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Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Nutrients Jun 2024Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive years. The disease's multifactorial etiology involves genetic, environmental, and hormonal components. Recent studies have highlighted the potential impact of dietary factors, particularly unsaturated fatty acids, on the modulation of SLE due to their anti-inflammatory properties. This meta-analysis aims to evaluate the association between unsaturated fatty acid consumption and the risk, progression, and clinical manifestations of SLE, providing evidence-based guidance for dietary management.
METHODS
We conducted a comprehensive search across major medical databases up to January 2024, focusing on studies that examined the intake of unsaturated fatty acids and the impact of such intake on SLE. Using the PICOS (population, intervention, comparator, outcomes, study design) framework, we included randomized controlled trials and case-control studies, assessing outcomes such as SLE activity, measured by SLE Disease Activity Index (SLEDAI) or the British Isles Lupus Assessment Group (BILAG) index, inflammation biomarkers. Studies were analyzed using either a fixed- or random-effects model based on heterogeneity ( statistic), with sensitivity analyses performed to assess the robustness of the findings.
RESULTS
Our search included 10 studies, encompassing a wide variety of designs and populations. The meta-analysis showed that a diet rich in unsaturated fatty acids is significantly associated with a reduction in SLEDAI scores (pooled SMD) of -0.36, 95% CI: -0.61 to -0.11, = 0.007, indicating a beneficial effect on disease activity. Additionally, we found that unsaturated fatty acid intake has a significant impact on HDL levels, suggesting a positive effect on lipid profiles. However, no significant effects were observed on levels of the inflammatory marker IL-6 or other lipid components (LDL and cholesterol). With minimal heterogeneity among studies ( ≤ 15%), sensitivity analysis confirmed the stability and reliability of these results, highlighting the potential role of unsaturated fatty acids in SLE management.
CONCLUSIONS
This meta-analysis suggests that dietary intake of unsaturated fatty acids may play a positive role in reducing SLE activity and may significantly affect HDL levels without having significant effects on inflammation markers or other lipid profiles. These findings support the inclusion of unsaturated fatty acids in the dietary management of SLE patients, although further research is required to refine dietary recommendations and explore the mechanisms underlying these associations.
Topics: Lupus Erythematosus, Systemic; Humans; Fatty Acids, Unsaturated; Female; Diet; Male; Biomarkers; Adult
PubMed: 38931327
DOI: 10.3390/nu16121974 -
Life (Basel, Switzerland) Jun 2024Stress is recognized as a significant trigger and exacerbator of various medical conditions, particularly in the field of cardiovascular disease (CVD). Given that heart... (Review)
Review
Stress is recognized as a significant trigger and exacerbator of various medical conditions, particularly in the field of cardiovascular disease (CVD). Given that heart rate variability (HRV) offers insight into the functioning of the autonomic nervous system and has been identified as a predictive factor for increased cardiovascular mortality, exploring the correlation between stress and HRV is pertinent. We systematically reviewed trials where researchers investigated the effects of stress-reducing interventions on biomarkers and time-domain/frequency-domain parameters of HRV in CVD. Eligible studies underwent meta-analysis utilizing a random-effects model. The meta-analysis showed overall beneficial effects of stress-reducing interventions on HRV for the standard deviation of Normal-to-Normal intervals (SDNN) in short-term and 24 h assessments, as well as for the low-frequency power (LF) in short-term assessment. Overall effect sizes were notably high and showed significant -values (short-term SDNN: MD = 6.43, = 0.01; 24 h SDNN: MD = 10.92, = 0.004; short-term LF: MD = 160.11, < 0.001). Our findings highlight the significant impact of stress-reducing interventions in modulating HRV by influencing short-term SDNN and LF parameters, as well as the 24 h assessment of SDNN. These results emphasize the importance of stress-reducing measures in lowering the risk of further progression in CVD and improving patient outcomes.
PubMed: 38929732
DOI: 10.3390/life14060749 -
Life (Basel, Switzerland) May 2024Breast cancer is the most frequently diagnosed cancer in women worldwide. According to recent studies, alterations in the microbiota and epigenetic modulations are risk... (Review)
Review
Breast cancer is the most frequently diagnosed cancer in women worldwide. According to recent studies, alterations in the microbiota and epigenetic modulations are risk factors for this disease. This systematic review aims to determine the possible associations between the intestinal and mammary microbial populations, epigenetic modifications, and breast cancer. To achieve this objective, we conducted a literature search in the PubMed, Web of Science, and Science Direct databases following the PRISMA guidelines. Although no results are yet available in humans, studies in mice suggest a protective effect of maternal dietary interventions with bioactive compounds on the development of breast tumors in offspring. These dietary interventions also modified the gut microbiota, increasing the relative abundance of short-chain fatty acid-producing taxa and preventing mammary carcinogenesis. In addition, short-chain fatty acids produced by the microbiota act as epigenetic modulators. Furthermore, some authors indicate that stress alters the gut microbiota, promoting breast tumor growth through epigenetic and gene expression changes in the breast tumor microenvironment. Taken together, these findings show the ability of epigenetic modifications and alterations of the microbiota associated with environmental factors to modulate the development, aggressiveness, and progression of breast cancer.
