Augmented pathogen detection in brain abscess using metagenomic next-generation sequencing: a retrospective cohort study.

Brain abscess is a severe infection characterized by the accumulation of pus within the brain parenchyma. Accurate identification of the causative pathogens is crucial for effective treatment and improved patient outcomes. This 10-year retrospective, single-center study aimed to compare the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) in brain abscess. We reviewed 612 patients diagnosed with brain abscess and identified 174 cases with confirmed etiology. The median age was 52 years, with 69.5% males. Culture tests predominately identified gram-positive bacteria, particularly Streptococcus spp. Gram-negative bacteria, including Klebsiella spp., were also detected. However, mNGS revealed a more diverse pathogen spectrum, focusing on anaerobes (e.g., Fusobacterium spp., Parvimonas spp., Porphyromonas spp., Prevotella spp., and Tannerella spp.). mNGS exhibited significantly higher overall pathogen-positive rates in pus samples (85.0% vs 50.0%, P = 0.0181) and CSF samples (84.2% vs 7.9%, P < 0.0001) compared to culture. Furthermore, the detection rates for anaerobes displayed a notable disparity, with mNGS yielding significantly higher positive detections in both pus samples (50.0% vs 10%, P = 0.0058) and CSF samples (18.4% vs 0%, P = 0.0115) when compared to culture methods. The assistance of mNGS in pathogen detection, particularly anaerobes in brain abscess, was evident in our findings. mNGS demonstrated the ability to identify rare and fastidious pathogens, even in culture-negative cases. These results emphasize the clinical value of mNGS as a supplement for brain abscess, enabling more comprehensive and accurate pathogen identification.IMPORTANCEThe accurate identification of pathogens causing brain abscess is crucial for effective treatment and improved patient outcomes. In this 10-year retrospective study, the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) was compared. The study analyzed 612 patients with brain abscess and confirmed etiology in 174 cases. The results showed that culture tests predominantly identified gram-positive bacteria, while mNGS unveiled a broader diverse pathogen spectrum, particularly anaerobes. The mNGS method exhibited significantly higher overall rates of pathogen positivity both in pus and cerebrospinal fluid (CSF) samples, surpassing the culture methods. Notably, mNGS detected a significantly higher number of anaerobes in both pus and CSF samples compared to culture methods. These findings underscore the clinical value of mNGS as a supplement for brain abscess diagnosis, enabling more comprehensive and accurate pathogen identification, particularly for rare and fastidious pathogens that evade detection by conventional culture methods.

A novel color-aided system for diagnosis of early gastric cancer using magnifying endoscopy with narrow-band imaging.

BACKGROUND: The Pink Zone Pattern (PP) sign is a typical color alteration of early gastric cancer (EGC) under magnifying endoscopic narrow-band imaging (ME-NBI). By integrating the color changes (PP sign) with the "vessel plus surface (VS)" classification system, we developed an innovative diagnostic system for EGC and named it "Pink Microsurface Microvascular (PSV)" system. Here, we aimed to elucidate the diagnostic performance of the PSV system for EGC. METHODS: We conducted a single-center prospective clinical study (before-after design) consisting of 2 cross-sectional studies at 2 separate periods. In the before phase, 184 suspected lesions were evaluated using the VS system under ME-NBI; in the after phase, 183 suspected lesions were evaluated using the PSV system. We compared the diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) between the VS group and the PSV group. RESULTS: The accuracy, sensitivity, specificity, PPV, and NPV of the VS system for EGC were 84.6%, 87.0%, 83.6%, 67.8%, and 94.2%, respectively, and those for the PSV system were 93.0%, 92.0%, 93.4%, 85.2%, and 96.6%, respectively. The accuracy, specificity, and PPV of the PSV system were superior to those of the VS system. However, the sensitivity and NPV did not significantly differ between the VS system and the PSV system. The VS system was inconclusive for 22 lesions (12.0%) and the PSV system was inconclusive for 11 lesions (6.0%). The PSV system could identify more suspicious lesions than the VS system. CONCLUSIONS: We propose a new PSV diagnostic system by combining the VS system and the PP sign. Compared with the VS system, the PSV system could identify more suspected lesions and improve the diagnostic performance of EGC.

