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Lipids in Health and Disease Feb 2024Myocardial ischemia-reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Myocardial ischemia-reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin (APN) is an adipocytokine with cardioprotective properties; however, the mechanisms of APN in MIRI are unclear. Therefore, based on preclinical (animal model) evidence, the cardioprotective effects of APN and the underlying mechanisms were explored.
METHODS
The literature was searched for the protective effect of APN on MIRI in six databases until 16 November 2023, and data were extracted according to selection criteria. The outcomes were the size of the myocardial necrosis area and hemodynamics. Markers of oxidation, apoptosis, and inflammation were secondary outcome indicators. The quality evaluation was performed using the animal study evaluation scale recommended by the Systematic Review Center for Laboratory animal Experimentation statement. Stata/MP 14.0 software was used for the summary analysis.
RESULTS
In total, 20 papers with 426 animals were included in this study. The pooled analysis revealed that APN significantly reduced myocardial infarct size [weighted mean difference (WMD) = 16.67 (95% confidence interval (CI) = 13.18 to 20.16, P < 0.001)] and improved hemodynamics compared to the MIRI group [Left ventricular end-diastolic pressure: WMD = 5.96 (95% CI = 4.23 to 7.70, P < 0.001); + dP/dtmax: WMD = 1393.59 (95% CI = 972.57 to 1814.60, P < 0.001); -dP/dtmax: WMD = 850.06 (95% CI = 541.22 to 1158.90, P < 0.001); Left ventricular ejection fraction: WMD = 9.96 (95% CI = 7.29 to 12.63, P < 0.001)]. Apoptosis indicators [caspase-3: standardized mean difference (SMD) = 3.86 (95% CI = 2.97 to 4.76, P < 0.001); TUNEL-positive cells: WMD = 13.10 (95% CI = 8.15 to 18.05, P < 0.001)], inflammatory factor levels [TNF-α: SMD = 4.23 (95% CI = 2.48 to 5.98, P < 0.001)], oxidative stress indicators [Superoxide production: SMD = 4.53 (95% CI = 2.39 to 6.67, P < 0.001)], and lactate dehydrogenase levels [SMD = 2.82 (95% CI = 1.60 to 4.04, P < 0.001)] were significantly reduced. However, the superoxide dismutase content was significantly increased [SMD = 1.91 (95% CI = 1.17 to 2.65, P < 0.001)].
CONCLUSION
APN protects against MIRI via anti-inflammatory, antiapoptotic, and antioxidant effects, and this effect is achieved by activating different signaling pathways.
Topics: Rats; Animals; Myocardial Reperfusion Injury; Rats, Sprague-Dawley; Adiponectin; Myocardial Infarction; Signal Transduction; Apoptosis
PubMed: 38368320
DOI: 10.1186/s12944-024-02028-w -
Frontiers in Pharmacology 2024To evaluate the intervention effect of resveratrol on rat model of myocardial ischemia-reperfusion injury. The relevant studies on the intervention of resveratrol on...
To evaluate the intervention effect of resveratrol on rat model of myocardial ischemia-reperfusion injury. The relevant studies on the intervention of resveratrol on rat models of myocardial ischemia reperfusion injury were searched in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang and China Science and Technology Journal Database from the start of database establishment to January 2023. Data were extracted from studies that met the inclusion criteria. The results included electrocardiogram (ECG) and myocardial injury markers: ST changes, cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH); hemodynamic indicators: heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximum rate of increase of left ventricular pressure (+dp/dtmax), maximum rate of decrease of left ventricular pressure (-dp/dtmax); oxidative damage indicators: nitric oxide (NO), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA); inflammatory factors: tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); apoptosis index: B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), cardiomyocyte apoptosis index (AI); heart tissue structure: myocardial infarction size. Finally, a meta-analysis of these results was conducted. The methodological quality of the studies was assessed using the SYRCLE Bias Risk tool. A total of 43 studies were included in the meta-analysis, and the quality of the included studies was assessed. It was found that the evidence quality of these 43 studies was low, and no study was judged to have low risk bias in all risk assessments. The results showed that resveratrol could reduce ST segment, cTn-I, cTn-T, CK, CK-MB, LDH, LVEDP, ROS, MDA, TNF-α, IL-6, AI levels and myocardial infarction size. HR, LVDP, LVSP, +dp/dtmax, NO, Bcl-2, and SOD levels were increased. However, resveratrol had no significant effect on -dp/dtmax and Bax outcome measures. Resveratrol can reduce ST segment in rat model of myocardial ischemia-reperfusion injury, alleviate myocardial injury, improve ventricular systolic and diastolic ability in hemodynamics, reduce inflammatory response and oxidative damage, and reduce myocardial necrosis and apoptosis. Due to the low quality of the methodologies included in the studies, additional research is required.
