Quantification of Resection Margin following Sublobar Resection in Lung Cancer Patients through Pre- and Post-Operative CT Image Comparison: Utilizing a CT-Based 3D Reconstruction Algorithm.

Sublobar resection has emerged as a standard treatment option for early-stage peripheral non-small cell lung cancer. Achieving an adequate resection margin is crucial to prevent local tumor recurrence. However, gross measurement of the resection margin may lack accuracy due to the elasticity of lung tissue and interobserver variability. Therefore, this study aimed to develop an objective measurement method, the CT-based 3D reconstruction algorithm, to quantify the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. An automated subvascular matching technique was first developed to ensure accuracy and reproducibility in the matching process. Following the extraction of matched feature points, another key technique involves calculating the displacement field within the image. This is particularly important for mapping discontinuous deformation fields around the surgical resection area. A transformation based on thin-plate spline is used for medical image registration. Upon completing the final step of image registration, the distance at the resection margin was measured. After developing the CT-based 3D reconstruction algorithm, we included 12 cases for resection margin distance measurement, comprising 4 right middle lobectomies, 6 segmentectomies, and 2 wedge resections. The outcomes obtained with our method revealed that the target registration error for all cases was less than 2.5 mm. Our method demonstrated the feasibility of measuring the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. Further validation with a multicenter, large cohort, and analysis of clinical outcome correlation is necessary in future studies.

High Fatty Acid-Binding Protein 4 Expression Associated with Favorable Clinical Characteristics and Prognosis in Papillary Thyroid Carcinoma.

Fatty acid-binding protein 4 (FABP4), a fatty acid transporter that coordinates lipid metabolism, is reported to exert a tumorigenic role in certain cancers. We investigated the effects of FABP4 in the carcinogenesis of thyroid cancer. Bioinformatics data about FABP4 in thyroid cancer were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Sixteen paired papillary thyroid cancer (PTC) tissues from Taipei Medical University (TMU) were gathered, and commercial thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure FABP4 messenger (m)RNA and protein levels. By analyzing data from the GEO and TCGA, we showed that FABP4 mRNA was reduced in PTC and follicular thyroid carcinoma (FTC). In addition, a lower FABP4 mRNA level in PTC was associated with poor clinical parameters and outcomes in the TCGA database. Moreover, FABP4 transcripts and proteins were downregulated in PTC and FTC, and its mRNA expression was associated with PTC staging in clinical specimens. In the TCGA database and TMU cohort, FABP4 mRNA levels were associated with thyroglobulin (r = 0.511 and r = 0.656, respectively), thyroid peroxidase (r = 0.612 and r = 0.909, respectively), and sodium iodide symporter (r = 0.485 and r = 0.637, respectively) transcripts. In conclusion, FABP4 mRNA and protein levels were reduced in PTC and FTC, and may be used as a potential indicator for thyroid cancer evolution in clinical settings. Further, well-designed research to dissect the molecular mechanism of FABP4 in modulating thyroid carcinogenesis is needed.

Deep Learning Analysis for Predicting Tumor Spread through Air Space in Early-Stage Lung Adenocarcinoma Pathology Images.

The presence of spread through air spaces (STASs) in early-stage lung adenocarcinoma is a significant prognostic factor associated with disease recurrence and poor outcomes. Although current STAS detection methods rely on pathological examinations, the advent of artificial intelligence (AI) offers opportunities for automated histopathological image analysis. This study developed a deep learning (DL) model for STAS prediction and investigated the correlation between the prediction results and patient outcomes. To develop the DL-based STAS prediction model, 1053 digital pathology whole-slide images (WSIs) from the competition dataset were enrolled in the training set, and 227 WSIs from the National Taiwan University Hospital were enrolled for external validation. A YOLOv5-based framework comprising preprocessing, candidate detection, false-positive reduction, and patient-based prediction was proposed for STAS prediction. The model achieved an area under the curve (AUC) of 0.83 in predicting STAS presence, with 72% accuracy, 81% sensitivity, and 63% specificity. Additionally, the DL model demonstrated a prognostic value in disease-free survival compared to that of pathological evaluation. These findings suggest that DL-based STAS prediction could serve as an adjunctive screening tool and facilitate clinical decision-making in patients with early-stage lung adenocarcinoma.

