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European Journal of Clinical... Jan 2021The coronavirus pandemic has affected more than 20 million people so far. Elevated cytokines and suppressed immune responses have been hypothesized to set off a cytokine... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The coronavirus pandemic has affected more than 20 million people so far. Elevated cytokines and suppressed immune responses have been hypothesized to set off a cytokine storm, contributing to ARDS, multiple-organ failure and, in the most severe cases, death. We aimed to quantify the differences in the circulating levels of major inflammatory and immunological markers between severe and nonsevere COVID-19 patients.
METHODS
Relevant studies were identified from PubMed, EMBASE, Web of Science, SCOPUS and preprint servers. Risk of bias was assessed for each study, using appropriate checklists. All studies were described qualitatively and a subset was included in the meta-analysis, using forest plots.
RESULTS
Based on 23 studies, mean cytokine levels were significantly higher (IL-6: MD, 19.55 pg/mL; CI, 14.80, 24.30; IL-8: MD, 19.18 pg/mL; CI, 2.94, 35.43; IL-10: MD, 3.66 pg/mL; CI, 2.41, 4.92; IL-2R: MD, 521.36 U/mL; CI, 87.15, 955.57; and TNF-alpha: MD, 1.11 pg/mL; CI, 0.07, 2.15) and T-lymphocyte levels were significantly lower (CD4+ T cells: MD, -165.28 cells/µL; CI, -207.58, -122.97; CD8+ T cells: MD, -106.51 cells/µL; CI, -128.59, -84.43) among severe cases as compared to nonsevere ones. There was heterogeneity across studies due to small sample sizes and nonuniformity in outcome assessment and varied definitions of disease severity. The overall quality of studies was sub-optimal.
CONCLUSION
Severe COVID-19 is characterized by significantly increased levels of pro-inflammatory cytokines and reduced T lymphocytes. Well-designed and adequately powered prospective studies are needed to amplify the current evidence and provide definitive answers to dilemmas regarding timing and type of anti-COVID-19 therapy particularly in severe patients.
Topics: CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; COVID-19; Cytokine Release Syndrome; Cytokines; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Lymphocyte Count; Receptors, Interleukin-2; SARS-CoV-2; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 33058143
DOI: 10.1111/eci.13429 -
Journal of Clinical Medicine Oct 2021Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure.... (Review)
Review
Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival.
PubMed: 34682792
DOI: 10.3390/jcm10204667 -
Medicine Nov 2018In the current meta-analysis, we focus on the exploration of percutaneous catheter drainage (PCD) in terms of its overall safety as well as efficacy in the treatment of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the current meta-analysis, we focus on the exploration of percutaneous catheter drainage (PCD) in terms of its overall safety as well as efficacy in the treatment of infected pancreatitis necrosis based on qualified studies.
METHODS
The following electronic databases were searched to identify eligible studies through the use of index words updated to May 2018: PubMed, Cochrane, and Embase. Relative risk (RR) or mean difference (MD) along with 95% confidence interval (95% CI) were utilized for the main outcomes.
RESULTS
A total of 622 patients in the PCD group and 650 patients in the control group from 13 studies were included in the present meta-analysis. The aggregated results indicated that the incidence of bleeding was decreased significantly (RR: 0.42, 95% CI: 0.25-0.70) in the PCD group as compared with the control group. In addition, PCD decreased the mortality (RR: 0.76, 95% CI: 0.41-1.42), hospital duration (SMD: -0.22, 95% CI: -0.77 to -0.33), duration in intensive care unit (ICU) (SMD: -0.13, 95% CI: -0.30 to -0.04), pancreatic fistula (RR: 0.73, 95% CI: 0.46-1.17), and organ failure (RR: 0.91, 95% CI: 0.45-1.82) in comparison with the control group, but without statistical significance.
CONCLUSION
Our findings provide evidence for the treatment effect of PCD in the decrease of bleeding, mortality, duration in hospital and ICU, pancreatic fistula, organ failure as compared with the surgical treatment. In conclusion, further studies based on high-quality RCTs with larger sample size and long-term follow-ups are warranted for the confirmation of PCD efficacy in treating infected pancreatitis necrosis.
Topics: Drainage; Hemorrhage; Hospital Mortality; Humans; Infections; Intensive Care Units; Length of Stay; Minimally Invasive Surgical Procedures; Multiple Organ Failure; Pancreatic Fistula; Pancreatitis, Acute Necrotizing
PubMed: 30461605
DOI: 10.1097/MD.0000000000012999 -
Stem Cell Research & Therapy May 2022Intestinal ischemia-reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intestinal ischemia-reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments.
