Survival Of Patients Research Articles

A phase II trial of Naxitamab plus stepped-up dosing of GM-CSF for patients with high-risk neuroblastoma in first complete remission.

Naxitamab is a humanized form of the murine anti-GD2 monoclonal antibody (mAb) 3F8. In an international trial, naxitamab+GM-CSF was effective against chemo-resistant high-risk neuroblastoma (HR-NB), leading to approval by the Food and Drug Administration. We now report results with patients in 1st complete remission (CR). The primary objective of this phase II protocol 16-1643 (Clinicaltrials.gov NCT03033303) was to assess event-free survival (EFS) of HR-NB patients in 1st CR treated with naxitamab+GM-CSF plus isotretinoin. HR-NB was defined as MYCN-amplified disease (any age) or metastatic disease at age >18 months. Cycles of immunotherapy were administered monthly up to 5 cycles and comprised: 1) subcutaneously-administered priming doses of GM-CSF 250µg/m2/day on days -4-to-0 (Wednesday-Sunday), followed by a step-up to 500µg/m2/day on days +1-to-+5 (Monday-Friday), and 2) naxitamab infused intravenously (30-90") on days +1, +3, and +5 (Monday-Wednesday-Friday, i.e., 3 doses/cycle). Naxitamab was 3mg/kg/infusion (9mg/kg/cycle, i.e., ~270mg/m2/cycle). Isotretinoin 160mg/m2/day started post-cycle 2, x14 days/course, x6 courses. Fifty-nine HR-NB patients (53 stage 4, 6 stage 3) were enrolled 2/2017-7/2020. At 36 months, EFS/OS were 73%/93%, but 50/59 patients received post-protocol treatment (vaccine and/or DFMO). 6/18 relapses were isolated in the central nervous system (CNS). Longer time from diagnosis to enrollment was a significantly adverse prognostic factor (p=0.04). 21/59 patients took no isotretinoin. Treatment was tolerable allowing outpatient administration. Naxitamab+GM-CSF is a good option to consolidate 1st CR of HR-NB patients, including those who did not undergo ASCT. Efforts to prevent CNS relapse are warranted.

Abstract A036: Comparison of immunotherapies response in hepatocellular carcinoma HCC with viral hepatitis vs non-viral hepatitis

Abstract Background: Hepatocellular carcinoma (HCC), the most common liver cancer, accounts for 80% of diagnosed cases. Immunotherapy is increasingly used for advanced HCC and other solid tumors. Approximately 13% of cancers are associated with infections. HCC etiology varies by regionally, with 54% of cases in Asia and sub-Saharan Africa due to hepatitis B, while hepatitis C is more common in Italy and Japan. Hepatitis infections disrupt liver signaling, causing inflammation and abnormal cell regeneration. In HCC progression, inflammation serves as a “double-edged sword.” While chronic inflammation is a significant driver of tumor development and immune evasion, it can also promote tumor cell death, either directly through ferroptosis or indirectly by enhancing anticancer immune responses, thereby potentially inhibiting HCC progression. This study aimed to evaluate immunotherapy response in HCC associated with viral hepatitis compared to non-viral hepatitis. Methods: HCC patients were analyzed using data from the cBioPortal database, from a cohort study of hepatobiliary cancers. Only HCC patients who received nivolumab, pembrolizumab, atezolizumab, bevacizumab, durvalumab, tremelimumab, ipilimumab, ramucirumab, or daratumumab, either as monotherapy or in combination were included. We excluded all cases of cholangiocarcinoma (CCA), HCC with CCA, and those not treated with immunotherapy. We calculated median overall survival (OS) for immunotherapy-treated HCC patients with viral hepatitis compared to those with non-viral hepatitis. Survival analysis was conducted using the Kaplan–Meier (KM) method. Results: Among 1,370 hepatobiliary cancer cases, 289 were identified as HCC. After excluding patients who did not receive immunotherapy, a total of 101 cases remained, of which 56 (55.4%) had viral HCC, and 45 (44.6%) had non-viral HCC. Most patients were white 62 (61%), and 27 (26%) had cirrhosis. Additionally, 66 (65%) had TERT mutations, 45 (43%) had TP53 mutations. Of the total, 52 (51%) had died, while 49 (48%) were still alive. All patients received at least one immunotherapy cycle, with 65 (64.4%) receiving it as a palliative setting. Viral HCC was associated with a median OS of 60 months (95% CI,38.24-NA), while non-viral HCC showed median OS of 40 months (95% CI,25.34-NA) (p=0.106). Conclusion: Our study highlighted that HCC patients with underlying viral infections achieve better outcomes from immunotherapy, evidenced by a longer OS compared to patients with non-viral HCC. This suggests that viral HCC may have a unique tumor biology or immune environment that enhances the response to immunotherapy, leading to improved survival outcomes relative to non-viral cases. Citation Format: Saifudeen Abdelrahim, Ebtesam Al-Najjar, Bayan Khasawneh, Abdullah Esmail, Ala Abudayyeh. Comparison of immunotherapies response in hepatocellular carcinoma HCC with viral hepatitis vs non-viral hepatitis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr A036.

