statistically significant decrease in LV longitudinal strain (p <0.001), LV circumferential strain (p <0.001) and left atrial strain (p = 0.014) in the MIS-C group when compared to the control group. There was a statistically significant decrease in LV longitudinal strain (p = 0.028) in the acute COVID-19 group. All patients with abnormal LVEF had abnormal strain. However 14 patients (41%) in the MIS-C group and 3 (27%) in the acute COVID-19 group had preserved LVEF but abnormal strain. Abnormal strain persisted in one-third of patients in the MIS-C and acute COVID-19 groups on outpatient follow up. Conclusion: Patients with MIS-C and acute COVID-19 can develop myocardial dysfunction as seen by abnormal strain. Strain may provide an additional tool in detecting subtle myocardial dysfunction. It can be routinely employed at diagnosis and at follow up evaluation of these patients.

Despite their close links, ecology and evolution have remained separate disciplines to this day. Breaking down the wall between the two disciplines is essential for at least two reasons. First, this wall is an obstacle to the study of most microorganisms, which constitute a large part of the Earth's biodiversity. Asexual reproduction, gene transfer and the lack of a clear definition of the species taxonomic level blur the distinction between ecological changes in species abundances and evolutionary changes in genotype frequencies in microbes. Second, a key question that biodiversity science will have to address in the coming decades is how ecological systems will cope with rapid environmental change. Generalising the concept of adaptation across multiple timescales and levels of organisation would provide an integrative framework for studying the combined ecological and evolutionary responses to environmental change, and thus help us to address one the major scientific challenges of our time.

Background: Despite the WHO recommendation that pregnant women be prioritised for seasonal influenza vaccination, coverage in the Western Pacific Region remains low. Our goal was to provide additional data for the Western Pacific region about the value of maternal influenza vaccination to pregnant women and their families. Methods: We conducted a 16-year retrospective cohort to evaluate risks associated with influenza-associated maternal acute respiratory infection (ARI) in New Zealand. ARI hospitalisations during the May-September influenza season were identified using select ICD-10-AM primary and secondary discharge codes from chapter J00-J99 (diseases of the respiratory system). Cox proportional hazards models were used to calculate crude and adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results: We identified 822,391 pregnancies among New Zealand residents between 2003 and 2018; 5,095 (0.6%) had >1 associated ARI hospitalisation during the influenza season; these pregnancies were at greater risk of preterm birth (aHR 1.5, 95% CI 1.3-1.7), and low birthweight (aHR 1.7, 95% CI 1.5-2.0) than pregnancies without such hospitalisations. We did not find an association between maternal ARI hospitalisation and fetal death (aHR 1.1, 95% CI 0.6-1.4) during the influenza season. Maternal influenza vaccination was associated with reduced risk of preterm birth (aHR 0.8, 95% CI 0.7-0.9), and low birthweight (aHR 0.9, 95%CI 0.8-0.9), and fetal death (aHR 0.5%, 95% CI 0.3-0.7). Conclusion: In this population-based cohort, being hospitalised for an ARI during the influenza season while pregnant was a risk-factor for delivering a preterm or a low birthweight infant and vaccination reduced this risk.

Species richness, evenness, and taxonomic diversity have been proposed and used as indicators of biodiversity. However, the governing equations for the dynamics of these indicators are often unknown and an understanding of their mechanism is limited. By employing a nonlinear forecasting-based method to the time series of 10 biodiversity indicators of a marine fish community, we aimed to detect changes in their dynamics and classify the indicators according to the level and timing of dynamic changes. The 10 biodiversity indicators were classified into three super-groups: Group I (species richness and community center of distribution) with the most unchanged dynamics; Group II (species diversity and total abundance) with dynamics that had an abrupt change in the middle, presumably due to an increase in local temperature; and Group III (species evenness) with highly variable dynamics. Finally, a hypothesis regarding the mechanistic basis of the dynamic similarities between the biodiversity indicators was proposed.

