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The Journal of Heart and Lung... Sep 2023Airway complications (AC) are one of leading causes of morbidity and mortality after lung transplant (LTx), but their predictors and outcomes remain controversial. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Airway complications (AC) are one of leading causes of morbidity and mortality after lung transplant (LTx), but their predictors and outcomes remain controversial. This study aimed to identify potential risk factors and prognosis of AC.
METHODS
A systematic review was performed by searching PubMed, Embase, and Cochrane Library. All observational studies reporting outcome and potential factors of AC after LTx were included. The incidence, mortality, and estimated effect of each factor for AC were pooled by using the fixed-effects model or random-effects model.
RESULTS
Thirty-eight eligible studies with 52,116 patients undergoing LTx were included for meta-analysis. The pooled incidence of AC was 12.4% (95% confidence interval [CI] 9.5-15.8) and the mean time of occurrence was 95.6 days. AC-related mortality rates at 30-days, 90-days, 6 months, 1 year, and 5 years were 6.7%, 17.9%, 18.2%, 23.6%, and 66.0%, respectively. Airway dehiscence was the most severe type with a high mortality at 30 days (60.9%, 95% CI 20.6-95.2). We found that AC was associated with a higher risk of mortality in LTx recipients (hazard ratio [HR] 1.71, 95% CI 1.04-2.81). Eleven significant predictors for AC were also identified, including male donor, male recipient, diagnosis of COPD, hospitalization, early rejection, postoperative infection, extracorporeal membrane oxygenation, mechanical ventilation, telescopic anastomosis, and bilateral and right-sided LTx.
CONCLUSION
AC was significantly associated with higher mortality after LTx, especially for dehiscence. Targeted prophylaxis for modifiable factors and enhanced early bronchoscopy surveillance after LTx may improve the disease burden of AC.
Topics: Humans; Male; Transplant Recipients; Retrospective Studies; Lung; Prognosis; Lung Transplantation; Risk Factors; Postoperative Complications
PubMed: 37088339
DOI: 10.1016/j.healun.2023.04.011 -
Journal of Critical Care Oct 2023The initiation of the extracorporeal membrane oxygenation (ECMO) is associated with complex coagulatory and inflammatory processes and consequently needed... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The initiation of the extracorporeal membrane oxygenation (ECMO) is associated with complex coagulatory and inflammatory processes and consequently needed anticoagulation. Systemic anticoagulation bears an additional risk of serious bleeding, and its monitoring is of immense importance. Therefore, our work aims to analyze the association of anticoagulation monitoring with bleeding during ECMO support.
MATERIAL AND METHODS
Systematic literature review and meta-analysis, complying with the PRISMA guidelines (PROSPERO-CRD42022359465).
RESULTS
Seventeen studies comprising 3249 patients were included in the final analysis. Patients experiencing hemorrhage had a longer activated partial thromboplastin time (aPTT), a longer ECMO duration, and higher mortality. We could not find strong evidence of any aPTT threshold association with the bleeding occurrence, as less than half of authors reported a potential relationship. Finally, we identified the acute kidney injury (66%, 233/356) and hemorrhage (46%, 469/1046) to be the most frequent adverse events, while almost one-half of patients did not survive to discharge (47%, 1192/2490).
CONCLUSION
The aPTT-guided anticoagulation is still the standard of care in ECMO patients. We did not find strong evidence supporting the aPTT-guided monitoring during ECMO. Based on the weight of the available evidence, further randomized trials are crucial to clarify the best monitoring strategy.