PubMed: 38313308
DOI: 10.3389/fphar.2024.1301502 -
Transplantation and Cellular Therapy Jun 2024Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor T cell (CAR-T) therapies approved for relapsed/refractory... (Meta-Analysis)
Meta-Analysis Comparative Study
Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor T cell (CAR-T) therapies approved for relapsed/refractory aggressive large B cell lymphoma (LBCL). Significant costs and complex manufacturing underscore the importance of evidence-based counseling regarding the outcomes of these treatments. With the aim of examining the efficacy and safety of axi-cel versus tisa-cel in patients with relapsed/refractory aggressive LBCL, we performed a systematic literature search of comparative studies evaluating outcomes in relapsed/refractory aggressive LBCL after treatment with axi-cel or tisa-cel. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for response, progression-free survival (PFS), overall survival (OS), cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematotoxicity. Meta-analysis and meta-regression were used to generate summary statistics. A total of 2372 participants were included in the 8 studies in our analysis. The dropout rate between apheresis and infusion was 13% for axi-cel versus 18% for tisa-cel, and the median time from apheresis to infusion was 32 days versus 45 days. Axi-cel showed higher odds for a complete response (OR, 1.65; P < .001) and was associated with higher odds for PFS at 1 year after infusion (OR, .60; P < .001). OS appeared to be improved with axi-cel (OR, .84; 95% CI, .68 to 1.02; P = .08), whereas the cumulative incidence of nonrelapse mortality (NRM) was 11.5% for axi-cel versus 3.7% for tisa-cel (P = .002). The main predictors for survival were lactate dehydrogenase level, Eastern Cooperative Oncology Group Performance Status, and response to bridging, and axi-cel maintained superior efficacy even in elderly patients. In terms of safety, axi-cel was associated with significantly higher odds of any-grade CRS (OR, 3.23; P < .001), but not of grade ≥3 CRS (P = .92). Axi-cel was associated with significantly higher odds of severe ICANS grade ≥3 (OR, 4.03; P < .001). In terms of hematotoxicity, axi-cel was significantly associated with higher odds of severe neutropenia at 1 month after infusion (OR, 2.06; P = .003). As a result, axi-cel was associated with significantly greater resource utilization, including prolonged hospital stay, more frequent intensive care admission, and use of agents such as tocilizumab for toxicity management. We provide strong evidence of the greater efficacy of axi-cel versus tisa-cel in relapsed/refractory aggressive LBCL. The higher toxicity and NRM seen with axi-cel might not counterbalance the overall results, highlighting the need for timely intervention and careful selection of patients, balancing resource utilization and clinical benefit.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Biological Products; Immunotherapy, Adoptive; Antigens, CD19; Receptors, Antigen, T-Cell; Cytokine Release Syndrome; Treatment Outcome
PubMed: 38281590
DOI: 10.1016/j.jtct.2024.01.074 -
Cureus Dec 2023This systematic review and meta-analysis was planned with the objective of evaluating the level of Lactate Dehydrogenase (LDH) in oral submucous fibrosis patients and in... (Review)
Review
This systematic review and meta-analysis was planned with the objective of evaluating the level of Lactate Dehydrogenase (LDH) in oral submucous fibrosis patients and in controls and comparing them. For this meta-analysis, we searched Google Scholar, PubMed, Scopus, and Directory of Open Access Journals (DOAJ) databases using a search methodology that included combinations of MeSH terms and keywords and included cross-sectional studies to evaluate the levels of LDH in patients with Oral Submucous Fibrosis (OSMF), Oral Squamous Cell Carcinoma (OSCC) and compared it with the controls. The total number of records identified through database searching was 4161 (n). Analysis of the quality of the studies was done using the National Heart, Lungs and Blood Institute (NHLBI) tool for case-control studies. Twelve case-control studies which matched the inclusion criteria were included after the literature search. The meta-analysis was carried out using R Studio (version 4.1.3, 2022; The R Foundation for Statistical Computing, Vienna, Austria). The pooled estimate that has been calculated from the salivary LDH course for OSMF was 15.35% and from the serum LDH course for OSMF was 6.82%. There was a visual observation of the funnel's plot asymmetry suggesting publication bias. After adjusting the publication bias, the t values for salivary and serum LDH were 41% and 14.71%, respectively, which was less than 50%, indicating that the meta-analysis was statistically significant. The evaluation of salivary and serum LDH can be a useful method for early diagnosis of OSMF as well as OSCC. To infer that individuals may have OPMD or OSCC, specific values for salivary and serum LDH must be found in further investigations.
