Kaplan-Meier Analysis Research Articles

In a prospective, multicenter study, the 31-GEP identified patients at increased risk of tumor recurrence and added significant prognostic value to AJCC staging

Cutaneous melanoma (CM) guidelines base management decisions on a patient’s American Joint Committee on Cancer (AJCC) tumor stage. However, limitations in staging accuracy suggest additional tools could improve risk-aligned patient management decisions. The 31-gene expression profile (GEP) test identifies patients with CM with low (Class 1A), intermediate (Class 1B/2A), or high (Class 2B) risk for sentinel lymph node (SLN) positivity, recurrence, metastasis, and death. In this multicenter, prospective study, we validated the 31-GEP for risk of recurrence and demonstrated the added value of 31-GEP to AJCC staging. Patients were included in the prospective CONNECTION study if they were tested with the 31-GEP from 2018 to the present (n=876). Survival was estimated using Kaplan-Meier analysis and 31-GEP stratification tested with the log-rank test. Cox regression was performed to identify predictors of recurrence. ANOVA was used to compare Cox models for the most accurate recurrence prediction. Patients with a Class 1A result had significantly higher 3-year recurrence-free survival than those with a Class 1B/2A or Class 2B result (98.5% vs. 80.8% vs. 63.0%, p<0.001). The 31-GEP had higher sensitivity (75.0% vs. 37.5%) and negative predictive value (98.6% vs. 96.9%) than AJCC staging. Multivariable analysis demonstrated that Class 1B/2A (hazard ratio, HR=3.12, p=0.037) and Class 2B (HR=5.91, p=0.002) were significant predictors of recurrence in addition to stage IB (HR=4.02, p=0.02), IIA (HR=6.06, p=0.006), IIC (HR=17.14, p<0.001), and III (HR=8.84, p<0.001). Stage IIB (HR=4.63, p=0.057) was not significant. Comparing a staging-only model to a 31-GEP+staging model showed that adding 31-GEP to staging significantly improved prediction accuracy over staging alone (ANOVA: c2=10.58, p=0.005). In this prospective study, the 31-GEP stratified risk of recurrence, was a significant predictor of recurrence, and added significant predictive value to AJCC staging. The 31-GEP identifies patients at high risk of recurrence who should be managed more intensely, and adding 31-GEP to staging allows better risk-aligned care decisions, which can lead to improved patient outcomes.

Unlocking survival benefits: primary tumor resection in de novo stage IV breast cancer patients

ABSTRACT Background For patients with de novo stage IV breast cancer (BC), the conditions under which the primary tumor resection (PTR) may offer benefit remain unclear. Methods The SEER database provides treatment data for patients with de novo stage IV BC. We screened cases of metastatic BC diagnosed from 2010 to 2015, with primary endpoints of overall survival (OS) and cancer-specific survival (CSS). Results 9252 patients with stage IV de novo BC were enrolled. For OS, median survival time (MST) was 38 months with systematic treatment (ST) compared to 52 months with ST plus PTR (p < 0.001). For CSS, MST was 38 months for ST versus 54 months for ST plus PTR (p < 0.001). The results of the Cox proportional hazards regression analysis regarding PTR, for OS: bone metastasis (aHR 0.664, 95%CI 0.583–0.756, p < 0.001); liver-lung metastasis (aHR 0.528, 95%CI 0.327–0.853, p = 0.009). For CSS: bone metastasis (aHR 0.655, 95%CI 0.571–0.751, p < 0.001); liver-lung metastasis (aHR 0.549, 95%CI 0.336–0.889, p = 0.017). Kaplan-Meier analysis indicated that in patients with bone metastases and liver-lung metastases, PTR could improve survival outcomes. Conclusion Liver-lung metastases and bone metastases in patients with de novo stage IV BC could enhance both OS and CSS through PTR.

Abstract B028: The Role of cDC1 Gene Signatures in gastric cancer prognosis and immune microenvironment modulation