A nomogram for predicting lymph node metastasis in early gastric signet ring cell carcinoma.

At present, the risk factors for lymph node metastasis in early gastric signet ring cell carcinoma (SRCC) remain unclear. However, it is worth noting that the LNM rate and prognosis of early gastric SRCC are superior to those of other undifferentiated cancers. With advancements in endoscopic technology, the 5-year survival rate following endoscopic treatment of early gastric cancer is comparable to traditional surgery while offering a better quality of life. The objective of this study was to develop a nomogram that can predict lymph node status in early gastric SRCC before surgery, aiding clinicians in selecting the optimal treatment strategy. A research cohort was established by retrospectively collecting data from 183 patients with early gastric SRCC who underwent radical gastrectomy with lymph node dissection at our hospital between January 2014 and June 2022. The predictors of early gastric signet ring cell carcinoma lymph node metastasis were identified in the study cohort using the least absolute selection and shrinkage operator (Lasso) and multivariate regression analysis, and a nomogram was developed. The discrimination, accuracy, and clinical practicability of the nomogram were assessed using receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis. The incidence of lymph node metastasis was 21.9% (40/183) overall. Multivariate logistic regression analysis revealed that tumor size and lymphovascular invasion (LVI) were independent risk factors for lymph node metastasis. Lasso regression analysis demonstrated that tumor size, invasion depth, LVI, E-cadherin expression, dMMR, CA242, NLR, and macroscopic type were associated with lymph node metastasis. The integrated discrimination improvement (IDI) (P = 0.034) and net reclassification index (NRI) (P = 0.023) were significantly improved when dMMR was added to model 1. In addition, the area under curve (AUC) (P = 0.010), IDI (P = 0.001) and NRI (P < 0.001) of the model were significantly improved when type_1 was included. Therefore, we finally included tumor size, invasion depth, dMMR, and macroscopic type to establish a nomogram, which had good discrimination (AUC = 0.757, 95% CI 0.687-0.828) and calibration. Decision curve analysis showed that the nomogram had good clinical performance. We have developed a risk prediction model for early gastric signet ring cell carcinoma that accurately predicts lymph node involvement, providing clinicians with a valuable tool to aid in patient counseling and treatment decision-making.

The Pink Zone Pattern (PP) sign: A novel simple marker for early gastric cancer.

BACKGROUND: We previously found a pink-colored change in early gastric cancer (EGC) lesions under magnifying endoscopy with narrow-band imaging (ME-NBI) and named it the "Pink Zoon Pattern" (PP) sign, which appeared independent of microvascular and microstructural changes. The aim of this study was to further investigate the characteristics of the PP sign in EGC. METHODS: The consecutive patients with suspicious gastric lesions detected by ME-NBI and confirmed by pathology at Zhejiang Cancer Hospital between November 2020 and December 2021 were enrolled in the study. The suspicious lesions were observed and assessed by the "VS" system and the PP sign respectively. RESULTS: We found that in the PP-positive group, 238 lesions (96.0%) were diagnosed as malignant. The overall accuracy, sensitivity, and specificity were 84.7%, 85.3%, and 81.8%. Among 164 EGC lesions diagnosed with low confidence (Grades 2, 3, and 4) using the VS system, the overall accuracy of PP to discriminate tumor from normal was 82.3%. The sensitivity and specificity were 82.7% and 81.5% respectively. CONCLUSIONS: The PP sign could be a new simple sign for the diagnosis of EGC and as an effective supplement to VS system when using ME-NBI.

Memory Th17 cell-mediated protection against lethal secondary pneumococcal pneumonia following influenza infection.

