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International Journal of Molecular... May 2024Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell)... (Meta-Analysis)
Meta-Analysis Review
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Topics: Multiple Myeloma; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Treatment Outcome; Quality of Life; Neoplasm Recurrence, Local; Cytokine Release Syndrome
PubMed: 38732213
DOI: 10.3390/ijms25094996 -
International Journal of Molecular... Apr 2024Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body... (Review)
Review
Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body temperature, and immune response. In this review, we highlight the relevance of the different mediators that control adipose tissue activity through a systematic review of the main players present in white and brown adipose tissues. Among them, inflammatory mediators secreted by the adipose tissue, such as classical adipokines and more recent ones, elements of the immune system infiltrated into the adipose tissue (certain cell types and interleukins), as well as the role of intestinal microbiota and derived metabolites, have been reviewed. Furthermore, anti-obesity mediators that promote the activation of beige adipose tissue, e.g., myokines, thyroid hormones, amino acids, and both long and micro RNAs, are exhaustively examined. Finally, we also analyze therapeutic strategies based on those mediators that have been described to date. In conclusion, novel regulators of obesity, such as microRNAs or microbiota, are being characterized and are promising tools to treat obesity in the future.
Topics: Humans; Animals; Obesity; Adipose Tissue; Adipokines; MicroRNAs; Gastrointestinal Microbiome; Adipose Tissue, Brown; Adipose Tissue, White; Inflammation Mediators; Energy Metabolism
PubMed: 38731880
DOI: 10.3390/ijms25094659 -
Journal of Clinical Medicine May 2024: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing,... (Review)
Review
: Chordomas pose a challenge in treatment due to their local invasiveness, high recurrence, and potential lethality. Despite being slow-growing and rarely metastasizing, these tumors often resist conventional chemotherapies (CTs) and radiotherapies (RTs), making surgical resection a crucial intervention. However, achieving radical resection for chordomas is seldom possible, presenting therapeutic challenges. The accurate diagnosis of these tumors is vital for their distinct prognoses, yet differentiation is hindered by overlapping radiological and histopathological features. Fortunately, recent molecular and genetic studies, including extracranial location analysis, offer valuable insights for precise diagnosis. This literature review delves into the genetic aberrations and molecular biology of chordomas, aiming to provide an overview of more successful therapeutic strategies. : A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 28 January 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to "chordomas", "molecular biology", "gene aberrations", and "target therapies". The studies included in this review consist of preclinical cell studies, case reports, case series, randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on genetic and biological aberrations in chordomas. : Of the initial 297 articles identified, 40 articles were included in the article. Two tables highlighted clinical studies and ongoing clinical trials, encompassing 18 and 22 studies, respectively. The clinical studies involved 185 patients diagnosed with chordomas. The tumor sites were predominantly sacral ( = 8, 44.4%), followed by clivus ( = 7, 38.9%) and lumbar spine ( = 3, 16.7%). Primary treatments preceding targeted therapies included surgery ( = 10, 55.6%), RT ( = 9, 50.0%), and systemic treatments ( = 7, 38.9%). Various agents targeting specific molecular pathways were analyzed in the studies, such as imatinib (a tyrosine kinase inhibitor), erlotinib, and bevacizumab, which target EGFR/VEGFR. Common adverse events included fatigue (47.1%), skin reactions (32.4%), hypertension (23.5%), diarrhea (17.6%), and thyroid abnormalities (5.9%). Clinical outcomes were systematically assessed based on progression-free survival (PFS), overall survival (OS), and tumor response evaluated using RECIST or CHOI criteria. Notably, stable disease (SD) occurred in 58.1% of cases, and partial responses (PRs) were observed in 28.2% of patients, while 13.7% experienced disease progression (PD) despite targeted therapy. Among the 22 clinical trials included in the analysis, Phase II trials were the most prevalent (40.9%), followed by I-II trials (31.8%) and Phase I trials (27.3%). PD-1 inhibitors were the most frequently utilized, appearing in 50% of the trials, followed by PD-L1 inhibitors (36.4%), CTLA-4 inhibitors (22.7%), and mTOR inhibitors (13.6%). : This systematic review provides an extensive overview of the state of targeted therapy for chordomas, highlighting their potential to stabilize the illness and enhance clinical outcomes.
