-
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 -
Vaccines Jun 2024As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged,... (Review)
Review
As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged, including new-onset antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV). We systematically reviewed new-onset AAV following COVID-19 vaccination case reports and case series published in three databases before January 2024 following PRISMA guidelines to understand the characteristics of possible causal relationships or coincidences. In total, 404 articles were screened respectively by title, abstracts, and full-texts. Thirty-four papers fulfilled the inclusion criteria and have been analyzed, covering 44 patients with new-onset AAV after COVID-19 vaccination with no prior history of COVID-19 infection. Data regarding patients' metrics, comorbidities, vaccination characteristics, symptoms, diagnostics, treatment, and outcomes were investigated and summarized. The cohort consisted predominantly of females. AAV diagnosis was confirmed via biopsy, with renal dysfunction as a prevailing manifestation. In most cases, the first symptoms of AAV developed after the second dose; moreover, Pfizer-BioNTech was the most frequently administered vaccine among the analyzed cohort. Primary treatment involved glucocorticoid therapy, with a mostly favourable response. This systematic review aims to raise awareness among clinicians in the field regarding this rare but possible complication, to promote the prompt recognition and diagnosis of de novo ANCA-positive small-vessel vasculitis in timely association with SARS-CoV-2 vaccination.
PubMed: 38932385
DOI: 10.3390/vaccines12060656 -
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 -
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 -
European Respiratory Review : An... Apr 2024This review quantifies the mean treatment effect of exercise-based interventions on balance and falls risk in people with COPD. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This review quantifies the mean treatment effect of exercise-based interventions on balance and falls risk in people with COPD.
METHODS
A structured search strategy (2000-2023) was applied to eight databases to identify studies evaluating the impact of exercise-based interventions (≥14 days in duration) on balance or falls in people with COPD. Pooled mean treatment effects (95% confidence intervals (CIs), 95% prediction intervals (PIs)) were calculated for outcomes reported in five or more studies. Inter-individual response variance and the promise of behaviour change techniques (BCTs) were explored.
RESULTS
34 studies (n=1712) were included. There were greater improvements in balance post intervention compared to controls for the Berg Balance Scale (BBS) (mean 2.51, 95% CI 0.22-4.80, 95% PI -4.60-9.63), Timed Up and Go (TUG) test (mean -1.12 s, 95% CI -1.69- -0.55 s, 95% PI -2.78-0.54 s), Single-Leg Stance (SLS) test (mean 3.25 s, 95% CI 2.72-3.77 s, 95% PI 2.64-3.86 s) and Activities-specific Balance Confidence (ABC) scale (mean 8.50%, 95% CI 2.41-14.58%, 95% PI -8.92-25.92%). Effect on falls remains unknown. Treatment effects were larger in male mixed-sex groups for the ABC scale and SLS test, and in balance training other exercise-based interventions for the BBS and TUG test. Falls history was not associated with changes in balance. Meta-analysis of individual response variance was not possible and study-level results were inconclusive. Eleven promising BCTs were identified (promise ratio ≥2).
CONCLUSION
Evidence for the effect of exercise-based interventions eliciting clinically important improvements in balance for people with COPD is weak, but targeted balance training produces the greatest benefits. Future exercise interventions may benefit from inclusion of the identified promising BCTs.
Topics: Humans; Accidental Falls; Postural Balance; Pulmonary Disease, Chronic Obstructive; Exercise Therapy; Male; Treatment Outcome; Female; Aged; Risk Factors; Middle Aged; Recovery of Function; Lung
PubMed: 38925795
DOI: 10.1183/16000617.0003-2024 -
Complementary Therapies in Medicine Jun 2024Oxidative stress and inflammation play critical roles in the pathogenesis of many chronic diseases. Dark chocolate (DC)/cocoa, as a rich source of polyphenols like... (Review)
Review
Effect of dark chocolate/ cocoa consumption on oxidative stress and inflammation in adults: A GRADE-assessed systematic review and dose-response meta-analysis of controlled trials.
