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Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796 -
Photodiagnosis and Photodynamic Therapy Jun 2024Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of... (Review)
Review
BACKGROUND
Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of PPIX, causing photosensitivity and increased liver disease risk. Many also have iron deficiency and anemia. We investigated outcomes of oral iron supplements in individuals with EPP.
METHODS
A systematic review identified literature on oral iron supplements in EPP patients. Subsequently, we administered iron supplements to EPP patients with iron deficiency. The primary outcome was impact on PPIX level. Secondary outcomes were adverse events and relative differences in hemoglobin and iron parameters.
RESULTS
The systematic review found 13 case reports and one uncontrolled clinical trial with uncertain results. From our department 10 patients with EPP and iron deficiency took daily dosages of 330 mg of ferrous fumarate for two months. Five of our patients had anemia at baseline. After 2 months of supplementation seven patients had increased PPIX level compared to baseline, two had decrease, one remained unchanged. The administration of iron led to a rise in ferritin, and in four of the anemic patients also to an improvement in blood hemoglobin. A small transiently elevation in plasma alanine transaminase concentration was observed during supplementation.
CONCLUSIONS
Overall, iron supplementation in EPP patients replenished iron stores and elevated erythrocyte PPIX and plasma alanine transaminase. For anemic patients, there was some degree of normalization of the hemoglobin level. If iron therapy is needed for EPP patients, monitoring of photosensitivity, PPIX, hemoglobin, and plasma liver enzymes is advisable.
Topics: Humans; Protoporphyria, Erythropoietic; Protoporphyrins; Dietary Supplements; Male; Female; Adult; Iron; Anemia, Iron-Deficiency; Middle Aged; Treatment Outcome
PubMed: 38734198
DOI: 10.1016/j.pdpdt.2024.104211 -
Nutrition Reviews May 2024Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This...
CONTEXT
Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This vitamin makes up mitochondrial complexes and participates as an enzymatic cofactor in several mechanisms associated with energy metabolism.
OBJECTIVE
This systematic review collected and discussed the most relevant results on the role of riboflavin in the energy metabolism of lipids, proteins, and carbohydrates.
DATA SOURCES
A systematic search was carried out in the PubMed-Medline, Scopus, Embase, and Web of Science databases using the PICOS (Population, Intervention, Comparison, Outcome, Study design) strategy.
DATA EXTRACTION
The screening of studies went through 2 stages following predefined eligibility criteria. The information extracted covered reference details, study design, population characteristics, experimental model, treatment parameters and dosage, route of administration, duration of treatment, and results found.
DATA ANALYSIS
The risk of bias was assessed using the SYRCLE Risk of Bias (RoB) tool for in vivo studies and the QUIN tool adapted for in vitro studies, utilizing 10 domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases, to evaluate the methodological quality of the included studies.
CONCLUSION
This review concludes that riboflavin regulates energy metabolism by activating primary metabolic pathways and is involved in energy balance homeostasis.
PubMed: 38719205
DOI: 10.1093/nutrit/nuae041 -
Nutrition Reviews Apr 2024Gestational weight gain (GWG) is known to be a risk factor for offspring obesity, a precursor of cardiometabolic diseases. Accumulating studies have investigated the...
CONTEXT
Gestational weight gain (GWG) is known to be a risk factor for offspring obesity, a precursor of cardiometabolic diseases. Accumulating studies have investigated the association of GWG with offspring cardiometabolic risk factors (CRFs), leading to inconsistent results.
OBJECTIVE
This study synthesized available data from cohort studies to examine the effects of GWG on offspring CRFs.
DATA SOURCE
Four electronic databases, including PubMed, Web of Science, Scopus, and Embase, were searched through May 2023.
DATA EXTRACTION
Cohort studies evaluating the association between GWG and CRFs (fat mass [FM], body fat percentage [BF%], waist circumference [WC], systolic blood pressure [SBP] and diastolic blood pressure, high-density-lipoprotein cholesterol [HDL-C] and low-density-lipoprotein cholesterol, triglyceride [TG], total cholesterol, fasting blood glucose, and fasting insulin levels) were included. Regression coefficients, means or mean differences with 95% confidence intervals [CIs], or standard deviations were extracted.
