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Therapeutic Advances in Respiratory... 2023In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In coronavirus disease 2019 (COVID-19) patients, elevated levels of inflammatory cytokines from over stimulation of immune cells have become a concern due to the potential outburst of cytokine storm that damages the tissues and organs, especially the lungs. This leads to the manifestation of COVID-19 symptoms, such as pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure, and eventually death. Mesenchymal stromal/stem cells (MSCs) are currently one of hopeful approaches in treating COVID-19 considering its anti-inflammatory and immunomodulatory functions. On that account, the number of clinical trials concerning the use of MSCs for COVID-19 has been increasing. However, the number of systematic reviews and meta-analysis that specifically discuss its potential as treatment for the disease is still lacking. Therefore, this review will assess the safety and efficacy of MSC administration in COVID-19 patients.
OBJECTIVES
To pool evidence on the safety and efficacy of MSCs in treating COVID-19 by observing MSC-related adverse effects as well as evaluating its effects in reducing inflammatory response and improving pulmonary function.
DATA SOURCES AND METHODS
Following literature search across six databases and one trial register, full-text retrieval, and screening against eligibility criteria, only eight studies were included for data extraction. All eight studies evaluated the use of umbilical cord-derived mesenchymal stromal/stem cell (UC-MSC), infused intravenously. Of these eight studies, six studies were included in meta-analysis on the incidence of mortality, adverse events (AEs), and serious adverse events (SAEs), and the levels of C-reactive protein (CRP) and interleukin (IL)-6. Meta-analysis on pulmonary function was not performed due to insufficient data.
RESULTS
MSC-treated group showed significantly lower risk of mortality than the control group ( = 0.03). No statistical significance was observed on the incidence of AEs ( = 0.78) and SAEs ( = 0.44), and the levels of CRP ( = 0.06) and IL-6 ( = 0.09).
CONCLUSION
MSCs were safe for use, with lower risk of mortality and no association with AEs. Regarding efficacy, descriptive analysis showed indications of improvement on the inflammatory reaction, lung clearance, and oxygenation status despite the lack of statistical significance in meta-analysis of CRP and IL-6. Nevertheless, more studies are needed for affirmation.
REGISTRATION
This systematic review and meta-analysis was registered on the PROSPERO database (no. CRD42022307730).
Topics: Humans; COVID-19; SARS-CoV-2; Interleukin-6; Mesenchymal Stem Cell Transplantation; Cytokines; Mesenchymal Stem Cells
PubMed: 37128999
DOI: 10.1177/17534666231158276 -
Journal of Clinical Medicine Jul 2023The acute phase of COVID-19 often leaves patients with persistent pulmonary deficits. Pulmonary Rehabilitation (PR) has been recommended as an essential part of... (Review)
Review
The acute phase of COVID-19 often leaves patients with persistent pulmonary deficits. Pulmonary Rehabilitation (PR) has been recommended as an essential part of post-acute COVID-19 management. In light of the global pandemic, telerehabilitation has been increasingly employed to deliver PR. This systematic review aimed to evaluate the effectiveness of telemedicine-driven PR in patients recovering from the acute phase of COVID-19, assessing variations in telerehabilitation practices and identifying the degree of change in mental health, physical health, quality of life, and lung function. A systematic search was conducted across PubMed, Web of Science, Cochrane, and Scopus up until April 2023. Studies focusing on telerehabilitation in PR for post-acute COVID-19 patients with outcomes including pulmonary function, exercise capacity, and quality of life were included after careful assessment of this study's protocol. The selection process involved careful scrutiny of abstracts and full texts, and the quality assessment was performed using the National Heart, Lung, and Blood Institute (NHLBI) tool. Seven studies, published between 2021 and 2022, involving a total of 412 patients, were included. The evaluated telerehabilitation programs stretched between 4 and 10 weeks, involving a mobile app or video connection with the patient, integrating a mix of aerobic and resistance training, breathing exercises, functional activities, and muscle strengthening. Findings revealed that telemedicine-driven PR significantly improved physical health, measured by the step test score (73 vs. 71), 6MWD (30.2 vs. 17.1) and BPAQ, mental health evaluated by SF-12 (6.15 vs. 4.17) and PHQ-4, quality of life measured by the SF-12 (7.81 vs. 3.84), SGRQ (31.5 vs. 16.9), and CAT scores, and some parameters of pulmonary function in post-acute COVID-19 patients (mMRC, STST, and MVV). This review substantiates the potential of telemedicine-driven PR to improve various health outcomes in post-acute COVID-19 patients. The findings underscore the importance of integrating telerehabilitation into the management of post-acute COVID-19 and call for further exploration of its long-term effects, cost-effectiveness, and best practices.
