Small Liver Research Articles

Wilson’s Disease and Autoimmune Hepatitis Coexistence: A Cause of Diagnostic Delay

This case report describes a 27-year-old housewife who presented with a progressive and insidious onset of abdominal distension, loss of appetite, and fatigue which started 3 months before her presentation. The physical assessment showed moderate ascites and small liver size, and no other peripheral evidence of chronic liver disease was observed. A diagnosis of liver cirrhosis and was confirmed by investigations and imaging, where ascites responded well to therapy with diuretics. Investigations for the cause of cirrhosis was established through the diagnosis of autoimmune hepatitis, and she was started on steroids and azathioprine with partial improvement in liver biochemistry. She presented 8 months later with neuropsychiatric symptoms in the form of slurred speech and difficulty walking. Accordingly, Wilson’s disease was suspected to be the cause and further investigations confirmed this. A chelating agent, D penicillamine, was added to her immunosuppressive treatment. Nine months later she showed slow improvement in her neurological symptoms and was referred for assessment for liver transplantation. Wilson’s disease, although rare, should be suspected in patients with decompensated liver disease. The dominance of clinical and epidemiological features of autoimmune hepatitis as a common causative pathology for chronic liver disease in young and middle-aged ladies may hide the presence of other serious different pathologies such as Wilson’s disease.

Flow cytometric analysis of innate lymphoid cells: challenges and solutions.

The three groups of helper innate lymphoid cells (ILCs), namely ILC1, ILC2 and ILC3, have been identified by flow cytometry by combinations of cell surface markers. Here, we review various ways ILCs are currently identified, focusing on potential problems and their solutions. The first step to identify all ILCs is to exclude other lymphocytes and myeloid cells by their lineage-specific markers (Lin). However, the Lin cocktail varies in various studies, and the definition of Lin- population containing ILCs is often ambiguous, resulting in contamination of Lin+ cells, particularly T cells. We have designed combinations of cell surface markers to identify ILC populations in various tissues of B6 mice by flow cytometry. To minimize T cell contamination, TCR/CD3ϵ antibodies were used separately from the Lin cocktail. ILCs identified by surface markers are confirmed by the expression of the transcription factors GATA3, RORγt, T-bet and Eomes. ILC1s in the B6 mouse liver are identified by Lin-NKp46+NK1.1+TCR/CD3ϵ-CD49a+CD49b-. However, defining ILC1s in other tissues remains a challenge. ILC2s in the lung are identified by Lin-TCR/CD3ϵ- Thy1+CD127+ST2+ whereas ILC2s in the small intestine and liver are identified by Lin-TCR/CD3ϵ-Thy1+GATA3+RORγt-. ILC3s in B6 mouse spleen, liver, lung and small intestine are identified by Lin-TCR/CD3ϵ- Thy1+CD127+RORγt+. The ILC population is heterogeneous and the strategies to identify ILCs have to be designed for each ILC population and tissue. Excluding T cells in all cases is crucial, and a combination of transcription factors GATA3, RORγt, T-bet, and Eomes should be used to identify ILCs. Using CD3ϵ/TCRs in a different fluorochrome not in Lin cocktail minimizes contamination of T cells specifically identify individual ILC populations in various tissues.

Periphery of porcine hepatic lobes has the smallest length density of hepatic sinusoids and bile canaliculi: A stereological histological study with implications for liver biopsies

