Liver functional assessment using time-associated change in the liver-to-spleen signal intensity ratio on enhanced magnetic resonance imaging: a retrospective study.

BACKGROUND: Liver-to-spleen signal intensity ratio (LSR) is evaluated by magnetic resonance imaging (MRI) in the hepatobiliary phase and has been reported as a useful radiological assessment of regional liver function. However, LSR is a passive (non-time-associated) assessment of liver function, not a dynamic (time-associated) assessment. Moreover, LSR shows limitations such as a dose bias of contrast medium and a timing bias of imaging. Previous studies have reported the advantages of time-associated liver functional assessment as a precise assessment of liver function. For instance, the indocyanine green (ICG) disappearance rate, which is calculated from serum ICG concentrations at multiple time points, reflects a precise preoperative liver function for predicting post-hepatectomy liver failure without the dose bias of ICG or the timing bias of blood sampling. The aim of this study was to develop a novel time-associated radiological liver functional assessment and verify its correlation with traditional liver functional parameters. METHODS: A total of 279 pancreatic cancer patients were evaluated to clarify fundamental time-associated changes to LSR in normal liver. We defined the time-associated radiological assessment of liver function, calculated using information on LSR from four time points, as the "LSR increasing rate" (LSRi). We then investigated correlations between LSRi and previous liver functional parameters. Furthermore, we evaluated how timing bias and protocol bias affect LSRi. RESULTS: Significant correlations were observed between LSRi and previous liver functional parameters such as total bilirubin, Child-Pugh grade, and albumin-bilirubin grade (P < 0.001 each). Moreover, considerably high correlations were observed between LSRi calculated using four time points and that calculated using three time points (r > 0.973 each), indicating that the timing bias of imaging was minimal. CONCLUSIONS: This study propose a novel time-associated radiological assessment, and revealed that the LSRi correlated significantly with traditional liver functional parameters. Changes in LSR over time may provide a superior preoperative assessment of regional liver function that is better for predicting post-hepatectomy liver failure than LSR using the hepatobiliary phase alone.

Spleen Stiffness Performance in the Noninvasive Assessment of Gastroesophageal Varices after Transjugular Intrahepatic Portosystemic Shunts.

OBJECTIVES: To investigate the performance of spleen stiffness (SS) by using two-dimensional shear-wave elastography (2D-SWE) for assessing the severity of gastroesophageal varices (GEVs) after transjugular intrahepatic portosystemic shunt (TIPS). METHODS: 102 eligible patients were categorized as in the post-TIPS short-term (n = 69) and long-term (n = 38) follow-up groups. The performance of SS by using 2D-SWE for evaluating the severity of GEVs was compared with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), liver stiffness spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension (PH) risk score, platelet count-to-spleen diameter ratio (PSR), and varices risk score by using receiver operating characteristic (ROC) curve and DeLong test. RESULTS: In the post-TIPS short-term follow-up group, area under the receiver operating characteristic curves (AUCs) of SS were 0.585 for mild (cutoff value = 30.3 kPa), 0.655 for moderate (cutoff value = 30.6 kPa), and 0.739 for severe (cutoff value = 31.9 kPa) GEVs, which were higher than other parameters for severe GEVs. AUCs of SS were lower than other parameters for mild and moderate GEVs, but no difference was found (p > 0.05). In the post-TIPS long-term follow-up group, AUCs of SS were 0.778 for mild (cutoff value = 28.9 kPa), 0.82 for moderate (cutoff value = 29.9 kPa), and 0.824 for severe (cutoff value = 37.7 kPa) GEVs, which were higher than other parameters except for severe GEVs. AUC of SS was lower than other parameters for severe GEVs, but no significant difference was found (p > 0.05). CONCLUSION: SS is an effective noninvasive tool to predict GEV severity during the post-TIPS follow-up.

Time-dependent Diffusion in Transient Splenial Lesion: Comparison between Oscillating-gradient Spin-echo Measurements and Monte-Carlo Simulation.