BACKGROUND
Oxidative stress and inflammation play critical roles in the pathogenesis of many chronic diseases. Dark chocolate (DC)/cocoa, as a rich source of polyphenols like flavonoids, has anti-inflammatory and antioxidant properties that may confer health benefits, but findings in this context are inconsistent.
OBJECTIVE
This systematic review and dose-response meta-analysis aimed to provide a comprehensive overview of the controlled trials (CTs) that have examined the effects of DC/cocoa on oxidative stress and inflammation biomarkers in adults.
SEARCH METHODS
Databases including PubMed, Web of Science, and Scopus, were searched for relevant studies through April 2024.
SELECTION CRITERIA
Studies assessed C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), nitric oxide (NO), P-selectin, E-selectin and thiobarbituric acid reactive substances (TBARS) in adults were included.
DATA ANALYSIS
Based on the random-effects model, we calculated WMDs, SMDs and 95 % confidence intervals (CIs). Sensitivity, sub-group, meta-regression and dose-response analyses were also conducted.
RESULTS
Thirty-three eligible CTs with 1379 participants were included. All studies reported the intervention types (cocoa powder, beverages and chocolate bars) and dosage. However, sixteen studies didn't do/report testing for purity and potency by independent groups. Also, none of the studies mentioned the risk of contamination with heavy metals. Another limitation was the lack of blinding assessment in studies. DC/cocoa significantly reduced MDA (SMD: -0.69, 95 %CI: -1.17, -0.2, p = 0.005) and increased NO levels (SMD: 2.43, 95 %CI: 1.11,3.75, p < 0.001); However, it has no significant effects on the other outcomes. Greater anti-inflammatory effects occurred at higher flavonoid doses (>450 mg/day) and for shorter durations (≤4 weeks) in the non-healthy participants. Non-linear dose-response relationships between cocoa dosage and CRP level and also between flavonoid dosage and IL-6 level were observed. Based on the GRADE evaluation, just CRP and MDA results were considered as high certainty evidence and the other outcomes results were categorized as very low to moderate certainty.
CONCLUSIONS
DC/cocoa may improve systemic oxidative status and inflammation in adults. However, further studies should be performed to determine its benefits.
PubMed: 38925412
DOI: 10.1016/j.ctim.2024.103061 -
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 -
ESC Heart Failure Jun 2024Biomarkers are paramount for managing heart failure (HF) patients as prognostic and therapeutic efficacy index tools. Systemic levels of brain-derived neurotrophic...
AIMS
Biomarkers are paramount for managing heart failure (HF) patients as prognostic and therapeutic efficacy index tools. Systemic levels of brain-derived neurotrophic factor (BDNF) can add to the HF biomarker scenario, allowing for potentiated efficacy in diagnosis, prognostic stratification, and prediction of patient response to a given therapeutic intervention because BDNF is one of the primary rulers of myocardial function. Yet, whether BDNF is a reliable clinical biomarker awaits clinical validation. Hence, we aimed to answer this relevant question via a systematic review and meta-analysis of existing studies.
METHODS AND RESULTS
International databases, including PubMed, Scopus, Embase, and the Web of Science, were comprehensively searched for studies assessing BDNF levels in patients with HF versus non-HF controls or as a prognostic factor for HF complications. Data were extracted and analysed by random-effect meta-analysis. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were computed to pool the results of studies. We included 11 studies in the final review, among which six underwent meta-analysis. These studies analysed 1420 HF patients, with a mean age of 65.4 ± 11.2 years. Meta-analysis revealed that patients with HF had significantly lower circulating BDNF levels than healthy controls (SMD -2.47, 95% CI -4.39 to -0.54, P-value = 0.01). Moreover, patients with higher New York Heart Association functional classification had lower levels of BDNF. Adverse clinical outcomes such as all-cause mortality and HF rehospitalization were also associated with lower levels of BDNF in individual studies.