Circulating GDF15 May Estimate Vasculitis Activity and Predict Poor Outcomes During the Disease Course of ANCA-Associated Vasculitis

Objective: This study investigated whether circulating growth differentiation factor 15 (GDF15) at diagnosis could estimate the Birmingham Vasculitis Activity Score (BVAS) and potentially predict all-cause mortality and end-stage kidney disease (ESKD) during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: This study included 79 patients selected from a cohort of Korean patients with AAV. Circulating GDF15 was measured from patients’ sera collected at diagnosis and stored at −80 °C. Clinical data at diagnosis and during follow-up were reviewed. Results: The median age was 64.0 years (40.5% men, and 59.5% women). Median circulating GDF15 was measured as 995.0 pg/mL. Of the 79 patients, 6 (7.6%) died and 20 (25.3%) progressed to ESKD during the disease course. Circulating GDF15 levels were significantly correlated with BVAS (r = 0.340) at diagnosis. Patients with circulating GDF15 ≥ 3350.5 pg/mL exhibited a significantly higher risk of the highest tertile of BVAS than those without (relative risk [RR], 11.229). Similarly, patients with circulating GDF15 ≥ 2239.5 pg/mL and ≥2208.5 pg/mL showed higher risks of all-cause mortality (RR, 7.733) and progression to ESKD (RR 7.125) than those without. Patients with circulating GDF15 ≥ 2239.5 pg/mL and ≥2208.5 pg/mL also showed significantly lower patient and ESKD-free survival rates than those without. Conclusions: Circulating GDF15 at diagnosis is useful in estimating BVAS and potentially predicts all-cause mortality and ESKD progression in patients with AAV.

Severe pneumonia caused by Chlamydia abortus complicated by hemophagocytic syndrome: a case report

BackgroundPneumonia caused by Chlamydia abortus (C. abortus) is uncommon, particularly when complicated by severe acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal disease characterized by the uncontrolled activation and non-malignant expansion of macrophages and T lymphocytes. This report describes a case of severe pneumonia complicated by hemophagocytic lymphohistiocytosis, caused by Chlamydia abortus.Case introductionA 42-year-old female with no history of underlying medical conditions, no known exposure to poultry or avian animals, and no consumption of undercooked sheep or ewes contaminated with infected placenta, presented to the respiratory medicine department with a 3-day history of fever, cough, and sputum production. Initially diagnosed with community-acquired pneumonia, she was treated with piperacillin-tazobactam for 5 days. However, despite 12 h of high-flow oxygen therapy, her oxygenation did not improve, and she was transferred to the ICU, where she received additional treatments, including moxifloxacin and methylprednisolone. Her condition worsened further, prompting the initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and bronchoalveolar lavage for metagenomic next-generation sequencing (mNGS) analysis. The mNGS results identified Chlamydia abortus with a count of 180,791, leading to the cessation of moxifloxacin and the addition of omadacycline to her regimen. After 13 days of ECMO therapy, her condition improved, and the ECMO was discontinued. The endotracheal tube was successfully removed 15 days after intubation. However, 3 days later, the patient developed recurrent fever, pancytopenia, elevated ferritin, blood lipids, soluble CD25, and decreased natural killer cell activity, leading to a diagnosis of hemophagocytic lymphohistiocytosis (HLH). She was treated with ruxolitinib, etoposide, and other supportive medications. Despite treatment, her condition continued to deteriorate. Three days later, the family opted to discontinue therapy due to financial constraints. She passed away 12 h later.ConclusionChlamydia abortus infection can result in severe acute respiratory distress syndrome (ARDS), necessitating prompt diagnosis and active clinical intervention. This case is unique due to the rare occurrence of HLH following Chlamydia abortus infection, a pathogen not commonly associated with this condition. Metagenomic next-generation sequencing (mNGS) offers a distinct advantage in rapidly and accurately identifying rare pathogen infections, while extracorporeal membrane oxygenation (ECMO) can be an effective treatment for severe pneumonia caused by Chlamydia abortus. It highlights the importance of early recognition and management of HLH in patients with severe, unexplained infections, particularly in those with unusual pathogens. Additionally, Chlamydia abortus infection may be complicated by HLH. Clinicians should remain vigilant for patients presenting with unexplained high fever, hepatosplenomegaly, and pancytopenia, and HLH screening should be initiated promptly. Early intervention can significantly improve patient survival rates.