BackgroundPorcine liver is widely used in hepatologic research as a large animal model with many anatomical and physiological similarities with humans. However, only limited information on porcine liver spatial microstructure has been published, especially regarding the hepatic sinusoids and bile canaliculi. The aim of our study was to quantify the sinusoidal and bile canalicular network in healthy male and female porcine livers and to map the variability of these structures with heterogenous distribution to improve the evaluability of liver biopsy samples. MethodsLivers from 12 healthy piglets (6 females and 6 neutered males) were sampled into 36 tissue samples per organ, representing six hepatic lobes and three different regions related to the hepatic vasculature (peripheral, paracaval and paraportal region). Histological sections were processed with a random orientation of the cutting plane. The endothelium and the bile canaliculi were stained using Ricinus communis agglutinin I lectin histochemistry. The length densities of hepatic sinusoids LV(sinusoids,liver), of bile canaliculi LV(bile canaliculi,liver) and volume fraction VV(sinusoids,liver) and surface density SV(sinusoids,liver) of sinusoids were estimated using stereological methods. The newly acquired morphometric data were compared with previously published data on density of porcine hepatocytes and fractions of connective tissue. ResultsThe peripheral region had smallest LV(sinusoids,liver), smallest LV(bile canaliculi,liver) and greatest VV(sinusoids,liver). The six hepatic lobes had statistically comparable length densities of both sinusoids and bile canaliculi, but the left lateral lobe had smallest VV(sinusoids,liver). Regions with greater LV(sinusoids,liver) had also greater LV(bile canaliculi,liver) and SV(sinusoids,liver) and were accompanied by greater density of smaller hepatocytes. Regions with smaller LV(sinusoids,liver) and LV(bile canaliculi,liver) contained a greater fraction of interlobular connective tissue. ConclusionsThe length density of hepatic sinusoids is smaller in the peripheral regions of the porcine liver than in other regions related to the hepatic vasculature – paracaval and paraportal regions, and smaller in castrated males than in females. Greater length density of liver sinusoids was linked with greater local density of bile canaliculi, with local increase in the density of smaller hepatocytes and, simultaneously, with smaller fractions of hepatic connective tissue. The intrahepatic and inter-sexual variability of the porcine liver morphology needs to be taken into account when designing and interpreting experiments involving the histological quantification of the microvascular network. The complete primary morphometric data describing the distribution of morphometric parameters within porcine liver were made available in a form facilitating the power analysis to justify the minimal number of tissue samples or animals required when designing further histological evaluation studies. The macroscopic map of microvessels and bile canaliculi variability facilitates their assessment in liver biopsies in the pig.

Toxic effects of benfluralin on zebrafish embryogenesis via the accumulation of reactive oxygen species and apoptosis

The dinitroaniline herbicide benfluralin is used weed control in conventional systems and poses a high risk of accumulation in aquatic systems. Previous studies have shown the toxic effects of benfluralin on non-target organisms; however, its developmental toxicity in vertebrates has not yet been reported. This study demonstrated the developmental toxicity of benfluralin and its mechanism of action, using zebrafish as an aquatic vertebrate model. Benfluralin induces morphological and physiological alterations in body length, yolk sac, and heart edema. We also demonstrated a reactive oxygen species (ROS) increase of approximately 325.53 % compared with the control group after 20 μM benfluralin-treatment. In addition, the malformation of the heart and vascular structures was identified using transgenic flk1:eGFP zebrafish models at 20 μM concentration benfluralin exposure. Moreover, benfluralin induced small livers, approximately 59.81 % of normal liver size, via abnormal development of the liver as observed in the transgenic L-fabp:dsRed zebrafish. Benfluralin also inhibits normal growth via abnormal expression of cell cycle regulatory genes and increases oxidative stress, inflammation, and apoptosis. Collectively, we elucidated the mechanisms associated with benfluralin toxicity, which lead to various abnormalities and developmental toxicities in zebrafish. Therefore, this study provides information on the parameters used to assess developmental toxicity in other aquatic organisms, such as herbicides, pesticides, and environmental contaminants.

Tissue re-distribution of budesonide in rats co-administrated with curcumin by ultra performance liquid chromatography-tandem mass spectrometry

Budesonide (BUD), a locally acting glucocorticoid with low side effects, is recommended in several Crohn's disease (CD) drug treatment guidelines as the first choice for early treatment. Nevertheless, the extensive first-pass effect mediated by P-glycoprotein (P-gp) and Cytochrome P450 3A4 (CYP3A4) leads to low bioavailability and limits further applications. Curcumin (CUR), a natural polyphenol derived from turmeric, has been found to influence the in vivo processes of drugs by affecting the activity of P-gp and CYP3A4. However, the pharmacokinetic interactions between BUD and CUR remains elusive, so an ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was established for the simultaneous determination of BUD and CUR in the tissue. The results showed that the area under the concentration-time curve 0 to time (AUC0→t) of BUD in the colon and kidney increased by approximately 32.35% and 39.03% respectively in the co-administered group compared to the single-drug group, while the small intestine, liver and plasma decreased by 80.03%, 67.34% and 24.34% respectively compared to the single-drug group. Therefore, long-term treatment with CUR can increase the concentration of BUD in the colonic area without increasing its systemic exposure, thus potentially reducing the incidence of side effects.