Topics: Humans; Partial Thromboplastin Time; Anticoagulants; Extracorporeal Membrane Oxygenation; Retrospective Studies; Hemorrhage; Heparin
PubMed: 37244207
DOI: 10.1016/j.jcrc.2023.154332 -
Journal of Nanobiotechnology Jan 2024Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins,... (Review)
Review
Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
Topics: Humans; Exosomes; Tissue Distribution; Drug Delivery Systems; Extracellular Vesicles; Neoplasms; Pharmaceutical Preparations
PubMed: 38172932
DOI: 10.1186/s12951-023-02259-6 -
Physiology (Bethesda, Md.) Nov 2023The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular... (Review)
Review
The array of ion channels and transporters expressed in cell membranes, collectively referred to as the transportome, is a complex and multifunctional molecular machinery; in particular, at the plasma membrane level it finely tunes the exchange of biomolecules and ions, acting as a functionally adaptive interface that accounts for dynamic plasticity in the response to environmental fluctuations and stressors. The transportome is responsible for the definition of membrane potential and its variations, participates in the transduction of extracellular signals, and acts as a filter for most of the substances entering and leaving the cell, thus enabling the homeostasis of many cellular parameters. For all these reasons, physiologists have long been interested in the expression and functionality of ion channels and transporters, in both physiological and pathological settings and across the different domains of life. Today, thanks to the high-throughput technologies of the postgenomic era, the omics approach to the study of the transportome is becoming increasingly popular in different areas of biomedical research, allowing for a more comprehensive, integrated, and functional perspective of this complex cellular apparatus. This article represents a first effort for a systematic review of the scientific literature on this topic. Here we provide a brief overview of all those studies, both primary and meta-analyses, that looked at the transportome as a whole, regardless of the biological problem or the models they used. A subsequent section is devoted to the methodological aspect by reviewing the most important public databases annotating ion channels and transporters, along with the tools they provide to retrieve such information. Before conclusions, limitations and future perspectives are also discussed.
Topics: Humans; Biomedical Research; Homeostasis; Membrane Potentials
PubMed: 37668550
DOI: 10.1152/physiol.00010.2023 -
International Journal of Molecular... Jul 2023Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various... (Review)
Review
Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Topics: Animals; Aquaporins; Water; Homeostasis; Brain; Seizures
PubMed: 37569297
DOI: 10.3390/ijms241511923 -
Molecular Psychiatry Dec 2023The γ-aminobutyric acid (GABA)ergic system is the primary inhibitory neurotransmission system in the mammalian brain. Its dysregulation has been shown in multiple brain... (Meta-Analysis)
Meta-Analysis
The γ-aminobutyric acid (GABA)ergic system is the primary inhibitory neurotransmission system in the mammalian brain. Its dysregulation has been shown in multiple brain conditions, but in Alzheimer's disease (AD) studies have provided contradictory results. Here, we conducted a systematic review with meta-analysis to investigate whether the GABAergic system is altered in AD patients compared to healthy controls (HC), following the PRISMA 2020 Statement. We searched PubMed and Web of Science from database inception to March 18, 2023 for studies reporting GABA, glutamate decarboxylase (GAD) 65/67, GABA, GABA and GABA receptors, GABA transporters (GAT) 1-3 and vesicular GAT in the brain, and GABA levels in the cerebrospinal fluid (CSF) and blood. Heterogeneity was estimated using the I index, and the risk of bias was assessed with an adapted questionnaire from the Joanna Briggs Institute Critical Appraisal Tools. The search identified 3631 articles, and 48 met the final inclusion criteria (518 HC, mean age 72.2, and 603 AD patients, mean age 75.6). Random-effects meta-analysis [standardized mean difference (SMD)] revealed that AD patients presented lower GABA levels in the brain (SMD = -0.48 [95% CI = -0.7, -0.27], adjusted p value (adj. p) < 0.001) and in the CSF (-0.41 [-0.72, -0.09], adj. p = 0.042), but not in the blood (-0.63 [-1.35, 0.1], adj. p = 0.176). In addition, GAD65/67 (-0.67 [-1.15, -0.2], adj. p = 0.006), GABA receptor (-0.51 [-0.7, -0.33], adj. p < 0.001), and GABA transporters (-0.51 [-0.92, -0.09], adj. p = 0.016) were lower in the AD brain. Here, we showed a global reduction of GABAergic system components in the brain and lower GABA levels in the CSF of AD patients. Our findings suggest the GABAergic system is vulnerable to AD pathology and should be considered a potential target for developing pharmacological strategies and novel AD biomarkers.
Topics: Alzheimer Disease; Humans; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Brain; Aged; Receptors, GABA; GABA Plasma Membrane Transport Proteins; Female; Male
PubMed: 37419974
DOI: 10.1038/s41380-023-02140-w -
Evidence-based Dentistry Sep 2023A systematic appraisal and statistical aggregation of primary studies in humans. (Meta-Analysis)
Meta-Analysis
DESIGN
A systematic appraisal and statistical aggregation of primary studies in humans.