A Robust YOLOv8-Based Framework for Real-Time Melanoma Detection and Segmentation with Multi-Dataset Training

Background: Melanoma, the deadliest form of skin cancer, demands accurate and timely diagnosis to improve patient survival rates. However, traditional diagnostic approaches rely heavily on subjective clinical interpretations, leading to inconsistencies and diagnostic errors. Methods: This study proposes a robust YOLOv8-based deep learning framework for real-time melanoma detection and segmentation. A multi-dataset training strategy integrating the ISIC 2020, HAM10000, and PH2 datasets was employed to enhance generalizability across diverse clinical conditions. Preprocessing techniques, including adaptive contrast enhancement and artifact removal, were utilized, while advanced augmentation strategies such as CutMix and Mosaic were applied to enhance lesion diversity. The YOLOv8 architecture unified lesion detection and segmentation tasks into a single inference pass, significantly enhancing computational efficiency. Results: Experimental evaluation demonstrated state-of-the-art performance, achieving a mean Average Precision (mAP@0.5) of 98.6%, a Dice Coefficient of 0.92, and an Intersection over Union (IoU) score of 0.88. These results surpass conventional segmentation models including U-Net, DeepLabV3+, Mask R-CNN, SwinUNet, and Segment Anything Model (SAM). Moreover, the proposed framework demonstrated real-time inference speeds of 12.5 ms per image, making it highly suitable for clinical deployment and mobile health applications. Conclusions: The YOLOv8-based framework effectively addresses the limitations of existing diagnostic methods by integrating detection and segmentation tasks, achieving high accuracy and computational efficiency. This study highlights the importance of multi-dataset training for robust generalization and recommends the integration of explainable AI techniques to enhance clinical trust and interpretability.

CGREF1 facilitates the cell proliferation, migration and invasion of hepatocellular carcinoma cells via regulation of EIF3H/ Wnt/β-Catenin signaling axis

BackgroundAlthough Cell growth regulator with EF-hand domain 1 (CGREF1) has been predicted to be upregulated in multiple cancer types, its definitive function role in carcinogenesis, particularly in hepatocellular carcinoma (HCC), remains poorly characterized.MethodsComprehensive bioinformatics analysis was initially conducted using the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to investigate CGREF1 mRNA expression patterns in HCC tissues and their clinical correlation with patient survival outcomes. Experimental validation was subsequently performed through real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and Western blot techniques. Functional characterization studies employing genetic knockdown and overexpression models in HCC cell lines demonstrated CGREF1’s regulatory effects on malignant phenotypes, as evidenced by 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and Transwell migration and invasion assays. were adopted to investigate the role of CGREF1 in the proliferation, invasion, and migration of HCC cells. Mechanistic investigations integrating bioinformatics predictions with Western blot analysis revealed CGREF1 mediated-modulation of the Wnt/β-Catenin signaling axis, elucidating its molecular underpinnings in HCC progression.ResultsThe results demonstrated that CGREF1 is highly expressed in HCC tissues, and HCC patients with elevated CGREF1 expression exhibited significantly shorter survival times. Upregulation of CGREF1 promoted the proliferation, migration, and invasion of HCC cells, whereas inhibition of CGREF1 expression suppressed these phenotypes. Mechanistically, CGREF1 activates the Wnt/β-Catenin signaling pathway through the upregulation of eukaryotic translation initiation factor 3 H subunit (EIF3H). Furthermore, partial inhibition of EIF3H attenuated the effects of CGREF1 overexpression on the proliferation, migration, and invasion of HCC cells.ConclusionCGREF1 is upregulated in HCC and acted as an oncogene through the CGREF1/EIF3H/Wnt/β-Catenin signaling axis. These findings suggest that CGREF1 may emerge as a potential therapeutic target for HCC.

Fabrication of Folic Acid-Derived Carbon Dot-Conjugated Chitosan Nanospheres as Theragnostic Agents for pH-Responsive Anticancer Drug Delivery.

The favorable success rate in cancer treatment predominantly depends on precise diagnosis with target-specific drug delivery, which can regulate the patient survival outcome rate. Moreover, proper tracking of the system's pH is very much crucial as most of the therapeutic's action and release rate depend on it. Therefore, this work has been intended to fabricate a folic acid-derived carbon dot (FACD) decorated with chitosan (Cs) in order to form nanospheres (FACD-Cs-Ns) for anticancer doxorubicin hydrochloride (Dox.HCl) drug delivery through imaging in cancer therapeutic treatment. The engineered FACD-Cs-Ns demonstrated a spherical shape with an extensive surface area, rich in carboxyl and hydroxyl groups that play a key role in its pH-responsive characteristics through protonation and deprotonation interactions. Thanks to their impressive fluorescence traits and excellent stability, FACD-Cs-Ns are particularly well suited for imaging-guided cancer therapy. Their remarkable cytocompatibility with normal cells and significant toxicity toward cancer cells, along with pH-responsive properties, render them as ideal candidates for targeted drug delivery to cancer cells. The G2/M and S phases' arrest in the cell cycle analysis study once more validated excellent in vitro experimental conditions. The impressive selectivity and cytotoxicity of Dox-loaded FACD-Cs-Ns toward cancer cells can be attributed to enhanced cellular uptake via folate-receptor-mediated endocytosis, which is overexpressed in these cells. These findings elucidate that the FACD-Cs-Ns nanoprobe is an excellent material for pH-responsive anticancer drug delivery and image-guided cancer therapy.