Abstract Background and Aim: Gastric cancer (GC) continues to be a major global health burden, with a growing body of evidence highlighting the critical role of conventional type 1 dendritic cells (cDC1s) within the tumor microenvironment. This study aims to elucidate the prognostic significance of cDC1-associated genes—CD141, XCR1, CLEC9A, CADM1, and BTLA—in gastric cancer, as well as to explore the biological mechanisms that underpin their effects on patient outcomes. Materials and Methods: We conducted a comprehensive analysis of RNA- seq data from The Cancer Genome Atlas (TCGA-STAD) and Gene Expression Omnibus (GEO) datasets, focusing on the expression profiles of five cDC1-related genes. Patients were stratified into high and low expression groups based on a defined cDC1 gene signature. To assess the impact of these signatures, we utilized gene set variation analysis (GSVA) to examine relevant oncogenic pathways and performed Kaplan-Meier survival analysis along with Cox proportional hazards modeling to evaluate their prognostic value. Results: Our findings demonstrate that patients exhibiting a high cDC1-related gene signature had significantly worse overall and disease-free survival within the TCGA-STAD cohort. Further analysis revealed marked differences in CD8+ T cell infiltration and cytotoxic activity between the high and low cDC1 signature groups. Additionally, the high cDC1 signature group was strongly associated with upregulated expression of immune checkpoint proteins and the activation of oncogenic pathways, indicating a highly immunosuppressive tumor microenvironment. Conclusions: This study suggests that the cDC1-related gene signature may serve as a potent prognostic biomarker in gastric cancer, offering new insights into the complex interactions between the tumor and immune microenvironment. These results could pave the way for innovative therapeutic strategies that target the immune landscape in gastric cancer, potentially improving patient outcomes. Citation Format: Song-hee han. The Role of cDC1 Gene Signatures in gastric cancer prognosis and immune microenvironment modulation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B028.

The Long-Term Functional and Oncologic Outcomes of Kidney-Sparing Surgery in Upper Tract Urothelial Carcinoma.

This study investigated the utilization of kidney-sparing surgery (KSS) as an alternative option to radical nephroureterectomy (RNU) in managing upper urinary tract urothelial carcinoma (UTUC) patients. Our study aimed to compare the functional outcomes and oncological outcomes between KSS and RNU. We retrospectively analyzed 252 patients with UTUC without clinical node positivity or metastasis who had been treated with either RNU or KSS. We collected information on each patient, including clinicopathological factors, renal function variations, and oncological outcomes. Hemodialysis-free survival (HDFS), stage 4 chronic kidney disease (CKD4) progression-free survival (PFS), recurrence-free survival (RFS), and overall survival (OS) were assessed using inverse probability of treatment weighting (IPTW)-weighted Kaplan-Meier analysis. The hazard ratio for oncological and functional outcomes of KSS was analyzed using the Cox proportional hazards model. The OS at 8 years was 77.06% (RNU) and 70.59% (KSS) and did not significantly differ between the two groups (p=0.691), although the KSS group experienced a higher recurrence rate. Functional outcomes indicated no significant difference in postoperative renal function at 1year; however, KSS was associated with better preservation of renal function (23.44% vs. 28.23%), albeit not statistically significant (p=0.055). Kaplan-Meier analysis revealed no significant disparities in CKD4 PFS between the KSS and RNU groups involved in the study (p=0.089), although the KSS group displayed poorer HDFS than the RNU group (p=0.001). KSS had no compromising survival outcomes when compared with RNU, not only in low-risk patients but also in high-risk patients with a normal contralateral kidney. The efficacy of renal function preservation was presented in this study, however the results were below our expectations.

SLITRK2 as a prognostic and immunological biomarker in gastric cancer.

SLIT and NTRK-like protein 2 (SLITRK2) encodes a transmembrane protein that regulates neurite outgrowth. Some studies have demonstrated that SLITRK2 overexpressed in glioma. But the expression pattern, prognostic value and immunologic function of SLITRK2 in tumors remains unknown. The expression pattern of SLITRK2 among pan-cancers was examined through the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). We analyzed the association between SLITRK2 expression level and tumor stage among pan-cancers. Kaplan-Meier survival analysis was utilized to investigate the prognostic relevance of SLITRK2 across 33 different types of cancers. Moreover, the correlations among SLITRK2 expression, immune cell infiltration, immunomodulatory related genes, tumor mutation burden (TMB), microsatellite instability (MSI) were evaluated. The relationship between SLITRK2 expression and crucial genes mutations was also illustrated. By using tissue microarray (TMA), the expression of SLITRK2 in 89 paired gastric cancer (GC) tissues was investigated. Our study indicated that SLITRK2 expression varied across cancers. Elevated SLITRK2 expression was positively related to advanced tumor stage, poor overall survival (OS) and reduced disease-free survival (DFS). Bioinformatic analyses underscore SLITRK2's role in immune response, with its expression significantly tied to immune cell infiltration and marker expression. Based on TMA data, SLITRK2 expression level was positively associated with differentiation, lymph node metastasis, AJCC stage, TNM stage, and poor survival outcome in GC patients. Our findings provided that SLITRK2 may function as a biomarker by regulating immune cell infiltration. In addition, we verified that high SLITRK2 expression was correlated with poor prognosis in GC.

