Transfer learning radiomics based on multimodal ultrasound imaging for staging liver fibrosis.

OBJECTIVES: To propose a transfer learning (TL) radiomics model that efficiently combines the information from gray scale and elastogram ultrasound images for accurate liver fibrosis grading. METHODS: Totally 466 patients undergoing partial hepatectomy were enrolled, including 401 with chronic hepatitis B and 65 without fibrosis pathologically. All patients received elastography and got liver stiffness measurement (LSM) 2-3 days before surgery. We proposed a deep convolutional neural network by TL to analyze images of gray scale modality (GM) and elastogram modality (EM). The TL process was used for liver fibrosis classification by Inception-V3 network which pretrained on ImageNet. The diagnostic performance of TL and non-TL was compared. The value of single modalities, including GM and EM alone, and multimodalities, including GM + LSM and GM + EM, was evaluated and compared with that of LSM and serological indexes. Receiver operating characteristic curve analysis was performed to calculate the optimal area under the curve (AUC) for classifying fibrosis of S4, ≥ S3, and ≥ S2. RESULTS: TL in GM and EM demonstrated higher diagnostic accuracy than non-TL, with significantly higher AUCs (all p < .01). Single-modal GM and EM both performed better than LSM and serum indexes (all p < .001). Multimodal GM + EM was the most accurate prediction model (AUCs are 0.950, 0.932, and 0.930 for classifying S4, ≥ S3, and ≥ S2, respectively) compared with GM + LSM, GM and EM alone, LSM, and biomarkers (all p < .05). CONCLUSIONS: Liver fibrosis can be staged by a transfer learning modal based on the combination of gray scale and elastogram ultrasound images, with excellent performance. KEY POINTS: • Transfer learning consists in applying to a specific deep learning algorithm that pretrained on another relevant problem, expected to reduce the risk of overfitting due to insufficient medical images. • Liver fibrosis can be staged by transfer learning radiomics with excellent performance. • The most accurate prediction model of transfer learning by Inception-V3 network is the combination of gray scale and elastogram ultrasound images.

Portal hypertension in hepatitis B-related cirrhosis: Diagnostic accuracy of liver and spleen stiffness by 2-D shear-wave elastography.

AIM: To assess the diagnostic accuracy of liver and spleen stiffness measured by 2-D shear-wave elastography (SWE) in evaluation of clinically significant and severe portal hypertension (CSPH and SPH, respectively). METHODS: Clinical data of 155 hepatitis B-related cirrhosis patients and their liver and spleen stiffness (L-SWE and S-SWE, respectively) were collected. The diagnostic performances of L-SWE, S-SWE, the liver stiffness-spleen diameter to platelet ratio score (LSPS) and portal hypertension risk score were evaluated. RESULTS: One hundred and four patients were eligible for analysis. Clinically significant and severe PH were detected in 84 and 74 patients, respectively. Liver and spleen stiffness were significantly correlated with hepatic venous pressure gradient in overall, CSPH, and SPH groups (rL = 0.607, 0.554, and 0.412; rS = 0.665, 0.566, and 0.467, respectively; all P < 0.05). The area under the receiver operating characteristic curves of L-SWE, S-SWE, LSPS, and PH risk score were 0.72 (95% confidence interval [CI], 0.49-0.95), 0.81 (95% CI, 0.55-0.97), 0.76 (95% CI, 0.51-0.96), and 0.73 (95% CI, 0.55-0.88) for CSPH, and 0.77 (95% CI, 0.51-0.93), 0.85 (95% CI, 0.59-0.96), 0.80 (95% CI, 0.58-0.98), and 0.80 (95% CI, 0.59-0.93) for SPH. The best cut-off of L-SWE for determining CSPH and SPH were 16.1 kPa (sensitivity, 78%; specificity, 72%) and 23.5 kPa (sensitivity, 81%; specificity, 79%). For S-SWE, the best cut-offs were 25.3 kPa (sensitivity, 85%; specificity, 79%) and 33.4 kPa (sensitivity, 74%; specificity, 70%). A cut-off of L-SWE <13.2 kPa or S-SWE <23.2 kPa was able to rule out CSPH, whereas a cut-off of L-SWE >24.9 kPa or S-SWE >34.2 kPa was able to rule in CSPH. CONCLUSIONS: Liver and spleen stiffness measured by 2-D SWE are reliable and promising non-invasive parameters to assess CSPH and SPH.

A Nude Mouse Model of Orthotopic Liver Transplantation of Human Hepatocellular Carcinoma HCCLM3 Cell Xenografts and the Use of Imaging to Evaluate Tumor Progression.