DATA ANALYSIS
Thirty-three cohort studies were included in the meta-analysis. Higher GWG (per increase of 1 kg) was associated with greater offspring FM (0.041 kg; 95% CI, 0.016 to 0.067), BF% (0.145%; 95% CI, 0.116 to 0.174), WC (0.154 cm; 95% CI, 0.036 to 0.272), SBP (0.040 mmHg; 95% CI, 0.010 to 0.070), and TG (0.004 mmol/L; 95% CI, 0.001 to 0.007), and with lower HDL-C (-0.002 mmol/L; 95% CI, -0.004 to 0.000). Consistently, excessive GWG was associated with higher offspring FM, BF%, WC, and insulin, and inadequate GWG was associated with lower BF%, low-density lipoprotein cholesterol, total cholesterol, and TG, compared with adequate GWG. Most associations went non-significant or attenuated with adjustment for offspring body mass index or FM.
CONCLUSIONS
Higher maternal GWG is associated with increased offspring adiposity, SBP, TG, and insulin and decreased HDL-C in offspring, warranting a need to control GWG and to screen for cardiometabolic abnormalities of offspring born to mothers with excessive GWG.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42023412098.
PubMed: 38607346
DOI: 10.1093/nutrit/nuae027 -
Obesity Reviews : An Official Journal... Jul 2024Adipose tissue is the first and primary target organ of obesity and the main source of circulating miRNAs in patients with obesity. This systematic review aimed to... (Review)
Review
Adipose tissue is the first and primary target organ of obesity and the main source of circulating miRNAs in patients with obesity. This systematic review aimed to analyze and summarize the generation and mechanisms of adipose-derived miRNAs and their role as early predictors of various obesity-related complications. Literature searches in the PubMed and Web of Science databases using terms related to miRNAs, obesity, and adipose tissue. Pre-miRNAs from the Human MicroRNA Disease Database, known to regulate obesity-related metabolic disorders, were combined for intersection processing. Validated miRNA targets were sorted through literature review, and enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes via the KOBAS online tool, disease analysis, and miRNA transcription factor prediction using the TransmiR v. 2.0 database were also performed. Thirty miRNAs were identified using both obesity and adipose secretion as criteria. Seventy-nine functionally validated targets associated with 30 comorbidities of these miRNAs were identified, implicating pathways such as autophagy, p53 pathways, and inflammation. The miRNA precursors were analyzed to predict their transcription factors and explore their biosynthesis mechanisms. Our findings offer potential insights into the epigenetic changes related to adipose-driven obesity-related comorbidities.
Topics: Humans; Obesity; MicroRNAs; Computational Biology; Adipose Tissue; Biomarkers
PubMed: 38590187
DOI: 10.1111/obr.13748 -
Critical Reviews in Oncology/hematology May 2024Asparaginase is essential in the initial management of acute lymphoblastic leukemia (ALL) but frequently leads to venous thromboembolism (VTE). Using anticoagulants for... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of the effectiveness of primary thromboprophylaxis in acute lymphoblastic leukemia during early-phase therapy including asparaginase or its prolonged form.
Asparaginase is essential in the initial management of acute lymphoblastic leukemia (ALL) but frequently leads to venous thromboembolism (VTE). Using anticoagulants for primary VTE prevention has been studied with no consensus. We conducted a systematic literature search in PubMed, Scopus, and Web of science and performed random-effect meta-analysis using Mantel-Haenszel method in RevMan 5.4 to analyze primary pharmacological thromboprophylaxis during asparaginase treatment in early-phase (induction, consolidation, or intensification phase) therapy in patients with ALL with all ages and followed with subgroup analysis by age. Meta-analysis of 13 articles describing the effect of antithrombin supplementation in 1375 patients showed that antithrombin prophylaxis decreases the risk of VTE by 43% (RR, 0.57; 95% CI, 0.38 - 0.83; p=0.004), with mild heterogeneity (I=35%, p=0.10) and moderate certainty by GRADE. 8 articles included for meta-analysis of low-molecular weight heparin (LMWH) treatment in 612 patients showed that it decreased the risk of VTE by nearly 40% (RR, 0.61; 95% CI, 0.45 - 0.81; p=0.00081), with minimal heterogeneity (I=14%, p=0.31) but low certainty. Subgroup analysis showed that only prophylaxis with antithrombin supplementation significantly decreased the VTE rate in adult patients with moderate certainty. In pediatric patients, one nonrandomized prospective study showed that LMWH combined with antithrombin has a better thromboprophylaxis effect than antithrombin alone. In the PREVAPIX-ALL trial, prophylaxis with direct factor Xa inhibitor Apixaban did not benefit children younger than 18 years except for cases of obesity. We concluded that thromboprophylaxis with antithrombin is effective in ALL patients older than 18 years during the early phase of therapy, and LMWH combined with antithrombin supplementation might be effective for pediatric patients with ALL. Apixaban is effective in pediatric ALL patients with obesity and needs further study in other high-risk patients.