PubMed: 37510969
DOI: 10.3390/jcm12144854 -
Frontiers in Oncology 2023High-grade B cell lymphomas with concomitant and and/or rearrangements (HGBCL-DH/TH) have a poor prognosis when treated with the standard R-CHOP-like...
BACKGROUND AND AIM
High-grade B cell lymphomas with concomitant and and/or rearrangements (HGBCL-DH/TH) have a poor prognosis when treated with the standard R-CHOP-like chemoimmunotherapy protocol. Whether this can be improved using intensified regimens is still under debate. However, due to the rarity of HGBCL-DH/TH there are no prospective, randomized controlled trials (RCT) available. Thus, with this systematic review and meta-analysis we attempted to compare survival in HGBCL-DH/TH patients receiving intensified vs. R-CHOP(-like) regimens.
METHODS
The PubMed and Web of Science databases were searched for original studies reporting on first-line treatment in HGBCL-DH/TH patients from 08/2014 until 04/2022. Studies with only localized stage disease, ≤10 patients, single-arm, non-full peer-reviewed publications, and preclinical studies were excluded. The quality of literature and the risk of bias was assessed using the Methodological Index for Non-Randomized Studies (MINORS) and National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Random-effect models were used to compare R-CHOP-(like) and intensified regimens regarding 2-year overall survival (2y-OS) and 2-year progression-free survival (2y-PFS).
RESULTS
Altogether, 11 retrospective studies, but no RCT, with 891 patients were included. Only four studies were of good quality based on aforementioned criteria. Intensified treatment could improve 2y-OS (hazard ratio [HR]=0.78 [95% confidence interval [CI] 0.63-0.96]; p=0.02) as well as 2y-PFS (HR=0.66 [95% CI 0.44-0.99]; p=0.045).
CONCLUSIONS
This meta-analysis indicates that intensified regimens could possibly improve 2y-OS and 2y-PFS in HGBCL-DH/TH patients. However, the significance of these results is mainly limited by data quality, data robustness, and its retrospective nature. There is still a need for innovative controlled clinical trials in this difficult to treat patient population.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022313234.
PubMed: 37546419
DOI: 10.3389/fonc.2023.1188478 -
Pharmaceuticals (Basel, Switzerland) Jun 2023Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC)... (Review)
Review
Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC) may cause an antineutrophil cytoplasmic antibody (ANCA)-associated systemic small vessel vasculitis (AAV). We aimed to characterize the phenotype of persons developing pulmonary-renal syndrome (PRS) in LAC-induced AAV and summarize its treatment and outcomes. Pubmed and Web of Science were searched (until September 2022). Reports that described co-existing diffuse alveolar hemorrhage and glomerulonephritis in an adult (age ≥ 18) with confirmed or suspected LAC exposure were included. Reports, demographics, clinical and serologic features, treatment and outcome characteristics were extracted. Of the 280 records identified, eight met the inclusion criteria, including eight unique cases. Persons were aged 22-58 years, and 50% were women. Cutaneous involvement occurred in only half of the cases. Other associated vasculitis findings and serologies were heterogeneous. All patients received immunosuppression with steroids, with cyclophosphamide and rituximab commonly added. We concluded that PRS could occur from LAC-induced AAV. Distinguishing LAC-induced AAV from primary AAV is challenging as clinical and serologic presentations overlap. Asking about cocaine use is requisite in persons presenting with PRS to guide diagnosis and appropriately counsel on cocaine cessation in conjunction with immunosuppression as treatment.
PubMed: 37375793
DOI: 10.3390/ph16060846 -
Journal of Orthopaedic Surgery and... Aug 2023With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function, but is often associated with massive blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip or knee arthroplasty. However, the optimal dose of TXA administration remains controversial. Therefore, we performed a meta-analysis combining data from 5 trials comparing the efficacy and safety of one fixed dose of 1 g intravenously administered TXA with two doses of 1 g each administered intravenously for hip or knee arthroplasty.
METHODS
PubMed, Medline, Embase, Web of Science, and The Cochrane Library were searched from January 2000 to February 2023. Our meta-analysis included randomized controlled trials and cohort studies comparing the efficacy and safety of different doses of intravenous TXA (IV-TXA) for THA or TKA. The observation endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, incidence of deep venous thrombosis (DVT), and incidence of pulmonary embolism (PE). Meta-analysis was performed according to Cochrane's guidelines and PRISMA statement. The Danish RevMan5.3 software was used for data merging.