PubMed: 38929688
DOI: 10.3390/life14060705 -
Medicina (Kaunas, Lithuania) May 2024: Multiple sclerosis (MS) is a chronic neurodegenerative disease often linked with systemic conditions such as periodontal diseases (PDs). This systematic review aims to... (Review)
Review
: Multiple sclerosis (MS) is a chronic neurodegenerative disease often linked with systemic conditions such as periodontal diseases (PDs). This systematic review aims to explore the association between inflammatory markers in saliva and PDs in MS patients, assessing the use of saliva as a non-invasive tool to monitor disease progression. : 82 publications were examined after a thorough search of scholarly databases to determine whether inflammatory markers were present in MS patients and whether they were associated with periodontal disease (PD). Quality and bias were assessed using the Newcastle-Ottawa Scale, resulting in eight articles that were thoroughly analyzed. : The results point to a strong correlation between MS and periodontal disorders, which may point to the same pathophysiological mechanism. It does, however, underscore the necessity of additional study to determine a definitive causal association. : The findings indicate a strong association between MS and PDs, likely mediated by systemic inflammatory responses detectable in saliva. The review highlights the importance of oral health in managing MS and supports the utility of saliva as a practical, non-invasive medium for monitoring systemic inflammation. Further research is necessary to confirm the causal relationships and to consider integrating salivary diagnostics into routine clinical management for MS patients.
Topics: Humans; Saliva; Multiple Sclerosis; Periodontal Diseases; Biomarkers; Inflammation
PubMed: 38929476
DOI: 10.3390/medicina60060859 -
International Journal of Molecular... Jun 2024Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim... (Review)
Review
Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim of this systematic review is to investigate the therapeutic potential of fluoxetine in cognitive decline in AD, focusing on its anti-degenerative mechanisms of action and clinical implications. According to PRISMA, we searched MEDLINE, up to 1 April 2024, for animal and human studies examining the efficacy of fluoxetine with regard to the recovery of cognitive function in AD. Methodological quality was evaluated using the ARRIVE tool for animal AD studies and the Cochrane tool for clinical trials. In total, 22 studies were analyzed (19 animal AD studies and 3 clinical studies). Fluoxetine promoted neurogenesis and enhanced synaptic plasticity in preclinical models of AD, through a decrease in Aβ pathology and increase in BDNF, by activating diverse pathways (such as the DAF-16-mediated, TGF-beta1, ILK-AKT-GSK3beta, and CREB/p-CREB/BDNF). In addition, fluoxetine has anti-inflammatory properties/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome. Only three clinical studies showed that fluoxetine ameliorated the cognitive performance of people with AD; however, several methodological issues limited the generalizability of these results. Overall, the high-quality preclinical evidence suggests that fluoxetine may have neuroprotective, antioxidant, and anti-inflammatory effects in AD animal models. While more high-quality clinical research is needed to fully understand the mechanisms underlying these effects, fluoxetine is a promising potential treatment for AD patients. If future clinical trials confirm its anti-degenerative and neuroprotective effects, fluoxetine could offer a new therapeutic approach for slowing down the progression of AD.
Topics: Fluoxetine; Alzheimer Disease; Humans; Animals; Cognitive Dysfunction; Disease Models, Animal; Neurogenesis; Neuronal Plasticity
PubMed: 38928248
DOI: 10.3390/ijms25126542 -
International Journal of Molecular... Jun 2024Coronary artery disease (CAD) and hypertension significantly contribute to cardiovascular morbidity and mortality. MicroRNAs (miRNAs) have recently emerged as promising... (Review)
Review
Coronary artery disease (CAD) and hypertension significantly contribute to cardiovascular morbidity and mortality. MicroRNAs (miRNAs) have recently emerged as promising biomarkers and therapeutic targets for these conditions. This systematic review conducts a thorough analysis of the literature, with a specific focus on investigating miRNA expression patterns in patients with CAD and hypertension. This review encompasses an unspecified number of eligible studies that employed a variety of patient demographics and research methodologies, resulting in diverse miRNA expression profiles. This review highlights the complex involvement of miRNAs in CAD and hypertension and the potential for advances in diagnostic and therapeutic strategies. Future research endeavors are imperative to validate these findings and elucidate the precise roles of miRNAs in disease progression, offering promising avenues for innovative diagnostic tools and targeted interventions.
Topics: Humans; Coronary Artery Disease; MicroRNAs; Hypertension; Biomarkers; Gene Expression Regulation
PubMed: 38928136
DOI: 10.3390/ijms25126430 -
Biomedicines Jun 2024The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of... (Review)
Review
BACKGROUND AND OBJECTIVES
The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of atezolizumab, examining its impact on survival outcomes, response rates, and safety measured by serious adverse events (SAEs).
