Correlation of PSA and survival in metastatic hormone-sensitive prostate cancer treated with rezvilutamide plus ADT in the CHART trial.

BACKGROUND: This exploratory analysis of the CHART trial (ClinicalTrials.gov: NCT03520478) investigated prostate-specific antigen (PSA) kinetics and the correlation between PSA and survival outcomes in high-volume, metastatic, hormone-sensitive prostate cancer (mHSPC). METHODS: A total of 654 patients were randomized 1:1 to receive either rezvilutamide plus androgen deprivation therapy (ADT; n = 326) or bicalutamide plus ADT (n = 328). PSA kinetics were evaluated, and the correlation between survival and the achievement of undetectable PSA (≤0.2 ng/mL) or ≥90% PSA reduction (PSA90) was assessed. FINDINGS: The rezvilutamide group exhibited higher proportions of ≥50% PSA reduction (PSA50; 98.2% vs. 87.5%), PSA90 (88.7% vs. 63.1%), and undetectable PSA (38.3% vs. 17.7%) responses compared to the bicalutamide group by 3 months. The rezvilutamide group demonstrated superior efficacy in delaying PSA progression compared to the bicalutamide group (hazard ratio [HR] 0.21, 95% confidence interval 0.16-0.27). The achievement of undetectable PSA and PSA90 by 6 months in the rezvilutamide group was associated with prolonged overall survival (undetectable PSA, HR = 0.34; PSA90, HR = 0.22), radiographic progression-free survival (HR = 0.36, HR = 0.26), time to PSA progression (HR = 0.25, HR = 0.17), and time to castration resistance (HR = 0.34, HR = 0.23) compared to those who did not achieve these PSA milestones. Stratification by baseline PSA level revealed consistent survival improvements with rezvilutamide plus ADT across quartiles. CONCLUSIONS: PSA kinetics is a valuable prognostic factor in mHSPC treated with rezvilutamide plus ADT, and the achievement of undetectable PSA and PSA90 is associated with improved survival. These findings highlight the importance of monitoring PSA kinetics in the management of mHSPC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

A Clinico-Genetic Score Incorporating Disease-Free Intervals and Chromosome 8q Copy Numbers: A Novel Prognostic Marker for Recurrence and Survival Following Liver Resection in Patients with Liver Metastases of Uveal Melanoma.

Surgical treatment of liver metastases of uveal melanoma (LMUM) could be proposed for selected patients. This retrospective study examined the prognostic significance of the genetic profiles of liver metastases after LMUM resection. A total of 86 patients treated with resection for LMUM, who underwent genetic analysis of liver metastasis, were included. A multivariable Cox model identified the independent predictors of recurrence-free survival (RFS) and overall survival (OS). The disease-free interval (DFI) and a chromosome 8q surgain (>3 copies) were independent predictors and categorized patients into three risk groups with distinct postoperative prognoses. For the low-, intermediate-, and high-risk scores of recurrence, the median RFS values were 15 months (95% CI: 10-22), 6 months (95% CI: 4-11), and 4 months (95% CI: 2-7), and the median OS values were 86 months (95% CI: 55-NR), 25 months (95% CI: 17-48), and 19 months (95% CI: 12-22), respectively. The predictive accuracy of this scoring system was demonstrated by a mean area under the curve (AUC(t)) of 0.77 (95% CI: 0.65-0.90) for RFS and 0.81 (95% CI: 0.70-0.92) for OS. This novel score, based on a DFI of ≤24 months combined with a chromosome 8q surgain, identifies patients at a high risk of early recurrence and could help clinicians to propose perioperative treatment.

Comprehensive in silico analysis of prognostic and immune infiltrates for FGFs in human ovarian cancer.