RESULTS
Five cohort studies involving 5542 patients met the inclusion criteria. Our meta-analysis showed that the two groups were significantly higher in total blood loss (mean difference (MD) = - 65.60, 95% confidence interval (CI) [- 131.46, 0.26], P = 0.05); blood transfusion rate (risk difference (RD) = 0.00, 95% CI [- 0.01, 0.02], P = 0.55); postoperative hemoglobin (MD = 0.02, 95% CI [- 0.09, 0.13], P = 0.31); postoperative hospital stay days (MD = - 0.13), 95% CI [- 0.35, 0.09], P = 0.25); DVT (RD = 0.00, 95% CI [- 0.00, 0.01], P = 0.67); PE (RD = 0.00, 95% CI [- 0.01, 0.00], P = 0.79). There was some inherent heterogeneity due to variance in sample size across each major study.
CONCLUSION
1 dose of 1 g and 2 doses of 1 g IV-TXA each time have similar effects on reducing blood loss, blood transfusion rate, postoperative hemoglobin level, and postoperative hospital stay after TKA or THA, without increasing the risk of postoperative complications risk. For patients at high risk of thromboembolic events, one dose of 1 g TXA throughout surgery may be preferred. However, higher-quality RCT is needed to explore the optimal protocol dose to recommend the widespread use of TXA in total joint arthroplasty. Trial registration We conducted literature selection, eligibility criteria evaluation, data extraction and analysis on the research program registered in Prospero (CRD42023405387) on March 16, 2023.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Venous Thrombosis; Blood Loss, Surgical; Arthroplasty, Replacement, Hip; Administration, Intravenous; Pulmonary Embolism; Hemoglobins
PubMed: 37563702
DOI: 10.1186/s13018-023-03929-9 -
Orthopaedic Surgery Apr 2023The optimal dose and efficacy of tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) in total knee arthroplasty (TKA) were under controversial, and we aimed to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The optimal dose and efficacy of tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) in total knee arthroplasty (TKA) were under controversial, and we aimed to make comparisons between different doses of TXA and EACA in intravenous (IV) or intra-articular (IA) applications in patients undergoing TKA.
METHODS
This network meta-analysis was guided by the Priority Reporting Initiative for Systematic Assessment and Meta-Analysis (PRISMA). According to the administrations of antifibrinolytic agents, patients in eligible studies were divided into three subgroups: (i) IA applications of TXA and EACA; (ii) IV applications (g) of TXA and EACA; (iii) IV applications (mg/kg) of TXA and EACA. Total blood loss (TBL), hemoglobin (HB) drops and transfusion rates were the primary outcomes, while drainage volume, pulmonary embolism (PE) or deep vein thrombosis (DVT) risk were the secondary outcomes. A multivariate Bayesian random-effects model was adopted in the network analysis.
RESULTS
A total of 38 eligible trials with different regimens were assessed. Overall inconsistency and heterogeneity were acceptable. Taking all primary outcomes into account, 1.0-3.0 g TXA were most effective in IA applications, 1-6 g TXA and 10-14 g EACA were most effective in IV applications (g), while 30 mg/kg TXA and 150 mg/kg EACA were most effective in IV applications (mg/kg). None of the regimens showed increasing risk for pulmonary embolism (PE) or deep vein thrombosis (DVT) compared with placebo.
CONCLUSION
0 g IA TXA, 1.0 g IV TXA or 10.0 g IV EACA, as well as 30 mg/kg IV TXA or 150 mg/kg IV EACA were most effective and enough to control bleeding for patients after TKA. TXA was at least 5 times more potent than EACA.
Topics: Humans; Administration, Intravenous; Aminocaproic Acid; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Bayes Theorem; Blood Loss, Surgical; Network Meta-Analysis; Pulmonary Embolism; Tranexamic Acid; Venous Thrombosis
PubMed: 36878889
DOI: 10.1111/os.13678 -
Orthopaedics & Traumatology, Surgery &... Apr 2023Direct oral anticoagulants (DOACs) are recommended as a possible pharmacologic venous thromboembolism (VTE) prophylaxis in patients undergoing total hip arthroplasty... (Meta-Analysis)
Meta-Analysis Review
The effectiveness and safety of direct oral anticoagulants compared to conventional pharmacologic thromboprophylaxis in hip fracture patients: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Direct oral anticoagulants (DOACs) are recommended as a possible pharmacologic venous thromboembolism (VTE) prophylaxis in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, current guidelines did not introduce recommendations for administration of DOACs as an option for pharmacologic VTE prophylaxis in patients undergoing hip fracture surgery (HFS). The purpose of this study is to compare the effectiveness and safety of DOACs administered for pharmacologic VTE prophylaxis in patients undergoing HFS to conventional pharmacologic VTE prophylaxis, as well as mortality between these thromboprophylaxis medications.