Correlation between thyroid dysfunction and efficacy of immune checkpoint inhibitors in patients with advanced solid tumors.

Immune checkpoint inhibitors (ICIs) are currently the first line of tumor immunotherapy for the treatment of a wide range of tumors. However, the main side effect of immune checkpoint inhibitors is that they cause immune-related adverse events (irAEs) in patients. The relationship between the occurrence of immune side effects in patients and efficacy is controversial. The objective of this study was to confirm the relationship between patients who develop thyroid dysfunction after immune checkpoint inhibitors and efficacy. This study was a retrospective real-world clinical study, and a total of 50 patients with advanced tumors treated with immune checkpoint inhibitors at Anqing People's Hospital from 2020.8 to 2022.5 were retrospectively collected. Among them, 30 patients with hypothyroidism and 20 patients with normal or hyperthyroidism occurred, and the treatment effects and prognostic differences between the two groups were compared. After PD1 treatment in all patients, there were 10 cases of partial remission(PR), 18 cases of stable disease(SD) and 2 cases of progressive disease(PD) in patients who developed hypothyroidism, with a disease control rate(DCR) of 93.3% and objective remission rate(ORR) of 33.3%. There were 0 complete remission (CR) patient, 3 PR patients, 11 SD patients, 6 PD patients, 70.0% DCR and 15.0% ORR in patients who did not develop hypothyroidism. The DCR and ORR of patients who developed hypothyroidism were better than those of non-hypothyroid patients, and the difference was statistically significant (P < 0.05). Kaplan-Meier survival analysis showed that progression-free survival (PFS) reached 9.2months (95% CI 7.726-10.779) in patients who developed hypothyroidism and did not hypothyroidism patients have a PFS of 7.3months (95% CI 5.604-8.505), with a statistically significant difference (P = 0.0341 < 0.05). Further subgroup analysis revealed that among patients who developed hypothyroidism, PFS was 3.3months (95% CI 0.630-5.440) in patients with cholangiocarcinoma, 6.89months (95% CI 5.604-8.505) in patients with non-small cell lung cancer, > 12months in patients with hepatocellular carcinoma, and 11.05months (95% CI 9.308-12.792) in patients with esophageal cancer months and PFS for patients with gastric cancer was 9.74months (95% CI 6.979-12.502). When patients with advanced tumors were treated with immune checkpoint inhibitors, DCR and ORR were higher in patients who developed hypothyroidism, and patients had better PFS. The benefits were greater in patients with gastric, esophageal, and hepatocellular carcinomas.

Association between D-dimer-to-albumin ratio and 28-days all-cause mortality in patients with sepsis.

We aimed to investigate the correlation between the serum D-dimer (D-D) to albumin (ALB) ratio (DAR) and 28-day all-cause mortality in patients with sepsis. Data from sepsis patients admitted to the intensive care unit (ICU) of Wuhan Fourth Hospital from October 2021 to January 2024 were collected. Univariate cox analysis was performed for mortality factors in sepsis patients, and multiple cox regression models were used to analyze independent mortality risk factors. The receiver operating characteristics (ROC) curve was used to analyze the value of DAR in predicting sepsis mortality, and the Kaplan-Meier method was used to plot the survival curve. A total of 833 patients with sepsis in the ICU of our hospital were selected and divided into alive group (n = 574) and death group (n = 171) according to their 28-day survival. In the death group, D-D and DAR levels were higher, while ALB levels was lower than in the alive group. Spearman analysis found that DAR level were positively correlated with APACHE II and SOFA scores. Multivariate cox regression analysis showed that DAR was an independent predictor of all-cause mortality within 28 days of admission for sepsis patients (HR = 17.956, 95% CI 3.435-93.851, p < 0.001). The ROC curve results showed that the cut-off value of DAR was 0.068, with a sensitivity of 78.4% and a Youden index of 0.375, predicting mortality in sepsis patients, with an area under curve (AUC) of 0.767 (95% CI 0.744-0.790, P < 0.001). Further analysis divided patients into low DAR (DAR < 0.068) and high DAR (DA ≥ 0.068) groups based on the optimal cut-off value. Kaplan-Meier analysis found higher mortality in the high DAR group. DAR is an independent predictor of all-cause mortality within 28 days of admission in sepsis patients. Combining these two indicators can improve clinical treatment guidance and reduce the risk of death.