The microstructural underpinnings of reduced diffusivity in transient splenial lesion remain unclear. Here, we report findings from oscillating gradient spin-echo (OGSE) diffusion imaging in a case of transient splenial lesion. Compared with normal-appearing white matter, the splenial lesion exhibited greater differences between diffusion time t = 6.5 and 35.2 ms, indicating microstructural changes occurring within the corresponding length scale. We also conducted 2D Monte-Carlo simulation. The results suggested that emergence of small and non-exchanging compartment, as often imagined in intramyelinic edema, does not fit well with the in vivo observation. Simulations with axonal swelling and microglial infiltration yielded results closer to the in vivo observations. The present report exemplifies the importance of controlling t for more specific radiological image interpretations.

An index based on deep learning-measured spleen volume on CT for the assessment of high-risk varix in B-viral compensated cirrhosis.

OBJECTIVES: Deep learning enables an automated liver and spleen volume measurements on CT. The purpose of this study was to develop an index combining liver and spleen volumes and clinical factors for detecting high-risk varices in B-viral compensated cirrhosis. METHODS: This retrospective study included 419 patients with B-viral compensated cirrhosis who underwent endoscopy and CT from 2007 to 2008 (derivation cohort, n = 239) and from 2009 to 2010 (validation cohort, n = 180). The liver and spleen volumes were measured on CT images using a deep learning algorithm. Multivariable logistic regression analysis of the derivation cohort developed an index to detect endoscopically confirmed high-risk varix. The cumulative 5-year risk of varix bleeding was evaluated with patients stratified by their index values. RESULTS: The index of spleen volume-to-platelet ratio was devised from the derivation cohort. In the validation cohort, the cutoff index value for balanced sensitivity and specificity (> 3.78) resulted in the sensitivity of 69.4% and the specificity of 78.5% for detecting high-risk varix, and the cutoff index value for high sensitivity (> 1.63) detected all high-risk varices. The index stratified all patients into the low (index value ≤ 1.63; n = 118), intermediate (n = 162), and high (index value > 3.78; n = 139) risk groups with cumulative 5-year incidences of varix bleeding of 0%, 1.0%, and 12.0%, respectively (p < .001). CONCLUSION: The spleen volume-to-platelet ratio obtained using deep learning-based CT analysis is useful to detect high-risk varices and to assess the risk of varix bleeding. KEY POINTS: • The criterion of spleen volume to platelet > 1.63 detected all high-risk varices in the validation cohort, while the absence of visible varix did not exclude all high-risk varices. • Visual varix grade ≥ 2 detected high-risk varix with a high specificity (96.5-100%). • Combining spleen volume-to-platelet ratio ≤ 1.63 and visual varix grade of 0 identified low-risk patients who had no high-risk varix and varix bleeding on 5-year follow-up.

Histomorphological assessment of isolated abdominal organs after targeted perfusion with the contrast agent Angiofil® in postmortem computed tomography angiography.

The current literature about histological alterations and artefacts associated with postmortem computed tomography angiography (PMCTA) is scarce and limited to qualitative research. The aim of this study was to describe and quantify histological alterations and artefacts in histologic specimens of the inner organs. The spleen, the liver, the kidneys and the pancreas were eviscerated in the course of standard forensic autopsy, followed by manual arterial and venous perfusion of the organs with the lipophilic contrast agent Angiofil®. Computed tomography (CT) of the organ packages was executed to evaluate if the perfusion with Angiofil® was sufficient. The CT scans revealed a good delineation of the vessel trees up to the organ periphery, suggesting a sufficient perfusion. Tissue samples were taken before and after perfusion, stained with hematoxylin-eosin (H&E) and examined by using microscopy. Native and perfused specimens were assessed on the basis of a qualitative rating scale in regard to the integrity of the cells, the tissue architecture and induced alterations. Subsequently the observed differences before and after perfusion with Angiofil® were analyzed quantitatively. While the liver, spleen and kidneys could be evaluated, further microscopic examinations of the pancreatic tissue were not possible due to vast autolytic changes. On the cellular level no changes in the liver, spleen and kidneys were observed after administering Angiofil®. While the tissue architecture of these organs remained intact, a significant blood volume displacement occurred. As a consequence, tissue with hypoemic or normal blood state demonstrated congestion. Further, optically empty spaces emerged regularly in the vessels and the parenchyma of each organ as a surrogate for the lipophilic contrast agent. With a few exceptions an adequate perfusion up to the microscopic level was observed. Following the results of this investigation, CT-controlled manual injection of Angiofil® into isolated organs may be an alternative to the generalized in situ application of contrast agents in the course of PMCTA. It is of eminent importance to know the artefacts induced by an Angiofil® injection in order to avoid a misinterpretation or a masking of findings. Thus, a collection of native tissue specimens has to be done before contrast agent application.