Streptococcus pneumoniae (Sp) frequently causes secondary pneumonia after influenza A virus (IAV) infection, leading to high morbidity and mortality worldwide. Concomitant pneumococcal and influenza vaccination improves protection against coinfection but does not always yield complete protection. Impaired innate and adaptive immune responses have been associated with attenuated bacterial clearance in influenza virus-infected hosts. In this study, we showed that preceding low-dose IAV infection caused persistent Sp infection and suppression of bacteria-specific T-helper type 17 (Th17) responses in mice. Prior Sp infection protected against subsequent IAV/Sp coinfection by improving bacterial clearance and rescuing bacteria-specific Th17 responses in the lungs. Furthermore, blockade of IL-17A by anti-IL-17A antibodies abrogated the protective effect of Sp preinfection. Importantly, memory Th17 responses induced by Sp preinfection overcame viral-driven Th17 inhibition and provided cross-protection against different Sp serotypes following coinfection with IAV. These results indicate that bacteria-specific Th17 memory cells play a key role in providing protection against IAV/Sp coinfection in a serotype-independent manner and suggest that a Th17-based vaccine would have excellent potential to mitigate disease caused by coinfection. IMPORTANCE Streptococcus pneumoniae (Sp) frequently causes secondary bacterial pneumonia after influenza A virus (IAV) infection, leading to increased morbidity and mortality worldwide. Current pneumococcal vaccines induce highly strain-specific antibody responses and provide limited protection against IAV/Sp coinfection. Th17 responses are broadly protective against Sp single infection, but whether the Th17 response, which is dramatically impaired by IAV infection in naïve mice, might be effective in immunization-induced protection against pneumonia caused by coinfection is not known. In this study, we have revealed that Sp-specific memory Th17 cells rescue IAV-driven inhibition and provide cross-protection against subsequent lethal coinfection with IAV and different Sp serotypes. These results indicate that a Th17-based vaccine would have excellent potential to mitigate disease caused by IAV/Sp coinfection.

Assessment of Helicobacter pylori infection by deep learning based on endoscopic videos in real time.

BACKGROUND AND AIMS: Endoscopic assessment of Helicobacter pylori infection is a simple and effective method. Here, we aimed to develop a deep learning-based system named Intelligent Detection Endoscopic Assistant-Helicobacter pylori (IDEA-HP) to assess H. pylori infection by using endoscopic videos in real time. METHODS: Endoscopic data were retrospectively obtained from Zhejiang Cancer Hospital (ZJCH) for the development, validation, and testing of the system. Stored videos from ZJCH were used for assessing and comparing the performance of IDEA-HP with that of endoscopists. Prospective consecutive patients undergoing esophagogastroduodenoscopy were enrolled to assess the applicability of clinical practice. The urea breath test was used as the gold standard for diagnosing H. pylori infection. RESULTS: In 100 videos, IDEA-HP achieved a similar overall accuracy of assessing H. pylori infection to that of experts (84.0% vs. 83.6% [P = 0.729]). Nevertheless, the diagnostic accuracy (84.0% vs. 74.0% [P<0.001]) and sensitivity (82.0% vs. 67.2% [P<0.001]) of IDEA-HP were significantly higher than those of the beginners. In 191 prospective consecutive patients, IDEA-HP achieved accuracy, sensitivity, and specificity of 85.3% (95% CI: 79.0%-89.3%), 83.3% (95% CI: 72.8%-90.5%), and 85.8% (95% CI: 77.7%-91.4%), respectively. CONCLUSIONS: Our results show that IDEA-HP has great potential for assisting endoscopists in assessing H. pylori infection status during actual clinical work.

Antigen-specific memory Th17 cells promote cross-protection against nontypeable Haemophilus influenzae after mild influenza A virus infection.