Conformational heterogeneity of the p53 tumor suppressor, wild-type and mutated forms, was investigated by computational modelling combined with all atoms Molecular Dynamics (MD) simulations. Four different punctual mutations (p53R175H, p53R248Q, p53R273H, p53R282W), which are known to affect the DNA binding and belong to the most frequent hot-spot mutations in human cancers, were taken into consideration. The MD trajectories of the wild-type and mutated p53 forms were analysed by Essential Dynamics, to extract relevant collective motions. The same trajectories were also analysed by the frustration method which allows to evaluate the degeneracy of the energy landscape. We found that punctual mutations can modulate the collective motions of p53 at different extent according to the specific mutation. Furthermore, mutations can affect the frustration level of p53 specially in the regions involved in the binding to physiological ligands. The regions of p53 with larger collective motions are also characterized by a high frustration level. The regions of p53 characterized by a high frustration level are also largely involved in wide collective motions. Such a correlation is discussed in connection with the intrinsic disordered character of p53 and also with its central functional role.

Degradation of solid polyethylene terephthalate (PET) by leaf branch compost cutinase (LCC) produces various PET-derived degradation intermediates (DIs), in addition to terephthalic acid (TPA), which is the recyclable terminal product of all PET degradation. Although DIs can also be converted into TPA, in solution, by LCC, the TPA that is obtained through enzymatic degradation of PET, in practice, is always contaminated by DIs. Here, we demonstrate that the primary reason for non-degradation of DIs into TPA in solution is the efficient binding of LCC onto the surface of solid PET. Although such binding enhances the degradation of solid PET, it depletes the surrounding solution of enzyme that could otherwise have converted DIs into TPA. To retain a sub-population of enzyme in solution that would mainly degrade DIs, we introduced mutations to reduce the hydrophobicity of areas surrounding LCC’s active site, with the express intention of reducing LCC’s binding to solid PET. Despite the consequent reduction in invasion and degradation of solid PET, overall levels of production of TPA were ~3.6-fold higher, due to the partitioning of enzyme between solid PET and the surrounding solution, and the consequent heightened production of TPA from DIs. Further, synergy between such mutated LCC (F125L/F243I LCC) and wild-type LCC resulted in even higher yields, and TPA of nearly ~100% purity.

A document by Mi-Rae ‍Park. Click on the document to view its contents.

The need for economic evaluation of new health care technologies, especially in the modern world era, is undisputable. Economic evidence alongside clinical evidence are the two main pillars of the Health Technology Assessment (HTA), a process which is followed for reimbursement medical technologies and budget allocation decisions. The role of epidemiological research is essential in obtaining the necessary data for the development of the economic evaluations. In this review paper, we adopt a stepwise approach, based on current guidelines for conducting economic evaluation (both budget impact and cost effectiveness analyses) for highlighting the need for modern epidemiological methods and tools in such a process. Epidemiological studies provide the data for the eligible patient population, the prevalence and incidence of disease, treatment effectiveness and health care resource utilization; these, in turn, are synthesized in an appropriate framework, together with real world data, for assisting in the budget allocation decisions.

DNA methylation is an important mechanism for the dynamic regulation of gene expression and silencing of transposons during plant developmental processes. Here, we analyzed genome-wide methylation patterns in sugarcane (Saccharum officinarum) leaves, roots, rinds, and piths at single-base resolution. DNA methylation patterns were similar among the different sugarcane tissues, whereas DNA methylation levels differed. We also found that DNA methylation in different genic regions or sequence contexts plays different roles in gene expression. Differences in methylation among tissues resulted in many differentially methylated regions (DMRs) between tissues, particularly CHH DMRs. Genes overlapping with DMRs tended to be differentially expressed (DEGs) between tissues, and these DMR-associated DEGs were enriched in biological pathways related to tissue function, such as photosynthesis, sucrose synthesis, stress response, transport, and metabolism. Moreover, we observed many DNA methylation valleys (DMVs), which always overlapped with transcription factors (TFs) and sucrose-related genes, such as WRKY, bZIP, WOX, SPS, and FBPase. Collectively, these findings provide significant insights into the complicated interplay between DNA methylation and gene expression and shed light on the epigenetic regulation of sucrose-related genes in sugarcane.

A 77-year-old woman underwent mitral valve replacement and tricuspid annuloplasty for severe mitral stenosis and tricuspid regurgitation with pulmonary hypertension. Two months later, the patient was readmitted because of marked edema. A new harsh pansystolic murmur was auscultated, and echocardiography revealed a jet from the left ventricle to the right atrium but no perivalvular leakage was detected at the mitral valve position. At operation, an 6mm defect adjacent to the tricuspid annulus in the interatrial septum and detachment of the anterior edge of the tricuspid ring were detected. The defect was closed using a pericardial patch. An inadequate stitch at the anteroseptal commissure in the previous operation led to left ventricular-right atrial communication.