Comparative effectiveness of primary tumor resection versus chemotherapy in patients with asymptomatic unresectable metastatic colorectal cancer: a retrospective cohort study using the target trial emulation framework.

Patients who undergo primary tumor resection (PTR) reportedly have significantly higher overall survival (OS) than those who do not undergo this procedure. However, this result is only evident in past retrospective studies, and clinical trial results did not show the same trend. Thus, it remains unclear whether primary tumor resection effectively increases survival in patients with metastatic colorectal cancer (mCRC) across different study designs. We compared the OS of patients with asymptomatic unresectable mCRC who underwent PTR with that of those who did not. This retrospective cohort study was designed to be a target trial emulation of a randomized controlled trial (RCT) that would have compared the effectiveness of PTR versus non-PTR in patients with asymptomatic unresectable mCRC from 2009 to 2017. A systematic review and meta-analysis were conducted to compare the efficacy of PTR and non-PTR in patients with mCRC, and corresponding results were compared. This cohort included 1,132 patients for a per-protocol analysis. The PTR group had non-significantly longer survival (adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-1.01) than the non-PTR group in our cohort. A meta-analysis including five RCTs (1,016 patients) and our cohort found that the PTR group did not have a significantly lower mortality rate than the non-PTR group. The results of this cohort study and previous RCTs suggest that PTR is not associated with improved survival compared to systemic chemotherapy combined with targeted therapy among asymptomatic unresectable mCRC patients. Therefore, routine PTR is not recommended in these patients.

[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.

Ultrasonic-assisted extraction of polysaccharide from Paeoniae Radix alba: Extraction optimization, structural characterization and antioxidant mechanism in vitro.

Paeoniae Radix alba is used in Traditional Chinese Medicine for the treatment of gastrointestinal disorders, immunomodulatory, cancer, and other diseases. In the current study, the yield of Paeoniae Radix alba polysaccharide (PRP) was significantly increased with optimal ultrasound-assisted extraction compared to hot water extraction. Further, an acidic polysaccharide (PRP-AP) was isolated from PRP after chromatographic separation and was characterized as a typical pectic polysaccharide with side chains of arabinogalactans types I and II. Moreover, it showed antioxidant effects on LPS-induced damage on IPEC-J2 cells determined by qRT-PCR and ELISA, including decreasing the pro-inflammatory factors' expressions and increasing the antioxidant enzymes activities, which was shown to be related to the Nrf2/Keap1 pathway modulated by PRP-AP. The metabolites change (such as itaconate, cholesterol sulfate, etc.) detected by untargeted metabolomic analysis in cells was also shown to be modulated by PRP-AP, and these metabolites were further utilized and protected cells damaged by LPS. These results revealed the cellular active mechanism of the macromolecular PRP-AP on protecting cells, and supported the hypothesis that PRP-AP has strong benefits as an alternative dietary supplement for the prevention of intestinal oxidative stress by modulating cellular metabolism.

Comparative Effectiveness of Adjuvant Therapy on Survival in Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: Postoperative survival outcomes are crucial in treatment decision making. This study aimed to compare the efficacy of adjuvant chemotherapy (AC)-alone with that of chemotherapy + targeted agents (CTA) in patients with metastatic colorectal cancer (mCRC) and to investigate the association between neoadjuvant therapy and survival. PATIENTS AND METHODS: Patients who underwent primary tumor excision and metastasectomy were identified in the Taiwan Cancer Registry from 2010 to 2019. The analysis assessed the influence of adjuvant therapy on survival and examined the interactions between adjuvant therapy types (AC-alone and CTA) and patient characteristics with respect to overall survival. RESULTS: Overall, 1,728 and 757 patients received AC alone and CTA, respectively. Compared to AC alone, adjuvant CTA yielded similar mortality after surgery [hazard ratio (HR)=1.03; 95% confidence interval (CI)=0.91-1.17] but resulted in marginally reduced mortality among patients treated with neoadjuvant therapy with targeted agents (HR=0.6; 95%CI=0.34-1.05) after propensity score matching. In patients with mCRC, those who received targeted agents preoperatively and postoperatively in combination with AC had the highest mortality rate (HR=1.75; 95%CI=1.33-2.32). CONCLUSION: Overall survival is comparable between adjuvant CTA and AC alone, but adjuvant CTA may be more beneficial in patients with mCRC who undergo neoadjuvant therapy with targeted agents.

