Diagnostic Accuracy of Unenhanced Computed Tomography for Evaluation of Acute Abdominal Pain in the Emergency Department.

Importance: Intravenous (IV) contrast medium is sometimes withheld due to risk of complication or lack of availability in patients undergoing computed tomography (CT) for abdominal pain. The risk from withholding contrast medium is understudied. Objective: To determine the diagnostic accuracy of unenhanced abdominopelvic CT using contemporaneous contrast-enhanced CT as the reference standard in emergency department (ED) patients with acute abdominal pain. Design, Setting, and Participants: This was an institutional review board-approved, multicenter retrospective diagnostic accuracy study of 201 consecutive adult ED patients who underwent dual-energy contrast-enhanced CT for the evaluation of acute abdominal pain from April 1, 2017, through April 22, 2017. Three blinded radiologists interpreted these scans to establish the reference standard by majority rule. IV and oral contrast media were then digitally subtracted using dual-energy techniques. Six different blinded radiologists from 3 institutions (3 specialist faculty and 3 residents) interpreted the resulting unenhanced CT examinations. Participants included a consecutive sample of ED patients with abdominal pain who underwent dual-energy CT. Exposure: Contrast-enhanced and virtual unenhanced CT derived from dual-energy CT. Main outcome: Diagnostic accuracy of unenhanced CT for primary (ie, principal cause[s] of pain) and actionable secondary (ie, incidental findings requiring management) diagnoses. The Gwet interrater agreement coefficient was calculated. Results: There were 201 included patients (female, 108; male, 93) with a mean age of 50.1 (SD, 20.9) years and mean BMI of 25.5 (SD, 5.4). Overall accuracy of unenhanced CT was 70% (faculty, 68% to 74%; residents, 69% to 70%). Faculty had higher accuracy than residents for primary diagnoses (82% vs 76%; adjusted odds ratio [OR], 1.83; 95% CI, 1.26-2.67; P = .002) but lower accuracy for actionable secondary diagnoses (87% vs 90%; OR, 0.57; 95% CI, 0.35-0.93; P < .001). This was because faculty made fewer false-negative primary diagnoses (38% vs 62%; OR, 0.23; 95% CI, 0.13-0.41; P < .001) but more false-positive actionable secondary diagnoses (63% vs 37%; OR, 2.11, 95% CI, 1.26-3.54; P = .01). False-negative (19%) and false-positive (14%) results were common. Interrater agreement for overall accuracy was moderate (Gwet agreement coefficient, 0.58). Conclusion: Unenhanced CT was approximately 30% less accurate than contrast-enhanced CT for evaluating abdominal pain in the ED. This should be balanced with the risk of administering contrast material to patients with risk factors for kidney injury or hypersensitivity reaction.

Accuracy of Ultrasound Imaging for Etiology of New-Onset Painless Jaundice.

PURPOSE: Ultrasound (US) is considered a first-line study for painless jaundice. However, in our hospital system, patients with new-onset painless jaundice often have a contrast-enhanced computed tomography (CECT) or magnetic resonance cholangiopancreatography (MRCP) regardless of the sonographic findings. Thus, we investigated the accuracy of US for detection of biliary dilatation in patients with new-onset painless jaundice. METHODS: Our electronic medical record was searched from January 1, 2012, to January 1, 2020, for adult patients with new-onset painless jaundice. Presenting complaint/setting, laboratory values, imaging studies/findings, and final diagnoses were recorded. Patients with pain or known liver disease were excluded. A gastrointestinal physician reviewed the laboratory values/chart to classify the type of suspected obstruction. Two radiologists blindly re-reviewed the US scans, and κ between the radiologists was calculated. Fisher exact test and the 2-sample t test were used for statistical analysis. RESULTS: Three hundred sixty patients presented with jaundice (>3 mg/dL), of whom 68 met the inclusion criteria (no pain and no known liver disease). Laboratory values had an overall accuracy of 54%, but were accurate in 87.5% and 85% for obstructing stones/pancreaticobiliary cancer. Ultrasound demonstrated overall accuracy of 78%, but only 69% for pancreaticobiliary cancer and 12.5% for common bile duct stone. Seventy-five percent of the patients underwent follow-up CECT or MRCP regardless of presenting setting. In the emergency department or inpatient setting, 92% of the patients underwent CECT or MRCP regardless of US, and 81% had follow-up CECT or MRCP within 24 hours. CONCLUSION: A US-first strategy in the setting of new-onset painless jaundice is accurate only 78% of the time. In practice, US was almost never a stand-alone imaging examination in patients presenting to the emergency department or inpatient setting with new-onset painless jaundice, no matter the suspected diagnosis based on clinical and laboratory grounds or on the US findings themselves. However, for milder elevations of unconjugated bilirubin (suspicious for Gilbert disease) in the outpatient setting, a US demonstrating lack of biliary dilatation was often a definitive study for exclusion of pathology.