BACKGROUND This study aimed to develop a nude mouse model of orthotopic liver transplantation of HCCLM3 human hepatocellular carcinoma (HCC) cell xenografts and the use of imaging and histology to evaluate tumor development and progression. MATERIAL AND METHODS HCCLM3 cells were injected subcutaneously into 25 healthy male athymic BALB/c (nu/nu) nude mice. The tumors that developed were transplanted into the liver of a new set of nude mice. After four weeks and six weeks, the mice were imaged using ultrasound (US), software-assisted contrast-enhanced ultrasound (CEUS), fluorodeoxyglucose-positron emission tomography (FDG-PET). Histology was performed on the liver and liver tumors, and included immunohistochemistry for vascular endothelial growth factor (VEGF), CD31, CD34, and alpha-smooth muscle actin (alpha-SMA). RESULTS The success rate for orthotopic tumor transplantation in the mouse liver was 90% (18/20). Liver tumors measured 11.8±2.6 mm in diameter and 525.9±250.8 mm3 in volume on the sixth week. CEUS showed rapid wash-in and washout in the liver tumors, and PET showed low tumor cell metabolism. Bone metastases were present in 45% (9/20) of mice in the sixth week. Immunohistochemistry showed positive expression for VEGF, CD31, CD34, and alpha-SMA. CONCLUSIONS The nude mouse orthotopic liver transplantation model of human HCC was shown to be a reliable model that has the potential for future research on the pathogenesis and progression of HCC and studies on drug development.

Is Brachial Artery Blood Flow Measured by Sonography During Early Postoperative Periods Predictive of Arteriovenous Fistula Failure in Hemodialysis Patients?

OBJECTIVES: The aim of our study was to determine a brachial artery blood flow level measured by sonography during early postoperative periods that is predictive of arteriovenous fistula failure in hemodialysis patients. METHODS: Doppler sonography was used to estimate the blood flow in the brachial artery of 103 patients at 1 and 14 days after arteriovenous fistula creation. The performance of brachial artery blood flow during early postoperative periods for predicting fistula failure was evaluated, and optimal cutoff values were determined. RESULTS: During a 6-month follow-up, 85 fistulas were classified as mature, and 18 were classified as failures. The reproducibility of blood flow measurements in the brachial artery was good (intraclass correlation coefficient, 0.912). The blood flow in the failure group was significantly lower than that in the mature group at both 1 and 14 days after fistula creation (P < .05). During the first 2 postoperative weeks, the blood flow increased by 40.7% in the failure group versus 78.3% in the mature group. The areas under the receiver operating characteristic curves of brachial artery blood flow for predicting failure were 0.77 (95% confidence interval, 0.66-0.87; optimal cutoff value, 310 mL/min)at 1 day and 0.91 (95% confidence interval, 0.83-0.99; 413 mL/min) at 14 days after fistula creation. CONCLUSIONS: Brachial artery blood flow measured by sonography during early postoperative periods may be predictive of forearm fistula failure. Blood flow of less than 310 mL/min at 1 day and 413 mL/min at 14 days after fistula creation may indicate a risk of failure to mature.

Impact of rifaximin on cirrhosis complications and gastric microbiota in patients with gastroesophageal variceal bleeding: A pilot randomized controlled trial.

OBJECTIVES: The application of rifaximin, a non-absorbable antibiotic, in hepatic encephalopathy (HE) has been well established; however, its effect on other complications in cirrhotic patients with previous gastroesophageal variceal bleeding (GEVB) remains unclear. Therefore, we performed a pilot randomized controlled trial aiming to evaluate the impact of rifaximin on cirrhosis-related complications and changes in gastric microbiota. METHODS: Eighty cirrhotic patients who received prophylactic endoscopic treatment for variceal rebleeding were randomly assigned to the control or rifaximin treatment group (rifaximin 400 mg twice daily for 8 weeks). Primary outcome was the total liver-related score, consisting of changes in cirrhosis-related complications including rebleeding, ascites, HE and portal vein thrombosis (PVT). The 16S rDNA sequencing analysis was conducted with gastric lavage fluid samples for the analysis of gastric microbiota. RESULTS: During the 8-week follow-up, the total liver-related score decreased significantly upon rifaximin therapy (-0.35 ± 0.14 vs 0.05 ± 0.14, p = 0.0465) as well as serum C-reactive protein (CRP) (p = 0.019) and interleukin-8 (p = 0.025) compared with the control group. The rate of PVT recanalization was significantly higher in the rifaximin group (p = 0.012). Prominent difference in gastric microbiota between the two groups was observed, and the rifaximin group had a higher abundance of several taxa which were dysregulated in the progression of cirrhosis. CRP was correlated with several taxa including Alphaproteobacteria, Rhizobiales and Collinsella. CONCLUSIONS: Rifaximin may improve cirrhosis-related complications, including PVT, in patients with previous GEVB through anti-inflammatory and microbiota-modulating functions. TRIAL REGISTRATION NUMBER: NCT02991612.