DATA SOURCES
The researchers utilized PubMed (Medline) and Scopus databases as the primary data sources for this study. They performed a comprehensive literature search based on free keywords and Medical Subject Heading (MeSH) terms to enhance the search accuracy. The database search was concluded on November 13, 2022. Furthermore, a meticulous examination of the references cited in the selected studies was conducted to identify additional relevant articles that could be incorporated into the analysis.
STUDY SELECTION
The systematic review focused on partially or fully edentulous patients receiving dental implants and aimed to determine if the lack of keratinized mucosa at the implant site increased the risk of peri-implantitis compared to patients with adequate keratinized mucosa. Human studies with a minimum of 100 implants, cross-sectional, cohort, or case-control designs, and a follow-up period of at least one year were included. Studies lacking a clear case definition or information on peri-implantitis and those that did not investigate keratinized mucosa as a risk indicator were excluded.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently utilized a systematic review screening website (Rayyan, Qatar Computing Research Institute, Qatar Foundation) to select potential articles, and conflicts were resolved through discussion or consultation with a third reviewer. The data extraction process involved recording information from the included articles, such as study design, patient and implant numbers, prosthesis type (fixed or removable), follow-up duration, peri-implantitis case definition, prevalence at patient and implant levels, keratinized mucosa cutoff value, odds ratio (OR) of peri-implantitis considering keratinized mucosa, and conclusions on the potential effect of keratinized mucosa from each study. The Newcastle Ottawa scale (NOS) and a modified version of NOS were used, respectively, to assess the quality of cohort and cross-sectional studies. Studies scoring below 6 out of 9 points were classified as low quality. For the meta-analysis, the relationship between peri-implantitis and keratinized mucosa was evaluated using the odds ratio (OR) and standard error (SE). Heterogeneity was assessed through the Chi test and I index, determining whether a random-effects or fixed-effects model should be applied. Subgroup and cluster analyses were conducted based on specific criteria, and forest plots and funnel plots were generated to visualize results and identify potential study bias. Sensitivity analysis was performed to verify the robustness of the meta-analysis, with statistical significance set at p < 0.05. The Review Manager (RevMan) software facilitated data analysis. The GRADE rating system was used to determine the level of evidence, considering factors such as bias risk, imprecision, inconsistency, indirectness, and publication bias. The certainty of the evidence was evaluated based on the overall outcomes of analyzed subgroups.
RESULTS
Twenty-two primary studies were identified, and a meta-analysis was conducted on 16 cross-sectional studies. The prevalence of peri-implantitis ranged from 6.68% to 62.3% at the patient level and from 4.5% to 58.1% at the implant level. The overall analysis revealed a significant association between the lack of keratinized mucosa and a higher prevalence of peri-implantitis (OR = 2.78, 95% CI 2.07-3.74, p < 0.00001). Subgroup analyses with a consistent case definition of peri-implantitis (MBL ≥ 2 mm) showed similar results (OR = 1.96, 95% CI 1.41-2.73, p < 0.0001). Studies focusing on fixed prostheses only demonstrated that the lack of keratinized mucosa was associated with an increased prevalence of peri-implantitis (OR = 2.82, 95% CI 1.85-4.28, p < 0.00001). Among patients under regular implant maintenance, the absence of keratinized mucosa significantly raised the occurrence of peri-implantitis (OR = 2.08, 95% CI 1.41-3.08, p = 0.0002). Studies adjusting for other variables also confirmed a higher risk of peri-implantitis with inadequate keratinized mucosa (OR = 3.68, 95% CI 2.32-5.82, p = 0.007). Although some publication bias was observed, the certainty of evidence based on the GRADE system was judged to be "moderate."
CONCLUSIONS
The lack of keratinized mucosa increased the risk of peri-implantitis, emphasizing the need to consider it during dental implant placement. Inadequate data on patient-specific factors and the predominance of cross-sectional studies influenced the evidence quality (i.e., moderate). Future studies with consistent methodologies shall confirm these findings and identify additional risk indicators to improve implant dentistry practices.
Topics: Humans; Peri-Implantitis; Dental Implants; Cross-Sectional Studies; Mucous Membrane; Risk Factors
PubMed: 37537217
DOI: 10.1038/s41432-023-00913-4 -
International Journal of Antimicrobial... Feb 2024The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting...