The Role of Spleen and Liver Elastography and Color-Doppler Ultrasound in the Assessment of Transjugular Intrahepatic Portosystemic Shunt Function.

The reference standard for assessing transjugular intrahepatic portosystemic shunt (TIPS) function is venography with portosystemic pressure gradient (PPG) measurement. This procedure is invasive and expensive; thus, we assessed the feasibility, reproducibility and diagnostic accuracy of color-Doppler ultrasound (CDUS) and spleen and liver stiffness (LS) measurements for identifying TIPS dysfunction. Twenty-four patients (15 undergoing TIPS placement and nine undergoing TIPS revision) consecutively underwent CDUS examination and LS and spleen stiffness (SS) determination by transient elastography (TE) and point shear-wave elastography (pSWE). All parameters were taken before TIPS placement/revision (1-15 d before) and 24 h after, just before revision by venography. pSWE inter-observer agreement was assessed by intra-class correlation coefficient (ICC). CDUS and elastographic data were correlated (Pearson coefficient) with pressure gradients (hepatic venous pressure gradient [HVPG], PPG). Main determinants of TIPS dysfunction were investigated by linear regression. Forty-nine paired examinations were performed in total: 49 (100%) SS reliable measurements by pSWE and 38 (88%) by TE. The ICC for pSWE values was 0.90 (95% confidence interval [CI] 0.81‒0.94). SS values significantly correlated with HVPG and PPG (R = 0.51, p = 0.01). The area under the Receiver-Operating Characteristic (AUROC) curve of SS for diagnosing TIPS dysfunction was 0.86 (95% CI 0.70‒0.96) using a 25 kPa cutoff. At multivariate analysis, the flow direction of the intrahepatic portal vein branches and SS values were independently associated to TIPS dysfunction. The intrahepatic portal vein branches flow direction and SS value are two simple, highly sensitive parameters accurately excluding TIPS dysfunction. SS measurement by pSWE is feasible, reproducible and both positively and significantly correlates with HVPG and PPG values.

Assessment of in-vivo biocompatibility evaluation of phytogenic gold nanoparticles on Wistar albino male rats.

Nanomedicine is an interdisciplinary approach that involves toxicology and other medicinal applications. Gold nanoparticles (AuNPs) may serve as a promising model to address the size and shape-dependent biological response because they show good biocompatibility. This study is to prepare phytosynthesis AuNPs from ten different Cassia sp. Among them, the aqueous leaf extract of C. roxburghii produced greater efficient and stable AuNPs. The AuNPs were optimised for different physicochemical conditions. Highly stable AuNPs were synthesised at pH 7.0, 37°C, 1.0 ml of C. roxburghii leaf extract and 1.0 mM concentration of HAuCl4 with the particle size of ∼50 nm and these AuNPs were stable up to 12 months. To determine the safety profile of AuNPs in-vivo, the nanoparticles were injected intravenously into male Wistar albino rats in varying dosages. The authors noticed no significant difference in body weights, haematological and biochemical parameters and the histopathological sections of all vital organs. Highest accumulation was seen in spleen and least in brain. The authors' results show that the AuNPs were biocompatible and did not produce any adverse or abnormalities in-vivo. The implications of the bioaccumulation of AuNPs need to be further studied to rule out any adverse effects on long-term exposure.

Assessment of metals induced histopathological and gene expression changes in different organs of non-diabetic and diabetic rats.

