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JACC. Advances Nov 2023Guideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor...
BACKGROUND
Guideline-recommended low-density lipoprotein cholesterol (LDL-C) thresholds are often not achieved in women. The proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i) monoclonal antibodies can help further reduce LDL-C and major adverse cardiovascular events (MACE) although differences in efficacy by sex and type are less understood.
OBJECTIVES
The authors sought to determine if there are differences in the efficacy of LDL-C lowering and reduction in the risk of MACE by sex and type of PCSK9i.
METHODS
A comprehensive literature search was done through October 17, 2022, for published trials comparing PCSK9i vs control. Outcomes assessed were LDL-C reduction and incidence of MACE following the use of PCSK9i vs placebo, stratified by sex and type of PCSK9i used.
RESULTS
We identified 16 trials with 54,996 adults, and 15,143 (27.5%) of them were female. PCSK9i significantly reduced MACE compared to placebo in both women (HR: 0.86, 95% CI: 0.74-0.97, < 0.001) and men (HR: 0.85, 95% CI: 0.79-0.91, < 0.001) with no significant sex difference (MD -0.01, 95% CI: -0.14 to -0.13, = 0.930). PCSK9i also significantly reduced LDL-C levels in both sexes at 12 weeks (females: MD -62.57, 95% CI: -70.24 to -54.91, < 0.001; males: MD -66.19, 95% CI: -72.03 to -60.34, < 0.001) and 24 weeks (females: MD -47.52, 95% CI: -52.94 to -42.09, < 0.001; males: MD -54.07, 95% CI: -59.46 to -48.68, < 0.001). Significant sex difference was seen in the LDL reduction of PCSK9i for both 12 weeks (males vs females: MD -4.55, 95% CI: -7.34 to -1.75, < 0.01) and 24 weeks (males vs females: MD -7.11, 95% CI: -9.99 to -4.23, < 0.001).
CONCLUSIONS
The use of PCSK9i results in significant LDL-C and MACE reduction in both males and females. While there is no significant sex difference in MACE reduction, LDL-C reduction is greater in males than in females. Our data support the equal use of PCSK9i in all eligible patients, regardless of sex.
PubMed: 38938736
DOI: 10.1016/j.jacadv.2023.100669 -
Neurological Sciences : Official... Jun 2024Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) presents significant treatment challenges due to its chronic nature, varied clinical presentations, and rarity.... (Review)
Review
BACKGROUND
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) presents significant treatment challenges due to its chronic nature, varied clinical presentations, and rarity. Subcutaneous immunoglobulin (SCIG) has emerged as a maintenance therapy, offering potential advantages in administration and patient experience over the previously recognized intravenous immunoglobulin (IVIG).
METHODS
We included all clinical studies involving CIDP patients treated with SCIG from eleven databases up to March 2024.
RESULTS
50 clinical studies were included in the systematic review, with 22 involved in the meta-analysis. These studies offer clinical data on around 1400 CIDP patients. Almost all studies considered SCIG a maintenance therapy, with the majority of results suggesting it as a viable substitute that may offer comparable or enhanced advantages. Studies covered aspects such as efficacy, safety, quality of life, practicality, economic evaluation, and patient preference. Meta-analysis showed SCIG significantly improved muscle strength and sensory function, had fewer and milder side effects, reduced relapse rates, and received a strong preference.
CONCLUSIONS
Findings suggest that SCIG for CIDP maintenance not only provides a more feasible alternative, with economic evaluations showing considerable cost reductions over time, and patient preference for SCIG being pronounced, but may also deliver comparable or superior health outcomes. Ongoing research lines on formulations, techniques, and direct comparative studies are critical to further illuminate, enhance, and expand SCIG's role in treatment.
PubMed: 38937399
DOI: 10.1007/s10072-024-07640-3 -
American Journal of Clinical Oncology Jun 2024Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system...
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system activation and is often triggered by infections such as Epstein-Barr virus (EBV). Rituximab, an anti-CD20 monoclonal antibody, has been suggested as a treatment, particularly for EBV-associated HLH.
METHODS
A systematic review was conducted using PRISMA guidelines, with a literature search spanning PubMed, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria focused on studies that assessed rituximab's efficacy in treating HLH. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports.
RESULTS
Of 783 identified records, 24 studies were included in the final analysis. Rituximab was typically administered at 375 mg/m2, with varying doses and treatment frequency. Clinical response, often seen within 1 month, was assessed by improvements in clinical symptoms and laboratory findings. Survival rates posttreatment displayed a wide range, with instances of complete remission and disease-free periods, as well as reports of relapse and mortality.
