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Cureus Oct 2023Multisystem inflammatory syndrome in children (MIS-C) is a relatively new syndrome associated with coronavirus disease 2019 (COVID-19) that is characterized by a severe... (Review)
Review
Multisystem inflammatory syndrome in children (MIS-C) is a relatively new syndrome associated with coronavirus disease 2019 (COVID-19) that is characterized by a severe clinical course compared to pediatric COVID-19. This review aimed to compile the available evidence on the clinical presentation and management of MIS-C in children with COVID-19. During this systematic review, a comprehensive search was performed in the following databases: PubMed, Embase, Medline, Google Scholar, Cochrane, and Scopus, using predetermined search terms, such as Medical Subject Headings (MeSH) and keywords to find relevant studies on the MIS-C. Relevant data were extracted, and the quality of the studies was evaluated using suitable methods. The collected findings were synthesized and discussed in the study. The World Health Organization's (WHO) definition of MIS-C was the most favored due to its precision and inclusiveness. MIS-C primarily affected children aged 6-12 years, with male predominance. MIS-C involves a range of systems, including gastrointestinal, cardiovascular, hematologic, mucocutaneous, and respiratory. Radiographic findings revealed cardiovascular abnormalities, solid visceral organ involvement, and bowel abnormalities, reflecting a systemic inflammatory process. Laboratory investigations unveiled elevated inflammatory markers, neutrophil activation, release of extracellular traps in vessels, elevated procalcitonin, hyponatremia, hypoalbuminemia, low hemoglobin, and thrombocytopenia. The inflammatory markers and autoantibody profiles are essential in differentiating MIS-C from COVID-19. The preferred treatment primarily involves immunomodulatory therapies like intravenous immunoglobulin (IVIG), glucocorticoids, and interleukin-6 or 1RA inhibitors or a combination of those. In severe cases, extracorporeal membrane oxygenation (ECMO) and mechanical ventilation are necessary, leading to reduced mortality and quick recovery. This review found that the average hospital stay was seven days, and most discharged children fully recovered within seven days. MIS-C is a life-threatening post-COVID-19 condition and involves multiple systems due to systemic inflammation, with elevated inflammation markers. Recognition of multisystem involvement is crucial, and prompt identification and multidisciplinary treatment are vital for optimal outcomes.
PubMed: 37954764
DOI: 10.7759/cureus.46918 -
Transplantation Reviews (Orlando, Fla.) Jan 2024Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients are susceptible to cytomegalovirus (CMV) infection. The incidence of... (Review)
Review
INTRODUCTION
Solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) recipients are susceptible to cytomegalovirus (CMV) infection. The incidence of refractoriness to antivirals, with or without resistance, is unclear. The purpose of this review was to describe the epidemiology of refractory CMV infection in Spain to understand the current unmet needs.
METHODS
PubMed, EMBASE, Cochrane and MEDES were searched systematically for relevant articles. We included randomized controlled trials and observational studies published during the period from January 1990 to June 2021.
RESULTS
From 212 screened records, we selected 19 papers including 1973 transplant recipients. Refractory infection ranged from 3 to 10% in studies with SOT recipients. The incidence of CMV resistance ranged from 1% to 36% in these patients. The incidence of CMV refractory infection in HSCT recipients ranged from 11 to 50%, while values for resistant infection ranged from 0% to 21%.
CONCLUSION
The wide range of definitions and values observed does not allow us to establish the true incidence of refractory CMV infection with or without resistances in SOT and HSCT patients in Spain. This review highlights the gap between clinical practice and clinical trials' definitions which needed to be updated to be easier followed in current clinical practice.