BACKGROUND: Fibroblast growth factors (FGFs) are cell signaling proteins that perform multiple biological processes in many biological processes (cell development, repair, and metabolism). The dynamics of tumor cells, such as angiogenesis, transformation, and proliferation, have a significant impact on neoplasia and are modulated by FGFs. FGFs' expression and prognostic significance in ovarian cancer (OC), however, remain unclear. METHODS: Through a series of in silico analysis, we investigated the transcriptional, survival data, genetic variation, gene-gene interaction network, ferroptosis-related genes, and DNA methylation of FGFs in OC patients. RESULTS: We discovered that while FGF18 expression levels were higher in OC tissues than in normal OC tissues, FGF2/7/10/17/22 expression levels were lower in the former, and that FGF1/19 expression was related to the tumor stage in OC patients. According to the survival analysis, the clinical prognosis of individuals with OC was associated with the aberrant expression of FGFs. The function of FGFs and their neighboring genes was mainly connected to the cellular response to FGF stimulus. There was a negative correlation between FGF expression and various immune cell infiltration. CONCLUSIONS: This study clarifies the relationship between FGFs and OC, which might provide new insights into the choice of prognostic biomarkers of OC patients.

Prognostic Value of a Classification System for Iliofemoral Stenting in Patients with Chronic Venous Obstruction.

OBJECTIVE: This retrospective, multicentre study aimed to assess the prognostic value of a proposed classification system for chronic venous obstruction (CVO) patients undergoing successful interventional procedures. METHODS: This study analysed data from 13 vascular centres, including 1 033 patients with CVO treated between 2015 - 2019. The patients were classified into five category types: 1 - non-thrombotic iliac vein lesion; 2 - CVO of iliac segment; 3 - CVO of iliofemoral segment above common femoral vein confluence; 4 - CVO of iliofemoral segment extending into the femoral vein (FV) or deep femoral vein (DFV); and 5 - CVO of iliofemoral segment involving both DFV and FV. Stent deployment, complications, and follow ups were evaluated. Univariate and multivariate analyses were performed to identify predictors of primary patency loss. RESULTS: Mean age of the patients was 44.0 ± 14.7 years, with 59.9% being women. A median of two stents were used for unilateral cases and five stents for bilateral cases. At 12 months of follow up, primary patency rates for types 1 - 5 were 94.9%, 90.3%, 80.8%, 60.6%, and 39.4%, respectively. These rates were strongly correlated with the extension of CVO and showed significant differences between each type. Univariate analysis identified predictors of primary patency loss as the type of CVO, history of deep vein thrombosis, and the total number of stents. In the multivariate analysis, the significant independent predictors of primary patency loss were the type of CVO and the total number of stents. CONCLUSION: The proposed anatomical classification of iliofemoral CVO will help to predict intervention outcomes and facilitate comparison of stent outcomes in future studies. However, further evaluation and validation in prospective studies are needed to confirm the utility of this classification.

The Role of Hematocrit Levels in Diagnosing the Severity of Acute Pancreatitis: A Cross-Sectional Study at a Tertiary Care Center in Nepal.

Background and objective Acute pancreatitis (AP) is a frequent cause of hospitalization for gastrointestinal issues, with a significant proportion of cases requiring intensive care. Although various scoring systems are available to predict AP severity, they often involve inconvenience and can be time-consuming and expensive. Hematocrit, a simple, cost-effective, readily available hematological test, has been used to predict AP severity. However, its effectiveness has been inconsistent across different studies. In light of this, we aimed to analyze the role of hematocrit levels in determining AP severity. Methods We conducted a prospective study at Patan Hospital in Lalitpur, Nepal, from June 8, 2022, to June 27, 2023. Sixty-five AP patients were evaluated to determine the prognostic value of hematocrit at admission. The severity of AP was classified per the Revised Atlanta Classification. Results Among the patients, 52 (80%) had mild AP (MAP), five (7.69%) had moderately severe AP (MSAP), and eight (12.31%) had severe AP (SAP). The receiver operating characteristic (ROC) curve for admission hematocrit levels yielded an area under the curve (AUC) of 0.551 (95% CI: 0.423-0.675). A hematocrit cutoff value of 42% resulted in a sensitivity of 69.23% and a specificity of 46.15% for predicting severe AP (MSAP + SAP). Conclusions Based on our findings, hematocrit at admission is not a strong predictor of the severity of AP.

Role of interleukin 6 polymorphism and inflammatory markers in outcome of pediatric Covid- 19 patients.