Abstract B040: Streamlining survival analysis with an automated machine learning pipeline: A case study in kidney renal clear cell carcinoma

Abstract Background: Accurate survival prediction in cancer patients is crucial for personalized oncology, directly influencing treatment decisions and patient care. Integrating multi-omics data with clinical information can significantly enhance prognostic models. However, existing methods often necessitate extensive manual preprocessing and specialized bioinformatics expertise, limiting their practical use in research and clinical settings. This study presents the Cancer Patient Survival Model (CPSM), an R package providing an automated, streamlined pipeline for generating reliable, interpretable survival predictions from complex, high-dimensional data. Objective: The objective of this case study is to evaluate the utility of CPSM in analyzing survival probabilities and identifying prognostic markers for Kidney Renal Clear Cell Carcinoma (KIRC), using comprehensive data from The Cancer Genome Atlas (TCGA). Methods: We analyzed RNA sequencing data comprising 38,712 transcripts along with clinical variables from 534 KIRC patients. Using the preprocessing modules of the CPSM, 526 samples were retained and randomly split into training (90%) and independent test (10%) sets. CPSM's feature selection modules identified three distinct feature sets: (1) three key clinical variables (age, tumor subtype, histological grade), (2) a Prognostic Index (PI) score from nine genes selected via LASSO Cox regression, and (3) a set of univariate significant genes. Using CPSM’s model development module, we constructed four survival models: (1) Model 1 - clinical features only, (2) Model 2 - the PI score alone, (3) Model 3 - a combination of the PI score and key clinical features, and (4) Model 4 - an integration of significant univariate clinical and gene expression features. The performance of the models was evaluated using the concordance index (C-Index) and Integrated Brier Score (IBS). Results: Model 3, which integrated clinical features and the PI score, showed the best performance, achieving a C-Index of 0.79 in the training set and 0.76 in the test set, with IBS values of 0.16 and 0.23, respectively. A specific patient case (TCGA-CJ-6030-01) demonstrated that Model 3 predicted a median survival time of 73.81 months, within 5% of the actual survival time, underscoring its clinical relevance. Moreover, CPSM produced an intuitive nomogram with a C-Index of 0.76, allowing predictions of 1-year, 3-year, and 5-year survival probabilities, serving as a valuable tool for clinical decision-making. Conclusions: CPSM signifies a notable advancement in automated survival analysis by effectively integrating molecular and clinical data. The superior performance of Model 3 highlights the advantages of combining PI scores with clinical features to enhance prognostic accuracy in KIRC. This study emphasizes CPSM's potential utility in personalized oncology and establishes a foundation for future research on its application across various cancer types, including the integration of additional multi-omic data to further improve predictive performance. Citation Format: Harpreet Kaur, Pijush Das, Kevin Camphausen, Uma Shankavaram. Streamlining survival analysis with an automated machine learning pipeline: A case study in kidney renal clear cell carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B040.

Exploration of the Prognostic Value of m5C Methylation Protein NOP2 and NSUN6 in Colon Cancer.

Background: Colorectal cancer is a prevalent malignancy with high incidence and poor prognosis. This study explores the clinical significance of 5-methylcytosine RNA modification factors, specifically the NOP2/Sun RNA Methyltransferase (NSUN) family, in colorectal cancer. Methods: Utilizing data from The Cancer Genome Atlas database, we analyzed the expression levels of NSUN family members in tumor tissues, their prognostic relevance, and their relationship with immune cell infiltration. To further investigate, paraffin-embedded cancer tissue microarrays were used to assess the expression of NOP2 Nucleolar Protein (NOP2) and NSUN6 in colorectal cancer tissues and adjacent normal tissues. The correlation between the expression of these genes and patient prognosis was also examined. Results: Bioinformatic analysis revealed that NOP2 is highly expressed in tumors, whereas NOP2/Sun RNA Methyltransferase 6 (NSUN6) is linked to poor prognosis. Immune infiltration analysis demonstrated that NOP2 expression is significantly correlated with varying levels of immune cell infiltration, including a positive association with myeloid-derived suppressor cells (MDSCs), M1 macrophages, and natural killer cells and a negative correlation with regulatory T cells and M2 macrophages. NSUN6 expression showed a significant positive correlation with MDSC infiltration. Clinical sample analysis indicated that NOP2 expression is strongly associated with tumor grade and nerve invasion, whereas NSUN6 is significantly related to nerve invasion. Survival analyses revealed that high levels of NOP2 and NSUN6 are linked to shorter overall survival. Notably, NSUN6 expression, vascular invasion, and T stage emerged as key predictors of colorectal cancer patient survival. Conclusions: These findings suggest that NOP2 and NSUN6 may serve as valuable molecular markers for predicting poor prognosis in colorectal cancer, with potential applications in clinical decision-making.