Topics: Humans; Antiviral Agents; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Incidence; Organ Transplantation; Spain; Transplant Recipients
PubMed: 37949797
DOI: 10.1016/j.trre.2023.100804 -
Biomechanics and Modeling in... Feb 2024The gastrointestinal (GI) organs of the human body are responsible for transporting and extracting nutrients from food and drink, as well as excreting solid waste.... (Review)
Review
The gastrointestinal (GI) organs of the human body are responsible for transporting and extracting nutrients from food and drink, as well as excreting solid waste. Biomechanical experimentation of the GI organs provides insight into the mechanisms involved in their normal physiological functions, as well as understanding of how diseases can cause disruption to these. Additionally, experimental findings form the basis of all finite element (FE) modelling of these organs, which have a wide array of applications within medicine and engineering. This systematic review summarises the experimental studies that are currently in the literature (n = 247) and outlines the areas in which experimentation is lacking, highlighting what is still required in order to more fully understand the mechanical behaviour of the GI organs. These include (i) more human data, allowing for more accurate modelling for applications within medicine, (ii) an increase in time-dependent studies, and (iii) more sophisticated in vivo testing methods which allow for both the layer- and direction-dependent characterisation of the GI organs. The findings of this review can also be used to identify experimental data for the readers' own constitutive or FE modelling as the experimental studies have been grouped in terms of organ (oesophagus, stomach, small intestine, large intestine or rectum), test condition (ex vivo or in vivo), number of directions studied (isotropic or anisotropic), species family (human, porcine, feline etc.), tissue condition (intact wall or layer-dependent) and the type of test performed (biaxial tension, inflation-extension, distension (pressure-diameter), etc.). Furthermore, the studies that investigated the time-dependent (viscoelastic) behaviour of the tissues have been presented.
Topics: Animals; Cats; Humans; Swine; Gastrointestinal Tract; Stomach; Biomechanical Phenomena; Stress, Mechanical; Finite Element Analysis
PubMed: 37935880
DOI: 10.1007/s10237-023-01773-8 -
Korean Journal of Transplantation Dec 2023Despite widespread implementation of vaccination against coronavirus disease 2019 (COVID-19), solid organ transplant recipients (SOTRs) can remain particularly...
BACKGROUND
Despite widespread implementation of vaccination against coronavirus disease 2019 (COVID-19), solid organ transplant recipients (SOTRs) can remain particularly vulnerable to this disease. The present study was conducted to investigate the efficacy and safety of sotrovimab in the treatment of SOTRs with COVID-19.
METHODS
A search was performed of PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar to gather relevant evidence through July 25, 2023. The quality of the included studies was assessed using the risk of bias tool. Comprehensive Meta-Analysis software (ver. 3.0, Biostat) was employed for data analysis.
RESULTS
Ten studies, involving a total of 1,569 patients, were included. The meta-analysis revealed significant differences between the patients administered sotrovimab and those treated with the standard of care. These differences were observed in mortality rate (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.03-0.67), hospitalization rate (OR, 0.35; 95% CI, 0.21-0.57), intensive care unit (ICU) admission rate (OR, 0.16; 95% CI, 0.04-0.62), the need for supplemental oxygen therapy (OR, 0.22; 95% CI, 0.09-0.51), and the need for mechanical ventilation (OR, 0.09; 95% CI, 0.01-0.70). However, no significant difference was observed between sotrovimab and other treatments regarding the rates of hospitalization or ICU admission (P>0.05). Regarding safety, sotrovimab was associated with a lower rate of adverse events compared to the absence of sotrovimab (OR, 0.15; 95% CI, 0.02-0.86).
CONCLUSIONS
These results suggest that sotrovimab may improve efficacy outcomes among SOTRs with COVID-19. Nevertheless, additional high-quality trials are necessary to confirm these findings.
PubMed: 37916433
DOI: 10.4285/kjt.23.0038 -
Frontiers in Immunology 2023Recently, circulating donor-derive cell free DNA (dd-cfDNA) has gained growing attention in the field of solid organ transplantation. The aim of the study was to analyze...
OBJECTIVE
Recently, circulating donor-derive cell free DNA (dd-cfDNA) has gained growing attention in the field of solid organ transplantation. The aim of the study was to analyze circulating dd-cfDNA levels in graft rejection, ACR and AMR separately for each rejection type compared with non-rejection, and assessed the diagnostic potential of dd-cfDNA levels in predicting graft rejection after lung transplantation.
METHODS
A systematic search for relevant articles was conducted on Medline, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases without restriction of languages. The search date ended on June 1, 2023. STATA software was used to analyze the difference between graft rejection, ACR, AMR and stable controls, and evaluate the diagnostic performance of circulating dd-cfDNA in detecting graft rejection.