BACKGROUND AND OBJECTIVE
The use of extracorporeal membrane oxygenation (ECMO) as a cardiocirculatory or respiratory support has tremendously increased in critically ill patients. In the setting of ECMO support, invasive fungal infections are a severe cause of morbidity and mortality. This vulnerable population is at risk of suboptimal antifungal exposure due to an increased volume of distribution (Vd), drug sequestration and decreased clearance. Here, we aimed to summarize ex-vivo and clinical studies on the potential impact of ECMO on the pharmacokinetics (PK) of antifungal agents and dosing requirements.
METHODS
A systematic search of the literature within electronic databases PubMed and EMBASE was conducted from database inception to 30 April 2023. Inclusion criteria were as follows: critically ill patients receiving ECMO regardless of age and reporting at least one PK parameter.
RESULTS
Thirty-six studies met inclusion criteria, including seven ex-vivo experiments and 29 clinical studies evaluating three classes of antifungals: polyenes, triazoles and echinocandins. Based on the available ex-vivo PK data, we found a significant sequestration of highly lipophilic and protein-bound antifungals within the ECMO circuit such as voriconazole, posaconazole and micafungin but the PK of several antifungals remains to be addressed such as amphotericin B, isavuconazole and anidulafungin. Most clinical studies have shown increased Vd of some antifungals like fluconazole and micafungin, particularly in the pediatric population. Conflicting data exist about caspofungin exposure.
CONCLUSIONS
The available literature on the antifungal PK changes in ECMO setting is scarce. Whenever possible, therapeutic drug monitoring is highly advised to personalize antifungal therapy.
Topics: Humans; Antifungal Agents; Caspofungin; Critical Illness; Extracorporeal Membrane Oxygenation; Micafungin
PubMed: 38161046
DOI: 10.1016/j.ijantimicag.2023.107078 -
Perfusion Dec 2023The Coronavirus Disease 2019 (COVID-19) pandemic has been ongoing for over 3 years, during which numerous clinical and experimental studies have been conducted. The... (Review)
Review
BACKGROUND
The Coronavirus Disease 2019 (COVID-19) pandemic has been ongoing for over 3 years, during which numerous clinical and experimental studies have been conducted. The objective of this systematic review and meta-analysis was to assess the survival probability and complications of COVID-19 patients receiving extracorporeal membrane oxygenation (ECMO).
METHODS
We searched the databases by using Population-Intervention-Comparison-Outcome-Study Design (PICOS). We conducted a search of the PubMed, Web of Science, and EMBASE databases to retrieve studies published until December 10, 2022. A random-effects meta-analysis, subgroup analysis, and assessed the studies using the Newcastle-Ottawa Scale score. The results were presented as pooled morbidity with 95% confidence intervals.
RESULTS
The study was conducted on 19 studies that enrolled a total of 1494 patients, and the results showed a pooled survival probability of 66.0%. The pooled morbidity for intracranial hemorrhage was 8.7%, intracranial thrombosis 7.0%, pneumothorax 9.0%, pulmonary embolism 11.0%, pulmonary hemorrhage 9.0%, heart failure 14.0%, liver failure 13.0%, renal injury 44.0%, gastrointestinal hemorrhage 6.0%, gastrointestinal ischemia 6.0% and venous thrombosis 31.0%.
CONCLUSION
This systematic review and meta-analysis of observational studies focused on the survival probability and complications of COVID-19 patients undergoing ECMO, which are significant in evaluating the use of ECMO in COVID-19 patients and provide a basis for further research.
TRIAL REGISTRATION
Our study was registered on PROSPERO with registration number CRD42022382555.
PubMed: 38158713
DOI: 10.1177/02676591231224645 -
Resuscitation Dec 2023Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence... (Meta-Analysis)
Meta-Analysis Review
Prognostic factors associated with favourable functional outcome among adult patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis.
BACKGROUND
Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established.
METHODS
We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach.
FINDINGS
We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes).
INTERPRETATION
The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.
Topics: Adult; Humans; Female; Out-of-Hospital Cardiac Arrest; Cardiopulmonary Resuscitation; Prognosis; Odds Ratio; Extracorporeal Membrane Oxygenation; Retrospective Studies
PubMed: 37863420
DOI: 10.1016/j.resuscitation.2023.110004