METHODS
We conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu's score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3.
RESULTS
It included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu's score (- 1.96, 95% CI - 2.72 to - 1.19, P < 0.00001), less intestinal inflammation (IL-6 (- 2.73, 95% CI - 4.19 to - 1.27, P = 0.0002), TNF-α (- 3.00, 95% CI - 4.74 to - 1.26, P = 0.0007)) and oxidative stress (MDA (- 2.18, 95% CI - 3.17 to - 1.19, P < 0.0001)), and decreased serum levels of DAO (- 1.39, 95% CI - 2.07 to - 0.72, P < 0.0001), D-Lactate (- 1.54, 95% CI - 2.18 to - 0.90, P < 0.00001) and TNF-α (- 2.42, 95% CI - 3.45 to - 1.40, P < 0.00001). The possible mechanism for MSCs to treat intestinal IRI might be through reducing inflammation, alleviating oxidative stress, as well as inhibiting the apoptosis and pyroptosis of the intestinal epithelial cells.
CONCLUSIONS
Taken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.
Topics: Animals; Inflammation; Interleukin-6; Lactates; Mesenchymal Stem Cells; Reperfusion Injury; Tumor Necrosis Factor-alpha
PubMed: 35619154
DOI: 10.1186/s13287-022-02896-y -
Transplantation and Cellular Therapy Apr 2023Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication of the transplantation process that has been...
Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication of the transplantation process that has been consistently associated with substantially greater morbidity and mortality compared with HSCT recipients who do not develop TMA. This study aimed to systematically review published signs and symptoms of HSCT-TMA and compare patients with HSCT-TMA and HSCT recipients who do not develop TMA. Publications were identified using multiple search term variations for stem cell transplantation that were entered into the PubMed, Embase, and CINAHL databases. Two reviewers screened references at the abstract level before reviewing full texts against inclusion and exclusion criteria using a PICOS-T framework. Complication proportions were grouped by organ class and then by complication type. Meta-analyses were conducted using a random-effects model in RevMan 5.4. After 2338 references were screened, a total of 30 studies were included in our analyses. The majority of studies (n = 23; 14 adult, 5 pediatric, 4 both) examined allogeneic transplantations only. Four studies examined autologous transplantation only (all pediatric), and 3 studies included both transplantation types (all pediatric). HSCT-TMA was associated with renal dysfunction (odds ratio [OR], 11.04 for adult, allogeneic and 7.35 for pediatric, all transplantations), renal failure (OR, 2.41 for adult and pediatric, allogeneic), renal replacement therapy (OR, 6.99 for pediatric, all transplantations and 60.85 for adult, allogeneic), and hypertension (OR, 5.44 for adult, allogeneic). HSCT-TMA was associated with respiratory failure (OR, 8.00 for adult and pediatric, allogeneic), pulmonary hypertension (OR, 9.86 for adult and pediatric, allogeneic), need for pleurocentesis (OR, 5.45 for pediatric, all transplantations), noninvasive ventilation (OR, 6.15 for pediatric, all transplantations), and invasive mechanical ventilation (OR, 5.18 for pediatric, all transplantations). Additionally, HSCT-TMA was associated with neurologic symptoms (OR, 2.28 for adult and pediatric, allogeneic), pericardial effusion (OR, 2.56 for adult and pediatric, allogeneic and 8.76 for pediatric, all transplantations), liver injury (OR, 3.87 for adult, allogeneic), infection (OR, 9.25 for adult, allogeneic; 2.06 for pediatric, all transplantations), gastrointestinal (GI) bleeding (OR, 7.78 for adult and pediatric, allogeneic), and acute graft-versus-host disease grade III-IV (OR, 3.29 for adult and pediatric, allogeneic). This study represents the first systematic review of HSCT-TMA signs and symptoms. Current diagnostic criteria systems involve laboratory markers for multiorgan dysfunction, including renal dysfunction, liver injury, and general tissue damage. Diagnostic criteria include neurologic symptoms, increased need for transfusions, and hypertension. This study identified additional associations with HSCT-TMA, including increased pulmonary hypertension, respiratory failure, fever, GI bleeding, and pericardial effusion. These symptoms might be included for evaluation in future diagnostic criteria and current practice.
Topics: Adult; Child; Humans; Hematopoietic Stem Cell Transplantation; Hypertension; Hypertension, Pulmonary; Pericardial Effusion; Thrombotic Microangiopathies
PubMed: 36592719
DOI: 10.1016/j.jtct.2022.12.023 -
Pediatrics Jan 2022Cardiovascular dysfunction is associated with poor outcomes in critically ill children.