G protein subunit alpha i2's pivotal role in angiogenesis.

Here we explored the potential role of Gαi2 (G protein subunit alpha i2) in endothelial cell function and angiogenesis. Methods: Genetic methodologies such as shRNA, CRISPR/Cas9, dominant negative mutation, and overexpression were utilized to modify Gαi2 expression or regulate its function. Their effects on endothelial cell functions were assessed in vitro. In vivo, the endothelial-specific Gαi2 shRNA adeno-associated virus (AAV) was utilized to silence Gαi2 expression. The impact of this suppression on retinal angiogenesis in control mice and streptozotocin (STZ)-induced diabetic retinopathy (DR) mice was analyzed. Results: Analysis of single-cell RNA sequencing data revealed Gαi2 (GNAI2) was predominantly expressed in retinal endothelial cells and expression was increased in retinal endothelial cells following oxygen-induced retinopathy (OIR) in mice. Moreover, transcriptome analysis linking Gαi2 to angiogenesis-related processes/pathways, supported by increased Gαi2 expression in experimental OIR mouse retinas, highlighted its possible role in angiogenesis. In various endothelial cell types, shRNA-induced silencing and CRISPR/Cas9-mediated knockout (KO) of Gαi2 resulted in substantial reductions in cell proliferation, migration, invasion, and capillary tube formation. Conversely, Gαi2 over-expression in endothelial cells induced pro-angiogenic activities, enhancing cell proliferation, migration, invasion, and capillary tube formation. Furthermore, our investigation revealed a crucial role of Gαi2 in NFAT (nuclear factor of activated T cells) activation, as evidenced by the down-regulation of NFAT-luciferase reporter activity and pro-angiogenesis NFAT-targeted genes (Egr3, CXCR7, and RND1) in Gαi2-silenced or -KO HUVECs, which were up-regulated in Gαi2-overexpressing endothelial cells. Expression of a dominant negative Gαi2 mutation (S48C) also down-regulated NFAT-targeted genes, slowing proliferation, migration, invasion, and capillary tube formation in HUVECs. Importantly, in vivo experiments revealed that endothelial Gαi2 knockdown inhibited retinal angiogenesis in mice, with a concomitant down-regulation of NFAT-targeted genes in mouse retinal tissue. In contrast, Gαi2 over-expression in endothelial cells enhanced retinal angiogenesis in mice. Single-cell RNA sequencing data confirmed increased levels of Gαi2 specifically in retinal endothelial cells of mice with streptozotocin (STZ)-induced diabetic retinopathy (DR). Importantly, endothelial Gαi2 silencing ameliorated retinal pathological angiogenesis in DR mice. Conclusion: Our study highlights a critical role for Gαi2 in NFAT activation, endothelial cell activation and angiogenesis, offering valuable insights into potential therapeutic strategies for modulating these processes.

FGF9, a Potent Mitogen, Is a New Ligand for Integrin αvß3, and the FGF9 Mutant Defective in Integrin Binding Acts as an Antagonist.

FGF9 is a potent mitogen and survival factor, but FGF9 protein levels are generally low and restricted to a few adult organs. Aberrant expression of FGF9 usually results in cancer. However, the mechanism of FGF9 action has not been fully established. Previous studies showed that FGF1 and FGF2 directly bind to integrin αvß3, and this interaction is critical for signaling functions (FGF-integrin crosstalk). FGF1 and FGF2 mutants defective in integrin binding were defective in signaling, whereas the mutants still bound to FGFR suppressed angiogenesis and tumor growth, indicating that they act as antagonists. We hypothesize that FGF9 requires direct integrin binding for signaling. Here, we show that docking simulation of the interaction between FGF9 and αvß3 predicted that FGF9 binds to the classical ligand-binding site of αvß3. We show that FGF9 bound to integrin αvß3 and generated FGF9 mutants in the predicted integrin-binding interface. An FGF9 mutant (R108E) was defective in integrin binding, activating FRS2α and ERK1/2, inducing DNA synthesis, cancer cell migration, and invasion in vitro. R108E suppressed DNA synthesis and activation of FRS2α and ERK1/2 induced by WT FGF9 (dominant-negative effect). These findings indicate that FGF9 requires direct integrin binding for signaling and that R108E has potential as an antagonist to FGF9 signaling.