Correlation between imaging findings on outpatient MR enterography (MRE) in adult patients with Crohn disease and progression to surgery within 5 years.

PURPOSE: To retrospectively evaluate which key imaging features described by SAR-AGA on outpatient surveillance MRE correlate with progression to surgery in adults with CD. METHODS: 52 CD patients imaged with outpatient MRE from 10/2015 to 12/2016 and with available clinical information were included. Two abdominal radiologists reviewed the MRE for the presence of active inflammation, intramural edema, restricted diffusion, stricture, probable stricture, ulceration, sacculation, simple fistula, complex fistula, sinus tract, inflammatory mass, abscess, perienteric inflammation, engorged vasa recta, fibrofatty proliferation, and perianal disease. Bowel wall thickness, length of bowel involvement, and degree of upstream dilation in strictures were quantified. Subsequent bowel resection, prior bowel surgery, and available laboratory values were recorded. The association between progression to surgery and imaging features was evaluated using a logistic regression model adjusting for demographics, prior bowel surgery, medication usage, and body mass index. RESULTS: 19.2% (10/52) of patients progressed to surgery. Restricted diffusion, greater degree of upstream dilation from stricture, complex fistula, perienteric inflammation, and fibrofatty proliferation were significantly more common in patients progressing to surgery (all p < 0.05). κ for these significant findings ranged 0.568-0.885. Patients progressing to surgery had longer length bowel involvement (p = 0.03). Platelet count, ESR, and fecal calprotectin were significantly higher, and serum albumin was significantly lower in patients progressing to surgery. Prior bowel surgery, sex, age, and all other parameters were similar. CONCLUSION: Radiologists should carefully describe bowel dilation upstream from strictures, penetrating and perienteric findings on outpatient MRE in CD patients, as these findings may herald progression to surgery.

Metabolic discrimination of synovial fluid between rheumatoid arthritis and osteoarthritis using gas chromatography/time-of-flight mass spectrometry.

INTRODUCTION: Rheumatoid arthritis (RA) and osteoarthritis (OA) are clinicopathologically different. OBJECTIVES: We aimed to assess the feasibility of metabolomics in differentiating the metabolite profiles of synovial fluid between RA and OA using gas chromatography/time-of-flight mass spectrometry. METHODS: We first compared the global metabolomic changes in the synovial fluid of 19 patients with RA and OA. Partial least squares-discriminant, hierarchical clustering, and univariate analyses were performed to distinguish metabolites of RA and OA. These findings were then validated using synovial fluid samples from another set of 15 patients with RA and OA. RESULTS: We identified 121 metabolites in the synovial fluid of the first 19 samples. The score plot of PLS-DA showed a clear separation between RA and OA. Twenty-eight crucial metabolites, including hypoxanthine, xanthine, adenosine, citrulline, histidine, and tryptophan, were identified to be capable of distinguishing RA metabolism from that of OA; these were found to be associated with purine and amino acid metabolism. CONCLUSION: Our results demonstrated that metabolite profiling of synovial fluid could clearly discriminate between RA and OA, suggesting that metabolomics may be a feasible tool to assist in the diagnosis and advance the comprehension of pathological processes for diseases.

Comparison of Prostate Imaging and Reporting Data System V2.0 and V2.1 for Evaluation of Transition Zone Lesions: A 5-Reader 202-Patient Analysis.