PubMed: 38264399
DOI: 10.7759/cureus.51008 -
Prophylactic use of interleukin 6 monoclonal antibody can reduce CRS response of CAR-T cell therapy.Frontiers in Medicine 2023Chimeric antigen receptor T (CAR-T) cell immunotherapy is becoming one of the most promising treatments for hematological malignancies, however, complications such as...
BACKGROUND
Chimeric antigen receptor T (CAR-T) cell immunotherapy is becoming one of the most promising treatments for hematological malignancies, however, complications such as cytokine release syndrome (CRS) seriously threaten the lives of patients. Interleukin 6(IL-6) monoclonal antibody is the common and useful treatment of CRS, however, it is not clear whether prophylactic use IL-6 monoclonal antibody before CAR-T therapy can reduce the incidence of CRS.
PURPOSE
This study aims to systematically evaluate whether the prophylactic use of IL-6 monoclonal antibody can reduce the incidence of CRS.
DATA SOURCES AND METHODS
We searched the PubMed, Embase, web of Science, and Cochrane Library databases for studies that reported the prophylactic use of IL-6 monoclonal antibody in the treatment of CRS-related complications of CAR-T cell immunotherapy before December 2022. The literature is screened according to the established inclusion and exclusion criteria, relevant data are extracted, and the quality of the literature is evaluated using the scale Cochrane bias risk assessment tool, and the Review Manager 5.3 is used to draw for related charts. Since the two experimental data only provide the median, the maximum and minimum values of the data, the mean and standard (Standard Deviation, SD) are calculated by this document Delai, and finally use Review Manager for data processing, and STATA software for supplementation.
RESULTS
A total of 2 trials with a total of 37 participants were included in this study. Meta-analysis showed that compared with no use of IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced the incidence of CRS [RR: 0.41 95% confidence interval (0.20, 0.86) I[2] = 0.0% = 0.338 = -2.369 ( = 0.018)]. In subgroup analysis, compared with those who did not use IL-6 monoclonal antibody to prevent CRS, IL-6 monoclonal antibody was given to patients at 8 mg/kg one hour before CAR-T cell infusion, which reduced lactate dehydrogenase (LDH)[MD: -617.21, 95% confidence interval (-1104.41, -130.01) I[2] = 0% = 0.88 = 2.48 ( = 0.01)], prophylactic use of IL-6 monoclonal antibody has a significant effect on reducing peak C-reactive protein (CRP) after CAR-T therapy [MD: -11.58, 95% confidence interval (-15.28, -7.88) I[2] = 0.0% = 0.73 z = 6.14 ( < 0.00001)].
CONCLUSION
The prophylactic use of IL-6 monoclonal antibody can significantly reduce the incidence of CRS complications after CAR-T therapy, can also reduce LDH vaule and peak CRP vaule after CAR-T therapy.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023487662, identifier CRD42023487662.
PubMed: 38264058
DOI: 10.3389/fmed.2023.1265835 -
Cureus Dec 2023Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL... (Review)
Review
Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL remain underexplored, contributing to diagnostic complexities and a high mortality rate. This study endeavors to elucidate the salient clinical and investigative features of stroke linked to this condition. A systematic review was performed using the PubMed database from the incident to August 2023 including search categories for IVL and stroke. All studies, excluding review articles, were included in this study. There were 58 cases with a confirmed diagnosis of IVL associated with stroke, with a mean age of 62.9 ± 9.6 years (female 50%). Classical lateralizing stroke symptoms were noted in only 69% of cases. Other clinical syndromes included altered sensorium (31%), rapidly progressive cognitive impairment (23%), seizures (22%), and gait disturbances (19%). Common hematological abnormalities included elevated lactate dehydrogenase (LDH, 97%), erythrocyte sedimentation rate (ESR, 79%), C-reactive protein (CRP, 61%), interleukin-2, microglobulins, and cerebrospinal fluid (CSF) protein. CSF flow cytometry was not diagnostic, and cytology was mostly negative. The dynamic pattern for DWI/T2 lesions was predominant and primarily located in the subcortical regions. Diffuse background slowing (64%) was a major finding in the electroencephalogram. Seventy-one percent of cases died (n=45) mostly due to delayed diagnosis. Only 31% were treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone) chemotherapy, among whom 25% died. This study suggests that IVL-associated strokes carry a high mortality rate, largely due to challenges in timely diagnosis and therapy. Unlike classical stroke syndrome, key indicators to aid in early diagnosis include a clinical syndrome of multiple non-lateralizing neurological symptoms, dynamic MRI DWI/T2-lesions primarily located in subcortical regions, elevated serum LDH, ESR, CRP, interleukins, microglobulin, CSF protein, and CSF polymerase chain reaction analysis, apart from tissue examination. Larger studies should be performed to establish diagnostic and predictive scores.