Diabetes is a complex metabolic disorder and different environmental toxicants including heavy metals have been involved in diabetes induction. Therefore, assessment of the environmental risk factors and heavy metals induced toxicity have become critical for reducing the consequences of metals pollutants. Previously, we reported heavy metals induced nephrotoxicity in non-diabetic and diabetic rats. Here, we extended our analysis by examining the heavy metals induced organs (heart, kidney, liver, pancreas, and spleen) damage in diabetic and non-diabetic Wistar rats using histopathology and quantitative real-time PCR (qRT-PCR). Following the generation of the diabetic rat model, the animals were exposed to heavy metals including lead (Pb), arsenic (As), manganese (Mn) and cadmium (Cd). Both non-diabetic and diabetic rats were exposed to heavy metals for 30 days and subsequently, the heart, kidney, liver, pancreas and spleen tissues were examined. Heavy metal treatment resulted in irregularly arranged myofibrils and vacuolization in the heart tissue of metal treated groups as evident from hematoxylin and eosin (H & E) staining. The kidney tissue of rats treated with heavy metals showed tubular degeneration, fibrosis, hemorrhage, and vacuolation. The liver of the heavy metals treated rats exhibited cellular degeneration and necrosis. The pancreatic tissue of streptozotocin injected untreated and metal treated rats revealed severe degeneration, necrosis, degranulation, shrinkage, and depression in the islets of Langerhans. Increased red pulp area and congestion were observed in the spleen of the metal mixture treated non-diabetic and diabetic rats. In line with the histological data, the qRT-PCR analysis showed downregulated expression of Bcl2 and upregulation of Caspase-3 in non-diabetic and diabetic metal treated rats as compared to the non-diabetic untreated rats. In conclusion, the present study revealed, diabetic rats are more prone to metal alone as well as metal mixture induced organ damage as compared to non-diabetic rats.

Assessment of liver fibrosis severity using computed tomography-based liver and spleen volumetric indices in patients with chronic liver disease.

OBJECTIVES: To evaluate whether the liver and spleen volumetric indices, measured on portal venous phase CT images, could be used to assess liver fibrosis severity in chronic liver disease. METHODS: From 2007 to 2017, 558 patients (mean age 48.7 ± 13.1 years; 284 men and 274 women) with chronic liver disease (n = 513) or healthy liver (n = 45) were retrospectively enrolled. The liver volume (sVolL) and spleen volume (sVolS), normalized to body surface area and liver-to-spleen volume ratio (VolL/VolS), were measured on CT images using a deep learning algorithm. The correlation between the volumetric indices and the pathologic liver fibrosis stages combined with the presence of decompensation (F0, F1, F2, F3, F4C [compensated cirrhosis], and F4D [decompensated cirrhosis]) were assessed using Spearman's correlation coefficient. The performance of the volumetric indices in the diagnosis of advanced fibrosis, cirrhosis, and decompensated cirrhosis were evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The sVolS (ρ = 0.47-0.73; p < .001) and VolL/VolS (ρ = -0.77-- 0.48; p < .001) showed significant correlation with liver fibrosis stage in all etiological subgroups (i.e., viral hepatitis, alcoholic and non-alcoholic fatty liver, and autoimmune diseases), while the significant correlation of sVolL was noted only in the viral hepatitis subgroup (ρ = - 0.55; p < .001). To diagnose advanced fibrosis, cirrhosis, and decompensated cirrhosis, the VolL/VolS (AUC 0.82-0.88) and sVolS (AUC 0.82-0.87) significantly outperformed the sVolL (AUC 0.63-0.72; p < .001). CONCLUSION: The VolL/VolS and sVolS may be used for assessing liver fibrosis severity in chronic liver disease. KEY POINTS: • Volumetric indices of liver and spleen measured on computed tomography images may allow liver fibrosis severity to be assessed in patients with chronic liver disease.