CONTEXT
Cardiovascular dysfunction is associated with poor outcomes in critically ill children.
OBJECTIVE
We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children.
DATA SOURCES
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest.
STUDY SELECTION
Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded.
DATA EXTRACTION
Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member.
RESULTS
Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition.
LIMITATIONS
All included studies were observational and many were retrospective.
CONCLUSIONS
The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction.
Topics: Cardiovascular Diseases; Cardiovascular System; Child; Critical Illness; Humans; Multiple Organ Failure; Organ Dysfunction Scores
PubMed: 34970677
DOI: 10.1542/peds.2021-052888F -
Pediatrics Jan 2022Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism.
CONTEXT
Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism.
OBJECTIVE
To develop consensus criteria for endocrine dysfunction in critically ill children by assessing the association of various biomarkers with clinical and functional outcomes.
DATA SOURCES
PubMed and Embase were searched from January 1992 to January 2020.
STUDY SELECTION
We included studies in which researchers evaluated critically ill children with abnormalities in glucose homeostasis, thyroid function and adrenal function, performance characteristics of assessment and/or scoring tools to screen for endocrine dysfunction, and outcomes related to mortality, organ-specific status, and patient-centered outcomes. Studies of adults, premature infants or animals, reviews and/or commentaries, case series with sample size ≤10, and non-English-language studies were excluded.
DATA EXTRACTION
Data extraction and risk-of-bias assessment for each eligible study were performed by 2 independent reviewers.
RESULTS
The systematic review supports the following criteria for abnormal glucose homeostasis (blood glucose [BG] concentrations >150 mg/dL [>8.3 mmol/L] and BG concentrations <50 mg/dL [<2.8 mmol/L]), abnormal thyroid function (serum total thyroxine [T4] <4.2 μg/dL [<54 nmol/L]), and abnormal adrenal function (peak serum cortisol concentration <18 μg/dL [500 nmol/L]) and/or an increment in serum cortisol concentration of <9 μg/dL (250 nmol/L) after adrenocorticotropic hormone stimulation.
LIMITATIONS
These included variable sampling for BG measurements, limited reporting of free T4 levels, and inconsistent interpretation of adrenal axis testing.
CONCLUSIONS
We present consensus criteria for endocrine dysfunction in critically ill children that include specific measures of BG, T4, and adrenal axis testing.
Topics: Adrenal Cortex Function Tests; Blood Glucose; Child; Critical Illness; Endocrine System Diseases; Homeostasis; Humans; Hydrocortisone; Hyperglycemia; Hypoglycemia; Multiple Organ Failure; Organ Dysfunction Scores; Thyroid Function Tests
PubMed: 34970672
DOI: 10.1542/peds.2021-052888M -
Annals of Medicine Dec 2022Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Critical illness may lead to activation of the sympathetic system. The sympathetic stimulation may be further increased by exogenous catecholamines, such as vasopressors and inotropes. Excessive adrenergic stress has been associated with organ dysfunction and higher mortality. -Blockers may reduce the adrenergic burden, but they may also compromise perfusion to vital organs thus worsening organ dysfunction. To assess the effect of treatment with -blockers in critically ill adults, we conducted a systematic review and meta-analysis of randomized controlled trials.
MATERIALS AND METHODS
We conducted a search from three major databases: Ovid Medline, the Cochrane Central Register for Controlled Trials and Scopus database. Two independent reviewers screened, selected, and assessed the included articles according to prespecified eligibility criteria. We assessed risk of bias of eligible articles according to the Cochrane guidelines. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Sixteen randomized controlled trials comprising 2410 critically ill patients were included in the final review. A meta-analysis of 11 trials including 2103 patients showed a significant reduction in mortality in patients treated with -blockers compared to control (risk ratio 0.65, 95%CI 0.53-0.79; < .0001). There was no significant difference in mean arterial pressure or vasopressor load. Quality of life, biventricular ejection fraction, blood lactate levels, cardiac biomarkers and mitochondrial function could not be included in meta-analysis due to heterogenous reporting of outcomes.
CONCLUSIONS
In this systematic review we found that -blocker treatment reduced mortality in critical illness. Use of -blockers in critical illness thus appears safe after initial hemodynamic stabilization. High-quality RCT's are needed to answer the questions concerning optimal target group of patients, timing of -blocker treatment, choice of -blocker, and choice of physiological and hemodynamic parameters to target during -blocker treatment in critical illness.KEY MESSAGESA potential outcome benefit of -blocker treatment in critical illness exists according to the current review and meta-analysis. Administration of -blockers to resuscitated patients in the ICU seems safe in terms of hemodynamic stability and outcome, even during concomitant vasopressor administration. However, further studies, preferably large RCTs on -blocker treatment in the critically ill are needed to answer the questions concerning timing and choice of -blocker, patient selection, and optimal hemodynamic targets.
