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European Journal of Medical Research Apr 2024Contrast-induced nephropathy (CIN) is a form of acute kidney injury (AKI) occurring in patients undergoing cardiac catheterization, such as coronary angiography (CAG) or... (Review)
Review
BACKGROUND
Contrast-induced nephropathy (CIN) is a form of acute kidney injury (AKI) occurring in patients undergoing cardiac catheterization, such as coronary angiography (CAG) or percutaneous coronary intervention (PCI). Although the conventional criterion for CIN detection involves a rise in creatinine levels within 72 h after contrast media injection, several limitations exist in this definition. Up to now, various meta-analyses have been undertaken to assess the accuracy of different biomarkers of CIN prediction. However, the existing body of research lacks a cohesive overview. To address this gap, a comprehensive umbrella review was necessary to consolidate and summarize the outcomes of prior meta-analyses. This umbrella study aimed to offer a current, evidence-based understanding of the prognostic value of biomarkers in predicting CIN.
METHODS
A systematic search of international databases, including PubMed, Scopus, and Web of Science, from inception to December 12, 2023, was conducted to identify meta-analyses assessing biomarkers for CIN prediction. Our own meta-analysis was performed by extracting data from the included studies. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were assessed using Meta-Disc and CMA softwares.
RESULTS
Twelve studies were ultimately included in the umbrella review. The results revealed that neutrophil gelatinase-associated lipocalin (NGAL) exhibited the highest area under the curve (AUC), followed by cystatin-C, urinary kidney injury molecule-1 (uKIM-1), and brain natriuretic peptide (BNP) with AUCs of 0.91, 0.89, 0.85, and 0.80, respectively. NGAL also demonstrated the highest positive likelihood ratio [effect size (ES): 6.02, 95% CI 3.86-9.40], followed by cystatin-C, uKIM-1, and BNP [ES: 4.35 (95% CI 2.85-6.65), 3.58 (95% CI 2.75-4.66), and 2.85 (95% CI 2.13-3.82), respectively]. uKIM-1 and cystatin-C had the lowest negative likelihood ratio, followed by NGAL and BNP [ES: 0.25 (95% CI 0.17-0.37), ES: 0.25 (95% CI 0.13-0.50), ES: 0.26 (95% CI 0.17-0.41), and ES: 0.39 (0.28-0.53) respectively]. NGAL emerged as the biomarker with the highest diagnostic odds ratio for CIN, followed by cystatin-C, uKIM-1, BNP, gamma-glutamyl transferase, hypoalbuminemia, contrast media volume to creatinine clearance ratio, preprocedural hyperglycemia, red cell distribution width (RDW), hyperuricemia, neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), high-sensitivity CRP, and low hematocrit (P < 0.05).
CONCLUSION
NGAL demonstrated superior diagnostic performance, exhibiting the highest AUC, positive likelihood ratio, and diagnostic odds ratio among biomarkers for CIN, followed by cystatin-C, and uKIM-1. These findings underscore the potential clinical utility of NGAL, cystatin-C and uKIM-1 in predicting and assessing CIN.
Topics: Humans; Acute Kidney Injury; Biomarkers; Contrast Media; Coronary Angiography; Creatinine; Lipocalin-2; Percutaneous Coronary Intervention; Meta-Analysis as Topic
PubMed: 38561791
DOI: 10.1186/s40001-024-01782-y -
International Journal of Molecular... Jun 2023Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to... (Review)
Review
Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF/MEK/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K/AKT/mTOR and RAF/MEK/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012-2023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K/AKT/mTOR pathway, and 7 to the RAF/MEK/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF/MEK/ERK and PI3K/AKT/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.
Topics: Humans; MAP Kinase Signaling System; Proto-Oncogene Proteins c-akt; Pituitary Neoplasms; Phosphatidylinositol 3-Kinases; TOR Serine-Threonine Kinases; Mitogen-Activated Protein Kinase Kinases; Carcinogenesis
PubMed: 37446128
DOI: 10.3390/ijms241310952 -
Breast Cancer Research and Treatment Apr 2024The cyclin-dependent kinase (CDK) 4/6 inhibitors significantly altered the treatment landscape of hormone-positive (HR+), HER2- metastatic breast cancer (MBC). However,... (Meta-Analysis)
Meta-Analysis Review
The association between HER2-low status and survival in patients with metastatic breast cancer treated with Cyclin-dependent kinases 4 and 6 inhibitors: a systematic review and meta-analysis.