BACKGROUND: IL-6 polymorphisms were associated to viral infection outcomes through affection of IL-6 production and it is an early indicator of tissue injury and systemic inflammatory response. The study aimed to determine whether genetic IL-6 polymorphisms, serum interleukin-6 level and inflammatory markers (Presepsin, CXCL-10, C3, and C4) are associated with the prediction of disease severity in pediatric COVID-19 patients and its possible use as a prognostic tool in pediatric patients admitted to hospital. METHODS: This prospective cohort study was conducted on 150 children with COVID-19. Patients were divided according to the severity of infection into four groups: group I (mild) 67 cases; group II (moderate) 53 cases, group III (severe) 17 cases and group IV (critical) 14 cases. Serum Interleukin 6, CXCL-10, Presepsin, renal and liver functions, electrolytes, C3, C4, ferritin, and D dimer serum levels were assessed in all patients. The Kruskal Wallis test used to compare parametric quantitative data between studied groups and Mann Whitney test for each pair of groups. Non-parametric quantitative data was compared between studied groups using a one-way ANOVA test and post-hoc Bonferroni analysis for each pair of groups. RESULTS: Group I: 35 males and 32 females with a median age of 16 months. Group II: 17 males and 35 females with a median age of 13 months. Group III: 6 males and 11 females with a median age of 12 months and group IV: 3 males and 11 females with a median age of 12 months. There was no statistical difference between the studied groups regarding gender and age. Serum levels of IL- 6, serum ferritin; D-dimer, Presepsin and CXCL 10 were significantly higher in both severe and critical groups than the other 2 groups (mild and moderate). ROC curve analysis showed that interleukin-6 and Presepsin were good markers for prediction of severity of COVID-19 among the diseased children. For severe cases, the sensitivity of interleukin-6 was 76.47% and specificity was 92.31%. For critical cases, the sensitivity of interleukin-6 was 71.43% and specificity was 82.35%. The sensitivity of Presepsin was 76.47% and specificity was 88.46% in severe cases. For critical cases, the sensitivity of Presepsin was 78.57% and specificity of 91.2%. There was significant difference in IL-6 572 allelic among moderate cases with the most frequent 42.3% for genotype (GC) and allelic among severe cases with the most frequent 47.1% for genotype (GC). Significant difference in IL-6 174 allelic among critical cases with the most frequent 78.6% for genotype (CC). CONCLUSIONS: Children whom expressed GC genotypes of IL6 (-572G > C) polymorphism are at a considerably higher risk of developing a severe disease. This risk is significantly larger in the severe group of children than in children in critical condition who have GC genotypes of IL6 (-174 G > C) polymorphism. While IL6 (-597G > A) polymorphism has no role in COVID 19 severity in children.

Prognostic value of electronic health records-based frailty measures for all-cause mortality in older patients with non-small cell lung cancer.

INTRODUCTION: Frailty screening is important to guide treatment decisions for older patients with non-small cell lung cancer (NSCLC). However, the performance of frailty measures (FMs) remains unclear. This study aimed to evaluate the prognostic value of FMs based on electronic health records (EHR) data in clinical settings for all-cause mortality in older patients with NSCLC. MATERIALS AND METHODS: We retrospectively analyzed 4253 patients aged ≥65 years, newly diagnosed with NSCLC (2007-2018) using EHR data from the National Cancer Center, Korea. Frailty was measured by either laboratory tests (frailty index based on routine laboratory tests [FI-Lab]), comorbidities and performance status (electronic Frailty index [eFI]), or both (combined frailty index [FI-combined]). Patients were categorized as frail or non-frail. Cox proportional hazards models and C-index were used to estimate the predictive ability of FMs for all-cause mortality in 1 year, 3 years, and 5 years post-diagnosis, adjusting for age, sex, and SEER stage. RESULTS: EHR-based FMs could enhance the prognostic ability to predict the survival of older patients with NSCLC. In the total population, FI-Lab showed the largest predictive value, especially for 1-year mortality with an adjusted hazard ratio for frail vs. non-frail groups of 2.25 (95 % CI 2.02-2.51) and C-index of 0.74 compared to 0.72 in the base model (p-value<0.001). FI-Lab could improve the prognostic ability for 1-year mortality in patients with regional and distant SEER stages and those receiving systemic therapy, whereas FI-combined could improve the prediction of 3-year and 5-year mortality in patients with localized disease and receiving surgery. DISCUSSION: Easy-to-use FMs derived from EHR data can enhance the prediction of all-cause mortality in older patients with NSCLC. Oncologists can utilize comprehensive FMs comprising comorbidities, functional status, and subclinical tests or FI-Lab, depending on the patient's medical condition, to facilitate shared cancer care planning.