Topics: Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Asparaginase; Venous Thromboembolism; Anticoagulants; Heparin, Low-Molecular-Weight; Antithrombins
PubMed: 38583546
DOI: 10.1016/j.critrevonc.2024.104347 -
Experimental Brain Research May 2024Alzheimer's disease (AD) represents the most common type of dementia. A crucial mechanism attributed to its development is amyloid beta (Aβ) dynamics dysregulation. The... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's disease (AD) represents the most common type of dementia. A crucial mechanism attributed to its development is amyloid beta (Aβ) dynamics dysregulation. The extent to which exercise can modulate this phenomenon is uncertain. The aim of this study was to summarize the existing literature evaluating this issue. A comprehensive systematic search was performed in Pubmed, Scopus, Embase, Web of Science, and SciELO databases and completed in August 2023, aiming to identify randomized controlled trials investigating the effect of exercise upon Aβ-related pathology. The keywords "exercise" and "amyloid beta", as well as all their equivalents and similar terms, were used. For the analysis, the negative or positive dementia status of the subjects was initially considered and then the soluble amyloid precursor protein (sAPP) components and Aβ fragments separately. A meta-analysis was performed and involved eight studies (moderate-to-high quality) and 644 assessments, which were 297 for control and 347 for exercise. No overall effect favoring exercise interventions was observed for both negative (SMD95%=0,286 [-0,131; 0,704]; p = 0,179) or positive AD dementia status (SMD95%=0,110 [-0,155; 0,375]; p = 0,416). The absence of an overall effect favoring exercise interventions was also found for Aβ peptides (SMD95%=0,226 [-0,028; 0,480]; p = 0,081) and for sAPP components (SMD95%=-0,038 50 [-0,472; 0,396]; p = 0,863) levels. Our findings suggest that exercise interventions do not improve Aβ-related pathology in both healthy individuals and individuals with dementia (SMD95%=0,157 [-0,059; 0,373]; p = 0,155), indicating that the beneficial effects of exercise for AD reported in previous studies are related to other mechanistic effects rather than direct amyloid effects (PROSPERO registration number: CRD42023426912).
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Exercise; Exercise Therapy; Randomized Controlled Trials as Topic
PubMed: 38551691
DOI: 10.1007/s00221-024-06821-y -
Brain Connectivity May 2024The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature...
The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature oligodendrocytes and thus in the adult brain. In multiple sclerosis (MS) this regenerative capability is halted resulting in neurodegeneration. We aimed to systematically search and synthesize evidence on mechanisms and phenomena associated with subventricular zone (SVZ) dysfunction in MS. Our systematic review was reported according to the PRISMA-ScR statement. MEDLINE, SCOPUS, ProQuest, and Google Scholar were searched using the terms "subventricular zone" and "multiple sclerosis," including English-written and postmortem studies. Twenty studies were included. Thirteen studies on models of experimental autoimmune encephalomyelitis (EAE) reported among others strong stathmin immunoreactivity in the SVZ of EAE models, the role of MOG immunization in neurogenesis impairment, the effect of parenchymal OPCs and NSCs in myelin repair, and the importance of ependymal cells (E1/E2) and ciliated B1 cells in SVZ stem cell signaling. CXCR4 signaling and transcriptional profiles of SVZ microglia, Gli1 pathway, and galactin-3 were also explored. Studies in humans demonstrated microstructural SVZ damage in progressive MS and the persistence of black holes near the SVZ, whereas postmortem confirmed the generation of polysialic acid-neural cell adhesion molecule and NG2-positive progenitors through SVZ activation, SVZ stathmin immunoreactivity, Shh pathway, and Gal-3 upregulation. Oligodendrogenesis defects translate to reduced remyelination, a hallmark of MS that determines its end-phenotype and disease course. The role of inflammation and subsequent SVZ microenvironment disruption is evident in MS pathology.