The Vps13-like protein BLTP2 is pro-survival and regulates phosphatidylethanolamine levels in the plasma membrane to maintain its fluidity and function.

Lipid transport proteins (LTPs) facilitate nonvesicular lipid exchange between cellular compartments and have critical roles in lipid homeostasis1. A new family of bridge-like LTPs (BLTPs) is thought to form lipid-transporting conduits between organelles2. One, BLTP2, is conserved across species but its function is not known. Here, we show that BLTP2 and its homolog directly regulate plasma membrane (PM) fluidity by increasing the phosphatidylethanolamine (PE) level in the PM. BLTP2 localizes to endoplasmic reticulum (ER)-PM contact sites34, 5, suggesting it transports PE from the ER to the PM. We find BLTP2 works in parallel with another pathway that regulates intracellular PE distribution and PM fluidity6, 7. BLTP2 expression correlates with breast cancer aggressiveness8-10. We found BLTP2 facilitates growth of a human cancer cell line and sustains its aggressiveness in an in vivo model of metastasis, suggesting maintenance of PM fluidity by BLTP2 may be critical for tumorigenesis in humans.

Treatment outcome and prognostic factors of external auditory canal squamous cell carcinoma: A retrospective study in a tertiary center.

Objective: Squamous cell carcinoma (SCC) of the external auditory canal (EAC) is a rare malignancy with various treatment strategies and outcomes. The purpose of this study was to evaluate the clinical characteristics and survival outcomes and identify prognostic factors in patients with SCC of EAC. Methods: Twenty-one patients with SCC of EAC treated in a single tertiary center between 2009 and 2021 were retrospectively reviewed and analyzed. The modified Pittsburgh classification system was applied for staging. Factors associated with survival were identified by univariate survival analysis. Results: The mean age at diagnosis was 61 years (range: 41-79 years). Early-stage (T1 + T2) accounts for 38.1% of the series and advanced-stage (T3 + T4) accounts for 61.9%. Eighteen (85.7%) patients underwent primary surgery with curative intent. The 5-year overall survival rate of the 21 patients was 67.4%. Tumor invasion to the otic capsule, eustachian tube, sigmoid sinus, and dura were associated with poor prognosis in univariate analysis (p = .046; .008; .027; and .08, respectively). Conclusions: Factors predictive of less favorable survival include the history of COM, tumor invasion to the otic capsule, eustachian tube, sigmoid sinus, and dura. It is important to make a precise and systemic preoperative evaluation of disease extent. Level of Evidence: 4.

Ultrasensitive and Rapid Detection of Procalcitonin via Waveguide-Enhanced Nanogold-Linked Immunosorbent Assay for Early Sepsis Diagnosis.

Sepsis, a life-threatening inflammatory response, demands economical, accurate, and rapid detection of biomarkers during the critical "golden hour" to reduce the patient mortality rate. Here, we demonstrate a cost-effective waveguide-enhanced nanogold-linked immunosorbent assay (WENLISA) based on nanoplasmonic waveguide biosensors for the rapid and sensitive detection of procalcitonin (PCT), a sepsis-related inflammatory biomarker. To enhance the limit of detection (LOD), we employed sandwich assays using immobilized capture antibodies and detection antibodies conjugated to gold nanoparticles to bind the target analyte, leading to a significant evanescent wave redistribution and strong nanoplasmonic absorption near the waveguide surface. Experimentally, we detected PCT for a wide linear response range of 0.1 pg/mL to 1 ng/mL with a record-low LOD of 48.7 fg/mL (3.74 fM) in 8 min. Furthermore, WENLISA has successfully identified PCT levels in the blood plasma of patients with sepsis and healthy individuals, offering a promising technology for early sepsis diagnosis.

Factors associated with mental illness in patients with rheumatoid arthritis initiating b/ts DMARDs: A population-based study.