A novel HLA-C*07 allele, HLA-C*07:1024, was identified in a Chinese individual.

One nucleotide replacement at nucleotide 397 of HLA-C*07:02:01:01 results in a new allele, HLA-C*07:1024.

Quantitative Diagnosis of Nonalcoholic Fatty Liver Disease with Ultrasound Attenuation Imaging in a Biopsy-Proven Cohort.

RATIONALE AND OBJECTIVES: To evaluate the performance of attenuation imaging (ATI) based on ultrasound for detection of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This prospective study was approved by our institutional review board (B2021-092R). Written informed consent was obtained from all patients. This study included 60 patients who had clinical suspicion of NAFLD and were referred for liver biopsy after ATI and controlled attenuation parameter (CAP) examinations between September 2020 and December 2021. The histologic hepatic steatosis was graded. The area under curve (AUC) analysis was performed. RESULTS: The success rate of the ATI examination was 100%. The intraobserver reproducibility of ATI was 0.981. The AUCs of ATI for detecting ≥S1, ≥S2, and S3 were 0.968 (cut-off value of 0.671 dB/cm/MHz), 0.911 (cut-off value of 0.726 dB/cm/MHz), and 0.766 (cut-off value of 0.757 dB/cm/MHz), respectively. The AUCs of CAP for detecting ≥S1, ≥S2, and S3 were 0.916 (cut-off value of 258.5 dB/m), 0.872 (cut-off value of 300.0 dB/m), and 0.807 (cut-off value of 315.0 dB/m), respectively. The diagnostic values showed no significant difference between ATI and CAP in detecting ≥S1, ≥S2, and S3 (P = .281, P = .254, and P = .330, respectively). The ATI had significant correlations with high-density lipoprotein cholesterol (P < .001), and with triglycerides (P = .015). CONCLUSION: ATI showed good feasibility and diagnostic performance in the detection of varying degrees of hepatic steatosis in NAFLD patients.

Increased portal vein diameter is predictive of portal vein thrombosis development in patients with liver cirrhosis.

BACKGROUND: Cirrhotic patients with portal vein thrombosis (PVT) may have a high risk of hepatic decompensation and increased mortality. This study aimed to investigate if increased portal vein diameter is associated with PVT development. METHODS: A total of 174 cirrhotic patients were enrolled between February 1 and August 31, 2017. All participants were divided into PVT (n=62) and non-PVT (n=112) groups based on the thrombus that was detected by ultrasonography and confirmed by computed tomography angiography (CTA). RESULTS: The study participants, aged 54.7±10.5 years (PVT) and 55.8±11.6 years (non-PVT), were included in this analysis. The Child-Pugh score of PVT or non-PVT was 6.6±1.3 and 5.8±0.9, respectively. Hepatitis B virus (HBV) is the primary etiological agent of cirrhosis. Logistic regression, receiver operating characteristic (ROC), and nomograph analysis designated portal diameter as the strongest independent risk factor for predicting PVT development [odds ratio (OR): 3.96, area under the ROC curve (AUC): 0.88; P<0.01], and the cutoff with predictive value for PVT development was >12.5 mm. No differences were observed in the overall survival (OS) in cirrhosis with or without PVT or stratifying on portal diameter based on the cutoff value. CONCLUSIONS: Increased portal diameter is associated with an increased risk of PVT development. Patients with cirrhosis and increased portal diameter are a high-risk subgroup that may need thromboprophylaxis.

Conserved genes in a path from commensalism to pathogenicity: comparative phylogenetic profiles of Staphylococcus epidermidis RP62A and ATCC12228.

BACKGROUND: Staphylococcus epidermidis, long regarded as an innocuous commensal bacterium of the human skin, is the most frequent cause of nosocomial infections associated with implanted medical devices. This conditional pathogen provides a model of choice to study genome landmarks correlated with the transition between commensalism and pathogenicity. Traditional investigations stress differences in gene content. We focused on conserved genes that have accumulated small mutation differences during the transition. RESULTS: A comparison of strain ATCC12228, a non-biofilm forming, non-infection associated strain and strain RP62A, a methicillin-resistant biofilm clinical isolate, revealed consistent variation, mostly single-nucleotide polymorphisms (SNPs), in orthologous genes in addition to the previously investigated global changes in gene clusters. This polymorphism, scattered throughout the genome, may reveal genes that contribute to adaptation of the bacteria to different environmental stimuli, allowing them to shift from commensalism to pathogenicity. SNPs were detected in 931 pairs of orthologs with identical gene length, accounting for approximately 45% of the total pairs of orthologs. Assuming that non-synonymous mutations would mark recent evolution, and hence be associated to the onset of the pathogenic process, analysis of ratios of non-synonymous SNPs vs synonymous SNPs suggested hypotheses about possible pathogenicity determinants. The N/S ratios for virulence factors and surface proteins differed significantly from that of average SNPs. Of those gene pairs, 40 showed a disproportionate distribution of dN vs dS. Among those, the presence of the gene encoding methionine sulfoxide reductase suggested a possible involvement of reactive oxygen species. This led us to uncover that the infection associated strain was significantly more resistant to hydrogen peroxide and paraquat than the environmental strain. Some 16 genes of the list were of unknown function. We could suggest however that they were likely to belong to surface proteins or considered in priority as important for pathogenicity. CONCLUSION: Our study proposed a novel approach to identify genes involved in pathogenic processes and provided some insight about the molecular mechanisms leading a commensal inhabitant to become an invasive pathogen.