PubMed: 38731241
DOI: 10.3390/jcm13092711 -
Arthritis Research & Therapy May 2024Targeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Targeted small-molecule drugs in the treatment of systemic lupus erythematosus (SLE) have attracted increasing attention from clinical investigators. However, there is still a lack of evidence on the difference in the efficacy and safety of different targeted small-molecule drugs. Therefore, this study was conducted to assess the efficacy and safety of different targeted small-molecule drugs for SLE.
METHODS
Randomized controlled trials (RCTs) on targeted small-molecule drugs in the treatment of SLE in PubMed, Web of Science, Embase, and Cochrane Library were systematically searched as of April 25, 2023. Risk of bias assessment was performed for included studies using the Cochrane's tool for evaluating the risk of bias. The primary outcome indicators were SRI-4 response, BICLA response, and adverse reaction. Because different doses and courses of treatment were used in the included studies, Bayesian network meta-regression was used to investigate the effect of different doses and courses of treatment on efficacy and safety.
RESULTS
A total of 13 studies were included, involving 3,622 patients and 9 targeted small-molecule drugs. The results of network meta-analysis showed that, in terms of improving SRI-4, Deucravacitinib was significantly superior to that of Baricitinib (RR = 1.32, 95% CI (1.04, 1.68), P < 0.05). Deucravacitinib significantly outperformed the placebo in improving BICLA response (RR = 1.55, 95% CI (1.20, 2.02), P < 0.05). In terms of adverse reactions, targeted small-molecule drugs did not significantly increase the risk of adverse events as compared to placebo (P > 0.05).
CONCLUSION
Based on the evidence obtained in this study, the differences in the efficacy of targeted small-molecule drugs were statistically significant as compared to placebo, but the difference in the safety was not statistically significant. The dose and the course of treatment had little impact on the effect of targeted small-molecule drugs. Deucravacitinib could significantly improve BICLA response and SRI-4 response without significantly increasing the risk of AEs. Therefore, Deucravacitinib is very likely to be the best intervention measure. Due to the small number of included studies, more high-quality clinical evidence is needed to further verify the efficacy and safety of targeted small-molecule drugs for SLE.
Topics: Humans; Lupus Erythematosus, Systemic; Randomized Controlled Trials as Topic; Treatment Outcome; Azetidines; Purines; Molecular Targeted Therapy; Sulfonamides; Pyrazoles
PubMed: 38730460
DOI: 10.1186/s13075-024-03331-8 -
Molecular Biology Reports May 2024Treatment-resistant depression (TRD) is a condition in a subset of depressed patients characterized by resistance to antidepressant medications. The global prevalence of... (Review)
Review
BACKGROUND
Treatment-resistant depression (TRD) is a condition in a subset of depressed patients characterized by resistance to antidepressant medications. The global prevalence of TRD has been steadily increasing, yet significant advancements in its diagnosis and treatment remain elusive despite extensive research efforts. The precise underlying pathogenic mechanisms are still not fully understood. Epigenetic mechanisms play a vital role in a wide range of diseases. In recent years, investigators have increasingly focused on the regulatory roles of miRNAs in the onset and progression of TRD. miRNAs are a class of noncoding RNA molecules that regulate the translation and degradation of their target mRNAs via interaction, making the exploration of their functions in TRD essential for elucidating their pathogenic mechanisms.
METHODS AND RESULTS
A systematic search was conducted in four databases, namely PubMed, Web of Science, Cochrane Library, and Embase, focusing on studies related to treatment-resistant depression and miRNAs. The search was performed using terms individually or in combination, such as "treatment-resistant depression," "medication-resistant depression," and "miRNAs." The selected articles were reviewed and collated, covering the time period from the inception of each database to the end of February 2024. We found that miRNAs play a crucial role in the pathophysiology of TRD through three main aspects: 1) involvement in miRNA-mediated inflammatory responses (including miR-155, miR-345-5p, miR-146a, and miR-146a-5p); 2) influence on 5-HT transport processes (including miR-674,miR-708, and miR-133a); and 3) regulation of synaptic plasticity (including has-miR-335-5p,has-miR- 1292-3p, let-7b, and let-7c). Investigating the differential expression and interactions of these miRNAs could contribute to a deeper understanding of the molecular mechanisms underlying TRD.
CONCLUSIONS
miRNAs might play a pivotal role in the pathogenesis of TRD. Gaining a deeper understanding of the roles and interrelations of miRNAs in TRD will contribute to elucidating disease pathogenesis and potentially provide avenues for the development of novel diagnostic and therapeutic strategies.