Topics: Adrenergic beta-Antagonists; Adult; Critical Illness; Humans; Multiple Organ Failure; Quality of Life; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 35838226
DOI: 10.1080/07853890.2022.2098376 -
Journal of Zhejiang University.... Jul 2019Paraquat (PQ), a highly effective herbicide, is widely used worldwide. PQ poisoning can cause multiple organ failure, in which the lung is the primary target organ.... (Meta-Analysis)
Meta-Analysis
Paraquat (PQ), a highly effective herbicide, is widely used worldwide. PQ poisoning can cause multiple organ failure, in which the lung is the primary target organ. After PQ poisoning, the patient mortality rate is as high as 90%, and there is currently no specific antidote. The main clinical treatment is the use of glucocorticoids and cyclophosphamide for pulse therapy, but its effectiveness and safety are still uncertain. We investigated the effectiveness and safety of immunosuppressive pulse therapy with glucocorticoids and cyclophosphamide to evaluate the treatment value in patients with acute PQ poisoning. This meta-analysis, combined with seven trials that enrolled a total of 426 patients, showed that immunosuppressive pulse therapy with glucocorticoids and cyclophosphamide for PQ poisoning significantly reduced mortality of the study group (59.3%, 134/226) compared with the control group (81.0%, 162/200). There was no significant difference of hepatitis or renal failure between the control and study groups, indicating that immunosuppressive pulse therapy was relatively safe. Several patients were reported to have leukopenia and returned to normal after 1-2 weeks without any abnormalities. Two cases of non-fatal sepsis were reported and considered to be a side effect of the immunosuppressive pulse therapy. Thus, immunosuppressive pulse therapy can efficiently reduce the mortality of PQ poisoning and it is relatively safe.
Topics: Antidotes; Cyclophosphamide; Drug Therapy, Combination; Glucocorticoids; Herbicides; Humans; Hypoxia; Immunosuppression Therapy; Immunosuppressive Agents; Paraquat; Poisoning; Randomized Controlled Trials as Topic; Risk; Sensitivity and Specificity; Sepsis; Treatment Outcome
PubMed: 31168972
DOI: 10.1631/jzus.B1800640 -
PloS One 2018Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paraquat (PQ) poisoning can cause multiple organ failure, in which the lung is the primary target organ. There is currently no treatment for PQ poisoning. Mesenchymal stem cells (MSCs), which differentiate into multiple cell types, have generated much enthusiasm regarding their use for the treatment of several diseases. The aim of this study was to systematically review and analyze published preclinical studies describing MSC administration for the treatment of PQ poisoning in animal models to provide a basis for cell therapy.
METHODS
The electronic databases PubMed and CBMdisc were searched in this systematic review and meta-analysis. The MSC treatment characteristics of animal models of PQ poisoning were summarized. After quality assessment was performed, the effects of MSC transplantation were evaluated based on the survival rate, lung wet/dry weight, fibrosis scores, oxidative stress response, and inflammatory response. Publication bias was assessed.
RESULTS
Eleven controlled preclinical studies involving MSC transplantation in animal models of PQ poisoning were included in this review. MSC therapy improved the survival rate and reduced the lung wet/dry weight and histopathological fibrosis changes in most studies. MSCs decreased serum or plasma malondialdehyde levels in the acute phase after 7 and 14 d and increased serum or plasma superoxide dismutase and glutathione levels at the same time points. IL-1β, TNF-α and TGF-β1 levels in blood or lung tissues were decreased to different degrees by MSCs. Lung hydroxyproline was decreased by MSCs after 14 d. No obvious evidence of publication bias was found.
CONCLUSION
MSCs showed anti-fibrosis therapeutic effects in animal models of lung injury caused by PQ poisoning, which may be related to reduced oxidative stress and inflammatory cytokine levels. Our review indicates a potential therapeutic role for MSC therapy to treat PQ poisoning and serves to augment the rationale for clinical studies.
Topics: Acute Lung Injury; Animals; Disease Models, Animal; Evaluation Studies as Topic; Humans; Mesenchymal Stem Cell Transplantation; Paraquat; Pulmonary Edema
PubMed: 29566055
DOI: 10.1371/journal.pone.0194748