Surgical pulmonary artery thrombectomy is a well-established emergency treatment for massive pulmonary embolism (PE) in which fibrinolysis or thrombolysis cannot happen. However, surgery for massive PE that requires peripheral pulmonary artery thrombus removal remains challenging. We established a simple and secure pulmonary artery thrombectomy method using cardiopulmonary bypass and cardiac arrest. In this procedure, the surgical assistant arm, typically used for coronary artery bypass grafting, is used to obtain a feasible working space during thrombectomy. We present seven consecutive massive PE cases treated with the present surgical method and successfully weaned from cardiopulmonary bypass or extracorporeal membrane oxygenation postoperatively. This procedure can be used to prevent right ventricular failure after surgery as surgeons can remove the thrombus up to the second branch of the pulmonary artery with direct vision.

Growth suppression and defense signaling are simultaneous strategies that plants invoke to respond to abiotic stress. Here, we show that the drought stress response of poplar trees ( Populus trichocarpa) is initiated by a suppression in cell wall derived methanol (MeOH) emissions and activation of acetic acid (AA) fermentation defenses. Temperature sensitive emissions dominated by MeOH (AA/MeOH < 30%) were observed from physiologically active leaves, branches, detached stems, leaf cell wall isolations, and whole ecosystems. In contrast, drought treatment resulted in a suppression of MeOH emissions and strong enhancement in AA emissions together with fermentation volatiles acetaldehyde, ethanol, and acetone. These drought-induced changes coincided with a reduction in stomatal conductance, photosynthesis, transpiration, and leaf water potential. The strong enhancement in AA/MeOH emission ratios during drought (400-3,500%) was associated with an increase in acetate content of whole leaf cell walls, which became significantly 13C 2-labeled following the delivery of 13C 2-acetate via the transpiration stream. The results are consistent with MeOH and AA production at high temperature in hydrated tissues associated with accelerated primary cell wall growth processes, which are downregulated during drought. Our observations are consistent with drought-induced activation of aerobic fermentation driving high rates of foliar AA emissions and enhancements in leaf cell wall O-acetylation. We suggest that atmospheric AA/MeOH emission ratios could be useful as a highly sensitive signal in studies investigating environmental and biological factors influencing growth-defense trade-offs in plants and ecosystems.

To prevent yield losses caused by climate change it is important to identify naturally tolerant genotypes with traits and related pathways that can be targeted for crop improvement. Here we report on the characterization of contrasting vegetative heat tolerance in two UK bread wheat varieties. Under chronic heat stress, the heat-tolerant cultivar Cadenza produced an excessive number of tillers which translated into more spikes and higher grain yield compared to heat-sensitive Paragon. RNAseq and metabolomics analyses revealed a set of about 400 heat-responsive genes common to both genotypes. Only 71 genes showed a genotype x temperature interaction. As well as known heat-responsive genes such as HSPs, several genes that have not been previously linked to the heat response, particularly in wheat, have been identified, including several dehydrins, a number of ankyrin-repeat protein-encoding genes, and lipases. Over 5000 genotype-specific genes were identified, including photosynthesis-related genes which might explain the observed ability of Cadenza to maintain photosynthetic rate under heat stress. Contrary to primary metabolites, secondary metabolites showed a highly differentiated heat response and genotypic differences. These included e.g., benzoxazinoid (DIBOA, DIMBOA) but in particular phenylpropanoids and flavonoids with known radical scavenging capacity, which was assessed via the DPPH assay. The most highly heat-induced metabolite was (glycosylated) propanediol, which is widely used in industry as an anti-freeze. To our knowledge this is the first report on its response to stress in plants. The identified metabolites and candidate genes provide novel targets for the development of heat tolerant wheat.

Nervous system involvement in IgG4-related systemic disease (IgG4-RD) is rarely reported and manifests as hypertrophic pachymeningitis and hypophysitis. In this report, a 33-year-old woman with neurological manifestations was diagnosed with IgG4-RD by biopsy. The patient showed improvement in symptoms after the treatment.

POLR3A is a main subunit encoding RNA polymerase III which is involved in transcription of many RNA structures. Here we report a new presentation of c.1771-6C>G intronic variant presenting as developmental regression, seizure and dystonia in a 6-year-old boy associated with striatum involvement in the brain MRI.

