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International Immunopharmacology Jun 2024Immunotherapy in combination with chemotherapy has been approved as an initial treatment strategy for unresectable advanced gastric cancer (GC). However, the efficacy of... (Review)
Review
Perioperative immune checkpoint inhibitors combined with chemotherapy versus chemotherapy for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Immunotherapy in combination with chemotherapy has been approved as an initial treatment strategy for unresectable advanced gastric cancer (GC). However, the efficacy of adding immunotherapy to perioperative chemotherapy in locally advanced resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) remains uncertain. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to compare the effectiveness of perioperative immune checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy alone in patients with locally advanced resectable GC/GEJC.
METHODS
A comprehensive search of online databases was conducted to identify RCTs published until November 30, 2023. Odds ratios (ORs) with 95% confidence interval (CI) were calculated for primary outcomes, including R0 resection rate, D2 lymphadenectomy, pathologic complete response (pCR), and treatment-related adverse events (TRAEs).
RESULTS
A total of 2718 patients from five RCTs (six reports) were included in the analysis. The pooled ORs of R0 resection rate and D2 lymphadenectomy demonstrated that combination therapy with ICIs showed no significant difference compared to chemotherapy alone. However, the addition of ICIs significantly improved pCR rates (OR = 3.43, 95 % CI 2.61-4.50, p < 0.0001). There were no significant differences observed in the incidence of any grade TRAEs and grade 3-4 TRAEs. However, ICIs combination therapy was associated with significantly higher incidences of any grade irAEs (OR = 4.03, 95 % CI: 2.70-6.00, p < 0.0001), as well as grade 3-4 irAEs (OR = 4.51, 95 % CI: 2.27-8.97, p < 0.0001).
CONCLUSIONS
This study represents the first meta-analysis to demonstrate that perioperative combination therapy with ICIs yields superior pCR rates for patients with locally advanced GC/GEJC compared to chemotherapy.
PubMed: 38941672
DOI: 10.1016/j.intimp.2024.112576 -
Medical Mycology Jun 2024In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and...
In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (∼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.
Topics: Humans; Drug Resistance, Fungal; Antifungal Agents; World Health Organization; Pichia; Incidence; Risk Factors; Candidiasis
PubMed: 38935911
DOI: 10.1093/mmy/myad132 -
Medical Mycology Jun 2024In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority...
In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%-60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%-80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%-1%), amphotericin B (0%), and flucytosine (0%-4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.
Topics: Candida tropicalis; Humans; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Candidiasis, Invasive; Incidence; Global Health; Risk Factors
PubMed: 38935905
DOI: 10.1093/mmy/myae040 -
Cancers Jun 2024Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in... (Review)
Review
Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in targeted therapy. We present a case of a 15-year-old girl with ameloblastoma successfully treated with targeted therapy and review the literature with this question: Is anti-MAPK targeted therapy safe and effective for treating ameloblastoma? This systematic review was registered in PROSPERO, adhered to PRISMA guidelines, and searched multiple databases up to December 2023, identifying 13 relevant studies out of 647 records, covering 23 patients treated with MAPK inhibitor therapies. The results were promising as nearly all patients showed a positive treatment response, with four achieving complete radiological remission and others showing substantial reductions in primary, recurrent, and metastatic ameloblastoma sizes. Side effects were mostly mild to moderate. This study presents anti-MAPK therapy as a significant shift from invasive surgical treatments, potentially enhancing life quality and clinical outcomes by offering a less invasive yet effective treatment alternative. This approach could signify a breakthrough in managing this challenging tumor, emphasizing the need for further research into molecular-targeted therapies.
PubMed: 38927880
DOI: 10.3390/cancers16122174 -
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 -
Asian Pacific Journal of Cancer... Jun 2024Lung cancer is one of the commonest cause of cancer associated mortality worldwide. Platelets have emerged as key players in cancer development and progression by...
INTRODUCTION
Lung cancer is one of the commonest cause of cancer associated mortality worldwide. Platelets have emerged as key players in cancer development and progression by supporting tumor growth, and dissemination. In the present systematic review, we analyzed RNA transfer between cancer cells and platelets and explored potential role of different platelet RNA profiles as onco-signature in diagnosis, subtyping, disease progression and treatment monitoring in carcinoma lung carcinoma.
MATERIALS AND METHODS
The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Manual of Systematic Reviews and Meta-analysis that included seven studies on patients with lung cancer, with data on tumor-educated platelets, and control group. The outcome measured was based on sensitivity, specificity, and ROC. PUBMED, SCOPUS, Central Cochrane Registry of Controlled Trials and Science Direct databases were searched using specific search terms until October 2023. QUADAS - 2 tool was used to assess quality, risk of bias and applicability concerns.
RESULTS
The analysis revealed AUC > 70% for different platelet mRNAs, with sensitivity and specificity of more than 60 %. AUC and sensitivity were highest for ITGA2B (AUC 0.922; sensitivity 92.8%). lncRNA GTF2H2-1 was the most specific platelet RNA. On QUADAS-2 tool, 3/7 articles were unclear in reference standards, patient flow timing, and 1/7 had high bias in both aspects. For applicability, 1/7 studies were unclear in reference standards, and 2/7 in index tests.
CONCLUSION
TEP RNA can aid in early diagnosis of lung cancer and of proven utility in its early-stage detection. TEP RNA can also monitor disease progression and treatment response.
Topics: Humans; Lung Neoplasms; Biomarkers, Tumor; Blood Platelets; Prognosis; RNA, Long Noncoding
PubMed: 38918651
DOI: 10.31557/APJCP.2024.25.6.1911 -
International Journal of Colorectal... Jun 2024Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR.