OBJECTIVE: The aim of the study was to compare the distribution of Prostate Imaging and Reporting Data System (PI-RADS) scores, interreader agreement, and diagnostic performance of PI-RADS v2.0 and v2.1 for transition zone (TZ) lesions. METHODS: The study included 202 lesions in 202 patients who underwent 3T prostate magnetic resonance imaging showing a TZ lesion that was later biopsied with magnetic resonance imaging/ultrasound fusion. Five abdominal imaging faculty reviewed T2-weighted imaging and high b value/apparent diffusion coefficient images in 2 sessions. Cases were randomized using a crossover design whereby half in the first session were reviewed using v2.0 and the other half using v2.1, and vice versa for the 2nd session. Readers provided T2-weighted imaging and DWI scores, from which PI-RADS scores were derived. RESULTS: Interreader agreement for all PI-RADS scores had κ of 0.37 (v2.0) and 0.26 (v2.1). For 4 readers, the percentage of lesions retrospectively scored PI-RADS 1 increased greater than 5% and PI-RADS 2 score decreased greater than 5% from v2.0 to v2.1. For 2 readers, the percentage scored PI-RADS 3 decreased greater than 5% and, for 2 readers, increased greater than 5%. The percentage of PI-RADS 4 and 5 lesions changed less than 5% for all readers. For the 4 readers with increased frequency of PI-RADS 1 using v2.1, 4% to 16% were Gleason score ≥3 + 4 tumor. Frequency of Gleason score ≥3 + 4 in PI-RADS 3 lesions increased for 2 readers and decreased for 1 reader. Sensitivity of PI-RADS of 3 or greater for Gleason score ≥3 + 4 ranged 76% to 90% (v2.0) and 69% to 96% (v2.1). Specificity ranged 32% to 64% (v2.0) and 25% to 72% (v2.1). Positive predictive value ranged 43% to 55% (v2.0) and 41% to 58% (v2.1). Negative predictive value ranged 82% to 87% (v2.0) and 81% to 91% (v2.1). CONCLUSIONS: Poor interreader agreement and lack of improvement in diagnostic performance indicate an ongoing need to refine evaluation of TZ lesions.

Enhanced γ-aminobutyric acid and sialic acid in fermented deer antler velvet and immune promoting effects.

Deer antler velvet is widely used in traditional medicine for its anti-aging, antioxidant, and immunity-enhancing effects. However, few studies have reported on the discovery of probiotic strains for deer antler fermentation to increase functional ingredient absorption. This study evaluated the ability of probiotic lactic acid bacteria to enhance the concentrations of bioactive molecules (e.g., sialic acid and gamma-aminobutyric acid [GABA]) in extracts of deer antler velvet. Seventeen strains of Lactobacillus spp. that were isolated from kimchi and infant feces, including L. sakei, L. rhamnosus, L. brevis, and L. plantarum, and those that improved the life span of Caenorhabditis elegans were selected for evaluation. Of the 17 strains, 2 (L. rhamnosus LFR20-004 and L. sakei LFR20-007) were selected based on data showing that these strains increased both the sialic acid and GABA contents of deer antler extract after fermentation for 2 d and significantly improved the life span of C. elegans. Co-fermentation with both strains further increased the concentrations of sialic acid, GABA, and metabolites such as short-chain fatty acids and amino acids. We evaluated the biological effects of the fermented antler velvet (FAV) on the antibacterial immune response in C. elegans by assessing worm survival after pathogen infection. The survival of the C. elegans conditioned with FAV for 24 h was significantly higher compared with that of the control worm group fed only normal feed (non-pathogenic E. coli OP50) exposed to E. coli O157:H7, Salmonella typhi, and Listeria monocytogenes. To evaluate the protective effects of FAV on immune response, cyclophosphamide (Cy), an immune-suppressing agent was treated to in vitro and in vivo. We found that FAV significantly restored viability of mice splenocytes and immune promoting-related cytokines (interleukin [IL]-6, IL-10, inducible nitric oxide synthase [iNOS], interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were activated compared to non-fermented deer antlers. This finding indicated the protective effect of FAV against Cy-induced cell death and immunosuppressed mice. Taken together, our study suggests that immune-promoting antler velvet can be produced through fermentation using L. rhamnosus LFR20-004 and L. sakei LFR20-007.