Topics: Humans; MicroRNAs; Depressive Disorder, Treatment-Resistant; Antidepressive Agents; Gene Expression Regulation; Epigenesis, Genetic
PubMed: 38727891
DOI: 10.1007/s11033-024-09554-x -
Food Science & Nutrition May 2024Consumption of plum does not yet clearly affect the lipid profile. To ascertain the advantages of plum consumption on adult lipid profiles, we conducted a systematic... (Review)
Review
Consumption of plum does not yet clearly affect the lipid profile. To ascertain the advantages of plum consumption on adult lipid profiles, we conducted a systematic review and meta-analysis. We used pertinent keywords to search the databases of PubMed, Scopus, and ISI Web of Science up to November 10th, 2022, in order to find trials that were eligible. According to the analyses, eating plum significantly lowers LDL levels compared to controls (WMD: -12.50 mg/dL, 95% CI: -22.06, -2.94, = .010). Although plum consumption did not result in significant changes in TG (WMD: 0.56 mg/dL, 95% CI: -6.02, 7.15, = .866), TC (WMD: -12.35 mg/dL, 95% CI: -25.05, 0.37, = .057), and HDL concentrations (WMD: -0.39 mg/dL, 95% CI: -4.69, 3.89, = .855) compared to the control group. Intake of plums, particularly the intervention type of dried plums, significantly decreased TC levels in unhealthy subjects, according to subgroup analysis. The consumption of plums had a notably statistically significant effect on LDL levels when the intervention type was dried plum and unhealthy subjects were enrolled. Due to the very low to moderate quality of meta-evidence, to show how eating plum improves lipid profile, further high-quality research are still essential.
PubMed: 38726435
DOI: 10.1002/fsn3.4000 -
Biological Trace Element Research May 2024The involvement of the immune oxidative stress response in the pathophysiology and pathogenesis of allergic asthma is well documented. However, reports on the role of... (Review)
Review
The involvement of the immune oxidative stress response in the pathophysiology and pathogenesis of allergic asthma is well documented. However, reports on the role of iron homeostasis in allergic asthma is scarce. Therefore, this study aims to identify iron-related genes and proteins in mouse models of allergic asthma. Related articles were identified from SCOPUS and Web of Science databases. The article search was limited to publications in English, within a 10-year period (2014 - 2023, up to 16 August 2023) and original/research papers. All identified articles were screened for eligibility using the inclusion and exclusion criteria. All eligible articles were quality appraised prior to data extraction. Five studies were selected for data extraction. Based on the extracted data, three themes and seven subthemes related to iron homeostasis were identified. The type of samples and analytical methods used were also identified. In conclusion, our study elucidates that iron-related proteins are regulated in animal models of allergic asthma. However, the currently available data do not allow us to conclude whether the disease model resulted in iron accumulation or depletion. Therefore, further studies with other related markers should be conducted.
PubMed: 38717673
DOI: 10.1007/s12011-024-04183-8 -
Current Obesity Reports May 2024The present study aims to review the existing literature to identify pathophysiological proteins in obesity by conducting a systematic review of proteomics studies.... (Review)
Review
PURPOSE OF REVIEW
The present study aims to review the existing literature to identify pathophysiological proteins in obesity by conducting a systematic review of proteomics studies. Proteomics may reveal the mechanisms of obesity development and clarify the links between obesity and related diseases, improving our comprehension of obesity and its clinical implications.
RECENT FINDINGS
Most of the molecular events implicated in obesity development remain incomplete. Proteomics stands as a powerful tool for elucidating the intricate interactions among proteins in the context of obesity. This methodology has the potential to identify proteins involved in pathological processes and to evaluate changes in protein abundance during obesity development, contributing to the identification of early disease predisposition, monitoring the effectiveness of interventions and improving disease management overall. Despite many non-targeted proteomic studies exploring obesity, a comprehensive and up-to-date systematic review of the molecular events implicated in obesity development is lacking. The lack of such a review presents a significant challenge for researchers trying to interpret the existing literature. This systematic review was conducted following the PRISMA guidelines and included sixteen human proteomic studies, each of which delineated proteins exhibiting significant alterations in obesity. A total of 41 proteins were reported to be altered in obesity by at least two or more studies. These proteins were involved in metabolic pathways, oxidative stress responses, inflammatory processes, protein folding, coagulation, as well as structure/cytoskeleton. Many of the identified proteomic biomarkers of obesity have also been reported to be dysregulated in obesity-related disease. Among them, seven proteins, which belong to metabolic pathways (aldehyde dehydrogenase and apolipoprotein A1), the chaperone family (albumin, heat shock protein beta 1, protein disulfide-isomerase A3) and oxidative stress and inflammation proteins (catalase and complement C3), could potentially serve as biomarkers for the progression of obesity and the development of comorbidities, contributing to personalized medicine in the field of obesity. Our systematic review in proteomics represents a substantial step forward in unravelling the complexities of protein alterations associated with obesity. It provides valuable insights into the pathophysiological mechanisms underlying obesity, thereby opening avenues for the discovery of potential biomarkers and the development of personalized medicine in obesity.