Secondary bacterial pneumonia after influenza A virus (IAV) infection is the leading cause of hospitalization and death associated with IAV infection worldwide. Nontypeable Haemophilus influenzae (NTHi) is one of the most common causes of secondary bacterial pneumonia. Current efforts to develop vaccines against NTHi infection focus on inducing antibodies but are hindered by antigenic diversity among NTHi strains. Therefore, we investigated the contribution of the memory T helper type 17 (Th17) response in protective immunity against IAV/NTHi coinfection. We observed that even a mild IAV infection impaired the NTHi-specific Th17 response and increased morbidity and mortality compared with NTHi monoinfected mice. However, pre-existing memory NTHi-specific Th17 cells induced by a previous NTHi infection overcame IAV-driven Th17 inhibition and were cross-protective against different NTHi strains. Last, mice immunized with a NTHi protein that induced a strong Th17 memory response were broadly protected against diverse NTHi strains after challenge with coinfection. These results indicate that vaccination that limits IAV infection to mild disease may be insufficient to eliminate the risk of a lethal secondary bacterial pneumonia. However, NTHi-specific memory Th17 cells provide serotype-independent protection despite an ongoing IAV infection and demonstrate the advantage of developing broadly protective Th17-inducing vaccines against secondary bacterial pneumonia.

Factors associated with non-lifting of colorectal mucosal lesions.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for colorectal tumors. However, lesions that cannot be lifted after submucosal injection are not indication for ESD. This is because the procedure is difficult, and the lesions are often considered as tumor invasion or submucosal fibrosis. The aims of this study are to evaluate the efficacy and safety of ESD for non-lifting lesions and to analyze the causes of non-lifting phenomenon. METHODS: This retrospective study included 29 patients with non-lifting colon lesions resected by ESD from February 2018 to September 2021. Cases were observed for demographics, endoscopic findings, treatment outcomes, adverse events and endoscopic follow-up. We studied the pathological features of lesions to explore the reasons for non-lifting. RESULTS: Among 29 cases of non-lifting lesions, 20 lesions (69.0%) were 30 mm in diameter or larger. Most of lesions (96.6%) were non-lifting in center, and only one lesions (3.4%) had non-lifting of one side. The en bloc and curative resection rates of ESD were 100 and 86.2%, respectively. There was one (3.4%) delayed bleeding, no perforations and other complications. No tumor recurrence occurred during the follow-up period. For pathological features, 16 (55.2%) non-lifting lesions had submucosal fibrosis and only 4 cases (13.8%) had deep submucosal invasion. There were 9 cases (31.0%) of non-lifting lesions due to musculo-fibrous of muscularis propria anomaly (MMPA). CONCLUSION: MMPA is another reason for non-lifting signs besides invasive carcinomas and submucosal fibrosis. ESD should be considered in patients with large non-lifting adenoma instead of surgery.

Risk factors of lymph node metastasis or lymphovascular invasion for superficial esophageal squamous cell carcinoma: A practical and effective predictive nomogram based on a cancer hospital data.

Background: Lymphovascular invasion (LVI) is mostly used as a preoperative predictor to establish lymph node metastasis (LNM) prediction models for superficial esophageal squamous cell carcinoma (SESCC). However, LVI still needs to be confirmed by postoperative pathology. In this study, we combined LNM and LVI as a unified outcome and named it LNM/LVI, and aimed to develop an LNM/LVI prediction model in SESCC using preoperative factors. Methods: A total of 512 patients who underwent radical resection of SESCC were retrospectively collected. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression were adopted to identify the predictive factors of LNM/LVI. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to select the potential predictive factors from the results of LASSO and logistic regression. A nomogram for predicting LNM/LVI was established by incorporating these factors. The efficacy, accuracy, and clinical utility of the nomogram were, respectively, assessed with the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Finally, the random forest (RF) algorithm was used to further evaluate the impact of these factors included in the nomogram on LNM/LVI. Results: Tumor size, tumor location, tumor invasion depth, tumor differentiation, and macroscopic type were confirmed as independent risk factors for LNM/LVI according to the results of logistic regression, LASSO regression, IDI, and NRI analyses. A nomogram including these five variables showed a good performance in LNM/LVI prediction (AUC = 0.776). The calibration curve revealed that the predictive results of this nomogram were nearly consistent with actual observations. Significant clinical utility of our nomogram was demonstrated by DCA. The RF model with the same five variables also had similar predictive efficacy with the nomogram (AUC = 0.775). Conclusion: The nomogram was adopted as a final tool for predicting LNM/LVI because its risk score system made it more user-friendly and clinically useful than the random forest model, which can help clinicians make optimal treatment decisions for patients with SESCC.