Comparison of Antioxidant Properties and Metabolite Profiling of Acer pseudoplatanus Leaves of Different Colors.

Acer pseudoplatanus (maple) is a widely grown ornamental plant. In addition to its ornamental and ecological value, it also has potentially high economic value. It is a rich source of polyphenols and exhibits antioxidant activity. However, the relationship between polyphenol content and antioxidant activity in maple leaves of different colors (green, yellow, and red) has not yet been investigated. In this study, the total polyphenol (TP), total flavonoid (TFlav), tannin (TET), chlorophyll a and b (Chl a and b), total anthocyanin (TAN), and total carotene (TAC) contents in maple leaves of different colors were evaluated. Their antioxidant activities were determined based on the inhibition of lipid oxidation, DPPH scavenging, ferric ion-reducing antioxidant power, and iron-chelating abilities. The concentrations of TP, TET, TFlav, TAN, and TAC in red maple leaves were higher than those in green and yellow maple leaves. In addition, red maple leaves showed a higher antioxidant effect than the leaves of the other two colors. We observed that antioxidant activity was positively correlated with TP, TFlav, and TAN and negatively correlated with Chl a and b. Finally, we analyzed the metabolites of the different colored (i.e., green, yellow, and red) maple leaves using gas chromatography/mass spectrometry (GC/MS) and found that the metabolite profile significantly varied between the different colors. These results suggest that red leaves are a good source of polyphenols and antioxidants and have potential use in the development of functional foods and medicinal applications.

Pathologic, Molecular, and Prognostic Radiologic Features of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy with variable biologic aggressiveness based on the tumor grade, presence or absence of vascular invasion, and pathologic and molecular classification. Knowledge and understanding of the prognostic implications of different pathologic and molecular phenotypes of HCC are emerging, with therapeutics that promise to provide improved outcomes in what otherwise remains a lethal cancer. Imaging has a central role in diagnosis of HCC. However, to date, the imaging algorithms do not incorporate prognostic features or subclassification of HCC according to its biologic aggressiveness. Emerging data suggest that some imaging features and further radiologic, pathologic, or radiologic-molecular phenotypes may allow prediction of the prognosis of patients with HCC. An invited commentary by Bashir is available online. Online supplemental material is available for this article. ©RSNA, 2021.

Antidiabetic Effect of Noodles Containing Fermented Lettuce Extracts.

The aim of the current study was to examine the antidiabetic effect of noodle containing fermented lettuce extract (FLE) on diabetic mice as a pre-clinical study. The γ-aminobutyric acid (GABA) content, antioxidant capacity, and total polyphenol content of the FLE noodles were analyzed and compared with those of standard noodles. In addition, oral glucose and sucrose tolerance, and fasting blood glucose tests were performed using a high-fat diet/streptozotocin-mediated diabetic mouse model. Serum metabolite profiling of mice feed standard or FLE noodles was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) to understand the mechanism changes induced by the FLE noodles. The GABA content, total polyphenols, and antioxidant activity were high in FLE noodles compared with those in the standard noodles. In vivo experiments also showed that mice fed FLE noodles had lower blood glucose levels and insulin resistance than those fed standard noodles. Moreover, glycolysis, purine metabolism, and amino acid metabolism were altered by FLE as determined by GC-TOF-MS-based metabolomics. These results demonstrate that FLE noodles possess significant antidiabetic activity, suggesting the applicability of fermented lettuce extract as a potential food additive for diabetic food products.

Inter-reader agreement of the Society of Abdominal Radiology-American Gastroenterological Association (SAR-AGA) consensus reporting for key phenotypes at MR enterography in adults with Crohn disease: impact of radiologist experience.