Short- and long-term immunosuppressive effects of melanoma influence the prognostic value of the sentinel lymph node status.

BACKGROUND: Presence of micrometastases in the sentinel lymph node (SLN) is currently used to assess prognosis of melanoma patients. The immunoactivity within the SLN is known to be influenced by the primary tumor (PT), which may in turn impact the SLNs' metastatic state. AIM: We characterize the temporal dependence and underlying mechanisms of the immunological effects of the PT on the SLN. METHODS: The prognostic value of SLN state as a function of PT removal time was evaluated. To put the results into a functional context, selected PTs and corresponding SLNs were analyzed for gene and protein expression patterns. RESULTS: In a cohort of 202 patients with known distant metastasis and similar PT prognostic characteristics, SLNs removed before or within one week after the PT (IM-SLN) had a higher incidence of micrometastases than those removed at least one week after the PT (DEL-SLN). The immunoactivity in IM-SLN was found to be lower than in DEL-SLN. Specifically, in IM-SLNs, T helper 17 / regulatory T-cells were predominant, whereas in DEL-SLNs, cytotoxic γδT-cells were more frequent. The higher immune activity in DEL-SLNs was probably facilitated by CD209+ antigen-presenting cells. Indeed, in PT with high TGFß expression CD209+ cells appear to be trapped and no increased immunoactivity was observed in DEL-SLN. CONCLUSIONS: Presence of micrometastases in DEL-SLNs have a higher negative prognostic value as in IM-SLNs since they indicate not only a melanoma's propensity to metastasize, but possibly also its capacity to escape immune responses.

Bioinformatics investigation of the prognostic value and mechanistic role of CD9 in glioma.

In recent years, CD9 has been extensively studied as a potential biomarker for cancer. However, the biological role of CD9 in gliomas remains unclear. This study investigates the function of CD9 in gliomas and its molecular mechanisms. Utilizing pan-cancer analysis with TCGA, CGGA, and GEO databases, differential expression of CD9 was observed in 11 tumor types within the TCGA cohort, and it was associated with patient survival rates. Analysis of the CGGA glioma database revealed that patients with high CD9 expression had lower survival rates. The area under the ROC curve (AUC) for GSE16011 was greater than 0.7, indicating a high discriminative ability. Through gene set enrichment analysis (GSEA), immune-related analysis, and CD9 mutation detection, CD9 was found to have the strongest correlation with neutrophil involvement (cor = 0.30, P < 0.05), and the high CD9 expression group exhibited higher rejection responses and TIDE scores, suggesting a lower likelihood of successful immunotherapy. The high CD9 expression group was more sensitive to 81 drugs, indicating potential therapeutic effects for gliomas. Furthermore, overexpression of CD9 in gliomas may be associated with gene mutations. Down-regulation or up-regulation of CD9 expression in the glioblastoma cell line LN229 showed that CD9 could positively regulate the migratory ability of LN229 cells. Further, several marker genes, such as VEGFR-2, TGF-ß1, CASP1 and PI3K, were down regulated in CD9 knockdown cell lines and up regulated in CD9 overexpression cell lines, compared with control cell line. This study preliminarily explores the role of CD9 in gliomas and its prognostic value, providing new insights for personalized treatment strategies in glioma therapy.

Pan-cancer analysis of ADAR1 with its prognostic relevance in low-grade glioma.