RETROSPECTIVE ASSESSMENT OF CLINICAL-MORPHOLOGICAL CHANGES OF THE HEPATOBILIARY SYSTEM IN LIVER CIRRHOSIS OF THE CHORNOBYL NPP ACCIDENT CLEAN-UP WORKERS. / RETROSPEKTYVNA OTsINKA KLINIKO-MORFOLOGIChNYKh ZMIN GEPATOBILIARNOÏ SYSTEMY PRY TsYROZI PEChINKY V UChASNYKIV LIKVIDATsIÏ NASLIDKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to retrospectively characterize changes in the hepatobiliary system in liver cirrhosis (LC) in the clean-up workers of the Chornobyl NPP accident and to determine the factors of disease progression according to the expert materials of the Central Interagency Expert Commission on Establishing the Causal Relationship of the Diseases with the influence of factors of Chornobyl NPP accident. MATERIALS AND METHODS: Based on the data of 60 cases of the Central Interagency Expert Committee on establishing the causal link of diseases with the impact of the Chornobyl NPP accident, the factors of development, concomitant pathology and indicators of the hepatobiliary system status in 49 deceased and 11 alive clean-up workers with LC were investigated. RESULTS: A retrospective study of the morphological changes of the hepatobiliary system in the clean-up workers with LC showed that the main pathologic anatomical diagnosis in 37.8 % of cases was small-nodal LC, in 8.9 % - micromacronodular, in 4.4 % - large-nodal, in 2.2 % - primary biliary LC, in the other 40 % of cases - LC with uncer- tain nodal structure, as well as 2 (4.4 %) cases of fatty liver and 1 case (2.2 %) of portal cirrhosis against the back- ground of fatty liver. Pathomorphological changes were characterized by expressed growth of fibrous tissue with replacement of the liver parenchyma (fields of fibrosis), increase in size and impaired structure of the liver, thick- ening and tightening of its capsule, fibrotic changes in other organs - gastric mucosa, pancreas, spleen, lungs, heart. Histological examination revealed lobe structure abnormalities, false lobules, periportal fibrosis, lymphoid-lympho- cytic infiltration, diffuse fatty small-sized and large-drop dystrophy, and hepatocyte atrophy. Common inflammato- ry processes and fibrotic changes of other organs and systems: cardiovascular, urinary, bronchopulmonary, stomach, pancreas and spleen made the course of the LC more severe. The most frequent were cardiovascular diseases, signi- ficantly more frequent among the deceased than alive patients: hypertension - 67.3 % and 45.5 %, p < 0.05, coro- nary heart disease - 57.1 % and 18 %, p < 0.05. In most cases, the cause of death in the clean-up workers with LC was hepatic and cellular failure (53.3 %), which together with hepatic-renal failure (17.8 %) made 71.1 %. CONCLUSION: Changes in the hepatobiliary system of change in in the clean-up workers with LC were characterized by marked growth of fibrotic tissue with replacement of the parenchyma and impaired liver structure, fibrotic changes in other organs, diffuse fatty small and large droplet dystrophy and atrophy of hepatocytes. The severe course of the LC with the manifestation of the disease at the stage of decompensation was due to a vague clinical picture, lack of subjective symptoms of liver disease, slow, steadily progressing development, lack of or inadequate examination and treatment, a significant number of concomitant pathology of other organs and systems. The fac- tors of the development of LC in the clean-up workers were the long course of chronic liver disease, numerous con- comitant pathology, long stay in the accident zone, the effect of ionizing radiation, as well as the lack of dispensa- ry supervision and adequate treatment.

Comparative safety analysis of bactericidal nano-colloids: Assessment of potential functional toxicity and radical scavenging action.

Extensive utilization of silver nanoparticles (AgNP) has raised concerns of their safety profile upon interaction with biological system. In past decade, various nanoparticles (NPs) with excellent antimicrobial potential have been synthesized, a majority of which have struggled with the established toxicity in biological systems. The NPs safety is still a hot debate and various strategies are being adopted to overcome this giant limitation. This paper successfully reports comparative toxicity profiles of previously synthesized antimicrobial NPs in our lab and concludes the effectiveness of biologically synthesized NPs for its safe usage in biological systems. In this study, five of our previously synthesized NPs that showed excellent antimicrobial potential were compared for their in vivo toxicity and corresponding radical scavenging activities. Based on lowest morbidity, mortality, weight loss, toxicity and agglomeration profile, best NPs with highest antimicrobial potentials were screened out and used for further biomedical applications. The previously reported NPs used in this study included Aerva javanica synthesized nanoparticles (AjNPs), Heliotropium crispium synthesized nanoparticles (HcNPs), and violacein capped nanoparticles (VNPs), these showed least toxicity upon in vivo histological analysis. AjNPs among them showed maximum safety and efficacy profile and consistently showed least production of reactive oxygen species, least mortality and morbidity rate as compared to other groups. Present study establishes that all these biologically synthesized NPs and specifically AjNPs can be efficiently employed as antimicrobial agents as they have not exhibited toxic profile and have shown least accumulation into the organs such as liver spleen and kidney.