PURPOSE
The cyclin-dependent kinase (CDK) 4/6 inhibitors significantly altered the treatment landscape of hormone-positive (HR+), HER2- metastatic breast cancer (MBC). However, biomarkers predicting long-term benefit and early progression are yet to be defined. Several studies suggested the possibility of diminished efficacy in patients with HER2-low disease. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between low-level HER2 expression and efficacy outcomes (PFS, OS, ORR) with CDK 4/6 inhibitors.
METHODS
The Pubmed, Web of Science, and Scopus databases were used to systematically filter the published studies from inception to 08 August 2023 for this systemic review. Studies including MBC patients treated with CDK 4/6 inhibitors and reported survival outcomes according to HER2 expression were included. We performed the meta-analyses with the generic inverse-variance method with a fixed-effects model and used HRs with 95% two-sided CIs as the principal summary measure.
RESULTS
Nine studies encompassing 2705 patients were included in the analyses. In the pooled analysis of nine studies, the risk of progression and/or death was higher in patients with HER2-low tumors compared to HER2-zero (HR: 1.22, 95% CI 1.10-1.35, p < 0.001). In the pooled analysis of five studies, although the median follow-up was short, the risk of death was higher in the HER2-low group compared to the HER2-zero group (HR: 1.22, 95% CI 1.04-1.44, p = 0.010).
CONCLUSION
The available evidence demonstrates a significantly higher risk of progression or death with CDK 4/6 inhibitors in HER2-low tumors. Further research is needed to improve outcomes in patients with HR+-HER2-low tumors.
Topics: Humans; Female; Breast Neoplasms; Receptor, ErbB-2; Protein Kinase Inhibitors; Cyclin-Dependent Kinase 4; Cyclins; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38240935
DOI: 10.1007/s10549-023-07226-1 -
Journal of Cancer Research and Clinical... Jan 2024The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive... (Meta-Analysis)
Meta-Analysis
PURPOSE
The numerous first-line treatment regimens for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) necessitate a comprehensive evaluation to inform clinical decision-making. We conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions.
METHODS
We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts from inception to June 1, 2023. NMA was performed to calculate and analyze progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events of grade 3 or higher (≥ 3 AEs).
RESULTS
Out of the 10,313 manuscripts retrieved, we included 28 RCTs involving 11,680 patients. Regarding PFS and ORR, the combination of trastuzumab with tyrosine kinase inhibitors (TKIs) was more favorable than dual-targeted therapy. If only using trastuzumab, combination chemotherapy is superior to monochemotherapy in terms of PFS. It is important to note that the addition of anthracycline did not result in improved PFS. For patients with hormone receptor-positive HER2-positive diseases, dual-targeted combined with endocrine therapy showed better benefit in terms of PFS compared to dual-targeted alone, but it did not reach statistical significance. The comprehensive analysis of PFS and ≥ 3 AEs indicates that monochemotherapy combined with dual-targeted therapy still has the optimal balance between efficacy and safety.
CONCLUSION
Monochemotherapy (Docetaxel) plus dual-target (Trastuzumab and Pertuzumab) therapy remains the optimal choice among all first-line treatment options for ABC. The combination of trastuzumab with TKIs (Pyrotinib) demonstrated a significant improvement in PFS and ORR, but further data are warranted to confirm the survival benefit.