Contrast-enhanced ultrasound with microbubbles containing sulfur hexafluoride and perfluorobutane with Kupffer phase for the detection of colorectal liver metastases.

To compare contrast-enhanced ultrasound (CEUS) with microbubbles containing sulfur hexafluoride (SHF) and perfluorobutane (PFB) for the detection of colorectal liver metastasis (CRLM). In this prospective study, conducted from September to November 2021, patients with colorectal cancer were consecutively recruited and underwent same-day ultrasound, SHF-CEUS, and PFB-CEUS. The reference standard was contrast-enhanced MRI and follow-up imaging. The size, depth, echogenicity, and calcification of each focal liver lesion were recorded. The number and conspicuity of CRLMs, based on washout appearance during the late phase (LP) (> 120 s)/Kupffer phase (KP), were evaluated offsite by two blinded readers. Overall, 230 lesions (CRLMs, n= 219; benign lesions, n= 11) in 78 patients were evaluated. Lesion conspicuity (p= 0.344) and accuracy in the detection of CRLM were comparable for SHF- and PFB-CEUS (0.877 for SHF vs. 0.770 for PFB, p= 0.087). More CRLMs ≥ 10 mm were identified by LP contrast washout in SHF-CEUS than in KP PFB-CEUS (p< 0.001). More CRLMs < 10 mm were identified by KP washout in PFB-CEUS than in LP SHF-CEUS (p< 0.001). Conspicuity was better on PFB-CEUS than on SHF-CEUS (p= 0.027). In hyperechoic lesions, lesions located deeper than 80 mm, and calcified lesions, CRLM conspicuity on PFB-CEUS was inferior to that on SHF-CEUS (p< 0.05). The overall accuracy of detection and conspicuity of washout in CRLMs were comparable between SHF and PFB-CEUS. PFB-CEUS has the advantage of identifying washout in small CRLMs. However, larger, hyperechogenic, deep-seated, or calcified lesions were better identified using SHF-CEUS. Accuracy of detection and conspicuity of washout in CRLMs were comparable between SHF- and PFB-CEUS. PFB-CEUS has the advantage in detecting small CRLMs, whereas SHF-CEUS is better for detecting larger, hyperechogenic, deep-seated, or calcified lesions. Contrast-enhanced ultrasound with sulfur hexafluoride in the late phase and perfluorobutane microbubbles in the Kupffer phase were comparable in terms of accuracy in the detection and conspicuity of colorectal liver metastases. Small colorectal liver metastases (< 10 mm) were more often identified in the Kupffer phase contrast-enhanced ultrasound imaging when using perfluorobutane microbubbles. Larger, hyperechogenic, deep-seated, or calcified lesions were better identified in the late phase contrast-enhanced ultrasound imaging (> 120 s) when using sulfur hexafluoride microbubbles.

Application of a preoperative scoring system for small liver lesions in predicting small hepatocellular carcinoma

Application of a preoperative scoring system for small liver lesions in predicting small hepatocellular carcinoma

The effects of a comparatively higher dose of 1000 mg/kg/d of oral L- or D-arginine on the L-arginine metabolic pathways in male Sprague-Dawley rats.

Oral L-arginine supplements are popular mainly for their nitric oxide mediated vasodilation, but their physiological impact is not fully known. L-arginine is a substrate of several enzymes including arginase, nitric oxide synthase, arginine decarboxylase, and arginine: glycine amidinotransferase (AGAT). We have published a study on the physiological impact of oral L- and D-arginine at 500 mg/kg/day for 4 wks in male Sprague-Dawley rats. We investigated the effects of oral L-arginine and D-arginine at a higher dose of 1000 mg/kg/d for a longer treatment duration of 16 wks in 9-week-old male Sprague-Dawley rats. We measured the expression and activity of L-arginine metabolizing enzymes, and levels of their metabolites in the plasma and various organs. L-arginine did not affect the levels of L-arginine and L-lysine in the plasma and various organs. L-arginine decreased arginase protein expression in the upper small intestine, and arginase activity in the plasma. It also decreased AGAT protein expression in the liver, and creatinine levels in the urine. L-arginine altered arginine decarboxylase protein expression in the upper small intestine and liver, with increased total polyamines plasma levels. Endothelial nitric oxide synthase protein was increased with D-arginine, the presumed metabolically inert isomer, but not L-arginine. In conclusion, oral L-arginine and D-arginine at a higher dose and longer treatment duration significantly altered various enzymes and metabolites in the arginine metabolic pathways, which differed from alterations produced by a lower dose shorter duration treatment published earlier. Further studies with differing doses and duration would allow for a better understanding of oral L-arginine uses, and evidence based safe and effective dose range and duration.