ADAR1, known as the primary enzyme for adenosine-to-inosine RNA editing, has recently been implicated in cancer development through both RNA editing-dependent and -independent pathways. These discoveries suggest that ADAR1's functions may extend beyond our current understanding. A pan-cancer analysis offers a unique opportunity to identify both common and distinct mechanisms across various cancers, thereby advancing personalized medicine. Low-grade glioma (LGG), characterized by a diverse group of tumor cells, presents a challenge in risk stratification, leading to significant variations in treatment approaches. Recently discovered molecular alterations in LGG have helped to refine the stratification of of these tumors and offered novel targets for predicting likely outcomes. This study aims to provide a detailed analysis of ADAR mRNA across multiple cancers, emphasizing its prognostic significance in LGG. We observed inconsistent mRNA and consistent protein expression patterns of ADAR1/ADAR in pan-cancer analyses that across tumor types. ADAR mRNA expression did not always correlate with ADAR1 protein expression. Nevertheless, the transcript levels correlated significantly with genetic alterations, tumor mutation burden, microsatellite instability, overall survival, recurrence-free survival, immune marker presence, immune infiltration, and the survival of patients undergoing immunotherapy in select cancers. Furthermore, ADAR and its top 50 associated genes were primarily involved in mRNA-related events, as identified through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Utilizing the Cox proportional hazards model, we developed a 3-gene signature (ADAR, HNRNPK, and SMG7), which effectively stratified patients into high- and low-risk groups, with high-risk patients exhibiting poorer overall survival, higher tumor grades, and a greater number of non-codeletions. Overall, this signature was inversely related to immune infiltration across cancers. Transcription factor SPI1 and miR-206, potential upstream regulators of the signature genes, were closely linked to patient survival in LGG. The promoter regions of these genes were hypermethylated, further associating them with patient outcomes. Additionally, these genes displayed consistent drug susceptibility patterns. In conclusion, our findings reveal multiple aspects of ADAR1's role in cancer and underscore its prognostic value in LGG, offering insights into potential therapeutic targets and strategies.

Systemic immune-inflammation and prognostic immune nutritional index in oral squamous cell carcinoma patients.

Aim: To investigate the systemic immune-inflammation index and prognostic immune nutritional index in the prognostic evaluation of oral squamous cell carcinoma.Materials & methods: We analyzed retrospectively the relationship between systemic immune-inflammation index, prognostic immune nutritional index and clinicopathological variables and the overall survival of 262 patients who underwent radical surgery.Results: Multivariate analysis showed high systemic immune-inflammation index (Hazard ratio = 3.062, 95% CI: 1.021-8.251), low prognostic immune nutritional index (Hazard ratio = 0.297, 95% CI: 0.139-0.636), tumor node metastasis classification 3-4 (Hazard ratio = 9.862, 95% CI: 4.658-20.880) patients have worse overall survival.Conclusion: Preoperative systemic immune-inflammation index and prognostic immune nutritional index are independent risk factors for prognostic survival status in oral squamous cell carcinoma.

[Box: see text].

Molecular Subtypes Based on Mitochondrial Oxidative Stress-related Gene Signature and Tumor Microenvironment Infiltration Characterization of Colon Adenocarcinoma.

BACKGROUND: As the most common subtype of colorectal cancer, colorectal adenocarcinoma (COAD) still needs better prognostic stratification methods and new intervention targets. The mitochondrial stress response, linked to mitochondrial homeostasis and cancer metabolism, warrants further investigation. METHODS: We identified mitochondrial oxidative stress-related genes (MOS) associated with COAD prognosis through the TCGA and GEO databases. Molecular subtype characteristics were identified based on MOS gene signatures, and an MOS scoring system was established to comprehensively evaluate its clinical value. Additionally, the effect of one of the screened genes, NDRG1, was investigated through a series of in vitro experiments, including Western blot, qRT-PCR, CCK8 assay, clone formation, and Transwell assay, to explore its impact on COAD proliferation and migration ability. RESULTS: Our analysis revealed that MOS gene signatures effectively distinguished molecular subtypes of COAD, and the MOS scoring system was found to be independent in predicting prognosis. Evaluation of microenvironment infiltration characteristics, mutation characteristics, immunotherapy response, and drug sensitivity analysis further suggested the potential clinical utility of this study. in vitro experimental results showed that NDRG1 significantly affected the proliferation and migration of COAD cells, partially verifying the reliability of our bioinformatics analysis. CONCLUSION: This study provides a novel perspective on the role of mitochondrial oxidative stress in COAD, proposing innovative prognostic evaluation methods and potential therapeutic targets, thus offering new directions for the clinical treatment of COAD.