Topics: Humans; Female; Network Meta-Analysis; Randomized Controlled Trials as Topic; Breast Neoplasms; Trastuzumab; Receptor, ErbB-2; Docetaxel; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38244085
DOI: 10.1007/s00432-023-05530-3 -
Medicine Nov 2023This study aimed to conduct a comparative analysis of the efficacy and safety of neoadjuvant chemotherapy combined with endocrine therapy against the backdrop of single... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to conduct a comparative analysis of the efficacy and safety of neoadjuvant chemotherapy combined with endocrine therapy against the backdrop of single neoadjuvant chemotherapy or endocrine therapy, specifically in the context of hormone receptor-positive (HR+) breast cancer treatment.
METHODS
We conducted a thorough literature search across several databases, including China National Knowledge Infrastructure, Wanfang, Weipu, Chinese Journal Full-text Database, PubMed, Web of Science, Cochrane Library, and EMBASE, adhering to the guidelines outlined in the PRISMA statement. Our specific focus was on identifying randomized controlled trials that directly compared the combined approach of neoadjuvant chemotherapy and endocrine therapy with single chemotherapy or endocrine therapy in the context of treating HR+ breast cancer. Subsequently, we utilized statistical packages implemented in R software to perform comparative analyses of key clinical indicators, encompassing the complete response, objective response rate (ORR), disease control rate, pathological complete response (pCR), and adverse reactions.
RESULTS
A total of 11 randomized controlled trials, involving 1359 patients, all of whom met our inclusion criteria and were thus included in our comprehensive analysis. Within this cohort, 688 patients (50.63%) administered neoadjuvant chemotherapy combined with endocrine therapy (NCET), 642 patients (47.24%) received neoadjuvant chemotherapy (NCT) alone, while 29 patients (2.13%) underwent neoadjuvant endocrine therapy (NET) alone. The results of our meta-analysis revealed that NCET exhibited a statistically significant enhancement in both ORR and pCR (P < .05). Nonetheless, when compared to NCT or NET, NCET did not yield a significant impact on complete response, disease control rate, and safety (P > .05). In addition, NCET demonstrated a significant improvement in ORR among patients with HR+, HER2-negative breast cancer (P < .05). However, it was also linked to a heightened incidence of serious adverse reactions within this particular patient subgroup (P < .05).
CONCLUSION
The combination of Neoadjuvant chemotherapy and endocrine therapy stands out as a significant contributor to enhancing the ORR and pCR for HR+ breast cancer patients. For breast cancer patients with HER2- status, NCET demonstrates a remarkable improvement in ORR but is also associated with the emergence of adverse reactions.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; China
PubMed: 37986364
DOI: 10.1097/MD.0000000000035928 -
Ecotoxicology and Environmental Safety Oct 2023Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry....
Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.
Topics: Animals; Rats; Kidney; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Podophyllotoxin; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Podophyllum; Drugs, Chinese Herbal
PubMed: 37651795
DOI: 10.1016/j.ecoenv.2023.115392 -
Journal of Immunotherapy (Hagerstown,... May 2024The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the...
Clinical Outcomes of PD-1/PD-L1 Inhibitors Among Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With BRAF, ERBB2/HER2, MET , or RET Alterations: A Systematic Literature Review.
The therapeutic landscape for patients with advanced or metastatic non-small cell lung cancer (NSCLC) is rapidly evolving due to advances in molecular testing and the development of new targeted therapies and immunotherapies. However, the efficacy of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in advanced or metastatic patients with NSCLC whose tumors harbor BRAF V600E mutation, HER2/ERBB2 alteration, MET exon 14 skipping mutation, or RET rearrangement is not completely understood. A systematic literature review was performed to summarize evidence from clinical trials and observational studies on objective response rate, progression-free survival, and overall survival in patients whose tumors express these biomarkers and who were treated with PD-1/PD-L1 inhibitors. Searches of Embase, MEDLINE, conference abstracts, and a clinical trial registry identified a total of 12 unique studies: 4 studies included patients with BRAF V600E mutation, 6 studies included patients with HER2/ERBB2 alteration, 7 studies included patients with MET exon 14 skipping mutation, and 5 studies included patients with RET rearrangement. Across studies, there was heterogeneity in treatment and patient characteristics and a lack of reporting on many important predictive and prognostic factors, including treatment regimens, patients' line of therapy, and tumor PD-L1 expression, which may explain the wide variation in objective response rate, progression-free survival, and overall survival across studies. Therefore, additional studies prospectively evaluating clinical outcomes of PD-1/PD-L1 inhibitors among patients with advanced or metastatic NSCLC whose tumors harbor emerging predictive or prognostic biomarkers are needed to determine whether this class of immunotherapy can provide additional survival benefits for these patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immune Checkpoint Inhibitors; Proto-Oncogene Proteins B-raf; B7-H1 Antigen; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins c-ret; Receptor, ErbB-2
PubMed: 38112201
DOI: 10.1097/CJI.0000000000000500 -
Frontiers in Endocrinology 2023Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT.