A Coarse-to-Fine Fusion Network for Small Liver Tumor Detection and Segmentation: A Real-World Study.

Liver tumor semantic segmentation is a crucial task in medical image analysis that requires multiple MRI modalities. This paper proposes a novel coarse-to-fine fusion segmentation approach to detect and segment small liver tumors of various sizes. To enhance the segmentation accuracy of small liver tumors, the method incorporates a detection module and a CSR (convolution-SE-residual) module, which includes a convolution block, an SE (squeeze and excitation) module, and a residual module for fine segmentation. The proposed method demonstrates superior performance compared to conventional single-stage end-to-end networks. A private liver MRI dataset comprising 218 patients with a total of 3605 tumors, including 3273 tumors smaller than 3.0 cm, were collected for the proposed method. There are five types of liver tumors identified in this dataset: hepatocellular carcinoma (HCC); metastases of the liver; cholangiocarcinoma (ICC); hepatic cyst; and liver hemangioma. The results indicate that the proposed method outperforms the single segmentation networks 3D UNet and nnU-Net as well as the fusion networks of 3D UNet and nnU-Net with nnDetection. The proposed architecture was evaluated on a test set of 44 images, with an average Dice similarity coefficient (DSC) and recall of 86.9% and 86.7%, respectively, which is a 1% improvement compared to the comparison method. More importantly, compared to existing methods, our proposed approach demonstrates state-of-the-art performance in segmenting small objects with sizes smaller than 10 mm, achieving a Dice score of 85.3% and a malignancy detection rate of 87.5%.

Evaluation of the Effect of Surgical Access on the Innate Immune Response During Liver Resections of Various Volume, Experimental Study

Introduction. The major components of the immune system are affected in almost all surgical operations, including those related to the tumor removal. The volume of the operation correlates with the level of the immune system suppression and frequency of complications. The issue of the effect of surgical access for liver resection with different volumes on surgical trauma and severity of the innate immune response are still challenging nowadays. The aim of the study is to evaluate the effect of open and laparoscopic surgical approaches on the severity of the innate immune response in small and large liver resections in laboratory animals.Methods. The study included 4 groups of rabbits, 10 animals each, formed depending on the surgical approach and the volume of liver resection: laparoscopic small and large liver resections, open small and large liver resections. The following parameters of the innate immune response were studied: phagocytic, cytotoxic and proliferative activity in dynamics. The experimental data were processed using the STATISTICA 6.0 software package (StatSoft, 2001). The results were considered statistically significant at p0.05.Results. Open extensive liver resections are characterized by a more significantly decreased phagocytic activity of neutrophils - from 95.7% to 32.05% - than similar interventions using laparoscopic access - from 96.4% to 52.4%, respectively. Cytotoxic activity in the group of animals exposed to surgery with laparotomy access decreased by 40% compared to 23% in animals exposed to laparoscopy surgery. There was registered a more than twice increased spontaneous and decreased induced proliferation in the postoperative period. Conclusion. The study results allow concluding on a positive effect manifested as a reduced surgical injury for liver resections of various volumes due to laparoscopic access; this is evidenced by the parameters of immune reactivity.

A Rare Case of Charcot-Leyden Crystals In liver biopsy in a 14-Year-Old Boy with Persistent Fever and Miliary Infiltrates

The presence of Charcot-Leyden Crystals in liver biopsy is rare. A report case of a 14-year-old boy who presented with persistent fever and respiratory symptoms. Chest X-ray and CT thorax showed miliary infiltrates. The Mantoux test was positive and sputum for acid-fast bacilli (AFB) was negative. The patient started antitubercular therapy (ATT). There was no response and the patient still had fever. Further evaluation with an ultrasound of the abdomen revealed multiple small liver abscesses with septic emboli in the spleen. Since the patient was non-responsive to antibiotics, biopsy from the lesion in the liver was suggested. Biopsy report revealed Charcot-Leyden crystals with no granulomas. The Patient was diagnosed as a case of systemic parasitic infestation. Albendazole under steroid cover was prescribed and the patient was afebrile on follow-up. It was concluded that the presence of CLCs in a biopsy specimen is rare but may be a cause of an underlying parasitic infestation. Early diagnosis and treatment with antiparasitic drugs can lead to a favorable outcome.