Influence of preoperative glaucoma medication on long-term outcomes of trabeculectomy.

This retrospective study evaluated the association between preoperative topical glaucoma medication containing preservatives and long-term trabeculectomy outcomes in 309 eyes from 201 patients with primary open-angle glaucoma, followed for over 10 years. The Glaucoma Medication Intensity Index (GMII) was calculated to quantify the cumulative preoperative exposure to these medications. Kaplan-Meier analysis revealed cumulative success rates of 89.3%, 59.2%, and 46% at 1, 10, and 20 years postoperatively. At 20 years, the success group had a significantly lower GMII (3.28 vs. 8.74, p = 0.004). A GMII threshold of ≥ 4.35 was associated with poorer long-term intraocular pressure (IOP) control and shorter surgical success duration. Cox regression analysis identified advanced age at surgery, higher GMII, and subsequent cataract surgery as significant risk factors for trabeculectomy failure. These findings underscore the adverse impact of prolonged preoperative use of glaucoma medications on long-term surgical outcomes, highlighting GMII as a valuable predictor for guiding preoperative management strategies.

Real-World Outcomes of Selective RET Inhibitor Selpercatinib in the United States: Descriptive, Retrospective Findings from Two Databases

Objectives: This study described real-world patient characteristics and outcomes among selpercatinib-treated patients in the United States, using the Flatiron Health electronic health record-derived deidentified database (FHD) for advanced/metastatic non-small cell lung cancer (a/mNSCLC) and Optum’s de-identified Clinformatics® Data Mart Database (CDM). Methods: Patients initiating selpercatinib treatment between 08MAY2020 and 30JUN2023 were included. We evaluated real-world time to selpercatinib treatment discontinuation or death (rwTTDd) and time to next treatment or death (rwTTNTd) using Kaplan–Meier analyses. Medication possession ratio (MPR) was estimated as a measure of medication adherence in CDM patients. Results: In a/mNSCLC patients from the FHD (N = 68), the median rwTTDd and rwTTNTd were 22.4 [95%CI: 13.3–NR] and 21.0 [95%CI: 11.6–NR] months, respectively. In CDM, these durations were 12.1 [95%CI: 9.6–NR] and 16.2 [95%CI: 9.6–NR] months for lung cancer (n = 43), while these were not reached for thyroid cancer (n = 24) patients. The median MPR was 0.98 [IQR: 0.84–1.00] among all patients in the CDM (N = 75), with 77.3% of patients adhering (MPR ≥ 0.80) to selpercatinib. Conclusions: Real-world outcomes in this older and frailer patient cohort align with phase 3 trial results, further supporting selpercatinib as the standard of care for patients with RET-altered cancers. Early testing for the detection of RET alterations remains essential.

High 11-ketotestosterone linked to shorter time to castration resistance in recurrent non-metastatic prostate cancer.

The contribution of 11-oxygenated androgens to the progression of lethal prostate cancer (PCa) remains unresolved. We hypothesized that evaluating circulating levels of 11-oxygenated androgens, such as the androgen receptor agonist 11-ketotestosterone (11KT), could serve as a potential predictor of the onset of castration resistant prostate cancer (CRPC). We used mass spectrometry to quantify 11-oxygenated androgens in post-operative plasma samples acquired from 145 patients who subsequently received androgen deprivation therapy (ADT) for biochemical recurrence (BCR) and achieved castrated testosterone (T) levels. Kaplan-Meier survival analyses and multivariable Cox models were used to investigate relationships between steroids and CRPC. Of 145 patients, 31 developed CRPC with a median time to CRPC of 57 months. 11-oxygenated androgens levels were unaffected by ADT, which stands in contrast to the observed changes in T and other steroids. 11KT was the most abundant androgen but was not linked to clinical features. Kaplan-Meier analysis revealed that 11KT levels above the median of 273 pg/mL were associated with a shorter time to CRPC (P = 0.03). In multivariable analyses, this was supported with an adjusted hazard ratio of 2.17 (95% confidence interval (CI) 0.99-4.71; P = 0.05). 11KT is a key component of the hormonal profile predictive of earlier onset of CRPC. Enhancing our understanding of the specific role of 11KT in the progression to CRPC could help optimize hormonal therapy for castration sensitive PCa and CRPC patients.

The Impact of Coronary Ischemia Assessment on Outcomes in Those With Scar-Dependent Ventricular Tachycardia.