Topics: Animals; Humans; Cell Differentiation; Encephalomyelitis, Autoimmune, Experimental; Lateral Ventricles; Multiple Sclerosis; Neural Stem Cells; Neurogenesis; Oligodendroglia
PubMed: 38534961
DOI: 10.1089/brain.2023.0081 -
Alimentary Pharmacology & Therapeutics May 2024The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting... (Review)
Review
BACKGROUND
The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting colorectal cancer and cancer precursors is limited. There is growing interest in using the non-haemoglobin contents of FIT residual buffer to enhance colonic neoplasia detection.
AIM
To establish from the literature a framework to catalogue candidate biomarkers within FIT residual buffer for non-invasive colorectal cancer screening.
METHODS
The search strategy evaluated PubMed, Scopus, Web of Science, Embase, and Google Scholar for publications through 25 October 2023, with search terms including FIT, buffer, OC-sensor, biomarkers, microbiome, microRNA (miR), colon, rectum, screening, neoplasm, and early detection. Studies employing home-based collection samples using quantitative FIT first processed for haemoglobin were included. One author reviewed all articles; a second author completed a 20% full-text audit to ensure adherence to eligibility criteria.
RESULTS
A broad search yielded 1669 studies and application of eligibility criteria identified 18 relevant studies. Multiple protein, DNA/RNA, and microbiome biomarkers (notably haptoglobin, miR-16, miR-27a-3p, miR-92a, miR-148a-3p, miR-223, miR-421, let-7b-5p, and Tyzzerella 4) were associated with colorectal neoplasia. Furthermore, studies highlighted the short-term stability of biomarkers for clinical use and long-term stability for research purposes.
CONCLUSIONS
This scoping review summarises the framework and progress of research on stability of biomarkers in FIT residual buffer and their associations with colorectal neoplasia to guide opportunities for further confirmatory studies to enhance colorectal cancer screening.
Topics: Humans; Early Detection of Cancer; Colorectal Neoplasms; Rectum; MicroRNAs; Hemoglobins; Occult Blood; Biomarkers; Feces; Mass Screening
PubMed: 38534182
DOI: 10.1111/apt.17947 -
Neurological Sciences : Official... Jul 2024Measles inclusion-body encephalitis (MIBE) is rare, with insights largely from case studies. We systematically analyzed subacute Sclerosing Panencephalitis (SSPE) cases... (Review)
Review
Clinical features, pathogenesis, pathology, neuroimaging, clinical course and outcome of measles inclusion-body encephalitis: a systematic review of published case reports and case series.
Measles inclusion-body encephalitis (MIBE) is rare, with insights largely from case studies. We systematically analyzed subacute Sclerosing Panencephalitis (SSPE) cases in immunocompromised patients, identifying distinctive clinical and neuroimaging features. These findings could facilitate MIBE diagnosis without the need for brain biopsies. Our systematic review on MIBE and HIV-related SSPE adhered to PRISMA guidelines and was registered with PROSPERO. We searched multiple databases and followed a detailed inclusion process with independent reviews and quality assessment. Data on patient demographics, clinical features, and outcomes were compiled. A review of 39 studies on 49 MIBE patients and 8 reports on HIV-positive SSPE patients was conducted. Acute lymphoblastic leukemia, HIV, organ transplants, and malignancies were common precursors to MIBE. Perinatal HIV was prevalent among SSPE cases. Seizures were the primary symptom in MIBE, often drug-resistant and progressing to status epilepticus or epilepsia partialis continua, whereas periodic myoclonus was universal in SSPE. Neuroimaging showed distinct patterns for each group, and histopathology confirmed measles virus presence in 39% of MIBE cases. MIBE patients typically progressed to coma and death. In conclusion, MIBE and SSPE in HIV-infected patients present with distinct clinical pictures but identical brain pathological abnormalities.
Topics: Humans; Subacute Sclerosing Panencephalitis; Neuroimaging; Measles; Brain
PubMed: 38512528
DOI: 10.1007/s10072-024-07480-1