The authors present a rare case of non-anion gap metabolic acidosis (NAGMA) in a patient with chronic kidney disease. We highlight the management, and possible aetiologies that lead to this problem. This case report hopes to allow clinicians to introduce evidence-based guidelines for the management of patients with NAGMA.

Ondansetron is an FDA-approved selective serotonin 5-HT3 receptor commonly indicated as an anti-emetic agent for nausea and vomiting. It is rare to observe fatal reactions from ondansetron despite having no allergies or previous exposure. We report a case of anaphylactoid reaction with spontaneous coronary vasospasms in response to intravenous ondansetron.

Giant ACC with intracranial extension and lower cranial nerve palsy is rarest. 60 year female presented with unilateral hearing loss, facial deviation and difficulty in swallowing. Imaging showed highly vascular infiltrating and osteolytic mass S/O glomus jugulare. Patient underwent percutaneous embolization followed by External carotid ligation and resection of mass.

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DIHS), is a rare but severe delayed-type drug hypersensitivity reaction [[](#ref-0001)1]. Its reported incidence ranges between 2 and 5 cases per million per year and the mortality between 5 and 10% [[](#ref-0002)2]. DRESS is characterized by the occurrence of an extensive rash with face edema, lymphadenopathy and fever and organ damage, all of which seems to result from massive drug-directed T cell response and associated eosinophilia. DRESS is a complex condition, its clinical presentation varies depending on the cutaneous manifestation(s), affected target organ(s) and reaction severity. The diagnosis of DRESS is further challenged by the clinical overlay with autoimmune, infectious and lymphoproliferative conditions, which have to be considered in the differential diagnosis (Table 1). Eosinophilia is detected in only 80 % of DRESS patients and can be masked by e.g. the administration of systemic glucocorticoids (GCS). Furthermore, there are various differences in the DRESS diagnostic criteria (Table 1) developed by the Japanese SCAR (JSPS) [[](#ref-0003)3] and RegiSCAR [[](#ref-0004)4] groups, the most notable being the inclusion of herpes viremia in the criteria developed by the JSPS. All these clinical challenges underline the importance of a systematic and comprehensive approach when encountering a patient with suspected DRESS. Based on the most recent literature and our clinical expertise, we therefore suggest the medical algorithm depicted in Figure 1. DRESS should be evoked as a differential diagnosis in patients with a rash suspected to be drug-related and associated with head-and-neck edema [[](#ref-0005)5]. Clinical history-taking is a critical element to consolidate or discard a drug-related etiology: most importantly, this should explore the dynamics of both possible DRESS clinical symptoms and drug exposure(s) (date of onset, way and length of administration, previous exposures / reactions). A long drug exposure prior to disease onset, i.e. 2-8 weeks, is indicative for DRESS rather than other drug hypersensitivities – but the duration may vary depending on the causative drug. A thorough clinical examination, basic laboratory work-up, electrocardiogram, and - if a rash is present - a skin biopsy should also be performed. If the clinical presentation and drug exposure history substantiate the DRESS diagnosis, additional investigations should be performed depending on the suspected target organ damage (cf. case “complementary, patient-specific work-up”). Once the diagnosis is established, a severity assessment is warranted, since DRESS can range from mild forms with very limited organ damage to fulminant ones, e.g. characterized by (multi-)organ failure. There are no consensual severity scoring. In this algorithm, we suggest the scoring system used in France (RCT DRESSCODE, https://clinicaltrial.gov NCT01987076).

This paper studies the cluster consensus of multi-agent systems (MASs) with objective optimization on directed and detail balanced networks, in which the global optimization objective function is a linear combination of local objective functions of all agents. Firstly, a directed and detail balanced network is constructed that depends on the weights of the global objective function. Secondly, two new continuous-time optimization algorithms are proposed based on time-invariant and time-varying cost functions to ensure that all agents reach cluster consensus within a fixed-time, and the global objective function asymptotically reaches the optimal solution. Finally, two examples are presented to show the efficacy of the theoretical results.