Guidance and outcomes of coronary ischemia assessment (IA) in those with structural heart disease (SHD), presenting with monomorphic ventricular tachycardia (MMVT) is unclear. To assess the impact of IA on arrhythmic and non-arrhythmic outcomes in those with SHD. Patients presenting with MMVT over a 6-year period to a tertiary center were retrospectively analyzed. Propensity score-matched analysis was performed comparing those undergoing IA to those who did not. The primary endpoint was a composite of VT recurrence, appropriate ICD therapy, heart failure hospitalization, and death. Secondary analysis of the individual components of the composite was performed. Kaplan-Meier, univariate and multivariate analysis was performed to compare the two groups and derive predictors of poor outcomes. Two hundred and seventeen patients (57.6% ICM) were analyzed. 55.8% underwent IA. Following propensity score-matching, 120 patients remained. At 12 months, freedom from the primary endpoint was 68.3% of those undergoing IA versus 43.3% who did not, p < 0.001, multivariate HR 0.56 (0.34-0.92). This was driven by a reduction in all-cause mortality, with a 12-month survival of 98.3% in those undergoing IA versus 86.5% in those not undergoing IA (p < 0.01). Coronary intervention was associated with a significantly higher event-free 12-month survival compared to those who did not undergo intervention (82.4% vs 51.5%, respectively, p = 0.01). Patients with SHD presenting MMVT who undergo an IA have significantly improved freedom from VT recurrence, appropriate ICD therapies, HF hospitalization, and death compared to those who do not, driven by a reduction in mortality.

Comprehensive assessment of cellular senescence in intestinal immunity and biologic therapy response in ulcerative colitis.

Ulcerative Colitis (UC) is an inflammatory disorder characterized by chronic intestinal inflammation and immune dysregulation. Despite a clear association between cellular senescence and chronic inflammation and immune dysregulation, the mechanisms underlying cellular senescence in UC remain unclear. We screened differentially expressed genes (DEGs) associated with cellular senescence in multiple UC datasets, performed immune infiltration analysis, and constructed clinical diagnostic models. Additionally, we investigated the relationship between key genes related to cellular senescence and disease remission in UC patients undergoing biologic therapy, validating their expression in a single-cell dataset. We identified six DEGs associated with cellular senescence (TWIST1, IGFBP5, MME, IFNG, ME1, FOS). Immune infiltration results indicated strong correlations of four of these genes with immune cells and pathways. Through WGCNA, GO, and KEGG analyses, we found that gene modules strongly associated with the expression of hub genes in cellular senescence were enriched in inflammation-related pathways. In the single-cell dataset, the expression of these six key genes exhibited similarities with Immune infiltration results. Additionally, we constructed a nomogram using these six genes for diagnosing UC, demonstrating good diagnostic capability and clinical efficacy. Kaplan-Meier survival analysis revealed a significant association between changes in the expression levels of these cell genes and disease remission in UC patients undergoing biologic therapy. This study utilizes bioinformatic analysis and machine learning to identify and analyze features associated with cellular senescence in multiple UC datasets. It provides insights into the role of cellular senescence in the premature onset of intestinal aging in UC and offers new perspectives for exploring novel therapeutic targets.

Right atrial strain measured by 2D speckle-tracking echocardiography is associated with poor cardiac outcomes in patients with heart failure.

Right heart failure (HF) is a poor prognostic factor in patients with HF. The right atrial (RA) function has attracted less attention than the right ventricular (RV) function. The association of RA reservoir strain evaluated by 2D speckle-tracking echocardiography (2DSTE) with clinical outcomes in patients with HF remains unclear. We prospectively enrolled patients with HF admitted to our hospital. We measured the RA, RV, left atrial (LA), and left ventricular (LV) strain using 2DSTE before discharge. The RA reservoir strain (RASr) was measured in the global right atrium. The primary endpoints were cardiac death and worsening of HF requiring rehospitalization or intravenous diuretics. Among 226 patients with HF, 72 primary endpoints were recorded during a median follow-up period of 1081days. Kaplan-Meier analysis showed a higher cardiac event rate in the low RASr group than in the high RASr group (P = 0.0089). Multivariate Cox hazard analysis showed that RASr was independently associated with cardiac events after adjusting for confounding factors [hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.51-0.96; P = 0.0347]. Decreased RASr could be a feasible marker of cardiac events in patients with HF.

Orthobiologic therapies delay the need for hip arthroplasty in patients with avascular necrosis of the femoral head: A systematic review and survival analysis.