PURPOSE: To assess inter-reader agreement of key features from the SAR-AGA recommendations for the interpretation and reporting of MRE in adult patients with CD, focusing on the impact of radiologist experience on inter-reader agreement of CD phenotypes. METHODS: Two experienced and two less-experienced radiologists retrospectively evaluated 99 MRE in CD patients (50 initial MRE, 49 follow-up MRE) performed from 1/1/2019 to 3/20/2020 for the presence of active bowel inflammation (stomach, proximal small bowel, ileum, colon), stricture, probable stricture, penetrating disease, and perianal disease. The MRE protocol did not include dedicated perianal sequences. Inter-rater agreement was determined for each imaging feature using prevalence-adjusted bias-adjusted kappa and compared by experience level. RESULTS: All readers had almost-perfect inter-reader agreement (κ > 0.90) for penetrating disease, abscess, and perianal abscess in all 99 CD patients. All readers had strong inter-reader agreement (κ: 0.80-0.90) in 99 CD patients for active ileum inflammation, proximal small bowel inflammation, and stricture. Less-experienced readers had significantly lower inter-reader agreement for active ileum inflammation on initial than follow-up MRE (κ 0.68 versus 0.96, p = 0.018) and for strictures on follow-up than initial MRE (κ 0.76 versus 1.0, p = 0.027). Experienced readers had significantly lower agreement for perianal fistula on follow-up than initial MRE (κ: 0.55 versus 0.92, p = 0.008). CONCLUSION: There was strong to almost-perfect inter-reader agreement for key CD phenotypes described in the SAR-AGA consensus recommendations including active ileum and proximal small bowel inflammation, stricture, penetrating disease, abscess, and perianal abscess. Areas of lower inter-reader agreement could be targeted for future education efforts to further standardize CD MRE reporting. Dedicated perianal sequences should be included on follow-up MRE.

Frequency and significance of incidental liver lesions on MR enterography in adult patients.

PURPOSE: To evaluate the frequency and significance of incidental liver lesions identified on MR enterography (MRE) examinations to determine if dedicated sequences for liver evaluation are necessary in the routine MRE protocol. METHODS: A retrospective departmental database search identified 353 adult (212 women and 141 men; mean [±SD] age, 41.4 [17.0] years; range 18.1-91.9 years) MRE examinations performed in 2017. Radiology reports were reviewed for the presence and characterization of liver lesions, follow-up recommendation, and known malignancy. Follow-up cross-sectional imaging reports were reviewed for liver lesion stability. A senior abdominal radiologist with expertise in liver imaging categorized liver lesions as benign, indeterminate, or malignant and re-characterized indeterminate lesions using follow-up imaging as benign or malignant. RESULTS: Seventy-nine MRE (22.4%) described liver lesions and follow-up imaging was recommended in 4/79 (5.1%). Seventy-six liver lesions (96.2%) were characterized as benign (cysts/hemangiomas) on routine interpretation and expert review. One of these was recommended for follow-up imaging on initial report, which was characterized as hemangioma by expert review. The remaining 3 lesions (3.8%) were characterized as indeterminate both by initial report and expert radiologist review but re-characterized as benign after reviewing follow-up examinations. CONCLUSION: All incidental liver lesions identified on MRE in our cohort were benign. Therefore, additional sequences evaluating the liver are unnecessary for routine MRE.

Comparison of Non-Tumoral Portal Vein Thrombosis Management in Cirrhotic Patients: TIPS Versus Anticoagulation Versus No Treatment.

BACKGROUND: There is a lack of consensus in optimal management of portal vein thrombosis (PVT) in patients with cirrhosis. The purpose of this study is to compare the safety and thrombosis burden change for cirrhotic patients with non-tumoral PVT managed by transjugular intrahepatic portosystemic shunt (TIPS) only, anticoagulation only, or no treatment. METHODS: This single-center retrospective study evaluated 52 patients with cirrhosis and non-tumoral PVT managed by TIPS only (14), anticoagulation only (11), or no treatment (27). The demographic, clinical, and imaging data for patients were collected. The portomesenteric thrombosis burden and liver function tests at early follow-up (6-9 months) and late follow-up (9-16 months) were compared to the baseline. Adverse events including bleeding and encephalopathy were recorded. RESULTS: The overall portomesenteric thrombosis burden improved in eight (72%) TIPS patients, three (27%) anticoagulated patients, and two (10%) untreated patients at early follow-up (p = 0.001) and in seven (78%) TIPS patients, two (29%) anticoagulated patients, and three (17%) untreated patients in late follow-up (p = 0.007). No bleeding complications attributable to anticoagulation were observed. CONCLUSION: TIPS decreased portomesenteric thrombus burden compared to anticoagulation or no treatment for cirrhotic patients with PVT. Both TIPS and anticoagulation were safe therapies.

Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3.

How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.

Metabolomic elucidation of the effects of media and carbon sources on fatty acid production by Yarrowia lipolytica.

Lipid production by oleaginous Yarrowia lipolytica depends highly on culture environments, such as carbon sources, carbon/nitrogen (C/N) ratios, types of media, and cellular growth phases. In this study, the effects of media and carbon sources on lipid and metabolite production were investigated by profiling fatty acids and intracellular metabolites of Y. lipolytica grown in various media. The highest total fatty acid yield 114.04 ±â€¯6.23 mg/g dry cell weight was achieved by Y. lipolytica grown in minimal medium with glycerol (SCG) in the exponential phase. The high lipid production by Y. lipolytica in SCG was presumed to be due to the higher C/N ratio in SCG than in the complex media. Moreover, glycerol promoted lipid production better than glucose in both complex and minimal media because glycerol can easily incorporate into the core of triglycerides. Metabolite profiling revealed that levels of long-chain fatty acids, such as stearic acid, palmitic acid, and arachidic acid, increased in SCG medium. Meanwhile, in complex media supplemented with either glucose or glycerol, levels of amino acids, such as cysteine, methionine, and glycine, highly increased. This metabolomic approach could be applied to modulate the global metabolic network of Y. lipolytica for producing lipids and other valuable products.

Radiologically Undetected Hepatocellular Carcinoma in Patients Undergoing Liver Transplantation: An Immunohistochemical Correlation With LI-RADS Score.

Orthotopic liver transplantation is the best option for patients with carefully selected unresectable disease because of underlying liver dysfunction. The 5-year survival rate after orthotopic liver transplantation for early detected hepatocellular carcinoma (HCC) is high, and a similar or even higher rate is reported in those with radiologically undetected HCC. This study evaluated and compared the histologic features of pretransplant radiologically undetected (14 patients, 25 tumors) versus detected (36 patients, 45 tumors) HCCs. Tumor size, tumor differentiation, number of unpaired arteries, mitotic count per 10 high-power fields, CD34 immunostain to assess microvessel density, and Ki67 immunostain were compared with the Liver Imaging Reporting and Data System score, which was retrospectively assigned to each tumor in both groups. The Liver Imaging Reporting and Data System score was significantly higher in the HCC detected group (P<0.001). The vast majority of the undetected HCCs (88%) was <2 cm in size. Only 12% of the undetected HCCs were ≥2 cm, whereas 51% of the detected HCCs were ≥2 cm in size. Higher rate of moderate to poor tumor differentiation was noted in the detected HCCs compared with the undetected group (89% vs. 60%; P=0.004). No statistically significant difference in the number and distribution of unpaired arteries, or mitotic count was observed in 2 groups (although fewer unpaired arteries were identified in the undetected group). The detected HCCs had a higher rate of 2+ CD34 staining compared with the undetected HCCs (68% vs. 27%; P=0.002), whereas the opposite was observed for 1+ CD34 staining (59% undetected HCCs vs. 17% detected HCCs; P=0.002). Ki67 proliferative index was not statistically different between the 2 groups (120.8/1000 cells detected HCCs vs. 81.8/1000 cells undetected HCCs; P=0.36). The factors associated with failing to detect HCCs pretransplant by radiologic studies include small tumor size (<2 cm), low-grade histologic differentiation, and low microvessel density (low CD34 staining). A significant association between the number and distribution of unpaired arteries and HCC detection has not been established by our study.

Systematic biomarker discovery and coordinative validation for different primary nephrotic syndromes using gas chromatography-mass spectrometry.