ADCY5 act as a putative tumor suppressor in glioblastoma: An integrated analysis.

Background: Adenylyl cyclase (AC) isoforms played a key role in the multiple cancer pathology, However, the expression, prognostic value and function of ADCY5 in Glioblastoma (GBM) have not been reported yet. This research intends to discover the expression, epigenetic alteration and biological function of ADCY5 in GBM and its value on patients' prognosis. Methods: ① Transcriptional level, epigenetic alteration, prognostic value and molecular network of ADCY5 were analyzed by using of public online datasets. ② The mRNA expression profile of ADCY5 was explored by using GEPIA database and protein expression levels were detected by HPA Database. ③ The prognostic value of ADCY5 was determined by Kaplan-Meier Plotter, GEPIA and CGGA database. ④ The epigenetic characteristics of ADCY5 were determined by DiseaseMeth database. ⑤ Identification of genes co-expressed with ADCY5 and potential mechanism analyses were performed by using DAVID cBioPorta and STRING. ⑥ Reverse transcription-polymerase chain reaction (RT-PCR), cell counting kit-8 (CCK-8), colony formation, wound-healing scratch and transwell assay were applied to detect relative mRNA expression and biological function of ADCY5 in GMB cells. Results: ADCY5 mRNA and protein were downregulated in GBM compared with normal tissues. Analysis of the genetics and epigenetics of ADCY5 suggested that its expression was negatively correlated with DNA methylation. High expression of ADCY5 was significantly associated with age, grade, IDH mutation, 1p19q_codeletion, radiotherapy and chemotherapy and acted as an independent prognostic factor in GBM. ADCY5 mRNA also down-expressed in GBM cell lines and re-expressed of ADCY5 could inhibit cell proliferation, viability, migration/invasion and epithelial-mesenchymal transition (EMT) in vitro. In the analysis of genes co-expressed with ADCY5, we found that cAMP/AKT pathway, cGMP-PKG pathway, Wnts pathway were dissimilarly enriched. Conclusion: Our study indicated that ADCY5 could act as an epigenetic biomarker in GBM, as well as a prognosis target in patients with GBM.

Comment on, "Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review".

The study by Ooi et al. (2022) systematically reviews the potential of Interleukin-6 (IL-6) as a prognostic biomarker for traumatic brain injury (TBI). By analyzing IL-6 levels in serum, cerebrospinal fluid (CSF), and brain parenchyma, the authors provide valuable insights into its role in predicting clinical outcomes. The study emphasizes the neuroinflammatory response and the mechanistic role of IL-6 in neuronal recovery, offering a strong rationale for its consideration as a biomarker. However, variability in IL-6 detection methods and timing of sample collection across studies highlights the need for standardization. Future research should focus on refining detection methods, exploring IL-6's temporal dynamics post-TBI, and accounting for interactions with other cytokines. Additionally, advanced statistical controls are recommended to better isolate IL-6's prognostic value. This research lays a solid foundation for future studies aimed at improving clinical prognostication in TBI.

Incremental prognostic value of cardiovascular magnetic resonance imaging in patients with severe LV dysfunction undergoing coronary artery bypass grafting.