The aim of this systematic review and survival analysis was to quantify the benefits of orthobiologic augmentation therapies for the treatment of avascular necrosis (AVN) of the femoral head and identify the most effective approach to delay the need for total hip arthroplasty (THA). A systematic review of the literature was performed on PubMed, Scopus, and Cochrane on clinical studies on orthobiologic therapies used alone or as an augmentation to core decompression or other procedures to address hip AVN. A qualitative analysis of the different biological therapies applied was performed. Afterward, the results of these procedures were quantitatively analysed to document their survivorship from THA compared to treatment groups without orthobiologics. Kaplan-Meier analysis was performed for all studies and then by categorising orthobiologics into treatment subgroups. A total of 106 studies were included (4505 patients). Different orthobiologic approaches have been evaluated: cell-based therapies including bone marrow aspirate concentrate (BMAC) and bone marrow mesenchymal stromal cells (BM-MSCs), platelet-rich plasma (PRP), or other bioactive molecules applied in the osteonecrotic area or as intra-arterial injections. The survival analysis at 120 months documented a higher (p < 0.0005) cumulative survivorship with orthobiologics (69.4%) compared to controls (48.5%). The superiority was shown specifically for BMAC (p < 0.0005), BM-MSCs (p < 0.0005), intra-arterial (p < 0.0005) and PRP (p = 0.011) approaches, but the direct comparison of these approaches with their controls confirmed benefits only for BMAC (p < 0.0005). This systematic review and survival analysis demonstrated that orthobiologics have the potential to improve survivorship in patients affected by hip AVN. In particular, the specific analysis of different orthobiologic products supported relevant benefits for BMAC augmentation in terms of survival from the need for THA, while no clear benefits were confirmed for other orthobiologics. Level III.

The 5-factor modified frailty index as a prognostic factor for stereotactic radiosurgery in meningioma management.

Meningiomas are the most frequent primary intracranial malignancy. While surgical resection can confer long term tumor control, stereotactic radiosurgery (SRS) is often used for small, asymptomatic tumors in the adjuvant setting. Frailty has been associated with increased rates of peri-operative morbidity but has yet to be defined in the setting of SRS for meningiomas. We therefore sought to examine the relationship between frailty and clinical/radiographic outcomes of patients with meningiomas who have undergone SRS. A single-center, retrospective cohort study classified patients by their 5-factor modified frailty index (mFI-5) score into pre-frail (0-1) and frail (2-5) at the time of SRS treatment. Evaluations of overall survival (OS), progression free survival (PFS), local control (LC), and distant control (DC) were performed using Kaplan-Meier analysis. Cox proportional hazards regression analysis was used to further define factors associated with OS/PFS. 94 patients met inclusion criteria and underwent SRS for meningioma treatment from 2019 to 2023. Analyses compared prefrail (0-1) and frail (2-5) individuals. Kaplan-Meier analysis demonstrated a near significant association between frailty and OS (HR 3.66, 95% CI 0.49-26.8 p = 0.05) with 3-year OS rates of 75.4% in the pre-frail versus 36.6% in the frail group. However, a significant relationship was demonstrated between frailty and PFS (HR: 2.95 95% CI 1.12-7.81, p = 0.02) with 3-year PFS rates of 90.5% in the pre-frail group versus 49.2% in the frail group. Univariable regression analysis demonstrated that frailty, prior surgical excision, and cumulative tumor volume predicted PFS. Frailty, as assessed by the mFI-5, did not independently predict OS but did predict PFS in individuals with meningioma undergoing SRS.

Utilization rates and heart transplantation outcomes of donation after circulatory death donors with prior cardiopulmonary resuscitation.