In-Hospital Proximal Femoral Fracture Mortality and Anesthesia: Do the First Postoperative 72 h Matter?

Background/Objectives: Proximal femoral fractures (PFFs) are a common worldwide ailment, causing high morbidity and mortality among the elderly, with one-year mortality estimated at 15–30%. This study aimed to identify factors influencing in-hospital patient survival after proximal femoral fracture surgery. Methods: A retrospective cohort study of patients over 65 admitted to an orthopedic surgery department due to a PFF over five years was carried out. Medical records, surgery reports, anesthesia and post-anesthesia care unit sheets, and laboratory archives were reviewed. Results: The study group consisted of 48 patients who died during the first postoperative week, while the control group consisted of 69 patients who were discharged for rehabilitation after a week. The study group was older, less active, and had higher rates of comorbidities. Anesthetic factors, such as the type of anesthesia and admixture of drugs, did not have a significant association with mortality. However, a binary logistic regression showed that age (OR = 1.15, p < 0.001), intraoperative lactate levels (OR = 5.86, p < 0.001), and post-anesthesia care unit (PACU) overnight stays (OR = 17.54, p < 0.001) were significantly associated with early mortality. Conclusions: The study highlights the challenge of identifying PFF patients at risk of early mortality and the need to better understand the decision-making algorithm to create a reliable scale that can predict mortality and adjust treatment. In our study, solid mortality parameters were age and intraoperative lactate levels. The most significant parameter was PACU overnight stay, which represents the anesthesiologist’s soft-skill-based decision that is challenging to scale and reproduce.

Long-Term Outcomes in Patients With Non-Ampullary Duodenal Neuroendocrine Tumors

Objectives: Although non-ampullary duodenal neuroendocrine tumors (NADNETs) are rare neoplasms, their incidence has been increasing. In this study, we aimed to analyze the long-term outcomes of patients with NADNETs who underwent endoscopic resection (ER) or surgery.Methods: This retrospective study included 55 adults (aged 26–78 years) diagnosed with NADNETs between 2009 and 2022 at Seoul National University Hospital. We categorized the patients into 3 groups: 21 underwent ER, 28 underwent surgical resection, and 6 had no detectable residual tumors after the initial biopsy during the follow-up period. Continuous data were examined using the Mann–Whitney U or Kruskal–Wallis tests, and categorical variables were analyzed using the χ<sup>2</sup> or Fisher’s exact tests.Results: A total of 21 patients, with a mean tumor size of 9.2±5.3 mm, underwent successful ER. After ER, three patients experienced perforation (14% [3/21]); two underwent primary repair surgery, and one recovered with conservative treatment. The mean tumor size of 28 patients who underwent surgical resection was 13.9±6.7 mm. There were no cases of postoperative bleeding or perforation; however, four patients experienced ileus and required prolonged hospital stays. The median follow-up periods for patients who underwent ER, surgical resection, and removal after the initial biopsy were 42, 48, and 42.5 months, respectively. During the follow-up period, no recurrence was observed in any group.Conclusions: Recurrence-free survival in patients undergoing ER for NADNETs, with an endoscopically measured size of approximately 10 mm, was comparable to that of patients undergoing surgical resection. However, ER carried a relatively high risk of perforation due to the challenging anatomical access and thin duodenal wall.

DLK1 distinguishes subsets of NF1-associated malignant peripheral nerve sheath tumors with divergent molecular signatures

Abstract Purpose: MPNST is the leading cause of premature death among individuals with NF1 and the transcriptional aberrations that precede malignant transformation and contribute to MPNST tumorigenesis remain poorly defined. Alterations involving CDKN2A and components of PRC2 have been implicated as early drivers of PNST evolution, but these events do not occur in all MPNST. Accordingly, emerging data has begun to highlight the importance of molecular-based stratification to improve outcomes in patients with NF1-PNST. Experimental design: Here we perform an integrated analysis of multiple, independent datasets obtained from human NF1 patients to gain critical insight into PNST evolution and MPNST heterogeneity. Results: We show that DLK1 is significantly increased in MPNST and provide evidence that DLK1 overexpression may precede histological changes consistent with malignancy. In complementary analyses, we find that serum levels of DLK1 are significantly higher in both mice and humans harboring MPNST compared to those without malignancy. Importantly, while DLK1 expression is increased in MPNST overall, through the integration of multiple, independent datasets we demonstrate that divergent levels of DLK1 expression distinguish MPNST subsets characterized by unique molecular programs and potential therapeutic vulnerabilities. Specifically, we show that overexpression of DLK1 is associated with the reactivation of embryonic signatures, an immunosuppressive microenvironment and a worse overall survival in patients with NF1-MPNST. Conclusions: Collectively, our findings provide critical insight into MPNST tumorigenesis and support prospective studies evaluating the utility of DLK1 tissue and serum levels in augmenting diagnosis, risk assessment and therapeutic stratification in the setting of NF1-PNST.