Non-endoscopic predictors of esophageal varices in children with chronic liver disease and their utility in resource-constrained countries.

BACKGROUND: Although endoscopy is the standard diagnostic screening test to identify esophageal varices in patients with chronic liver disease (CLD), selective endoscopy in patients who are at higher risk of having varices may be cost-effective in a resource-constrained country. The aim of this prospective study was to identify non-endoscopic parameters that may predict the presence of varices, especially high-risk esophageal varices in children with CLD. METHODS: From January 2016 through March 2018, consecutive children with CLD without a history of variceal bleeding were prospectively included. Esophagogastroduodenoscopy was done in all the children to detect and to grade esophageal varices. Both univariate and multivariate logistic regression analyses were done using SPSS version 22 to identify factors associated with esophageal varices. RESULTS: The mean age of 84 children was 9.7 ± 3.2 years (male 44). Esophageal varices were present in 71.4% of children and 55% of them had large varices. On univariate analysis, low platelet count (< 100,000/mm3) and splenomegaly were found to be associated with the presence of esophageal varices (p = 0.006 and 0.001, respectively) and large varices (p = 0.03 and 0.01, respectively). On multivariate analysis, both low platelet count and splenomegaly were independent predictors for the presence of esophageal varices (respectively, OR 11.21, 95% CI 1.2-96.9; and OR 11.39, 95% CI 3.19-40.59). CONCLUSIONS: Splenomegaly and low platelet count independently predict the presence of any grade of esophageal varices and can be used as screening tests to select children for endoscopy. This strategy may help in relieving medical, social, and economic costs in resource-constrained countries.

Understanding the Efficiency of Splenic Hemangiosarcoma Diagnosis Using Monte Carlo Simulations.

Hemangiosarcoma is a common neoplasm of the spleen in older dogs. However, diagnosis is complicated by necrosis and hemorrhage, which can mimic a number of benign processes. Currently, there is no consensus about the number of sections pathologists should examine to rule out hemangiosarcoma. To answer this question, we examined 413 histopathologic sections from 50 cases of canine hemangiosarcoma (mean: 8.1 sections per case; range, 5-14). Each section had the presence or absence of hemangiosarcoma determined by 2 board-certified anatomic pathologists. Then, 100 Monte Carlo simulations were performed, randomly selecting sections from each case 10 000 times and the results averaged. These simulations suggest that examination of 5 sections from a spleen with hemangiosarcoma yields a 95.02% chance of diagnosing hemangiosarcoma, while examination of 10 sections yields a 98.59% chance of diagnosis when hemangiosarcoma is in fact present. The data emphasize the need to submit the entire spleen for histopathologic examination in suspected cases of hemangiosarcoma and suggest that 5 sections obtained by a trained individual are likely sufficient for diagnosis.

Usefulness of noninvasive methods including assessment of liver stiffness by 2-dimensional shear wave elastography for predicting esophageal varices.

BACKGROUND: The aim of this study was to predict the presence of esophageal varices (EVs) by noninvasive tools combined with 2-dimensional shear wave elastography (2D-SWE), and to compare the diagnostic capabilities of 2D-SWE with those of transient elastography (TE). METHODS: Between January 2015 and December 2017, 289 patients with compensated advanced chronic liver disease (cACLD) who underwent consecutive 2D-SWE and EGD were enrolled. Capabilities for predicting the presence of EVs of 2D-SWE and models combining 2D-SWE with other noninvasive tools (modified LS-spleen-diameter-to-platelet-ratio score [mLSPS], platelet-spleen ratio score) were compared. A subgroup analysis was performed on 177 patients who also underwent simultaneous TE. RESULTS: The area under receiver operating characteristics (AUROCs) for detecting EVs for 2D-SWE alone vs. mLSPS, which included 2D-SWE, were 0.757 (95% confidence interval [CI], 0.701-0.810) and 0.813 (95% CI, 0.763-.857), respectively. The AUROCs for predicting varices needing treatment (VNT) for 2D-SWE and mLSPS were 0.712 (95% CI, 0.621-0.738) and 0.834 (95% CI, 0.785-0.875), respectively. For the 195 patients who underwent simultaneous TE and 2D-SWE, no differences in diagnostic performance were observed. CONCLUSIONS: The diagnostic performance of 2D-SWE is similar to that of TE for predicting the presence of EVs. The mLSPS, which includes 2D-SWE, seemed to be useful for predicting EVs.