CONCLUSION
Rituximab demonstrates the potential for significant clinical benefit in treating HLH, particularly when associated with EBV, showing promise in reducing disease activity and contributing to remission. These findings encourage further research and clinical trials to refine the therapeutic protocols and better understand the long-term effects of rituximab in HLH management.
PubMed: 38934172
DOI: 10.1097/COC.0000000000001119 -
Frontiers in Pharmacology 2024We conducted an overview to assess immune adverse effects associated with the COVID-19 vaccine, guiding safer choices and providing evidence-based information to...
BACKGROUND
We conducted an overview to assess immune adverse effects associated with the COVID-19 vaccine, guiding safer choices and providing evidence-based information to clinicians.
METHODS
Forty-three studies on adverse effects of vaccines were reviewed from PubMed, Embase, and Web of Science. Single-arm meta-analyses estimated summary effects, incidence, presentation, etc. An overview using single-arm meta-analysis and reported the findings following the guidelines outlined in the 'Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) specifically focusing on myocarditis and thrombosis. After screening 2,591 articles, 42 studies met the inclusion criteria. Methodological quality was evaluated using AMSTAR 2. Disagreements were resolved via consensus. Data analysis utilized a random-effects model in R software to estimate incidence rates of selected adverse events.
RESULTS
After removing 1,198 duplicates and screening out irrelevant articles from a total of 2,591, we included 42 studies. Adverse reactions to vaccinations include myocarditis, thrombosis, skin reactions, GBS, etc. thrombosis and myocarditis are the most dangerous diseases associated with vaccination. Myocarditis occurred in 6% of Vector vaccine recipients, compared to 61% of mRNA vaccine recipients. Thrombosis was more common after Vector vaccination (91%) than after mRNA vaccination (9%). Furthermore, eight studies conducted anti-PF4 antibody tests and yielded a positivity rate of 67%. Meta-analysis showed that among all patients with Vaccine-induced Thrombotic Thrombocytopenia, cerebral venous sinus thrombosis occurred in 66%, and intracranial hemorrhage occurred in 43%. The rates of deep vein thrombosis and pulmonary thromboembolism in vaccinated patients were 13% and 23%, respectively, with a pooled case fatality rate of 30%.
CONCLUSION
The results of this overview indicate the majority of adverse reactions are self-limiting and require minimal intervention, while rare occurrences such as myocarditis and thrombosis pose a potentially fatal threat.
PubMed: 38933672
DOI: 10.3389/fphar.2024.1308768 -
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 2024A systematic review with a meta-analysis was performed to gather available evidence on the effectiveness of monoclonal antibody nirsevimab in the prevention of lower... (Review)
Review
A systematic review with a meta-analysis was performed to gather available evidence on the effectiveness of monoclonal antibody nirsevimab in the prevention of lower respiratory tract diseases (LRTDs) due to respiratory syncytial virus (RSV) in children and newborns (CRD42024540669). Studies reporting on real-world experience and randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) until 1 May 2024. Our analysis included five RCTs, seven real-world reports, and one official report from the health authorities. Due to the cross-reporting of RCTs and the inclusion of multiple series in a single study, the meta-analysis was performed on 45,238 infants from 19 series. The meta-analysis documented a pooled immunization efficacy of 88.40% (95% confidence interval (95% CI) from 84.70 to 91.21) on the occurrence of hospital admission due to RSV, with moderate heterogeneity (I 24.3%, 95% CI 0.0 to 56.6). Immunization efficacy decreased with the overall length of the observation time (Spearman's r = -0.546, = 0.016), and the risk of breakthrough infections was substantially greater in studies with observation times ≥150 days compared to studies lasting <150 days (risk ratio 2.170, 95% CI 1.860 to 2.532). However, the effect of observation time in meta-regression analysis was conflicting ( = 0.001, 95% CI -0.001 to 0.002; = 0.092). In conclusion, the delivery of nirsevimab was quite effective in preventing hospital admissions due to LRTDs. However, further analyses of the whole RSV season are required before tailoring specific public health interventions.
PubMed: 38932369
DOI: 10.3390/vaccines12060640 -
Diagnostics (Basel, Switzerland) Jun 2024This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic... (Review)
Review
OBJECTIVE
This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with impacted third molars.
MATERIALS AND METHODS
A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as "dentigerous cysts", "odontogenic keratocysts", "immunohistochemistry", "Ki-67", and "p53" were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing definitive diagnoses or specific signs and symptoms related to DCs and OKCs, with results on protein expression derived from immunohistochemistry, immune antibody, proteomics, or protein expression methods.