The goal of this study is to identify systematic biomarker panel for primary nephrotic syndromes from urine samples by applying a non-target metabolite profiling, and to validate their utility in independent sampling and analysis by multiplex statistical approaches. Nephrotic syndrome (NS) is a nonspecific kidney disorder, which is mostly represented by minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous glomerulonephritis (MGN). Since urine metabolites may mirror disease-specific functional perturbations in kidney injury, we examined urine samples for distinctive metabolic changes to identify biomarkers for clinical applications. We developed unbiased multi-component covarianced models from a discovery set with 48 samples (12 healthy controls, 12 MCD, 12 FSGS, and 12 MGN). To extensively validate their diagnostic potential, new batch from 54 patients with primary NS were independently examined a year after. In the independent validation set, the model including citric acid, pyruvic acid, fructose, ethanolamine, and cysteine effectively discriminated each NS using receiver operating characteristic (ROC) analysis except MCD-MGN comparison; nonetheless an additional metabolite multi-composite greatly improved the discrimination power between MCD and MGN. Finally, we proposed the re-constructed metabolic network distinctively dysregulated by the different NSs that may deepen comprehensive understanding of the disease mechanistic, and help the enhanced identification of NS and therapeutic plans for future.

GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and hyperplasia. Fibroblast-like synoviocytes (FLS) in RA exhibit a tumor cell-like aggressive phenotype. Thus, gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) was employed to identify the characteristic metabolic profiling of RA FLS. METHODS: Metabolite profiling of RA FLS and osteoarthritis (OA) FLS was performed using GC/TOF-MS in conjunction with statistical analyses. We performed metabolite set enrichment analysis to establish which pathways are affected. RESULTS: A total of 129 metabolites were identified. A principal component analysis and hierarchical clustering analysis demonstrated clear differentiation of the metabolic profiling between RA FLS and OA FLS. The levels of 35 metabolites that belonged to the amines, fatty acids, phosphates, and organic acids class were significantly increased in RA FLS compared to those in OA FLS. Also, the levels of 26 metabolites that belonged to the amino acids, sugars, and sugar alcohols class were significantly decreased in RA FLS compared to those in OA FLS. The sugar metabolism (glycolysis and pentose phosphate pathway) and amino acid metabolism (tyrosine and catecholamine biosynthesis, and protein biosynthesis) were severely disturbed in RA FLS compared to those in OA FLS. CONCLUSIONS: Our metabolic results suggested that the alteration of sugar metabolism, lipolysis, and amino acid metabolism in RA FLS is related to synovial hyperplasia and inflammation. This is the first metabolomic study to determine metabolic changes characteristic of RA FLS, which will provide valuable information to gain in-depth insights into the pathogenesis of RA.

Soft-Tissue Sarcomas: An Update for Radiologists Based on the Revised 2013 World Health Organization Classification.

OBJECTIVE: Soft-tissue sarcomas are a diverse group of malignancies, and our rapidly improving understanding of their molecular pathogenesis and treatment is leading to better clinical outcomes. The revised 2013 World Health Organization (WHO) classification of soft-tissue sarcomas introduced several important changes. We provide a comprehensive overview of the relevant changes for radiologists. CONCLUSION: Rapid advances in the understanding of the pathogenesis and molecular biology of soft-tissue sarcomas led to major revisions in the 2013 WHO classification. To provide optimal multidisciplinary patient care, radiologists must remain up-to-date with the latest developments in the field of soft-tissue sarcomas to best correlate the histologic and imaging features of the various types of tumors and understand the unique patterns of treatment response and disease recurrence.

Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α-stimulated and curcumin-treated FLS was performed using GC/TOF-MS in conjunction with univariate and multivariate statistical analyses. A total of 119 metabolites were identified. Metabolomic analysis revealed that metabolite profiles were clearly distinct between TNF-α-stimulated vs. the control group (not stimulated by TNF-α or curcumin). Treatment of FLS with curcumin showed that the metabolic perturbation by TNF-α could be reversed to that of the control group to a considerable extent. Curcumin-treated FLS had higher restoration of amino acid and fatty acid metabolism, as indicated by the prominent metabolic restoration of intermediates of amino acid and fatty acid metabolism, compared with that observed in TNF-α-stimulated FLS. In particular, the abundance of glycine, citrulline, arachidonic acid, and saturated fatty acids in TNF-α-stimulated FLS was restored to the control level after treatment with curcumin, suggesting that the effect of curcumin on preventing joint inflammation may be elucidated with the levels of these metabolites. Our results suggest that GC/TOF-MS-based metabolomic investigation using FLS has the potential for discovering the mechanism of action of curcumin and new targets for therapeutic drugs in RA.