Heart donation after circulatory death (DCD) involves mandatory exposure to warm ischemic injury (WII) due to donor cardiac arrest resulting from withdrawal of life-support (WLS). However, potential DCD donors may also experience a cardiac arrest and undergo cardiopulmonary resuscitation (CPR) and associated WII before WLS. We sought to investigate the effect of previous donor-CPR in DCD heart-transplantation (HT). Between January-2020 and April-2023, we identified 11,415 adult HTs in UNOS of whom 9456 met study criteria and had information on donor-CPR. Follow-up was available till April-2024. Study cohort was divided into four groups based on DCD vs. donation after brain death (DBD) status and donor-CPR i.e., DCD/CPR+ (n = 387), DCD/noCPR (n = 305), DBD/CPR+ (n = 5158) and DBD/noCPR (n = 3606); and compared for HT characteristics and outcomes. With DBD/noCPR HTs as reference cohort, there were no significant differences in mortality in other HT cohorts (DCD/CPR+, DCD/noCPR and DBD/CPR+) upto 1-year of follow up using Kaplan-Meier analysis; and both unadjusted and adjusted Cox hazards-ratio models. Results were similar in propensity-matched cohorts. Duration of donor-CPR (≤20 min vs >20 min) did not influence HT survival; and rates of in-hospital secondary outcomes were similar. The utilization rates of both adult DCD/CPR+ (3.39 % to 9.71 %) and DCD/noCPR donors (4.41 % to 10.34 %) increased significantly (p < 0.01) during study period. The utilization rates of both DCD/CPR+ and DCD/noCPR donors have increased at an equal pace. A significant proportion of DCD HTs were from donors with prior CPR, but this was not associated with worse short-term survival.

Targeting PDGF-CC as a promising therapeutic strategy to inhibit cholangiocarcinoma progression.

Cholangiocarcinoma (CCA) is an aggressive malignancy with limited treatment options and poor prognosis. Platelet-Derived Growth Factor CC (PDGF-CC) has been implicated in the progression of various tumors, but its specific role in CCA is not well understood. This study aims to investigate the expression and function of PDGF-CC in CCA and evaluate its potential as a therapeutic target. We conducted gene expression analysis using the GEPIA database to compare PDGF-CC mRNA levels in CCA tissues and normal tissues. Serum samples from CCA patients were analyzed for PDGF-CC protein levels, and immunohistochemistry was used to assess PDGF-CC expression in tissue samples. The impact of PDGF-CC on CCA cell behavior was examined by knocking out PDGF-CC in HuCCT1 and QBC939 cell lines, followed by assessments of cell proliferation, migration, invasion, and colony formation in vitro. Additionally, the effects of PDGF-CC knockout were evaluated in xenograft models. The therapeutic potential of PDGF-CC inhibition was further explored using pharmacological inhibitors and antibodies. PDGF-CC mRNA and protein levels were significantly elevated in CCA tissues and patient sera compared to normal controls. Immunohistochemical analysis confirmed increased PDGF-CC expression in CCA tissues. High PDGF-CC expression correlated with poor overall survival in CCA patients, as shown by Kaplan-Meier analysis. Functional assays revealed that PDGF-CC knockout significantly reduced proliferation, migration, invasion, and colony formation in HuCCT1 and QBC939 cells, the lines with the highest PDGF-CC levels. In vivo, PDGF-CC knockout markedly decreased tumor growth in xenograft models. Pharmacological inhibition of PDGF-CC mirrored the effects of genetic knockout, suggesting it as a viable therapeutic strategy. This study underscores the critical role of PDGF-CC in CCA progression and supports the potential of PDGF-CC inhibitors as a therapeutic approach. Given the association between high PDGF-CC expression and poor prognosis, targeting PDGF-CC may improve outcomes for CCA patients. Further clinical investigations are warranted to develop PDGF-CC-targeted therapies for CCA.

Development and Evaluation of Automated Artificial Intelligence-Based Brain Tumor Response Assessment in Patients with Glioblastoma.

To develop and evaluate an automated, AI-based, volumetric brain tumor MRI response assessment algorithm on a large cohort of patients treated at a high-volume brain tumor center. We retrospectively analyzed data from 634 patients treated for glioblastoma at a single brain tumor center over a 5-year period (2017-2021). The mean age was 56 +/-13 years. 372/634 (59%) patients were male, and 262/634 (41%) patients were female. Study data consisted of 3,403 brain MRI exams and corresponding standardized, radiologist-based brain tumor response assessments (BT-RADS). An artificial intelligence (AI)-based brain tumor response assessment algorithm was developed using automated, volumetric tumor segmentation. AI-based response assessments were evaluated for agreement with radiologist-based response assessments and ability to stratify patients by overall survival. Metrics were computed to assess the agreement using BTRADS as the ground-truth, fixed-time point survival analysis was conducted to evaluate the survival stratification, and associated P-values were calculated. For all BT-RADS categories, AI-based response assessments showed moderate agreement with radiologists' response assessments (F1 = 0.587-0.755). Kaplan-Meier survival analysis revealed statistically worse overall fixed time point survival for patients assessed as image worsening equivalent to RANO progression by human alone compared to by AI alone (log-rank P=0.007). Cox proportional hazard model analysis showed a disadvantage to AI-based assessments for overall survival prediction (P=0.012). AI-based volumetric glioblastoma MRI response assessment following BT-RADS criteria yielded moderate agreement for replicating human response assessments and slightly worse stratification by overall survival. GBM＝ Glioblastoma; RANO＝ Response Assessment in Neuro-Oncology; BTRADS＝ Brain Tumor Reporting and Data System; NLP = Natural Language Processing.