PubMed: 38249220
DOI: 10.7759/cureus.50896 -
Therapeutic Advances in Hematology 2023Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and... (Review)
Review
BACKGROUND
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan has revolutionized the management of PNH, leading to improvements in overall survival and quality of life for patients.
OBJECTIVES
This systematic review aims to provide comprehensive evidence of the efficacy of complement inhibitors in relation to treatment duration.
DESIGN
This is a systematic review and meta-analysis.
DATA SOURCES AND METHODS
A thorough literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library up to 3 May 2022. We included all prospective interventional studies including single-arm trials. The primary outcomes of interest were lactate dehydrogenase (LDH) levels, hemoglobin (Hb) concentrations, transfusion avoidance, and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores.
RESULTS
Our study included a total of 27 studies, comprising 5 randomized controlled trials and 11 single-arm trials, with a total of 912 patients with PNH. We stratified the studies according to treatment duration, based on the most frequently reported period of 26 weeks. Our analysis showed that treatment-naïve patients who received complement inhibitors had a pooled estimate of a decrease in LDH levels from baseline by -1462.0 U/L (95% CI: -1735.6 to -1188.5) for treatment ⩽26 weeks and -1696.5 U/L (95% CI: -2122.7 to -1270.2) for treatment >26 weeks. The mean Hb levels were increased by 1.4 g/dL (95% CI: 0.5-2.3) and 1.9 g/dL (95% CI: 0.7-3.1) in each group. Treatment with any complement inhibitor prevented the need for transfusion in at least 50% of patients with PNH in all treatment periods. Clinically meaningful improvements in FACIT-F were observed both before and after 26 weeks, with a pooled estimate of 6.8 (95% CI: 6.0-7.6) and 9.5 (95% CI: 7.0-12.0), respectively.
CONCLUSION
Our findings suggest that complement inhibitors can result in positive treatment outcomes and sustained benefits for patients with PNH.
PubMed: 38105771
DOI: 10.1177/20406207231216080 -
Journal of Cancer Research and Clinical... Dec 2023Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint inhibitors (ICIs) have attracted substantial attention in clinical research. However, this treatment modality has benefitted only a limited number of patients. We conducted a meta-analysis of various biomarkers to decipher their prognostic implications in patients with head and neck squamous cell carcinoma (HNSCC) who are treated with ICIs, and thus identify predictive markers with practical clinical relevance.
METHODS
A systematic search of electronic databases was conducted to identify clinical studies that examined the correlation between biomarkers and treatment outcomes in the HNSCC patients. The included articles were screened and analyzed to extract data regarding overall survival (OS) and progression-free survival (PFS).
RESULTS
The relationship between the biomarkers included in the summary and prognosis was as follows: HPV positivity was associated with improved OS (HR = 0.76, 95% CI = 0.58-1.99), PFS (HR = 1.16, 95% CI = 0.81-1.67), and response (OR = 1.67, 95% CI = 1.37-2.99). PD-L1 positivity was associated with OS (HR = 0.71, 95% CI = 0.59-0.85), PFS (HR = 0.56 95% CI = 0.43-0.73), and response (OR = 2.16, 95% CI = 1.51-3.10). Neither HPV positivity nor PD-L1 positivity was associated with DCR. The following markers were collected for OS and PFS data and were associated with longer OS: lower Glasgow prognostic score (GPS/mGPS) grading, lower PS grading, high body mass index (BMI), low neutrophil-to-lymphocyte ratio (NLR), low platelet-to-lymphocyte ratio (PLR), high albumin (Alb), low lactate dehydrogenase (LDH). Factors associated with better PFS were lower GPS/mGPS grading, lower PS grading, high BMI, low NLR, high absolute lymphocyte count, and low LDH. Hyperprogressive disease was associated with worse OS and PFS. Fewer clinical studies have been completed on the tumor microenvironment and hypoxia, microsatellite instability/DNA mismatch repair, and microbiome and systematic analysis is difficult.