I would like to submit an erratum for the article with the title ‘Development of Kinetic Energy Density Functional Using Response Function Defined on the Energy Coordinate’ (Int. J. Quantum Chem. 2022;e26969, https://doi.org/10.1002/qua.26969). The corresponding author of the article is Hideaki Takahashi. The author found an error in producing the graph with the legend ‘OF-DFT’ in Fig. 8 in the article. The error in the graph is attributed to the fact that the atomic response function was spuriously multiplied by 2. We refer the editor to the main text of the erratum in more details. The graph was revised using the amended source code. Fortunately, it was found that the corrected graph was changed favorably as compared to the original one, showing better agreement with the reference calculation.

The performance of functionals and basis sets is evaluated using density functional theory with polarized continuum model to calculate redox potentials of small organic compounds in acetonitrile. Pople basis sets 6-31G, 6-31G*, 6-31G**, 6-31+G*, 6-31+G**, 6-31++G** and functionals at different levels of the Jacob’s Ladder are studied: PW91, PBE, M06-L, B3LYP, PBE0, M06-2X, CAM-B3LYP, $\omega$B97X-D3. It is shown that performance studies should not be done considering oxidation and reduction reactions together, but analyzing them separately. Functional M06-2X has a more consistent and uniform response both in reductions and oxidations and the presence of diffuse functions in the basis sets is relevant to the accuracy of the predictions. The computational effort against accuracy is also evaluated.