METHODS
In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I statistic and employed the R statistical software (version 4.2.3) for all analyses.
RESULTS
Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I = 0%).
CONCLUSION
This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.
Topics: Humans; Rectal Neoplasms; Chemotherapy, Adjuvant; Treatment Outcome; Survival Analysis; Disease-Free Survival; Neoadjuvant Therapy
PubMed: 38913175
DOI: 10.1007/s00384-024-04668-x -
Diagnostics (Basel, Switzerland) Jun 2024Targeted axillary dissection (TAD), employing marked lymph node biopsy (MLNB) alongside sentinel lymph node biopsy (SLNB), is increasingly recognised for its efficacy in... (Review)
Review
Assessing the Efficacy of Radioactive Iodine Seed Localisation in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy: A Systematic Review and Pooled Analysis.
Targeted axillary dissection (TAD), employing marked lymph node biopsy (MLNB) alongside sentinel lymph node biopsy (SLNB), is increasingly recognised for its efficacy in reducing false negative rates (FNRs) in node-positive early breast cancer patients receiving neoadjuvant systemic therapy (NST). One such method, I radioactive seed localisation (RSL), involves implanting a seed into a biopsy-proven lymph node either pre- or post-NST. This systematic review and pooled analysis aimed to assess the performance of RSL in TAD among node-positive patients undergoing NST. Six studies, encompassing 574 TAD procedures, met the inclusion criteria. Results showed a 100% successful deployment rate, with a 97.6% successful localisation rate and a 99.8% retrieval rate. Additionally, there was a 60.0% concordance rate between SLNB and MLNB. The FNR of SLNB alone was significantly higher than it was for MLNB (18.8% versus 5.3%, respectively; = 0.001). Pathological complete response (pCR) was observed in 44% of cases (248/564). On average, the interval from I seed deployment to surgery was 75.8 days (range: 0-272). These findings underscore the efficacy of RSL in TAD for node-positive patients undergoing NST, enabling precise axillary pCR identification and facilitating the safe omission of axillary lymph node dissection.
PubMed: 38893701
DOI: 10.3390/diagnostics14111175 -
Frontiers in Immunology 2024Leukocyte cell-derived chemotaxin-2 (LECT2) is an important cytokine synthesized by liver. Significant research interest is stimulated by its crucial involvement in... (Review)
Review
Leukocyte cell-derived chemotaxin-2 (LECT2) is an important cytokine synthesized by liver. Significant research interest is stimulated by its crucial involvement in inflammatory response, immune regulation, disease occurrence and development. However, bibliometric study on LECT2 is lacking. In order to comprehend the function and operation of LECT2 in human illnesses, we examined pertinent studies on LECT2 investigation in the Web of Science database, followed by utilizing CiteSpace, VOSview, and Scimago Graphica for assessing the yearly quantity of papers, countries/regions involved, establishments, authors, publications, citations, and key terms. Then we summarized the current research hotspots in this field. Our study found that the literature related to LECT2 has a fluctuating upward trend. "Angiogenesis", "ALECT2", "diagnosis", and "biliary atresia" are the current investigative frontiers. Our findings indicated that liver diseases (e.g. liver fibrosis and hepatic cell carcinoma), systemic inflammatory disease, and amyloidosis are the current research focus of LECT2. The current LECT2 research outcomes are not exceptional. We hope to promote the scientific research of LECT2 and exploit its potential for clinical diagnosis and treatment of related diseases through a comprehensive bibliometric review.
Topics: Humans; Bibliometrics; Intercellular Signaling Peptides and Proteins; Animals; Biomedical Research
PubMed: 38881894
DOI: 10.3389/fimmu.2024.1413466 -
Biomedicine & Pharmacotherapy =... Jul 2024The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives... (Review)
Review
The intricate crosstalk between long noncoding RNAs (lncRNAs) and epigenetic modifications such as chromatin/histone methylation and acetylation offer new perspectives on the pathogenesis and treatment of kidney diseases. lncRNAs, a class of transcripts longer than 200 nucleotides with no protein-coding potential, are now recognized as key regulatory molecules influencing gene expression through diverse mechanisms. They modulate the epigenetic modifications by recruiting or blocking enzymes responsible for adding or removing methyl or acetyl groups, such as DNA, N6-methyladenosine (m6A) and histone methylation and acetylation, subsequently altering chromatin structure and accessibility. In kidney diseases such as acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy (DN), glomerulonephritis (GN), and renal cell carcinoma (RCC), aberrant patterns of DNA/RNA/histone methylation and acetylation have been associated with disease onset and progression, revealing a complex interplay with lncRNA dynamics. Recent studies have highlighted how lncRNAs can impact renal pathology by affecting the expression and function of key genes involved in cell cycle control, fibrosis, and inflammatory responses. This review will separately address the roles of lncRNAs and epigenetic modifications in renal diseases, with a particular emphasis on elucidating the bidirectional regulatory effects and underlying mechanisms of lncRNAs in conjunction with DNA/RNA/histone methylation and acetylation, in addition to the potential exacerbating or renoprotective effects in renal pathologies. Understanding the reciprocal relationships between lncRNAs and epigenetic modifications will not only shed light on the molecular underpinnings of renal pathologies but also present new avenues for therapeutic interventions and biomarker development, advancing precision medicine in nephrology.
Topics: RNA, Long Noncoding; Humans; Epigenesis, Genetic; Histones; Acetylation; DNA Methylation; Kidney Diseases; Chromatin; Animals
PubMed: 38870627
DOI: 10.1016/j.biopha.2024.116922