Essential role of IL-17 in acute exacerbation of pulmonary fibrosis induced by non-typeable Haemophilus influenzae.

Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) has a poor prognosis and lacks effective therapy. Animal models that mimic AE-IPF can greatly accelerate investigation of its pathogenesis and development of effective therapy. However, there are few reports of animal models of AE-IPF caused by bacteria. Thus, our study aimed to establish a mouse model of bacterium-induced AE-IPF and explore the potential pathogenic mechanism of AE-IPF. Methods: Mice were instilled intranasally with bleomycin (BLM) followed by non-typeable Haemophilus influenzae (NTHi) strain NT127. Murine survival, bacterial load, body weight and pulmonary histopathological changes were evaluated. We analyzed the T cell and inflammatory cell responses in the lungs. Results: Infection with 107 CFU NT127 triggered AE in mice with PF induced by 30 µg BLM. Compared with BLM-instilled mice, the BLM/NT127-treated mice showed more obvious airway inflammation, lower survival rate, higher inflammatory cell response, and increased proportions and numbers of IL-17+CD4+, IL-17+ γδ T, IL-22+CD4+ and regulatory T (Treg) cells in lungs. γδ T cells were the predominant source of IL-17. IL-17 gene knockout mice with AE-IPF had quicker body weight recovery, milder pulmonary inflammation and fibrosis, stronger IL-22+CD4+T, TGF-ß+ γδ T and Treg cell responses, and weaker neutrophil and eosinophil responses than wild-type mice with AE-IPF. Conclusions: NTHi infection after BLM-induced IPF can cause AE-IPF in a murine model. This novel model can be used to investigate the pathogenesis of AE-IPF and develop new therapies for AE-IPF caused by bacteria. IL-17 is essential for the development of AE-IPF, and it may be a new therapeutic target for bacteria-induced AE-IPF.

A Novelly Developed Bipolar Needle Knife Can Be an Alternative Device Choice for Endoscopic Submucosal Dissection (With Video).

Background: Endoscopic submucosal dissection (ESD) is technically difficult with high rates of complications, such as perforation and bleeding. We aimed to explore the safety and cutting efficiency of a novelly devised bipolar knife for ESD procedure. Methods: Taking a traditional monopolar knife as a reference, the safety and feasibility of the novel bipolar knife were evaluated by an animal experiment and a human study. Furthermore, we assessed the usefulness and advantage of this novel bipolar knife by using the finite element method. Results: A porcine experiment confirmed that there was no significant difference in wound size and cutting speed between the monopolar and bipolar knives. The thermal damage and histopathological scores produced by the two knives were similar. In addition, the porcine experiment and patients' study identified that the incidence of postoperative complications, such as bleeding, perforation, and infection, had no statistical difference between the monopolar and bipolar groups. Finally, the finite element model showed that the length and depth of thermal damage caused by the bipolar knife were, respectively, 102.77-117.98% and 80.87-84.53% of those caused by the monopolar knife at the same power. Conclusion: The novel bipolar knife was theoretically safer than the monopolar knife and, at least, was confirmed not inferior to the monopolar knife in operability and cutting efficiency. Thus, the novel bipolar knife can be an alternative device choice for ESD.

Corrigendum: Prediction of Microvascular Invasion and Its M2 Classification in Hepatocellular Carcinoma Based on Nomogram Analyses.

[This corrects the article DOI: 10.3389/fonc.2021.774800.].

Correlation of the detection rate of upper GI cancer with artificial intelligence score: results from a multicenter trial (with video).