Objective: we aim to compare Intracoronary versus Intravenous abciximab regarding inflammatory markers and cardiac fuction.Materials and Methods: We conducted a computer search of four authentic databases. We included randomized controlled trials (RCTs) compared IC versus IV abciximab in myocardial infarction patients. Data were extracted from eligible studies and pooled in a meta-analysis model using RevMan software package (ver. 5.2; Cochrane collaboration, Oxford, UK). Our primary outcome was Thrombolysis in myocardial infarction flow grade 3 (TIMI). Our secondary outcomes were different inflammatory markers, Left ventricular ejection fraction and ST-segment resolution. Results: 15 RCTs with total number of patients 4904 were included in our final analysis. Our analysis indicated no significant differences in both routes of abciximab in TIMI flow grade 3 (RR= 1.01, 95% CI [0.99, 1.04], p=0.26). The inflammatory markers (peak troponin, peak creatine kinase, peak creatine kinase myocardial band) favors intracoronary more than the intravenous route of abciximab. Intracoronary abciximab is associated with better left ventricular ejection fraction versus intravenous route, (MD= 3.31, 95% CI [1.46, 5.16], p=0.0005). Intracoronary abciximab is significantly better than intravenous one regarding ST-segment resolution (RR= 1.09, 95% CI [1.02, 1.17], p=0.02).   Conclusion: IC abciximab can be used instead of IV route due to greater benefits linked to IC abciximab administration.     1. Introduction:Myocardial infarction (MI), commonly identified as heart attack, stands to be irreversible necrosis and death of the heart muscle occurs when a portion of the cardiac muscle is deprived of oxygen due to blockage of a coronary artery [1]. Percutaneous coronary intervention (PCI) is considered a non-surgical procedure. In patients with ST-elevation myocardial infarction (STEMI), PCI can be critical to survival as it reduces mortality [2,3]. However, suboptimal myocardial perfusion continues to be a major limitation of PCI [4].  Inhibition of platelet aggregation remains one of the main cornerstones in the setting of STEMI [5]. Abciximab (glycoprotein IIb/ IIIa inhibitor) administration during performing PCI decreases major adverse cardiac events. Intracoronary (IC) abciximab bolus administration during PCI results in more local platelet aggregation inhibition, and more recovery in myocardial reperfusion in comparison with standard intravenous bolus injection [6,7]. In addition, the study by Eitel [8], showing 6-month follow-up of 154 STEMI patients undergoing PCI, Intracoronary (IC) or intravenous (IV) bolus abciximab administration realized the infarct size was significantly lower in the IC abciximab group when compared with the intravenous group . However, Several clinical trials suggested that no differences between intracoronary and intravenous abciximab administration on myocardial damage, infarct size and/or reperfusion injury [9, 10]. The aim of this systematic review and metaanalysis is to determine the feasibility of Intracoronary versus intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention from recently published randomized clinical trials.      2. Methods:We performed this systematic review and meta-analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [11]. We followed The PRISMA (Preferred Reporting Items for Systematic reviews and meta-analysis) statement guidelines during the preparation of this review and meta-analysis [12]. 2.1. Literature searchWe performed a comprehensive electronic literature search of four databases (PubMed, Cochrane library, Scopus and ISI Web of science of Clinical Trials) .we used the following search strategy; (intracoronary OR intravenous) AND (abciximab OR glycoprotein iib/iiia receptor inhibitors OR ReoPro) AND (myocardial infarction OR heart failure OR angina OR heart attack OR cardiovascular disease OR coronary thrombosis). There were no restrictions by the language of the study or the year of publication. 2.2. Eligibility criteriaWe included the studies according to following inclusion criteria: (I) population: Patients who were in urgent myocardial infarction (ii) intervention: Intracoronary abciximab; (iii) comparator: Intravenous abciximab; (IV) study outcomes: Inflammatory markers; Peak troponin, peak creatine kinase (CK), peak creatine kinase myocardial band (CK-MB), left ventricular ejection fraction (LV-EF) and ST-segment resolution; and (V) study design: randomized controlled trials (RCTs) only. Eligibility screening was conducted in a two step-wise manner (title and abstract screening then full-text screening). Each step was performed by Ahmed Abdelhakim independently. 2.3. Data extractionWe extracted the data from included studies on a standardized data collection Excel sheet. We collected the following data: list of authors, year of publication, sample size and baseline characteristics of study participants. We also extracted the following outcome data: Peak troponin, peak creatine kinase (CK), peak creatine kinase myocardial band (CK-MB), left ventricular ejection fraction (LV-EF) and ST-segment resolution. 2.4. Risk of bias assessmentWe evaluated the quality of included studies and the risk of bias using the Cochrane risk of bias assessment tool, clearly described in (chapter 8.5) of the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 [13]. The Cochrane risk of bias assessment tool includes the following domains: selection bias, performance bias (blinding of participant and personnel), detection bias (blinding of outcome assessment), attrition bias, reporting bias and other potential sources of bias. The authors’ judgment is categorized as “Low risk,” “High risk,”or “Unclear risk” of bias. 2.4. Data synthesisWe used outcome measures as the following; for dichotomous data, we used pooled risks ratios (RR), and for continuous data, we used weighted mean difference (MD) using Mantel-Haenszel method. All statistical analyses were performed using the Revman software package (ver. 5.2; Cochrane Collaboration, Oxford, UK). We assessed statistical heterogeneity using the Chi-Square test, and its extent was measured using the I-Square test [14]. The random effects model was used in case of heterogeneity between studies; otherwise, the fixed-effects model was used. We performed a sensitivity analysis to assess the contribution of each study to the pooled estimate by excluding one trial at a time and recalculating the pooled mean difference for the remaining studies.         