METHODS
We performed a systematic review of multiple electronic databases for randomized controlled trials (RCTs) including patients who were subjected to HFS and prescribed either DOACs as pharmacologic VTE prophylaxis or a conventional VTE prophylaxis drug. We conducted a meta-analysis comparing effectiveness, safety and mortality of these agents between the patient groups studied. Three endpoints were studied. The first one regarding the effectiveness of the agents included clinical manifestations of VTE. The second one regarding the safety of the agents included clinical presentation of bleeding. The latter endpoint studied was mortality of patient groups studied. We generated forest plots to depict the relative risk of the above clinical manifestations between the two studied patient groups and to investigate if there is statistical significance for each patient group to present any of these clinical manifestations. Additionally, we calculated the inconsistency (I) statistic and assessed the risk of bias of RCTs included in our meta-analysis by using the modified Cochrane collaboration tool.
RESULTS
We selected 2 RCTs in this review including 279 patients totally. Patients of control groups in both eligible studies were administered enoxaparin, which is a low molecular weight heparin (LMWH). The meta-analysis found no statistically significant difference between patients prescribed DOACs and patients prescribed LMWH for VTE (95% CI 0.19 to 1.13, RR=0.46, p=0.09), deep vein thrombosis (DVT) (95% CI 0.21 to 1.32, RR=0.53, p=0.17) and pulmonary embolism (PE) (95% CI 0.03 to 3.12, RR=0.33, p=0.33), major bleeding events (95% CI 0.57 to 1.78, RR=1.01, p=0.97), minor bleeding events (95% CI 0.72 to 1.64, RR=1.09, p=0.69), all bleeding events (95% CI 0.79 to 1.38, RR=1.05, p=0.74) and mortality (95% CI 0.01 to 8.0, RR=0.33, p=0.5). The major risk of bias of the selected RCTs was the fact that either the researchers or the patients could have knowledge whether the latter were administered DOACs or LMWHs.
DISCUSSION
DOACs are not inferior compared to LMWHs regarding their effectiveness, safety and mortality in patients subjected to HFS. Further studies with larger patient samples should be conducted in the future, so that safer results and conclusions could be reached.
Topics: Humans; Anticoagulants; Venous Thromboembolism; Randomized Controlled Trials as Topic; Heparin, Low-Molecular-Weight; Enoxaparin; Hemorrhage; Hip Fractures
PubMed: 35817368
DOI: 10.1016/j.otsr.2022.103364 -
Research and Practice in Thrombosis and... Feb 2023Extracorporeal membrane oxygenation (ECMO) and COVID-19 significantly impact the coagulation system. A systematic review and meta-analysis were performed to explore the... (Review)
Review
BACKGROUND
Extracorporeal membrane oxygenation (ECMO) and COVID-19 significantly impact the coagulation system. A systematic review and meta-analysis were performed to explore the prevalence of thrombotic and bleeding events in patients with COVID-19 supported with ECMO, summarize anticoagulation regimens, and guide future research.
METHODS
Cochrane, EMBASE, Scopus, and PubMed were searched for studies examining thrombosis and bleeding in patients with COVID-19 requiring ECMO. The primary outcomes were the prevalences of different types of hemorrhage and thrombosis. The pooled estimated rates and relative risk (RR) were calculated to summarize the outcomes.
RESULTS
Twenty-three peer-reviewed studies involving 6878 subjects were included. For thrombotic events, the prevalence of circuit thrombosis was 21.5% (95% CI: 15.5%-27.6%; 1532 patients), that of ischemic stroke was 2.6% (95% CI: 1.5%-3.7%; 5926 patients), and that of pulmonary embolism (PE) was 11.8% (95% CI: 6.8%-16.8%; 5853 patients). For bleeding events, 37.4% of the patients experienced major hemorrhage (95% CI: 28.1%-46.8%; 1558 patients) and 9.9% experienced intracranial hemorrhage (ICH; 95% CI: 7.8%-12.1%; 6348 patients). COVID-19 cases on ECMO were complicated with more ICH than patients without COVID-19 on respiratory ECMO [RR = 2.23 (95% CI: 1.32-3.75)]. Anticoagulation strategies varied among centers.