BACKGROUND AND AIMS: The quality of EGD is a prerequisite for a high detection rate of upper GI lesions, especially early gastric cancer. Our previous study showed that an artificial intelligence system, named intelligent detection endoscopic assistant (IDEA), could help to monitor blind spots and provide an operation score during EGD. Here, we verified the effectiveness of IDEA to help evaluate the quality of EGD in a large-scale multicenter trial. METHODS: Patients undergoing EGD in 12 hospitals were consecutively enrolled. All hospitals were equipped with IDEA developed using deep convolutional neural networks and long short-term memory. Patients were examined by EGD, and the results were recorded by IDEA. The primary outcome was the detection rate of upper GI cancer. Secondary outcomes were part scores, total scores, and endoscopic procedure time, which were analyzed by IDEA. RESULTS: A total of 17,787 patients were recruited. The total detection rate of cancer-positive cases was 1.50%, ranging from .60% to 3.94% in each hospital. The total detection rate of early cancer-positive cases was .36%, ranging from .00% to 1.58% in each hospital. The average total score analyzed by IDEA ranged from 64.87 ± 16.87 to 83.50 ± 9.57 in each hospital. The cancer detection rate in each hospital was positively correlated with total score (r = .775, P = .003). Similarly, the early cancer detection rate was positively correlated with total score (r = .756, P = .004). CONCLUSIONS: This multicenter trial confirmed that the quality of the EGD result is positively correlated with the detection rate of cancer, which can be monitored by IDEA. (Clinical trial registration number: ChiCTR2000029001.).

"Pink Pattern" Visualized in Magnifying Endoscopy With Narrow-Band Imaging Is a Novel Feature of Early Differentiated Gastric Cancer: A Bridge Between Endoscopic Images and Histopathological Changes.

Background: A pink color change occasionally found by us under magnifying endoscopy with narrow-band imaging (ME-NBI) may be a special feature of early gastric cancer (EGC), and was designated the "pink pattern". The purposes of this study were to determine the relationship between the pink pattern and the cytopathological changes in gastric cancer cells and whether the pink pattern is useful for the diagnosis of EGC. Methods: The color features of ME-NBI images and pathological images of cancerous gastric mucosal surfaces were extracted and quantified. The cosine similarity was calculated to evaluate the correlation between the pink pattern and the nucleus-to-cytoplasm ratio of cancerous epithelial cells. Two diagnostic tests were performed by 12 endoscopists using stored ME-NBI images of 185 gastric lesions to investigate the diagnostic efficacy of the pink pattern for EGC. The diagnostic values, such as the area under the curve (AUC), the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of test 1 and test 2 were compared. Results: The cosine similarity between the color values of ME-NBI images and pathological images of 20 lesions was at least 0.744. The median AUC, accuracy, sensitivity, specificity, PPV, and NPV of test 2 were significantly better than those of test 1 for all endoscopists and for the junior and experienced groups. Conclusions: The pink pattern observed in ME-NBI images correlated strongly with the change in the nucleus-to-cytoplasm ratio of gastric epithelial cells, and could be considered a useful marker for the diagnosis of differentiated EGC.

Retrospective analysis of predictive factors for lymph node metastasis in superficial esophageal squamous cell carcinoma.

This study aimed to identify the risk factors of lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma and use these factors to establish a prediction model. We retrospectively analyzed the data from training set (n = 280) and validation set (n = 240) underwent radical esophagectomy between March 2005 and April 2018. Our results of univariate and multivariate analyses showed that tumor size, tumor invasion depth, tumor differentiation and lymphovascular invasion were significantly correlated with LNM. Incorporating these 4 variables above, model A achieved AUC of 0.765 and 0.770 in predicting LNM in the training and validation sets, respectively. Adding macroscopic type to the model A did not appreciably change the AUC but led to statistically significant improvements in both the integrated discrimination improvement and net reclassification improvement. Finally, a nomogram was constructed by using these five variables and showed good concordance indexes of 0.765 and 0.770 in the training and validation sets, and the calibration curves had good fitting degree. Decision curve analysis demonstrated that the nomogram was clinically useful in both sets. It is possible to predict the status of LNM using this nomogram score system, which can aid the selection of an appropriate treatment plan.