METHODS
Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0.
RESULTS
In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients.
CONCLUSION
This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort.
Topics: Humans; Thyroid Cancer, Papillary; Hashimoto Disease; Proto-Oncogene Proteins B-raf; Thyroid Neoplasms; Lymphatic Metastasis; Prevalence; Carcinoma, Papillary; Mutation
PubMed: 38047109
DOI: 10.3389/fendo.2023.1273498 -
Cancers Jul 2023Globally, prostate cancer is the fifth most common cause of cancer-related death among men, and metastatic castration-resistant prostate cancer has a high cancer-related... (Review)
Review
Globally, prostate cancer is the fifth most common cause of cancer-related death among men, and metastatic castration-resistant prostate cancer has a high cancer-related mortality rate. However, the aetiology of this disease is not yet fully understood. While human papillomavirus (HPV) has been associated with several types of cancer, including cervical, anal, and oropharyngeal cancers, studies investigating the relationship between HPV and prostate cancer have shown mixed results. This systematic review aimed to evaluate the causative association between HPV and prostate cancer using Bradford Hill's criteria. A comprehensive search of PubMed was conducted, and 60 out of 482 studies were included in the review. The included studies were evaluated based on nine Bradford Hill criteria, and information on the identification and transmission of the virus and potential oncogenic mechanisms was also extracted. The strength of association criterion was not met, and other criteria, such as consistency and coherence, were not fulfilled. However, biological plausibility was supported, and potential oncogenic mechanisms were identified. While some studies have reported the presence of HPV in prostate cancer tissues, the overall quality of evidence remains low, and the association between HPV and prostate cancer is weak. Nevertheless, the prostate is a potential reservoir for the transmission of HPV, and the HPV E6 and E7 oncoproteins and inflammation are likely to be involved in any oncogenic mechanisms. Further studies with a higher level of evidence are needed to establish a definitive link between HPV and prostate cancer.
PubMed: 37568712
DOI: 10.3390/cancers15153897 -
Biomedical Papers of the Medical... Dec 2023HPV16 status in oropharyngeal cancer (OPC) is an important prognostic factor. Its determination, based on immunistochemical analysis of p16 oncoprotein requires an... (Review)
Review
HPV16 status in oropharyngeal cancer (OPC) is an important prognostic factor. Its determination, based on immunistochemical analysis of p16 oncoprotein requires an invasive biopsy. Thus, alternative methods are being sought. Determining oral HPV16 status appears to be a promising alternative. However, it is not used routinely. This prompted us to perform a systematic literature review enabling us to evaluate the diagnostic and predictive ability of this approach. Thirty-four relevant studies were finally selected. For determination of HPV status in OPC, the calculated average sensitivity and specificity for oral sampling was 74% and 91%, respectively, with p16 tumour tissue marker being the gold standard. The method appears to be valuable in monitoring treatment response as well as the biological activity of the tumour, enabling early detection of persistent or relapsing carcinoma sufficiently long before its clinical and/or radiological manifestation. It can also contribute to identification of the primary tumour in cases of metastases of unknown origin. Last but not least, the screening HPV oral testing would help to identify individuals with persistent HPV oral infection who are at increased risk of development of OPC.
Topics: Humans; Papillomavirus Infections; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Carcinoma; Sensitivity and Specificity; Biomarkers, Tumor
PubMed: 37901925
DOI: 10.5507/bp.2023.040