RESULTS
The results indicated that circulating dd-cfDNA levels in graft rejection, ACR, and AMR were significantly higher than non-rejection (graft rejection: SMD=1.78, 95% CI: 1.31-2.25, 88.6%, < 0.001; ACR: SMD=1.03, 95% CI: 0.47-1.59, 89.0%, < 0.001; AMR: SMD= 1.78, 95% CI: 1.20-2.35, 89.8%, < 0.001). Circulating dd-cfDNA levels distinguished graft rejection from non-rejection with a pooled sensitivity of 0.87 (95% CI: 0.80-0.92) and a pooled specificity of 0.82 (95% CI: 0.76-0.86). The corresponding SROC yield an AUROC of 0.90 (95% CI: 0.87-0.93).
CONCLUSION
Circulating dd-cfDNA could be used as a non-invasive biomarker to distinguish the patients with graft rejection from normal stable controls.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023440467.
Topics: Humans; Organ Transplantation; Lung Transplantation; Biomarkers; Graft Rejection; Cell-Free Nucleic Acids
PubMed: 37885888
DOI: 10.3389/fimmu.2023.1263389 -
Clinical Microbiology and Infection :... Feb 2024Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial. (Meta-Analysis)
Meta-Analysis Review
Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.
BACKGROUND
Whether trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis prevents nocardiosis in solid organ transplant (SOT) recipients is controversial.
OBJECTIVES
To assess the effect of TMP-SMX in the prevention of nocardiosis after SOT, its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection.
METHODS
A systematic review and individual patient data meta-analysis.
DATA SOURCES
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, and Scopus up to 19 September 2023.
STUDY ELIGIBILITY CRITERIA
(a) Risk of nocardiosis between SOT recipients with and without TMP-SMX prophylaxis, or (b) sufficient details to determine the rate of TMP-SMX resistance in breakthrough nocardiosis.
PARTICIPANTS
SOT recipients.
INTERVENTION
TMP-SMX prophylaxis versus no prophylaxis.
ASSESSMENT OF RISK OF BIAS
Risk Of Bias In Non-randomized Studies-of Exposure (ROBINS-E) for comparative studies; dedicated tool for non-comparative studies.
METHODS OF DATA SYNTHESIS
For our primary outcome (i.e. to determine the effect of TMP-SMX on the risk of nocardiosis), a one-step mixed-effects regression model was used to estimate the association between the outcome and the exposure. Univariate and multivariable unconditional regression models were used to adjust for the potential confounding effects. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Individual data from three case-control studies were obtained (260 SOT recipients with nocardiosis and 519 uninfected controls). TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence). Variables independently associated with an increased risk of nocardiosis were older age, current use of corticosteroids, high calcineurin inhibitor concentration, recent acute rejection, lower lymphocyte count, and heart transplant. Breakthrough infections (66/260, 25%) were generally susceptible to TMP-SMX (pooled proportion 98%, 95% CI 92-100).
CONCLUSIONS
In SOT recipients, TMP-SMX prophylaxis likely reduces the risk of nocardiosis. Resistance appears uncommon in case of breakthrough infection.
Topics: Humans; Breakthrough Infections; Nocardia Infections; Organ Transplantation; Retrospective Studies; Transplant Recipients; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 37865337
DOI: 10.1016/j.cmi.2023.10.008 -
Injury Dec 2023Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review provides evidence for the use of VTE prophylactic interventions in trauma patients to produce evidence-based guidelines.
METHODS
A PRISMA-compliant review was conducted from Sep 2021 to June 2023, using Embase, Medline and Google Scholar. The inclusion criteria were: randomized-controlled trials (RCTs) in English published after 2000 of adult trauma patients comparing VTE prophylaxis interventions, with a sample size higher than 20. The network analysis was conducted using RStudio. The results of the pairwise comparisons were presented in the form of a league table. The quality of evidence and heterogeneity sensitivity were assessed. The primary outcome focused on venous thromboembolism (VTE), and examined deep vein thrombosis (DVT) and pulmonary embolism (PE) as separate entities. The secondary outcomes included assessments of bleeding and mortality. PROSPERO registration: CRD42021266393.