Acute Toxicity Assessment: Macroscopic and Ultrastructural Effects in Mice Treated with Oral Tetrodotoxin.

Tetrodotoxin (TTX) is an extremely toxic marine compound produced by different genera of bacteria that can reach humans through ingestion mainly of pufferfish but also of other contaminated fish species, marine gastropods or bivalves. TTX blocks voltage-gated sodium channels inhibiting neurotransmission, which in severe cases triggers cardiorespiratory failure. Although TTX has been responsible for many human intoxications limited toxicological data are available. The recent expansion of TTX from Asian to European waters and diversification of TTX-bearing organisms entail an emerging risk of food poisoning. This study is focused on the acute toxicity assessment of TTX administered to mice by oral gavage following macroscopic and microscopic studies. Necropsy revealed that TTX induced stomach swelling 2 h after administration, even though no ultrastructural alterations were further detected. However, transmission electron microscopy images showed an increase of lipid droplets in hepatocytes, swollen mitochondria in spleens, and alterations of rough endoplasmic reticulum in intestines as hallmarks of the cellular damage. These findings suggested that gastrointestinal effects should be considered when evaluating human TTX poisoning.

A comparative assessment of acute oral toxicity and traditional pharmacological activities between extracts of Fritillaria cirrhosae Bulbus and Fritillaria pallidiflora Bulbus.

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae Bulbus ("Beimu" in Chinese) is a famous traditional Chinese medicine used to treat cough, expectoration and asthma for more than 2000 years, which belongs to the Fritillaria genus in Liliaceae family. Bulbs of Fritillaria cirrhosa D.Don (BFC) and bulbs of Fritillaria pallidiflora Schrenk (BFP) are two important drugs of Beimu. Due to the significant similarities in their outward appearance characters and chemical profiles, BFC has often been adulterated with BFP in Chinese Traditional Medicine markets. AIM OF THE STUDY: This study aims to compare the oral acute toxicity and the traditional pharmacological activities including antitussive, expectorant and anti-inflammatory effects between the extract of BFC and BFP, to clear and definite if the BFP can be used as a substitute of the BFC in the application of traditional medicine. MATERIALS AND METHODS: The extracts were prepared through refluxing with 80% ethanol solvent. For the acute toxicity tests, graded doses of BFP extracts and the maximum dose of BFC extracts were administered orally to mice. The animals were observed for toxic symptoms and mortality daily for 14 days. For the pharmacological activities tests, graded doses of BFP and BFC extracts were administered orally to mice. To observe the effects relieving cough, expelling phlegm and lessening the ear swelling of BFC extracts and BFP extracts through ammonia liquor inducing cough, phenol red apophlegmating in mice and the xylene-induced auricular swelling of mouse, respectively. RESULTS: In the acute toxicity study, the LD50 value of BFP in mice was calculated to be 213.57 g/kg body weight, and the maximum feasible dose (MFD) value of BFC in mice was 452.14 g/kg. Histopathological analysis has shown inflammatory cells infiltration and cells edema in liver, multinucleated giant cell proliferation in spleen, perivascular exudate and hemorrhage in lung, glomerulus atrophy in kidney of mice after oral administrations of BFP extracts. But only liver cells edema was observed in BFC group. Both BFC extract and BFP extract significantly increased latent period of cough and inhibited cough frequency in mice induced by ammonia. Besides, the two extracts also obviously enhanced mice's tracheal phenol red output in expectorant assessment and inhibited the development of ear edema in anti-inflammatory evaluation assay. CONCLUSION: To summarize, the BFP has the significant similarities in morphological characteristics, chemical profiles and traditional pharmacological activities compared with the BFC. The result of this study provide some valid scientific support for using BFP as a plant substitute of the BFC, but considering the toxicity of BFP is much higher than BFC, we don't recommend long-term oral administration of BFP or exceeding recommended dosage of Chinese Pharmacopoeia 2015.

Liver and Spleen Stiffness Measurements for Assessment of Portal Hypertension Severity in Patients with Budd Chiari Syndrome.