3. Results:3.1. Results of the literature search:We retrieved 1640 studies after searching in different databases. After title and abstract screening, 20 articles were reliable for full-text screening. We excluded six of them and finally, 15 studies with a total number of 4904 patients matched our inclusion and were included in the final analysis. The PRISMA flow diagram of study selection is shown in figure 1.3.2. Characteristics of included studies:A total of 15 randomized controlled trials (RCTs) met our inclusion criteria [5–10,15–23] . The included studies compared intracoronary versus intravenous abciximab in myocardial infarction after percutaneous coronary intervention. Our primary outcome was Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 after PCI, different cardiac markers which were peak troponin, peak creatine kinase (CK) and peak creatine kinase myocardial band (CK-MB). Our secondary outcomes were different cardiac markers as: peak troponin, peak creatine kinase (CK) and peak creatine kinase myocardial band (CK-MB), left ventricular ejection fraction and ST-segment resolution. The summary of the included studies, their chief results, and the baseline characteristics are shown in table 1.3.3. Risk of bias assessment:The included RCTs were of from moderate to high quality as stated by the Cochrane risk of bias assessment tool. The summary of risk of bias assessment of RCTs is shown in figure 2 and the judgments are shown in supplementary file no.1. 3.4. Outcomes:3.4.1 TIMI grade 3 post-PCI:TIMI grade 3 post-PCI was reported in 13 studies. The pooled risk ratio (RR) showed no significant difference between intracoronary abciximab and intravenous abciximab (RR= 1.01, 95% CI [0.99, 1.04], p=0.26), figure 3. The pooled studies were homogeneous (p=0.33, I² = 11%); therefore, fixed effects model was conducted. 3.4.2. Peak troponin:Peak troponin was reported in five studies. The pooled standardized mean difference (SMD) showed a significant superiority of intracoronary abciximab in comparison with intravenous abciximab (SMD= -0.26, 95% CI [-0.43, -0.09], p=0.003), figure 4. The pooled studies were homogenous (p=0.13, I² = 44%); therefore, fixed effects model was conducted.3.4.3. Peak creatine kinase:Peak creatine kinase was reported in five studies. The pooled standardized mean difference (SMD) showed no significant difference in both intracoronary abciximab and intravenous abciximab (SMD= -0.18, 95% CI [-0.40, 0.03], p=0.003), figure 5. The pooled studies were heterogeneous (p=0.04, I² = 61%); therefore, random effects model was conducted. We resolved this heterogeneity by removal of both Bertrand et al. and thiele et al. favoring intracoronary abciximab in comparison with intravenous abciximab, (SMD= -0.33, 95% CI [-0.61, -0.05], p=0.03), (p=0.20, I² = 37%), figure 6.3.4.4. Peak creatine kinase myocardial band (CK-MB):Peak CK-MB was reported in three studies. The pooled standardized mean difference (SMD) favored intracoronary abciximab more than intravenous abciximab (SMD= -0.28, 95% CI [-0.48, -0.09], p=0.005), figure 7. The pooled studies were homogeneous (p=0.19, I² = 39%); therefore, fixed effects model was conducted.3.4.5 Left ventricular ejection fraction:Left ventricular ejection fraction was reported in five studies. The pooled mean difference (MD) favored intracoronary abciximab versus intravenous abciximab (MD= 3.31, 95% CI [1.46, 5.16], p=0.0005), figure 8. The pooled studies were homogeneous (p=0.24, I² = 27%); therefore, fixed effects model was conducted.3.4.6 ST-segment resolution:ST-segment resolution was reported in six studies. The pooled risk ratio (RR) favored intracoronary abciximab versus intravenous abciximab (RR= 1.09, 95% CI [1.02, 1.17], p=0.02), figure 9. The pooled studies were homogeneous (p=0.23, I² = 28%); therefore, fixed effects model was conducted.4. Discussion:In the last few years, a lot of pharmacological strategies have been suggested to further increase the survival of myocardial infarction patients performing primary PCI. Adjunctive abciximab use has been revealed to improve survival and myocardial perfusion and decline re-infarction risk [24–26]. A lot of attention has been increased on IC abciximab administration that could offer potential advantages over IV abciximab, due to more effective inhibition of glycoprotein IIb/ IIIa receptors and possible values from abciximib anti-inflammatory effects. However, we found a lot of debates in different studies about the greater benefits of IC versus IV abciximab. In this meta-analysis, we found intracoronary abciximab is similar to intravenous abciximab post-procedural in thrombolysis in myocardial infarction (TIMI) flow grade 3. Moreover, intracoronary abciximab is superior in reducing different inflammatory markers including peak troponin (Tn), peak creatine kinase (Ck) and peak creatine kinase myocardial band (CK-MB) more than intravenous abciximab. Intracoronary abciximab is linked to more improvement in left ventricular ejection fraction and ST-segment resolution. Abciximab represents a potent platelet aggregation inhibitor mainly by competitively attaching to the GP IIb/IIIa receptor on the plane of activated human platelets. Due to the higher attractiveness to this receptor, it prevents fibrinogen and von Willebrand factor attachment to activated platelets, inhibiting the final common pathway for platelet aggregation [27]. In addition, abciximab has dose-dependent antiplatelet, anti-inflammatory, antithrombotic actions, and help in disaggregation of the thrombus [27]. The interaction of abciximab with different receptors, such as the vitronectin [28] or