CONCLUSION
In our meta-analysis, different immune checkpoint factors were associated with different prognoses in HNSCC patients receiving immunotherapy. HPV, PD-L1, BMI, Alb, HPD, PS, GPS/mGPS, LDH, NLR, and PLR predicted the ICI outcome in HNSCC patients.
Topics: Humans; Prognosis; Immune Checkpoint Inhibitors; B7-H1 Antigen; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Biomarkers; Tumor Microenvironment
PubMed: 38078963
DOI: 10.1007/s00432-023-05504-5 -
Journal of Oral Biology and... 2023Tobacco and smoke associated with tobacco comprises of a mixture of more than 9500 chemical compounds, most of which have been identified as harmful. Two of the most... (Review)
Review
OBJECTIVES
Tobacco and smoke associated with tobacco comprises of a mixture of more than 9500 chemical compounds, most of which have been identified as harmful. Two of the most potent carcinogens found in cigarette smoke are N'-nitrosonornicotine (NNN) and polycyclic aromatic hydrocarbons (PAHs). The most commonly used method to detect and monitor nicotine addiction is via serum cotinine levels. Though considered the gold standard, there is a decline in preventive screening and diagnostic testing due to the fear of pain from invasive testing.
DATA SOURCES AND STUDY SELECTION
A structured literature search was performed using the search engines PubMed and Google scholar following the PRISMA guidelines for systematic reviews. The titles and abstracts were retrieved and analysed, followed by full-text relevant data extraction in addition to a risk-of-bias analysis.
DATA EXTRACTION AND SYNTHESIS
A total of 37 studies were included in the systematic review. Salivary cotinine levels were compared between smokers and non-smokers, cigarette smokers and water pipe smokers, water pipe smokers and non-smokers. Lactate dehydrogenase salivary levels were compared between smokers and non-smokers, and salivary thiocyanate were compared between smokers and non-smokers.
CONCLUSIONS
Identifying biomarkers with high performance in terms of sensitivity and specificity will contribute to accelerating future research in this domain.
PubMed: 38028231
DOI: 10.1016/j.jobcr.2023.10.003 -
International Journal of Environmental... Nov 2023High-intensity interval training (HIIT) is considered an effective method to improve fitness and health indicators, but its high-intensity exercises and the mechanical... (Review)
Review
High-intensity interval training (HIIT) is considered an effective method to improve fitness and health indicators, but its high-intensity exercises and the mechanical and metabolic stress generated during the session can lead to the occurrence of exercise-induced muscle damage. Therefore, this study aimed to describe, by means of a systematic review, the effects of a single HIIT session on exercise-induced muscle damage. A total of 43 studies were found in the Medline/PubMed Science Direct/Embase/Scielo/CINAHL/LILACS databases; however, after applying the exclusion criteria, only 15 articles were considered eligible for this review. The total sample was 315 participants. Among them, 77.2% were men, 13.3% were women and 9.5 uninformed. Their age ranged from 20.1 ± 2 to 47.8 ± 7.5 years. HIIT protocols included running with ergometers (n = 6), CrossFit-specific exercises (n = 2), running without ergometers (n = 3), swimming (n = 1), the Wingate test on stationary bicycles (n = 2), and cycling (n = 1). The most applied intensity controls were %vVOmax, "all out", MV, MAV, Vmax, and HRreserve%. The most used markers to evaluate muscle damage were creatine kinase, myoglobin, and lactate dehydrogenase. The time for muscle damage assessment ranged from immediately post exercise to seven days. HIIT protocols were able to promote changes in markers of exercise-induced muscle damage, evidenced by increases in CK, Mb, LDH, AST, ALT, pain, and muscle circumference observed mainly immediately and 24 h after the HIIT session.
Topics: Male; Humans; Female; Exercise; Running; Exercise Therapy; High-Intensity Interval Training; Muscles
PubMed: 37998313
DOI: 10.3390/ijerph20227082