Aims: Budd-Chiari Syndrome (BCS) is a rare vascular disease of the liver caused by the obstruction of the hepatic venous outflow located from the small hepatic venules up to the entrance of the inferior vena cava (IVC) into the right atrium. Current prognostic indexes are suboptimal for an individual prognostic assessment and subsequent management of patients with BCS. Liver (LSM) and spleen (SSM) stiffness measurements are widely validated prognostic tools in hepatology, but the evidence in patients with BCS is limited. This paper describes LSM and SSM in patients with BCS and their correlation with clinical, biochemical, and ultrasound findings from the same patients. Methods: We investigated a case series of seven patients with BCS diagnosis and available LSM and SSM evaluated by transient elastography (TE). Biochemical, imaging, and endoscopic findings nearest to the TE evaluation were recorded. Clinical outcomes and BCS evolution were described for each patient. When available, repeated TE assessments were also recorded. Results: Patients with acute nonfulminant manifestation of BCS presented near-the-upper-limit values (75 kPa) of LSM and SSM, which often persist until the placement of a transjugular intrahepatic portosystemic shunt (TIPS). On the other hand, TE values were markedly lower in patients with compensated BCS. In some patients with repeated TE measurement years after TIPS placement, LSM had decreased to values of <10 kPa years. SSM changes in these patients were, however, less evident. Conclusions: Extremely elevated values of LSM and SSM are suggestive of BCS. The evaluation of both LSM and SSM by TE could help clinicians in the initial evaluation, risk stratification, and therapy response monitoring of patients with BCS.

Preoperative assessment of splenic involvement in patients with peritoneal carcinomatosis with CT and MR imaging.

PURPOSE: To estimate the performances of computed tomography (CT) and magnetic resonance imaging (MRI) and those of the combination of CT with MRI in the identification of splenic involvement in patients with peritoneal carcinomatosis (PC). MATERIAL AND METHOD: CT and MRI examinations of 26 patients with PC with splenic involvement and 26 patients with PC and no splenic involvement treated by total cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were reviewed. There were 32 women and 20 men with a mean age of 53.44 ± 12.22 (SD) years (range: 20-73 years). Imaging examinations were reviewed separately as three independent imaging sets (CT only, MRI only and CT with MRI) by two independent readers. A consensus was reached during a joint reading session and these results were used for determining the performances of the three imaging sets in the diagnosis of splenic involvement using surgical and histopathological findings as standard of reference. RESULTS: Splenic involvement was histologically proven in 26/52 patients (50%). There were no significant differences in sensitivity, specificity and accuracy for the diagnosis of splenic involvement between CT, MRI and CT + MRI, with respectively 84.62%, 96.15% and 90.00% for CT, 84.62%, 84.62% and 85.00% for MRI and 92.31%, 92.31% and 92.00% for CT + MRI. CONCLUSION: CT and MRI have similar sensitivities, specificites and accuracies for the diagnosis of splenic involvement in patients with PC. The combination of CT and MRI does not significantly improve the preoperative diagnosis of splenic involvement in patients with PC compared to CT only.

Presurgical assessment of splenic tumors in dogs: a retrospective study of 57 cases (2012-2017).

The purpose of this study was to evaluate the clinical and imaging characteristics of canine splenic tumors and to establish guidelines for the presurgical assessment of splenic tumors in dogs. Fifty-seven dogs that underwent total splenectomy for the treatment of splenic tumors were evaluated by examining medical records, hematologic results, diagnostic imaging results, and histopathologic results. The maximum lesion size from ultrasonography was significantly different between malignant and benign tumors (p = 0.002). There was a correlation between tumor margination and type of splenic tumors (p = 0.045). Precontrast lesion attenuation on computed tomography was significantly different between splenic malignant and benign tumors (p = 0.001). The mean ± SD precontrast lesion attenuation of malignant tumors was 40.3 ± 5.9 Hounsfield units (HU), and for benign tumors, it was 52.8 ± 6.8 HU. In conclusion, some variables of the imaging examination could be used to distinguish the type of splenic tumor. Based on the study results, using a diagnostic flowchart would be effective in increasing the survival rate of patients with splenic malignant tumors. In addition, fine needle aspiration or magnetic resonance imaging prior to surgical exploration and histopathologic examination may be useful in achieving a more accurate diagnosis.