A Nomogram for Predicting Lymphovascular Invasion in Superficial Esophageal Squamous Cell Carcinoma.

The lymphovascular invasion (LVI) status facilitates the determination of the optimal therapeutic strategy for superficial esophageal squamous cell carcinoma (SESCC), but in clinical practice, LVI must be confirmed by postoperative pathology. However, studies of the risk factors for LVI in SESCC are limited. Consequently, this study aimed to identify the risk factors for LVI and use these factors to establish a prediction model. The data of 516 patients who underwent radical esophagectomy between January 2007 and September 2019 were retrospectively collected (training set, n=361, January 2007 to May 2015; validation set, n=155, June 2015 to September 2019). In the training set, least absolute shrinkage and selection operator (LASSO) regression and multivariate analyses were utilized to identify predictive factors for LVI in patients with SESCC. A nomogram was then developed using these predictors. The area under the curve (AUC), calibration curve, and decision curve were used to evaluate the efficiency, accuracy, and clinical utility of the model. LASSO regression indicated that the tumor size, depth of invasion, tumor differentiation, lymph node metastasis (LNM), sex, circumferential extension, the presence of multiple lesions, and the resection margin were correlated with LVI. However, multivariate analysis revealed that only the tumor size, depth of invasion, tumor differentiation, and LNM were independent risk factors for LVI. Incorporating these four variables, model 1 achieved an AUC of 0.817 in predicting LVI. Adding circumferential extension to model 1 did not appreciably change the AUC and integrated discrimination improvement, but led to a significant increase in the net reclassification improvement (p=0.011). A final nomogram was constructed by incorporating tumor size, depth of invasion, tumor differentiation, LNM, and circumferential extension and showed good discrimination (training set, AUC=0.833; validation set, AUC=0.819) and good calibration in the training and validation sets. Decision curve analysis demonstrated that the nomogram was clinically useful in both sets. Thus, it is possible to predict the status of LVI using this nomogram scoring system, which can aid the selection of an appropriate treatment plan.

A Critical Role of Peptidylprolyl Isomerase A Pseudogene 22/microRNA-197-3p/Peptidylprolyl Isomerase A Axis in Hepatocellular Carcinoma.

The burden of hepatocellular carcinoma (HCC) worldwide is increasing over time, while the underlying molecular mechanism of HCC development is still under exploration. Pseudogenes are classified as a special type of long non-coding RNAs (lncRNAs), and they played a vital role in regulating tumor-associated gene expression. Here, we report that a pseudogene peptidylprolyl isomerase A pseudogene 22 (PPIAP22) and its parental gene peptidylprolyl isomerase A (PPIA) were upregulated in HCC and were associated with the clinical outcomes of HCC. Further investigation revealed that PPIAP22 might upregulate the expression of PPIA through sponging microRNA (miR)-197-3p, behaving as competing endogenous RNA (ceRNA). PPIA could participate in the development of HCC by regulating mRNA metabolic process and tumor immunity based on the functional enrichment analysis. We also found a strong correlation between the expression levels of PPIA and the immune cell infiltration or the expression of chemokines, especially macrophage, C-C motif chemokine ligand 15 (CCL15), and C-X-C motif chemokine ligand 12 (CXCL12). Our findings demonstrate that the PPIAP22/miR-197-3p/PPIA axis plays a vital role in the progression of HCC by increasing the malignancy of tumor cells and regulating the immune cell infiltration, especially macrophage, through CCL15-CCR1 or CXCL12-CXCR4/CXCR7 pathways.

Prediction of Microvascular Invasion and Its M2 Classification in Hepatocellular Carcinoma Based on Nomogram Analyses.