Segmentectomy Versus Wedge Resection for Stage IA Lung Adenocarcinoma—A Population-Based Study

Background: Sublobar resection (SLR), including segmentectomy and wedge resection (WR), is an alternative to lobectomy for early-stage lung cancer due to its potential benefits in preserving lung function. However, the comparative outcomes between segmentectomy and WR for stage IA lung adenocarcinoma are equivocal. This population-based study aimed to compare overall survival between segmentectomy and WR. Methods: Data on patients with clinical stage IA lung adenocarcinoma were collected from the Taiwan Cancer Registry between 2011 and 2018. The primary endpoint was overall survival. Further subgroup survival analyses were conducted based on tumor size. Propensity score matching (PSM) was used to balance baseline differences such as age and tumor stage between the two groups. Predictors of survival other than the surgical procedure were analyzed using a Cox regression model. Results: In total, 6598 patients with stage IA lung adenocarcinoma undergoing SLR between 2011 and 2018 were enrolled, including 2061 and 4537 receiving segmentectomy and WR, respectively. The mean age was 60.3 ± 11.7 years, 66.2% were female, and 81.5% never smoked. After PSM, segmentectomy was associated with significantly better overall survival than WR (p = 0.019), especially for tumors larger than 2 cm (p < 0.001). Aside from segmentectomy, age ≤ 75 years, well-differentiated tumors, small tumor size, and the absence of nodal metastasis were associated with better overall survival. Conclusions: Segmentectomy offered superior overall survival for patients with tumors larger than 2 cm. For tumors smaller than 2 cm, the outcomes of segmentectomy and WR were comparable, offering flexibility in surgical decision-making. These findings highlight the need for individualized surgical approaches based on tumor characteristics.

Transplantation of Patients with Hepatocellular Carcinoma Through Increased Utilization of Machine Perfusion Technology

Background. With the intent to mitigate waitlist disparities, the median model for end-stage liver disease (MELD) at transplant minus 3 policy nevertheless decreased access to liver transplant for patients with hepatocellular carcinoma (HCC). However, the adoption of machine perfusion (MP) technologies has shown promise in improving deceased donor graft yield and utilization. To understand current use for patients with HCC, we examined liver transplant patterns with MP and the characteristics of patients with HCC receiving an MP liver. Methods. Adult patients with HCC undergoing deceased donor liver transplant from September 29, 2021, to March 30, 2024, were identified using the United Network for Organ Sharing Standard Transplant Analysis and Research files. Patients were excluded if listed as status 1A or they underwent multiorgan or split liver transplant. Multivariate analysis compared patients with HCC receiving an MP liver with those receiving a static cold storage liver. Results. Of 3774 liver recipients with HCC, 593 (15.7%) underwent transplant with an MP graft. Compared with patients donation after circulatory death graft receiving a graft with static cold storage preservation, those with MP had less advanced disease (ie, Child-Pugh class C cirrhosis 22.9% versus 29.9%, P < 0.01) and lower median match MELD (13 versus 17, P < 0.001). Tumor characteristics were similar between groups, including alpha-fetoprotein level, maximum tumor size, and locoregional treatments. Donor factors, and not tumor burden, were most predictive of receipt of an MP liver (donation after circulatory death graft: odds ratio [OR], 14.81; macrosteatosis >30%; OR, 3.85; donor age older than 60 y; OR, 2.34). A shorter waitlist time (6.5 versus 7.2 mo, P < 0.01), with similar 1-y patient survival (93.6% versus 93.2%, P = 0.82) and graft survival (92.0% versus 91.6%, P = 0.84), was also noted in patients undergoing MP transplant. Conclusions. The strategic use of MP livers may improve graft utilization and access to liver transplants, helping offset the disadvantages of the MELD at transplant minus 3 policy for patients with HCC.

Plasma Circulating lncRNAs: MALAT1 and NEAT1 as Biomarkers of Radiation-Induced Adverse Effects in Laryngeal Cancer Patients