BACKGROUND: Coronary artery disease (CAD) remains a significant global health issue, particularly when complicated by left ventricular ejection fraction (LVEF) < 35%. Although coronary artery bypass grafting (CABG) is recommended for such cases, the unclear prognosis necessitates further investigation. METHOD: This retrospective study aimed to determine whether cardiovascular magnetic resonance (CMR) imaging provides additional prognostic value in guiding effective clinical management. The study included patients with CAD and LVEF < 35% who underwent CABG surgery after enhanced CMR between March 2016 and March 2023. CMR was performed using a 3.0T scanner with steady-state free precession and phase-sensitive inversion recovery sequences. Prognostic analysis of clinical and CMR data was conducted, with the endpoint defined as cardiovascular death, revascularization, hospitalization for heart failure, or stroke. Statistical analysis included Student's t-test, chi-squared test, univariate and multivariate Cox regression analysis, receiver operating characteristic analysis, Harrell C statistical analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) analysis. RESULT: The study included 152 patients (mean age 58.6 ± 9.7 years; 138 men). During a mean follow-up of 2.0 years, 8 patients experienced cardiovascular death, while 1 case had revascularization, 13 had hospitalization for heart failure, and 11 had a stroke. Left atrial diameter index (LADi) (hazard ratio [HR], 1.08 [95% confidence interval (CI): 1.02-1.15]; P = 0.04) and late gadolinium enhancement (LGE) mass (HR, 1.03 [95% CI: 1.01-1.06]; P < 0.001) were associated with the endpoint, even after adjusting for multiple clinical variables. Adding LADi and LGE mass improved risk prediction for adverse events, as indicated by the C-index (0.738, p < 0.01), IDI (0.36), and NRI (0.13). CONCLUSION: Left atrial diameter index (LADi) and scar burden are valuable prognostic indicators in patients with LVEF < 35% undergoing CABG. They offer enhanced risk stratification beyond traditional clinical factors, highlighting their importance in guiding clinical management.

Clinical value of sequential circulating tumor DNA analysis using next-generation sequencing and epigenetic modifications for guiding thermal ablation for colorectal cancer metastases: a prospective study.

INTRODUCTION: While thermal ablation is now a standard treatment option for oligometastatic colorectal cancer patients, selecting those who will benefit most from locoregional therapies remains challenging. This proof-of-concept study is the first to assess the feasibility of routine testing of ctDNA before and after thermal ablation with curative intent, analyzed by next-generation sequencing (NGS) and methylation specific digital droplet PCR (ddPCR). Our prospective study primary objective was to assess the prognostic value of ctDNA before thermal ablation. METHODS: This single-center prospective study from November 2021 to June 2022 included colorectal cancer patients referred for curative-intent thermal ablation. Cell-free DNA was tested at different time points by next-generation sequencing and detection of WIF1 and NPY genes hypermethylation using ddPCR. The ctDNA was considered positive if either a tumor mutation or hypermethylation was detected; recurrence-free survival was used as the primary endpoint. RESULTS: The study enrolled 15 patients, and a total of 60 samples were analyzed. The median follow-up after ablation was 316 days, and median recurrence-free survival was 250 days. CtDNA was positive for 33% of the samples collected during the first 24 h. The hazard ratio for progression according to the presence of baseline circulating tumor DNA was estimated at 0.14 (CI 95%: 0.03-0.65, p = 0.019). The dynamics are provided, and patients with no recurrence were all negative at H24 for ctDNA. DISCUSSION: This study shows the feasibility of routine testing of ctDNA before and after thermal ablation with curative intent. We report that circulating tumor DNA is detectable in patients with low tumor burden using 2 techniques. This study emphasizes the potential of ctDNA for discerning patients who are likely to benefit from thermal ablation from those who may not, which could shape future referrals. The dynamics of ctDNA before and after ablation shed light on the need for further research and larger studies.

Myocardial work and risk stratification in patients with severe aortic valve stenosis referred for transcatheter aortic valve replacement.

Background: Transcatheter aortic valve replacement(TAVR) has shown clear survival benefits in severe aortic valve stenosis(AS). However, patients unable to recover left ventricle function remain at risk with poor long-term survival. This single-center prospective study aims to analyze the supplementary benefits of myocardial work(MW) assessment for baseline risk stratification in patients with severe AS referred for TAVR. Methods: A total of 110 patients with severe AS referred for TAVR were included in the study. Baseline ECG data, transthoracic echocardiographic(TTE) images and blood samples were obtained. The TTE examination was repeated one day and one month after valve replacement. The primary outcome of the study was a composite endpoint consisting of all-cause mortality and HF hospitalization. Results: During a mean follow-up period of 521 ± 343 days, 29patients(26.4 %) reached the composite endpoint. Baseline troponins, NT-proBNP, sST2, GWI and GCW showed statistically significant differences between groups. Patients with a baseline GWI<2323 mmHg% (sensitivity 0.63 and specificity 0.76)had significantly worse outcome following TAVR. A basic predictive model included QRS-length, TAPSE, LAVI and E/e'. The addition of biomarkers did not yield any further advantages whereas incorporating the GWI cut-off value of 2323 mmHg% significantly enhanced the predictive value. Although there were no significant changes in LVEF and GLS, all patients exhibited a significant reduction in GWI and GCW immediately after TAVR. Conclusion: Our findings provide evidence for the enhanced usefulness of MW analysis in the initial risk stratification of patients with severe AS referred for TAVR. Specifically, a baseline GWI<2323 mmHg% demonstrates an independent predictor associated with increased incidence of all-cause mortality and HF hospitalization following TAVR.