CONCLUSIONS
BDNF levels are decreased in patients with HF. Most importantly, we observed an association between lower BDNF levels and poor prognosis in patients with HF. Our study supports BDNF as an easy-to-dose diagnostic and prognostic biomarker to be implemented in clinical practice for HF. Further studies are warranted to address this ability specifically.
PubMed: 38923432
DOI: 10.1002/ehf2.14916 -
Journal of Medical Virology Jun 2024Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high-risk types of human papillomavirus (HPV). HPV viral...
Cervical cancer is the fourth most common cancer in women worldwide and is caused by persistent infection with high-risk types of human papillomavirus (HPV). HPV viral load, the amount of HPV DNA in a sample, has been suggested to correlate with cervical disease severity, and with clinical outcome of cervical cancer. In this systematic review, we searched three databases (EMBASE, PubMed, Web of Science) to examine the current evidence on the association between HPV viral load in cervical samples and disease severity, as well as clinical outcome. After exclusion of articles not on HPV, cervical cancer, or containing clinical outcomes, 85 original studies involving 173 746 women were included. The vast majority (73/85 = 85.9%) reported that a higher viral load was correlated with higher disease severity or worse clinical outcome. Several studies reported either no correlation (3/85 = 3.5%), or the opposite correlation (9/85 = 10.6%); possible reasons being different categorization of HPV viral load levels, or the use of specific sampling methods. Despite variations in study design and populations, the above findings suggest that HPV viral load is correlated to clinical outcome, and may become an important biomarker for treatment selection and response monitoring for cervical cancer.
Topics: Humans; Viral Load; Female; Papillomavirus Infections; Papillomaviridae; Uterine Cervical Neoplasms; Severity of Illness Index; DNA, Viral; Uterine Cervical Diseases; Human Papillomavirus Viruses
PubMed: 38922964
DOI: 10.1002/jmv.29741 -
Combinatorial Chemistry & High... Jun 2024Immune Checkpoint Inhibitors (ICIs) are becoming a new treatment approach for patients with unresectable hepatocellular carcinoma (uHCC). However, the results regarding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Immune Checkpoint Inhibitors (ICIs) are becoming a new treatment approach for patients with unresectable hepatocellular carcinoma (uHCC). However, the results regarding its efficacy compared with the standard regimen of targeted therapy are not consistent.
AIMS
Our aim was to conduct a meta-analysis of existing studies to reveal the differences in the efficacy and safety of the two systems of treatment.
METHODS
The related studies were searched in PubMed, Web of Science, the Cochrane Library, and Embase from inception to June 30th, 2022. Data on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and rate of treatment- related adverse events (TrAEs) with their 95% confidence intervals (CI) were pooled and analyzed by Stata 12.0 software.
RESULTS
A total of ten high-quality controlled clinical studies with 5,539 patients with uHCC were included. The hazard ratio (HR) of the OS and PFS were 0.80 (95% CI, 0.74-0.86) and 0.72 (95% CI, 0.58-0.89), respectively. In addition, the odds ratio (OR) of the ORR and DCR were 3.39 (95% CI, 2.75-4.17) and 1.20 (95% CI, 0.84-1.73), respectively. The ORR of ICIs monotherapy, ICIs plus anti-vascular endothelial growth factor (VEGF) and ICIs plus ICIs were 16% (95% CI, 0.13-0.18), 17% (95% CI, 0.10-0.27), and 20% (95% CI, 0.16-0.24), respectively. For all included studies, the OR of the overall TrAEs was 0.51(95% CI, 0.22-1.18), and grade ≥ 3 TrAEs was 0.78 (95% CI, 0.53-1.14).
CONCLUSION
ICIs were more effective than targeted drugs concerning survival periods and ORR in patients with uHCC while maintaining a stable safety profile.
PubMed: 38920069
DOI: 10.2174/0113862073297462240524064442