the Mac-1 receptor [29], may also be responsible for preventing leukocyte-intervened microvessels injury ultimately related to reperfusion. Furthermore, sCD40L is thought to be responsible for atherosclerosis expansion and platelet-rich thrombi maintenance inside the vessels [30]. Different studies supposed that the IC abciximab acts by enabling the disbanding of the standing and newly formed platelet-rich thrombi [31], augmenting the vitronectin receptors inhibition in the endothelial cells of the culprit vessel [32], and prevents the pro-inflammatory [33] actions of sCD40L. All these mechanisms may accountable for the great decline in sCD40L levels in IC Group compared to IV Group.These verdicts propose that higher local concentration accomplished by intracoronary administration resulting local platelet inhibition, thrombi dissolution and dislodgment of platelet fibrin thrombi causing improvement in different outcomes. Despite all of IC abciximab benefits, Desch et al. [6] realized that, although intracoronary abciximab leads to more occupied glycoprotein IIb/ IIIa receptors in contrast with the intravenous method, these properties are not extended more than 30 minutes following bolus administration. Accordingly, absence of constantly higher glycoprotein IIb/IIIa receptor occupied with time with IC abciximab may be linked to the different adverse clinical and reperfusion results. Two recent randomized clinical trials found a similarity between IC and IV abciximab in post-procedural TMI flow grade 3 supporting our finding [15,16]. However, another study realized more myocardial infarction patients experienced TIMI flow grade 3 in IC abciximab but the results were not statistically significant [23].  Timing of glycoprotein IIb/IIIa inhibitor administration stands to be very crucial where different clinical trials have concluded that earlier use produces higher pre-interventional TIMI flow grades with consequently progress in perfusion grades after doing PCI [34,35]. Regarding our selected inflammatory markers, Bertrand et al. established no significant benefit of intracoronary over intravenous abciximab in reducing the inflammatory markers contradicting our results [16]. Furthermore, peak troponin level is similar in both groups of abciximab as suggested by secco et al. [21] conflicting what we concluded. However, Gu et al. supported our finding where they concluded intracoronary abciximab is superior to intravenous abciximab in diminution of various markers associated with inflammation [23]. Moreover, a randomized controlled trial deduced more significant decline in peak troponin levels in IC abciximab [17]. Several studies have reported improved myocardial salvage, left ventricular functional recovery, and a smaller infarct size after intracoronary administration of abciximab (12). Moreover, Belandi et al. established more significant ventricular ejection fraction in patients who administrated IC abciximab assisting our verdict [7]. However, Bertrand et al did not show any significant difference regarding left ventricular ejection fraction opposing our results [16]. Another study opposed our results where it concluded no significant differences between intracoronary and intravenous abciximab in LV ejection fraction [10]. The ischemic injury relies on the microcirculation functional status. Many potential important factors were capable of interfering with microvascular function, such as diabetes, hyperlipidemia, hypertension, and smoking [7]. In a subgroup analysis study done by Piccolo et al. included all diabetic patients realized IC abciximab resulted in more significant improvement of the PCI effectiveness than IV abciximab, including increase in left ventricular function, myocardial salvage indicator and diminished death risk [36]. Bedjaoui et al realized both groups of abciximab are comparable in ST-segment resolution experienced by the patients opposing what we found [7]. However, Bellandi et al supported our results where they concluded intracoronary abciximab is significantly superior to intravenous one in achieving more patients with ST-segment resolution [7]. New application systems such as the ClearWay RX perfusion dedicated catheter (Atrium Medical Corporation, Hudson, New Hampshire) may add more improvement in the efficacy of intracoronary abciximab delivery. The system contains a perfusion balloon that obstructs antegrade blood flow while medications are infused through a microporous polytetrafluoroethylene surface. This design permits for high local drug concentrations in the vessel lumen and wall at the thrombus site together. In a randomized controlled trial of patients chose with severe acute coronary syndrome, abciximab delivery through this dedicated catheter caused significant decline in the amount of thrombus burden and increased microvascular flow in comparison with the conventional intracoronary drug administration through a guide catheter [37]. We should remark that GP IIb/IIIa receptor antagonists use in patients with acute STEMI performing PCI and receiving dual antiplatelet therapy is not habitually advised [38]. In fact, some recommendations stated that the GP IIb/IIIa receptor antagonist adjuvants administration should be directed to selected patients, such as those with large thrombus load or inadequate thienopyridine burden [38].To the best of our knowledge, this study provides great outstanding effectiveness of intracoronary abciximab over intravenous abciximab. Our limitations are limited number of included studies, large number of patients who were lost during their follow-up and we do not assess other inflammatory markers. We did not assess different safety outcomes between IC and IV abciximab including myocardial infarction incidence and bleeding rates. Our recommendations are to increase the number of double blinded randomized controlled trials with considering the priority of left ventricular ejection fraction and inflammatory markers other than troponin, CK, and CK-MB to be the main outcomes. 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