Serum lactate dehydrogenase as a prognostic marker for treatment response in IDH wild-type glioblastoma patients undergoing stupp protocol.

Elevated lactate dehydrogenase (LDH), a marker of tumor aggressiveness and metabolic alterations, may predict treatment response and overall survival across various tumors. This study investigates the correlation between serum LDH levels and clinical outcomes in glioblastoma patients treated with radiotherapy (RT) and temozolomide (TMZ). This retrospective study analysed patients with IDH wild-type glioblastoma (IDH-wt GB) treated at the Radiotherapy Department of Azienda Ospedaliero-Universitaria Senese from 2018 to 2023. Clinical data, including hematologic parameters (e.g., LDH), imaging (MRI), and MGMT promoter methylation status, were collected. All patients received RT and TMZ following the Stupp protocol. Serum LDH levels were measured one week before RT, and Radiological Response (RR) was assessed using RANO criteria. Overall survival (OS), progression-free survival (PFS), and RR were primary endpoints. Statistical analyses included Kaplan-Meier, Cox regression, and decision tree analysis for LDH cut-off determination. In a cohort of 147 IDH wild-type glioblastoma patients treated with the Stupp protocol, the median OS was 14 months and median PFS was 8 months. Elevated baseline LDH levels were associated with significantly poorer outcomes, showing a median OS of 9 months versus 20 months and a median PFS of 6 months versus 13 months for lower LDH levels (p < 0.001 and p = 0.0001, respectively). LDH levels also correlated with RR (p = 0,001), Multivariate analysis confirmed high LDH as an independent predictor of worse OS (HR = 2.31) and PFS (HR = 2.60), suggesting its utility as a prognostic biomarker. Elevated LDH levels before starting the Stupp protocol are clinically significant as they predict poorer overall survival and progression-free survival in glioblastoma patients and worse RR. Incorporating LDH measurements into treatment planning can help identify patients at higher risk of poor outcomes, allowing for more tailored and potentially aggressive treatment strategies to improve management and therapeutic responses in glioblastoma.

Association Between Fatty Liver Index and Incidence of Cataract Surgery in Individuals Aged 50 Years and Older Based on the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) Data: Longitudinal Retrospective Cohort Study.

Cataract is a leading cause of vision impairment. Obesity-related risk factors, including insulin resistance, increase the risk of cataract. The fatty liver index (FLI) is a biomarker for noninvasive fat layer prediction of nonalcoholic fatty liver disease. The FLI has been used to evaluate the metabolic contribution in other organs besides the eye. However, no study exists on the FLI and eye disease. This retrospective cohort study for the association between the FLI and incidence of cataract surgery in individuals older than 50 years was designed to show that a higher FLI is associated with an increased incidence of cataract surgery in individuals aged 50 years and older. This study was retrospectively designed based on the Korean National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) cohort (median follow-up of 9.8 years). Participants were assigned to 1 of 3 groups based on the FLI: low (FLI<30), intermediate (FLI 30-59), or high (FLI≥60). Kaplan-Meier survival analysis was performed on the cumulative incidence of all-cataract and senile-cataract surgery. Multivariable Cox proportional hazards regression models were used to study the association between the FLI group and cataract surgery after adjusting for potential confounders. Of the 138,347 included participants, the incidence of cataract surgery was 12.49% (4779/38,274), 13.95% (6680/47,875), and 14.16% (7496/52,930) in the low, intermediate, and high FLI groups, respectively. After adjusting for all confounding factors, hazard ratios (HRs; 95% CIs) in the high FLI group for all-cataract surgery were 1.111 (1.028-1.199) and 1.184 (1.101-1.274) in men and women, respectively, when compared with the low FLI group. HRs (95% CIs) in the high FLI group for senile-cataract surgery were 1.106 (1.022-1.197) and 1.147 (1.065-1.237) in men and women, respectively, when compared with the low FLI group. The project was conducted between August 2023 and February 2024 without donations from external bodies. Individuals with a higher FLI had a higher risk of all-cataract surgery. This association was maintained even after limiting the analyses to senile-cataract surgery.