RESULTS
Of the 159 studies initially identified, 138 met the inclusion criteria. Our analysis highlighted significantly higher expressions of Ki-67 (22.1% ± 4.7 vs. 10.5% ± 3.2, < 0.001), p53 (15.3% ± 3.6 vs. 5.2% ± 1.9, < 0.001), and Bcl-2 (18.4% ± 3.2 vs. 8.7% ± 2.4, < 0.001) in OKCs compared to DCs, indicating a higher proliferative index, increased cellular stress, and enhanced anti-apoptotic mechanisms in OKCs. Additionally, PCNA levels were higher in OKCs (25.6% ± 4.5 vs. 12.3% ± 3.1, < 0.001). Genetic mutations, particularly in the PTCH1 gene, were frequently observed in OKCs, underscoring their aggressive behavior and potential malignancy.
CONCLUSIONS
The findings emphasize the significant role of immunohistochemical markers in distinguishing between DCs and OKCs, with elevated levels of Ki-67, p53, Bcl-2, and PCNA in OKCs suggesting a higher potential for growth and recurrence. Genetic insights, including PTCH1 mutations, further support the need for personalized treatment approaches. These markers enhance diagnostic accuracy and inform targeted therapeutic strategies, potentially transforming patient management in oral and maxillofacial surgery.
PubMed: 38928661
DOI: 10.3390/diagnostics14121246 -
Scandinavian Journal of Immunology Jun 2024Stress has been associated with less effective vaccine responses in adults. This review aims to investigate the evidence for a similar association in children. A... (Review)
Review
Stress has been associated with less effective vaccine responses in adults. This review aims to investigate the evidence for a similar association in children. A systematic review search was conducted in January 2021 in three databases: Medline, Embase and PsycInfo. An updated search of the Medline database was systematically conducted until the most recent update on September 25th, 2023, to ensure the inclusion of the most current research available. Keywords related to stress, vaccines and children were used, and a total of 7263 (+1528) studies were screened by two independent investigators. Six studies met the inclusion criteria for data extraction and analysis. For quality assessment of the studies, the risk of bias in non-randomized studies-of interventions (ROBINS-I) tool was applied. Most of the studies suggest a negative role of stress on vaccine responses. However, the scarcity of studies, lack of confirmatory studies, risk of bias and heterogeneity according to age, type of vaccine, measures of stress and vaccine responses prevent a clear conclusion. Future studies should emphasize the use of as strict study designs as possible, including well-defined stress metrics and thorough examination of both pre- and post-vaccination responses. Systematic review registration: Prospero CRD42021230490.
PubMed: 38924129
DOI: 10.1111/sji.13394 -
PeerJ 2024To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis.
MATERIALS AND METHODS
Cochrane, PubMed, Embase, and Web of Science databases were comprehensively searched for relevant studies. Stata and RevMan5.4 were applied for meta-analysis and risk of bias assessment. Data on the best-corrected visual acuity (BCVA), central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), participants with ≥1 serious adverse events, and participants with ≥1 adverse events were analyzed.
RESULTS
Six studies were finally included. Meta-analysis showed statistical differences in BCVA [SMD = -0.65, 95% CI [-0.17 to -0.23], < 0.05], the presence of IRF and/or SRF [RR = 0.67, 95% CI [0.56-0.79], < 0.05], and the safety of participants with ≥1 serious adverse events [RR = 0.57, 95% CI [0.39-0.84], < 0.05] between the experimental group and the control group. However, no statistical differences were observed in CSFT [SMD = -1.16, 95% CI [-2.79 to 0.47], > 0.05] or the safety of participants with ≥1 adverse events [RR = 1.07, 95% CI [0.97-1.17], > 0.05].
CONCLUSIONS
Compared to other anti-VEGF drugs such as Aflibercept and Ranibizumab, intravitreal injection of 6 mg Brolucizumab is more effective and safer for n-AMD, especially in the presence of IRF and/or SRF, and for participants with ≥1 serious adverse events.
Topics: Humans; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Intravitreal Injections; Macular Degeneration; Treatment Outcome; Visual Acuity; Wet Macular Degeneration
PubMed: 38915383
DOI: 10.7717/peerj.17561 -
Clinical Epigenetics Jun 2024Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a... (Review)
Review
BACKGROUND
Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.
MAIN BODY
By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions.
CONCLUSION
The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.
Topics: Humans; Gastrointestinal Neoplasms; Epigenesis, Genetic; Major Histocompatibility Complex; Gene Expression Regulation, Neoplastic; Immunotherapy; DNA Methylation; Tumor Escape
PubMed: 38915093
DOI: 10.1186/s13148-024-01698-8