BACKGROUND AND AIMS: As a key pathological factor, microvascular invasion (MVI), especially its M2 grade, greatly affects the prognosis of liver cancer patients. Accurate preoperative prediction of MVI and its M2 classification can help clinicians to make the best treatment decision. Therefore, we aimed to establish effective nomograms to predict MVI and its M2 grade. METHODS: A total of 111 patients who underwent radical resection of hepatocellular carcinoma (HCC) from January 2015 to September 2020 were retrospectively collected. We utilized logistic regression and least absolute shrinkage and selection operator (LASSO) regression to identify the independent predictive factors of MVI and its M2 classification. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to select the potential predictive factors from the results of LASSO and logistic regression. Nomograms for predicting MVI and its M2 grade were then developed by incorporating these factors. Area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were respectively used to evaluate the efficacy, accuracy, and clinical utility of the nomograms. RESULTS: Combined with the results of LASSO regression, logistic regression, and IDI and NRI analyses, we founded that clinical tumor-node-metastasis (TNM) stage, tumor size, Edmondson-Steiner classification, α-fetoprotein (AFP), tumor capsule, tumor margin, and tumor number were independent risk factors for MVI. Among the MVI-positive patients, only clinical TNM stage, tumor capsule, tumor margin, and tumor number were highly correlated with M2 grade. The nomograms established by incorporating the above variables had a good performance in predicting MVI (AUCMVI = 0.926) and its M2 classification (AUCM2 = 0.803). The calibration curve confirmed that predictions and actual observations were in good agreement. Significant clinical utility of our nomograms was demonstrated by DCA. CONCLUSIONS: The nomograms of this study make it possible to do individualized predictions of MVI and its M2 classification, which may help us select an appropriate treatment plan.

A Novel Bipolar Polypectomy Snare Can Be an Alternative Choice for Endoscopic Resection.

Objective: Endoscopic resection (ER) is more difficult and has a higher rate of complications, such as perforation and bleeding. The aim of this study was to evaluate the safety and feasibility of a bipolar polypectomy snare for ER. Methods: Initial ER procedures in live pigs were carried out. Then, a human feasibility study was performed in patients with colorectal polyps. Finally, the finite element method was used to evaluate the safety and effectiveness of the new bipolar snare. Results: In the live animal model, there were no significant differences in wound size and cutting time between monopolar and bipolar groups. The histological results (histological scores) of the two groups in porcine experiments were almost the same except that the incision flatness of bipolar group was better than that of the monopolar group. Incidence of bleeding and perforation was similar between the two groups in pigs' and patients' study. At last, the finite element model showed that the vertical thermal damage depth produced by bipolar snare system was approximately 71-76% of that produced by monopolar snare system at the same power. Conclusions: The novel bipolar snare is feasible in patients with colorectal polyps and can be an alternative choice for ERs.

Development of a Genetic and Clinical Data-Based (GC) Risk Score for Predicting Survival of Hepatocellular Carcinoma Patients After Tumor Resection.

BACKGROUND/AIMS: Carnitine palmitoyltransferase 1A (CPT1A) is a rate-limiting enzyme in the transport of long-chain fatty acids for ß-oxidation. Increasing evidence has indicated that CPT1A plays an important role in carcinogenesis. However, the expression and prognostic value of CPT1A in hepatocellular carcinoma (HCC) have not been extensively studied. METHODS: Here, we collected 66 post-operative liver cancer tissue samples. Gene profile expression was tested by RT-PCR. Receiver operating characteristic (ROC) analysis was performed and multivariate analysis with Cox's Proportional Hazard Model was used for confirming the selected markers' predictive efficiency for HCC patients' survival. A simple risk scoring system was created based on Cox's regression modeling and bootstrap internal validation. RESULTS: Cox multivariate regression analysis demonstrated that CPT1A, tumor size, intrahepatic metastasis, TNM stage and histological grade were independent risk factors for the prognosis of HCC patients after surgery. Our genetic and clinical data-based (GC) risk scoring system revealed that HCC patients whose total score≥3 are more likely to relapse and die than patients whose total score < 3. Finally, the good discriminatory power of our risk scoring model was validated by bootstrap internal validation. CONCLUSIONS: The genetic and clinical data-based risk scoring model can be a promising predictive tool for liver cancer patients' prognosis after operation.