RESULTS
Of the 7,948 search results, 23 studies with a total of 21,312 participants fulfilled screening criteria, which included orthopaedic, spine, solid organ, brain, spinal cord, and multi-region trauma. Of the eight papers comparing chemical prophylaxis medications in patients with hip or lower limb injuries, fondaparinux and enoxaparin were found to be significantly superior to placebo in respect of prevention of DVT, with no increased risk of bleeding. Regarding mechanical prophylaxis, meta-analysis of two studies of inferior vena cava filters failed to provide significant benefits to major trauma patients.
CONCLUSION
Enoxaparin and fondaparinux are safe and effective options for VTE prevention in trauma patients, with fondaparinux being a cheaper and easier administration option between the two. Inconclusive results were found in mechanical prophylaxis, requiring more larger-scale RCTs.
Topics: Adult; Humans; Venous Thromboembolism; Enoxaparin; Fondaparinux; Network Meta-Analysis; Anticoagulants; Pulmonary Embolism; Hemorrhage; Multiple Trauma
PubMed: 37865011
DOI: 10.1016/j.injury.2023.111078 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
Frontiers in Immunology 2023Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response after vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) vs BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework.
METHODS
The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were symptomatic, laboratory-confirmed SARS-CoV-2 infection, SARS-CoV-2 infection, severe SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. Evidence was evaluated using the GRADE framework.
RESULTS
Overall, 17 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.75-0.97]; =0.0151; 67.7%), severe SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.77-0.93]; =0.0009; 0%), COVID-19-associated hospitalization (RR, 0.88 [95% CI, 0.79-0.97]; <0.0001; 0%), and COVID-19-associated mortality (RR, 0.63 [95% CI, 0.44-0.90]; =0.0119; 0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials. Based on nonrandomized studies, evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies.
CONCLUSION
This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.
Topics: Humans; BNT162 Vaccine; 2019-nCoV Vaccine mRNA-1273; COVID-19 Vaccines; COVID-19; SARS-CoV-2
PubMed: 37771594
DOI: 10.3389/fimmu.2023.1204831 -
Hepatology Communications Oct 2023Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and treatment options of the disease are scarce and contentious. Moreover, recommendations for therapeutic approaches are similarly sparse.
METHODS
A systematic review of the literature from 1988 to 2020 on graft-versus-host disease following liver transplantation was performed using the PubMed and MEDLINE databases. Medical subject headings, such as graft-versus-host disease and GvHD were used in combination with solid organ transplant, transplantation, or liver transplant. Following duplicate removal, 9298 articles were screened for suitability. A total of 238 full-text articles were analyzed for eligibility, resulting in 130 eligible articles for meta-analysis. Two hundred twenty-five patients developing graft-versus-host disease following liver transplantation reported herein were mainly published in case reports and case series.
RESULTS
Graft-versus-host disease occurred with an incidence of 1.2%. 85% developed following deceased donor liver transplant and 15% following living-related donor liver transplantation. The median follow-up period following liver transplantation was 84 days (interquartile range, 45-180). The median time from liver transplantation to graft-versus-host disease onset was 30 days (interquartile range, 21-42). The main clinical features included skin rash (59%), fever (43%), diarrhea (36%), and pancytopenia (30%). The overall mortality rate was 71%. Neither univariate (HR = 0.999; 95% CI, 0.493-2.023; p = 1.0) nor multivariate Cox regression analysis revealed a significant correlation between adaptation of immunosuppression and survival probability (HR = 1.475; 95% CI, 0.659-3.303; p = 0.3).
CONCLUSIONS
This systematic review suggests that an increase in immunosuppressive regimen does not yield any survival benefit in patients suffering from graft-versus-host disease following liver transplantation.
Topics: Humans; Liver Transplantation; Living Donors; Graft vs Host Disease; Immunosuppressive Agents; Risk Factors
PubMed: 37755878
DOI: 10.1097/HC9.0000000000000260