Background: The majority of head and neck cancers (HNCs) occur in the larynx. In clinical practice, adverse effects are frequently observed in laryngeal cancer (LC) patients undergoing radiotherapy (RT). Therefore, investigating markers that can predict these unfavorable events is of interest. Long non-coding RNAs (lncRNAs) have emerged as potential biomarkers for the early identification of patients susceptible to post-RT toxicity. MALAT1 and NEAT1 regulate various cellular processes, the inflammatory response, and resistance to anti-cancer treatments; however, their impact on the portability of post-RT adverse effects remains unknown. The aim of this study was to evaluate the clinical value of two plasma-circulating lncRNAs, MALAT1 and NEAT1, as predictive biomarkers for post-RT adverse effects in LC patients. Methods: The expression levels of the studied lncRNAs were determined using real-time quantitative reverse transcription PCR (qRT-PCR) in plasma samples obtained from 70 LC patients before the initiation of RT. These levels were then correlated with patient outcomes. Results: A low expression of MALAT1 was associated with a significantly higher probability of anemia, liver failure, and severe malnutrition (OR = 5.36; p = 0.040, OR = 6.07; p = 0.037, OR = 9.75; p < 0.001, respectively) after the completion of RT. Similarly, patients with low NEAT1 expression had a significantly higher risk of anemia, liver failure, and mild or severe malnutrition (OR = 5.26; p = 0.020, OR = 5.70; p = 0.016, OR = 13.09; p = 0.002, respectively). Simultaneous lower expression levels of both lncRNAs were significantly associated with shorter median overall survival (OS) in RT-treated LC patients (HR = 5.44; p = 0.001). Conclusions: The analysis of MALAT1 and NEAT1 expression indicates clinical utility in predicting toxic events induced by RT-based therapy.

Low expression of CD39 on monocytes predicts poor survival in sepsis patients

BackgroundSepsis is a critical condition associated with high morbidity and mortality, emphasizing the need for reliable biomarkers for its diagnosis and prognosis. This study uses advanced immunological techniques to evaluate monocytic CD39 (mCD39) expression as a potential marker in sepsis.MethodsThis prospective observational cohort study included 206 participants from the First Affiliated Hospital, Zhejiang University School of Medicine between April 2022 and September 2023. Participants were categorized into four groups: healthy donors, patients with mild infections, post-cardiac surgery patients (non-infectious inflammation), and sepsis patients. Peripheral Blood Mononuclear Cells were analyzed using mass cytometry time-of-flight (CyTOF) with a 42-marker immune panel and flow cytometry targeting monocytes. Statistical analyses included ROC curves for diagnostic and prognostic performance and Kaplan–Meier survival analysis for prognostic evaluation.ResultsSepsis patients exhibited significantly lower monocytic CD39 expression than mild infection and post-surgery groups (p < 0.05). The diagnostic performance analysis revealed that mCD39 effectively distinguished sepsis from mild infection (AUC = 0.877) and non-infectious inflammation (AUC = 0.935). Prognostic analysis identified low mCD39 expression as a strong predictor of short-term survival, with a 7-day survival AUC of 0.85 (p = 0.037). Kaplan–Meier analysis showed that sepsis patients with low mCD39 expression had significantly lower 28-day survival rates (56.7% vs. 80.6%, p = 0.016).ConclusionsLow CD39 expression on monocytes might serve as a potential diagnostic biomarker and a strong predictor of poor prognosis in sepsis patients.

Prognostic Significance of Key Molecular Markers in Thyroid Cancer: A Systematic Literature Review and Meta-Analysis

Background: Thyroid cancer (TC) involves diverse genetic alterations, with their prognostic significance often debated. Objectives: This study evaluates the impact of BRAF, TERT promoter, TP53, and PI3K pathway mutations detected via Next-Generation Sequencing (NGS) on overall survival (OS) and disease-free survival (DFS) in follicular-derived TC patients. Methods: A comprehensive search was conducted in MEDLINE, Scopus, and EMBASE databases from 2013 to 2023 for studies using NGS on TC patients. Hazard ratios (HR) and 95% confidence intervals (CI) for OS and DFS were extracted from original studies or estimated from Kaplan–Meier curves (KMC). A random-effects model, weighted by inverse variance, was used to calculate pooled HRs. Publication bias was assessed using Egger’s regression test and visual funnel plot analysis. Results: Of the 3921 initial studies, nine studies involving 1075 patients were included in the meta-analysis. BRAF mutations showed no significant effect on OS (HR = 1.11, 95% CI: 0.66–1.88) or DFS (HR = 1.23, 95% CI: 0.66–2.29). In contrast, TERT promoter mutations were strongly associated with worse OS (HR = 1.90, 95% CI: 1.17–3.09) and DFS (HR = 2.76, 95% CI: 1.86–4.10). TP53 and PI3K pathway mutations were linked to shorter OS (HR = 2.87, 95% CI: 1.44–5.86 and HR = 2.17, 95% CI: 1.05–4.15, respectively), though their impact on DFS remains unclear due to limited data. Conclusions: These findings highlight TERT promoter mutations as strong prognostic markers for both OS and DFS, while TP53 and PI3K mutations indicate higher mortality risk.

Prognostic Value of B-Type Natriuretic Peptide Level in Patients With Heart Failure With a Higher Left Ventricular Ejection Fraction.