PubMed: 38703299
DOI: 10.1007/s13679-024-00561-4 -
Diseases of the Colon and Rectum Jun 2024A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to...
BACKGROUND
A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment.
OBJECTIVE
The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy.
DESIGN
A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI).
SETTING
The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online.
MAIN OUTCOME MEASURES
The main outcome was to reach consensus (80% or more agreement).
RESULTS
The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response.
LIMITATIONS
This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice.
CONCLUSIONS
Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract.
UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO
ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).
Topics: Humans; Rectal Neoplasms; Neoadjuvant Therapy; Delphi Technique; Consensus; Chemoradiotherapy; Treatment Outcome; Diffusion Magnetic Resonance Imaging
PubMed: 38701503
DOI: 10.1097/DCR.0000000000003209 -
Medicine May 2024The application of transarterial chemoembolization (TACE) in combination with targeted therapy and immunotherapy (TACE-T-I) for unresectable hepatocellular carcinoma... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of transarterial chemoembolization combined with targeted therapy and immunotherapy versus with targeted monotherapy in unresectable hepatocellular carcinoma: A systematic review and meta-analysis.
BACKGROUND AND OBJECTIVE
The application of transarterial chemoembolization (TACE) in combination with targeted therapy and immunotherapy (TACE-T-I) for unresectable hepatocellular carcinoma (HCC) has gained increasing attention. However, there are variations in the efficacy and safety outcomes between TACE-T-I versus TACE combined with targeted drugs (TACE-T). This study aims to systematically evaluate the efficacy and safety of TACE-T-I versus TACE-T in unresectable HCC.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 21, 2023, for comparative studies on TACE-T-I versus TACE-T for unresectable HCC. Outcome measures included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and the incidence of treatment-related adverse events (TRAEs). OS was the primary outcome of this study. Weighted mean difference (WMD) or hazard ratio (HR) was used as the pooled statistic for OS and PFS. Relative risk (RR) was employed as the pooled statistic for ORR, DCR and the incidence of TRAEs. And 95% confidence intervals (CIs) were calculated for all effect measures. Data analysis was conducted using Stata 14.0 software.
RESULTS
The meta-analysis included 14 studies with 2144 patients. The pooled results showed that compared with patients in the TACE-T group, patients in the TACE-T-I group had higher ORR (RR = 1.61; 95%CI: 1.38-1.89) and DCR (RR = 1.17; 95%CI: 1.09-1.26). Patients in the TACE-T-I group experienced prolonged PFS (WMD = 3.08; 95%CI: 2.63-3.53) and OS (WMD = 5.76; 95%CI: 4.68-6.84). And the risk of disease progression (HR = 0.45; 95%CI: 0.37-0.55) and death (HR = 0.43; 95%CI: 0.38-0.49) was lower in the TACE-T-I group. Common TRAEs included fever, pain, abdominal pain, nausea, vomiting, elevated ALT, elevated AST, hypertension, hand-foot syndrome, proteinuria, and diarrhea. The incidence and severity of TRAEs in the TACE-T-I group were similar to those in the TACE-T group, with no significant differences (P > .05).
CONCLUSION
Current evidence suggests that, on the basis of TACE combined with targeted therapy, the addition of immunotherapy provides better clinical efficacy and survival benefits for unresectable HCC patients, with good tolerability.
Topics: Humans; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Liver Neoplasms; Immunotherapy; Combined Modality Therapy; Treatment Outcome; Molecular Targeted Therapy
PubMed: 38701263
DOI: 10.1097/MD.0000000000038037