CONCLUSIONS
Circuit thrombosis and major bleeding were the most common thrombotic and bleeding events. The incidence of ICH was significantly higher when ECMO was indicated for COVID-19 than for other respiratory diseases. There is no evidence for stronger anticoagulation practice, and remains no consistent anticoagulation strategy to reduce the occurrence of thrombosis and bleeding under the double "hit" of COVID-19 and ECMO.
PubMed: 36999123
DOI: 10.1016/j.rpth.2023.100103 -
Clinical Medicine Insights. Oncology 2023Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these... (Review)
Review
A Systematic Review of Clinical Practice Guidelines for Managing Pulmonary Toxicities Caused by Immune Checkpoint Inhibitors: Quality of Treatment Recommendations and Differences in Management Strategies Between Guidelines.
BACKGROUND
Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these toxicities.
METHODS
A systematic search of CPGs on checkpoint-associated pulmonary toxicities (ca-PT) was conducted in October 2022. PubMed, Embase, Cochrane Library, CINAHL, and Web of Science were searched. AGREE II and AGREE-REX were used to appraise CPGs and recommendations quality, respectively. Descriptive statistics, intraclass correlation coefficient, Kruskal-Wallis (H) test, and Spearman's correlation were used for analyses. P-values < .05 were considered statistically significant. Matrices were used to determine recommendation differences between CPGs. The study's design was based on the PRISMA 2020 checklist for systematic reviews. Protocol registration number: CRD42022358435.
RESULTS
Eight CPGs (two high-quality, three moderate-quality, and three low-quality) were identified. All CPGs covered pneumonitis. One CPG covered pleural effusions and pneumonitis/SARs-CoV-2-infection. Three CPGs covered sarcoidosis-like-reactions. CPGs for pulmonary fibrosis, airway disease, bronchiolitis, and diffuse alveolar damage, were unavailable. No CPG recommendation was based on a prospective study, and none were appraised as high-quality. Also, recommendations were not specific to histopathologic subtypes. AGREE II's "rigor of development," the domain that evaluates a guideline's methodological approach and strategies in gathering scientific evidence, correlated strongly with AGREE-REX's "overall quality" pneumonitis recommendations, r = .952; P < .01. Approximately 73% of recommendations on pneumonitis were similar between high-quality CPGs. About 16% to 74% of low-quality CPGs were similar to those recommended by high-quality CPGs.
CONCLUSION
Prospectively designed research projects focusing on all types of ca-PT and their histopathologic subtypes are urgently needed. Due to the lack of high-quality recommendations in available CPGs, the disparities in treatment recommendations between high-quality CPGs, and the similarities in recommendations that exists between high-quality and low-quality CPGs, clinicians should thoroughly assess and responsibly appraise all available CPG recommendations in formulating treatment strategies for ca-PT.
PubMed: 38033741
DOI: 10.1177/11795549231203153 -
Diagnostics (Basel, Switzerland) Jul 2023(1) Background: The current diagnostic algorithm for acute pulmonary embolism (PE) is associated with the overuse of CT pulmonary angiography (CTPA). An additional... (Review)
Review
(1) Background: The current diagnostic algorithm for acute pulmonary embolism (PE) is associated with the overuse of CT pulmonary angiography (CTPA). An additional highly specific blood test could potentially lower the proportion of patients with suspected PE that require CTPA. The aim was to summarize the literature on the diagnostic performance of biomarkers of patients admitted to an emergency department with suspected acute PE. (2) Methods: Medline and Embase databases were searched from 1995 to the present. The study selection process, data extraction, and risk of bias assessment were conducted by two reviewers. Eligibility criteria accepted all blood biomarkers except D-dimer, and CTPA was used as the reference standard. Qualitative data synthesis was performed. (3) Results: Of the 8448 identified records, only 6 were included. Eight blood biomarkers were identified, of which, three were investigated in two separate studies. Red distribution width and mean platelet volume were reported to have a specificity of ≥ 90% in one study, although these findings were not confirmed by other studies. The majority of the studies contained a high risk of selection bias. (4) Conclusions: The modest findings and the uncertain validity of the included studies suggest that none of the biomarkers identified in this systematic review have the potential to improve the current diagnostic algorithm for acute PE by reducing the overuse of CTPA.
PubMed: 37443693
DOI: 10.3390/diagnostics13132301