AIM: Mental health is an essential issue in patients with rheumatoid arthritis (RA) but remains unclear among those receiving biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). We aim to assess the incidence and factors associated with mental illness among patients with RA who underwent b/tsDMARD therapy. METHOD: We used Taiwan's National Health Insurance Research Database for the period 2001-2020 to identify patients with RA receiving b/tsDMARDs. The primary outcome was newly developed mental illness, including anxiety and mood disorders. We performed a Cox regression analysis to determine factors associated with mental illness and presented as hazard ratios (HR) with 95% confidence interval (CI). RESULTS: We enrolled 10 852 patients, with 7854 patients receiving tumor necrosis factors inhibitors (TNFi), 1693 patients receiving non-TNFi bDMARDs, and 1305 patients treated with tsDMARD. We found that 13.62% of enrolled patients developed mental illness, with an incidence rate of 4054 per 100 000 person-year. Those receiving tocilizumab (aHR 0.64, 95% CI: 0.51-0.82), abatacept (aHR 0.69, 95% CI: 0.55-0.86), or tsDMARDs (aHR 0.58, 95% CI: 0.47-0.73) had a lower risk of mental illness compared with those receiving TNFi. We also found that old age, low income, diabetes mellitus, use of cyclosporine, and use of steroids were associated with incident mental illness. CONCLUSION: This population-based study investigated the incidence and factors associated with mental illness among patients with RA receiving b/tsDMARDs. Our findings highlight the need for vigilance with respect to the possibility of mental illness in patients with RA.

FGF9, a potent mitogen, is a new ligand for integrin αvß3, and the FGF9 mutant defective in integrin binding acts as an antagonist.

FGF9 is a potent mitogen and survival factor, but FGF9 protein level is generally low and restricted to a few adult organs. Aberrant expression of FGF9 usually results in cancer. However, the mechanism of FGF9 action has not been fully established. Previous studies showed that FGF1 and FGF2 directly bind to integrin αvß3 and this interaction is critical for signaling functions (FGF-integrin crosstalk). FGF1 and FGF2 mutants defective in integrin binding were defective in signaling, whereas the mutants still bound to FGFR, and suppressed angiogenesis and tumor growth, indicating that they act as antagonists. We hypothesize that FGF9 requires direct integrin binding for signaling. Here we show that docking simulation of interaction between FGF9 and αvß3 predicted that FGF9 binds to the classical ligand-binding site of αvß3. We showed that FGF9 actually bound to integrin αvß3, and generated an FGF9 mutants in the predicted integrin-binding interface. An FGF9 mutant (R108E) was defective in integrin binding, activating FRS2α and ERK1/2, inducing DNA synthesis, cancer cell migration, and invasion in vitro. R108E suppressed DNA synthesis induced by WT FGF9 and suppressed DNA synthesis and activation of FRS2α and ERK1/2 induced by WT FGF9 (dominant-negative effect). These findings indicate that FGF9 requires direct integrin binding for signaling and that R108E has potential as an antagonist to FGF9 signaling.

Comparative Effectiveness of Cetuximab Versus Panitumumab in Patients With Metastatic Colorectal Cancer: A Nationwide Database Study.

BACKGROUND/AIM: The study aimed to determine the effectiveness of cetuximab and panitumumab on the survival of patients with metastatic colorectal cancer or those who had undergone conversion surgery and to identify their prognostic factors. PATIENTS AND METHODS: This retrospective cohort study used data from patients with metastatic colorectal cancer who received cetuximab or panitumumab as first-line targeted agent-based therapy. Overall survival and conversion surgery rates were evaluated, and the prognostic factors were determined. RESULTS: A total of 1,749 and 318 patients received cetuximab or panitumumab with chemotherapy, respectively. Overall survival and conversion surgery rates were similar between the cetuximab [hazard ratio (HR)=0.96] and panitumumab groups (HR=1.00). The prognostic factors associated with metastasectomy significantly lowered mortality among patients with metastatic colorectal cancer (HR=0.61). Older age (≥70 years), tumor stage 4B and 4C, right-sided tumors, mucinous adenocarcinoma, primary tumor resection, and the number of positive lymph nodes were associated with higher mortality and lower conversion surgery rates. CONCLUSION: Though panitumumab- and cetuximab-based therapies showed no differences, several factors, such as age over 70 years old, tumor stage 4B and 4C, undifferentiated carcinoma, mucinous carcinoma, right-sided tumor, number of positive lymph nodes, obstruction, and primary tumor resection increased the mortality risk of patients. This study underscores the importance of metastasectomy in current treatment guidelines and future clinical trials.

Redrawing Urokinase Receptor (uPAR) Signaling with Cancer Driver Genes for Exploring Possible Anti-Cancer Targets and Drugs.