Early reduction in total cholesterol to high-density lipoprotein cholesterol ratio predicts hydroxychloroquine efficacy in treating IgA nephropathy.

BACKGROUND: Hydroxychloroquine (HCQ) effectively improves lipid levels in patients with autoimmune diseases. This study aimed to examine the effect of HCQ on lipid profiles in patients with immunoglobulin A (IgA) nephropathy (IgAN) and determine whether alterations in lipid profiles can predict the efficacy of HCQ. METHODS: This study retrospectively analyzed 77 patients, and the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) decline rate after 3 months of HCQ treatment was selected as a predictor based on receiver operating curve analysis. Patients were then divided into low and high TC/HDL-C decline rate groups based on the optimal cutoff value. The Cox proportional hazard model and Kaplan-Meier curve were used to evaluate the value of the TC/HDL-C decline rate in predicting the efficacy of HCQ in patients with IgAN. RESULTS: Patients in the high TC/HDL-C decline rate group with ≥50% decrease in proteinuria from baseline experienced a significant improvement during the follow-up. Kaplan-Meier analysis revealed that a high TC/HDL-C decline rate was strongly associated with a higher proteinuria reduction rate in patients with IgAN. Furthermore, multivariate Cox analysis indicated that a higher reduction in the TC/HDL-C ratio (hazard ratio: 2.314; 95% confidence interval: 1.234-4.340; p = 0.009) was an independent predictive indicator for achieving ≥50% reduction in proteinuria with HCQ therapy in IgAN. CONCLUSION: HCQ effectively improves lipid profiles in patients with IgAN, and an early decrease in the TC/HDL-C ratio serves as a predictor of better outcomes in patients treated with HCQ.

Homologous recombination deficiency (HRD) is associated with better prognosis and possibly causes a non-inflamed tumour microenvironment in nasopharyngeal carcinoma.

Homologous recombination deficiency (HRD) score is a reliable indicator of genomic instability. The significance of HRD in nasopharyngeal carcinoma (NPC), particularly its influence on prognosis and the immune microenvironment, has yet to be adequately explored. Understanding HRD status comprehensively can offer valuable insights for guiding precision treatment. We utilised three cohorts to investigate HRD status in NPC: the Zhujiang cohort from local collection and the Hong Kong (SRA288429) and Singapore (SRP035573) cohorts from public datasets. The GATK (genome analysis toolkit) best practice process was employed to investigate germline and somatic BRCA1/2 mutations and various bioinformatics tools and algorithms to examine the association between HRD status and clinical molecular characteristics. We found that individuals with a negative HRD status (no-HRD) exhibited a higher risk of recurrence [hazard ratio (HR), 1.43; 95% confidence interval (CI), 2.03-333.76; p = 0.012] in the Zhujiang cohort, whereas, in the Singapore cohort, they experienced a higher risk of mortality (HR, 26.04; 95% CI, 1.43-34.21; p = 0.016) compared with those in the HRD group. In vitro experiments demonstrated that NPC cells with BRCA1 knockdown exhibit heightened sensitivity to chemoradiotherapy. Furthermore, the HRD group showed significantly higher tumour mutational burden and tumour neoantigen burden levels than the no-HRD group. Immune infiltration analysis indicated that HRD tissues tend to have a non-inflamed tumour microenvironment. In conclusion, patients with HRD exhibit a comparatively favourable prognosis in NPC, possibly associated with a non-inflammatory immune microenvironment. These findings have positive implications for treatment stratification, enabling the selection of more precise and effective therapeutic approaches and aiding in the prediction of treatment response and prognosis to a certain extent.