MATERIALS AND METHODS
A literature search was conducted using PubMed, Scopus, and Web of Science, focusing on articles published up to February 2024. The review followed the PRISMA guidelines and synthesized outcomes from four randomized trial studies involving atezolizumab administered at 1200 mg IV every three weeks, alone or in combination with chemoradiotherapy.
RESULTS
A total of 284 patients received atezolizumab, the majority being advanced stage cervical cancer (IVA-IVB). Median follow-up times ranged from 9 weeks to 32.9 months. It was found that combining atezolizumab with standard therapies extended median progression-free survival (PFS) from 10.4 to 13.7 months and overall survival (OS) from 22.8 to 32.1 months, according to the phase III trial. Monotherapy and initial treatment settings with atezolizumab also showed promising efficacy, with disease-free survival rates at 24 months reaching 79% compared to 52% with standard therapy alone. However, the treatment was associated with high rates of SAEs, reaching up to 79% in more intensive treatment combinations.
CONCLUSIONS
Atezolizumab demonstrates significant potential in improving PFS and OS in patients with cervical cancer, supporting its inclusion as a first-line treatment option. Despite the efficacy benefits, the high incidence of SAEs necessitates careful patient selection and management strategies to mitigate risks. This systematic review supports the continued evaluation of atezolizumab in broader clinical trials to refine its therapeutic profile and safety measures in the context of cervical cancer treatment.
PubMed: 38927498
DOI: 10.3390/biomedicines12061291 -
Neuropsychopharmacology Reports Jun 2024Alzheimer's disease (AD) is the most common cause of dementia worldwide. Omega-3 fatty acids (n-3-PUFA) are essential to normal neural development and function.... (Review)
Review
BACKGROUND
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Omega-3 fatty acids (n-3-PUFA) are essential to normal neural development and function. Souvenaid®, a medical supplement that contains n-3-PUFA's: eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA), has emerged as an alternative, slowing cognitive decline in AD patients. In this study, we investigated the effect of dietary supplementation with n-3-PUFA, EPA, DHA, and Souvenaid® in AD patients.
AIM
This systematic review and meta-analysis aim to establish the relationship between n-3-PUFA, EPA, DHA, and Souvenaid® with cognitive effects, ventricular volume and adverse events in AD patients.
METHODS
A systematic search of randomized control trials (RCT), cohorts, and case-control studies was done in PubMed, Scopus, Web of Science, Cochrane, and Embase for AD adult patients with dietary supplementation with n-3-PUFA, EPA, DHA, or Souvenaid® between 2003 and 2024.
RESULTS
We identified 14 studies with 2766 subjects aligned with our criteria. Most publications described positive cognitive outcomes from supplements (58%). The most common adverse events reported were gastrointestinal symptoms. CDR scale showed reduced progression of cognitive decline (SMD = -0.4127, 95% CI: [-0.5926; -0.2327]), without subgroup differences between different dietary supplement interventions. ADCS-ADL, MMSE, ADAS-cog, adverse events, and ventricular volume did not demonstrate significant differences. However, Souvenaid® showed a significant negative effect (SMD = -0.3593, 95% CI: -0.5834 to -0.1352) in ventricular volumes.
CONCLUSIONS
The CDR scale showed reduced progression of cognitive decline among patients with n-3-PUFA supplemental interventions, with no differences between different n-3-PUFA supplements.
PubMed: 38924283
DOI: 10.1002/npr2.12455 -
PloS One 2024Vitamins D, E, A, B, C, and Omega-3 play crucial roles in modulating inflammatory and oxidative stress pathways, both implicated in abdominal aortic aneurysm (AAA)...
BACKGROUND
Vitamins D, E, A, B, C, and Omega-3 play crucial roles in modulating inflammatory and oxidative stress pathways, both implicated in abdominal aortic aneurysm (AAA) development. Recent research has explored the potential impact of dietary supplements on AAA progression. The systematic review aims to assess interventional studies investigating the effects of various dietary supplements on the development and severity of abdominal aortic aneurysms.
METHOD
A systematic search using relevant keywords related to abdominal aortic aneurysm and dietary supplements was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). Quality assessment for animal studies employed SYRCLE and the Cochrane Collaboration Risk of Bias Tool for randomized control trials. The study protocol is registered in PROSPERO under the registry code CRD42023455958.
RESULTS
Supplementation with Omega-3, Vitamins A, C, D, E, and the Vitamin B family exhibited positive effects in AAA progression. These supplements contributed to a reduction in AAA diameter, elastin degradation, inflammatory responses, and reactive oxygen species. Additional supplements such as Zinc, methionine, and phytoestrogen also played roles in mitigating AAA progression.
CONCLUSION
The findings of this study underscore the potential role of dietary supplements in the progression of AAA. Predominantly based on animal studies, the results indicate that these supplements can limit AAA progression, primarily evidenced by their ability to mitigate inflammatory processes and oxidative stress pathways.
Topics: Aortic Aneurysm, Abdominal; Dietary Supplements; Humans; Disease Progression; Animals; Vitamins; Fatty Acids, Omega-3; Oxidative Stress
PubMed: 38923975
DOI: 10.1371/journal.pone.0305265