Comparative proteomic analysis between the invasive and commensal strains of Staphylococcus epidermidis.

Staphylococcus epidermidis is one of the major causative agents for nosocomial infections. To reveal the pathogenesis factors, we performed the comparative proteomic analysis of invasive ATCC35984 and commensal ATCC12228 strains by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. The differentially expressed proteins were involved in carbohydrate metabolism, sugar binding, lipid degradation and amino acid binding. In addition, we demonstrated that the trap gene was transcribed by 3.657+/-0.156 (P<0.01) -fold higher in ATCC35984 than in ATCC12228. Levels of accumulation-associated protein (AAP) were found to be low by the immuno-dot blotting assay in ATCC12228, which is unable to form biofilm. Our results suggest that the target of RNAIII activating protein and AAP may contribute to S. epidermidis virulence and biofilm formation.

Hydrogen-rich saline attenuates postoperative liver failure after major hepatectomy in rats.

BACKGROUND/AIMS: A major hepatectomy occasionally lead to acute liver failure and death. We demonstrated the anti-oxidative and anti-inflammatory effects and functional mechanisms of hydrogen-rich saline (HS), a novel antioxidant, on an experimental model of rats after a partial hepatectomy (PH). METHODS: The rats underwent a 90% hepatectomy. HS was given intraperitoneally after the operation and every 8hours after. RESULTS: HS markedly improved the survival rate of two experimental groups after the massive hepatectomy and inhibited increases in serum levels of TBIL, DBIL, ALT and AST. The histopathological analysis demonstrated that HS attenuated inflammatory changes in the liver. HS administration markedly lowered the massive hepatectomy induced elevation of the serum hyaluronic acid (HA) concentrations. HS inhibited the formation of one of the markers of oxidative damage, malondialdehyde (MDA), and increased the activities of superoxide dismutase (SOD) in liver tissue. In the HS-treated group, increases in inflammatory cytokines, such as TNF-α, IL-6 and HMGB-1, were inhibited in the liver tissue. The NF-κB p65 staining revealed that HS inhibited the activation of the transcription factor nuclear factor kappa B (NF-kB). CONCLUSIONS: HS attenuates the massive hepatectomy induced liver injury not only by attenuating oxidative damage, but also by reducing the production of inflammatory cytokines, such as TNF-α, IL-6 and HMGB-1, in part through the inhibition of NF-kB activation.

[Identification of Tritielytrigia alien disomic addition line shannong 87074-519 with yellow rust resistance].

In this paper, Shannong 87074-519, a derivative of wheat-decaploid Elytrigia elongata, was identified by inoculation assessment, cytological analysis, simple sequence repeat (SSR), molecular marker technique,and genomic in situ hybridization (GISH). The results are as follows: the chromosome number of Shannong87074-519 in root tip cells was 2n=44, 22 bivalents were observed in most PMC at MI, and the average chromosome configuration was 2n=44=21.82 II+0.36 I , and the chromosome configuration (2n=43=21 II +1 I) was observed in most PMC of F1 between Shannong87074-519 and C.S. at MI. Therefore, it was an alien disomic addition line with one pair chromosome of Elytrigia elongata. Then the St total genomic DNA was labeled as probe in GISH, the green-yellow hybridization signal was observed in two intact chromosomes, indicating that Shannong87074-519 was added by one pair chromosome of St genome. The SSR-PCR technique was employed in the primer filtration, and the molecular marker BARC165 was singled out from 170 primers, which could amplify the specific molecular marker BARC165(268) of Elytrigia elongata in Shannong87074-519. Subsequently, the specific segment in Elytrigia elongata was cloned and labeled as probe in GISH of root tip cells of Shannong87074-519, the light yellow hybridization signal was observed in both chromatin at interphase and chromosome at mitotic metaphase, thus the BARC165(268) could be applied as a specific molecular marker to detect alien chromatin of Elytrigia elongata in Shannong87074-519. Because of the good agronomic characteristics, high immunity to yellow rust, and dominant new yellow rust resistant gene located at the added chromosome St, assigned as YrSt temporarily, Shannong87074-519 has very important value in wheat breeding and genetics improvement.