During tumorigenesis, urokinase (uPA) and uPA receptor (uPAR) play essential roles in mediating pathological progression in many cancers. To understand the crosstalk between the uPA/uPAR signaling and cancer, as well as to decipher their cellular pathways, we proposed to use cancer driver genes to map out the uPAR signaling. In the study, an integrated pharmaceutical bioinformatics approach that combined modulator identification, driver gene ontology networking, protein targets prediction and networking, pathway analysis and uPAR modulator screening platform construction was employed to uncover druggable targets in uPAR signaling for developing a novel anti-cancer modality. Through these works, we found that uPAR signaling interacted with 10 of 21 KEGG cancer pathways, indicating the important role of uPAR in mediating intracellular cancerous signaling. Furthermore, we verified that receptor tyrosine kinases (RTKs) and ribosomal S6 kinases (RSKs) could serve as signal hubs to relay uPAR-mediated cellular functions on cancer hallmarks such as angiogenesis, proliferation, migration and metastasis. Moreover, we established an in silico virtual screening platform and a uPAR-driver gene pair rule for identifying potential uPAR modulators to combat cancer. Altogether, our results not only elucidated the complex networking between uPAR modulation and cancer but also provided a paved way for developing new chemical entities and/or re-positioning clinically used drugs against cancer.

Association between early blood urea nitrogen-to-albumin ratio and one-year post-hospital mortality in critically ill surgical patients: a propensity score-matched study.

BACKGROUND: Blood urea nitrogen to albumin ratio (BAR) is increasingly recognized as an early predictor for short-term outcomes in critically ill patients, but the association of BAR with long-term outcomes in critically ill surgical patients remains underexplored. METHODS: We enrolled consecutive patients who were admitted to surgical intensive care units (ICUs) at Taichung Veterans General Hospital between 2015 and 2020, and the dates of death were retrieved from Taiwan's National Health Insurance Research Database. In addition to Cox regression, we also used propensity score matching to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year post-hospital mortality of the variables. RESULTS: A total of 8,073 eligible subjects were included for analyses. We found that age, male gender, high Charlson Comorbidity Index, high Acute Physiology and Chronic Health Evaluation II score, positive microbial culture, and leukocytosis were predictors for mortality, whereas high body mass index, scheduled surgery, and high platelet counts were protective factors against long-term mortality. The high BAR was independently associated with increased post-hospital mortality after adjustment for the aforementioned covariates (adjHR 1.258, 95% CI, 1.127-1.405). Notably, the association tended to be stronger in females and patients with fewer comorbidities and lower disease severity of critical illness. The propensity score matching, dividing subjects by BAR higher or lower than 6, showed a consistent association between week-one BAR and post-hospital mortality (adjHR 1.503, 95% CI 1.247-1.811). CONCLUSIONS: BAR is a newly identified predictor of short-term outcome, and we identified long-term outcome-relevant factors, including BAR, and the identified factors may be useful for risk stratification of long-term outcomes in patients discharged from surgical ICUs.

Different epidemiological characteristics between patients with non-hospital-onset and hospital-onset candidemia: a retrospective cohort study.

Candidemia is a life-threatening infectious disease that has varying incidences. Previous studies revealed the differences in clinical characteristics and outcomes between non-hospital-onset (NHO) and hospital-onset (HO) candidemia. This 4-year retrospective research included adult patients with candidemia in a tertiary medical centre in Taiwan, and cases were categorised as NHO and HO candidemia. Survival analysis and risk factors associated with in-hospital mortality were performed using the Kaplan-Meier method and multivariate Cox proportional-hazards models. The analysis included 339 patients, and the overall incidence was 1.50 per 1,000 admission person-year. Of the cases, 82 (24.18%) were NHO candidemia, and 57.52% (195/339) of patients were diagnosed with at least one malignancy. C. albicans was the most commonly isolated species, accounting for 52.21%. Patients with NHO candidemia had a higher proportion of C. glabrata but a lower ratio of C. tropicalis in comparison to the HO group. The all-cause in-hospital mortality rate was 55.75%. Multivariate Cox proportional-hazards models showed that NHO candidemia was a better outcome predictor (adjusted hazard ratio, 0.44). The administration of antifungal therapy within 2 days was a protective factor. In conclusion, NHO candidemia showed distinct microbiological characteristics and a better outcome than HO candidemia.