In heart failure (HF) patients with a higher left ventricular ejection fraction (LVEF), the B-type natriuretic peptide (BNP) level is yet to be fully assessed. Accordingly, we hypothesized that the BNP level should be higher in patients with a higher LVEF range based on the previous finding that such patients were associated with a worse prognosis. In our multicenter, prospective, observational cohort for the composite endpoint of all-cause death and readmission due to HF, including patients with LVEF >40% at hospital discharge, we obtained LVEF, E/e', and BNP levels in 231 patients. The concurrent atrial fibrillation (AF) was confirmed by electrocardiogram. Patients were divided into HF with mildly reduced EF (HFmrEF), HF with preserved EF (HFpEF) with LVEF ≥50 and <60%, and HFpEF with LVEF ≥60%. The BNP levels were not significantly different among these groups (median [interquartile range]: 195 [110-348] vs. 242 [150-447] vs. 220 [125-320] pg/mL, respectively; P=0.422). In contrast, a BNP level of ≥377 pg/mL could significantly differentiate event-free survival (P<0.001). In the multi-covariate Cox proportional hazards model, the BNP level was significantly related to event-free survival independent of LVEF, E/e', and concurrent AF. Without confounding the effects of LVEF, E/e', and concurrent AF, higher BNP levels are significantly and independently associated with event-free survival in HF patients with LVEF>40%.

Network pharmacological approach combined with weighted gene co-expression network analysis identifies CDKN2A as the keg target of Changweiqing against colorectal cancer

Background and objectiveChangweiqing (CWQ) is a Chinese herbal formula for the treatment of the gastrointestinal tract diseases, but its role in the treatment of colorectal cancer (CRC) has not been clarified. This study aimed to explore the molecular mechanism of CWQ in CRC treatment through bioinformatics analysis and network pharmacology.MethodsTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction database were used to collect the bioactive components of CWQ. The databases including DisgeNET, GeneCards, MalaCards, Online Mendelian Inheritance in Man and Comparative Toxicogenomics were used to obtain CRC-related targets. The Cancer Genome Atlas - colon adenocarcinoma dataset was used to obtain prognosis-related genes in CRC based on weighted gene co-expression network analysis (WGCNA). A protein-protein interaction network was constructed to screen core targets, with STRING database and Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery database. Molecular docking was performed with AutoDock Vina software. Core targets were further analyzed using Gene Expression Profiling Interactive Analysis platform, Human Protein Atlas database, University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) and GeneMANIA database. In vitro experiments were further performed to investigate the effects of quercetin, one of the main components of CWQ, on CRC cells.Results6356, 1901 and 2980 CRC-related genes were obtained from differential expression analysis, WGCNA and open access databases, respectively. CWQ contained a total of 70 bioactive ingredients, of which 64 ingredients had a total of 836 therapeutic targets. Functional enrichment analysis indicated that CWQ may be involved in regulating pathways in cancer, MAPK signaling pathway and AGE-RAGE signaling pathway, and further analysis identified 14 core targets of CWQ. These core targets were significantly correlated with cell cycle, p53 signaling pathway, FoxO signaling pathway and pathways in cancer. Among these core targets, cyclin-dependent kinase inhibitor 2 A (CDKN2A) expression was closely associated with shorter overall survival and clinical stage of CRC patients. The main bioactive ingredients of CWQ targeting CDKN2A were quercetin, luteolin, kaempferol, isorhamnetin, 7-O-methylisomucronulatol and 7-Methoxy-2-methyl isoflavone. Additionally, quercetin caused G0/G1 phase arrest and inhibited the viability of CRC cells.ConclusionThe active ingredients of CWQ may play an anti-CRC role through multi-targets and multi-pathways, regulating the cell cycle and cell viability of CRC cells.

Updates in Diagnostic Techniques and Experimental Therapies for Diffuse Intrinsic Pontine Glioma

Diffuse intrinsic pontine glioma (DIPG) is a rare but extremely malignant central nervous system tumor primarily affecting children that is almost universally fatal with a devastating prognosis of 8-to-12-month median survival time following diagnosis. Traditionally, DIPG has been diagnosed via MR imaging alone and treated with palliative radiation therapy. While performing surgical biopsies for these patients has been controversial, in recent years, advancements have been made in the safety and efficacy of surgical biopsy techniques, utilizing stereotactic, robotics, and intraoperative cranial nerve monitoring as well as the development of liquid biopsies that identify tumor markers in either cerebrospinal fluid or serum. With more molecular data being collected from these tumors due to more frequent biopsies being performed, multiple treatment modalities including chemotherapy, radiation therapy, immunotherapy, and epigenetic modifying agents continue to be developed. Numerous recent clinical trials have been completed or are currently ongoing that have shown promise in extending survival for patients with DIPG. Focused ultrasound (FUS) has also emerged as an additional promising adjunct invention used to increase the effectiveness of therapeutic agents. In this review, we discuss the current evidence to date for these advancements in the diagnosis and treatment of DIPG.