Biological Activities of p-Hydroxycinnamic Acids in Maintaining Gut Barrier Integrity and Function.

It is well established that p-Hydroxycinnamic acids (HCAs), including ferulic, caffeic, sinapic, and p-coumaric acids, possess a characteristic phenylpropanoid C6-C3 backbone and account for about one-third of the phenolic compounds in our diet. HCAs are typically associated with various plant cell wall components, including mono-, di-, and polysaccharides, sterols, polyamines, glycoproteins, and lignins. Interestingly, enzymes produced by intestinal microbes liberate HCAs from these associations. HCAs are completely absorbed in their free form upon ingestion and undergo specific reactions upon absorption in the small intestine or liver. The gut epithelium, composed of intestinal epithelial cells (IECs), acts as a physical barrier against harmful bacteria and a site for regulated interactions between bacteria and the gut lumen. Thus, maintaining the integrity of the epithelial barrier is essential for establishing a physiochemical environment conducive to homeostasis. This review summarizes the protective effects of HCAs on the intestinal barrier, achieved through four mechanisms: preserving tight junction proteins (TJPs), modulating pro-inflammatory cytokines, exerting antioxidant activity, and regulating the intestinal microbiota.

Percutaneous microcoil localization as an aid to ultrasound-guided hepatic gastrointestinal stromal tumor metastasis resection: A case report

Liver nodules that develop in children with cancer may represent primary malignancy, metastatic disease, or other conditions potentially requiring aggressive management. Laparoscopic methods have been utilized for nodule resection with perioperative ultrasonographic assistance. However, certain nodules in liver tissue can be difficult to identify on ultrasonography. Ultrasonography guided surgical resection after computer tomography (CT)-guided localization using microcoils is an innovative technique that has the potential to assist in the resection of small or deep liver nodules in children in these unique cases. A 15-year-old female presented with evidence of a hypermetabolic liver nodule on routine PET scan, 5 years following resection of a hepatic metastasis via right hepatic trisegmentectomy for primary gastrointestinal stromal tumor (GIST). Contrast-enhanced CT confirmed presence of a new suspicious liver nodule. Given the interval from initial treatment to the identification of this hepatic nodule, consent was received from patient and her family to surgically resect the nodule. However, pre-operatively the nodule could not be appreciated on ultrasonography. Interventional radiology was consulted for CT guided percutaneous microcoil localization of the hepatic nodule. CT-guided percutaneous microcoil localization with ultrasonographic guided liver resection allowed for complete resection of the liver nodule. We have successfully used an innovative technique of CT-guided microcoil placement to direct ultrasound-guided surgical resection of an otherwise ultrasound-occult liver nodule in the pediatric setting.

Precision cooling radiofrequency ablation under tumor boundary temperature control

Radiofrequency ablation (RFA) represents a convenient, minimally invasive, and cost-effective approach for the treatment of small liver cancers measuring less than 3 cm in diameter. Nonetheless, the existing RFA techniques encounter challenges in precisely controlling the extent of ablation and the risk of overheating, which can lead to damage on the surrounding tissues. The ability to control the ablation area also plays a crucial role in the success of RFA procedures. To address these issues, we introduce a novel method that utilizes tumor boundary temperature monitoring to achieve precise control over the RFA process. Through the utilization of COMSOL Multiphysics simulation software, the proposed method was verified by comprehensive simulation and modeling and its efficacy in achieving regional control was testified. Subsequently, ex vivo experiments were conducted employing a custom-designed cooling RFA instrument. The experimental results demonstrated that the RFA controlled by boundary temperature yielded an ablation area with a diameter approaching 30 mm. In comparison to the standard spherical solidification zone (characterized by both the ellipticity and regularity indices of 1), the cooling RFA discoloration zone, under boundary temperature control, exhibited a maximum deviation of 7% in the ellipticity index and 17% in the regularity index. The average ellipticity index was determined to be 0.96, while the average regularity index was 0.86. Collectively, these findings underscore the capability of the proposed temperature-controlled cooling RFA method to attain precise control over the ablation area, contributing to comprehensive ablation of tumor tissue within the target region.

A preliminary discussion on carnosine dipeptidase 1 as a potential novel biomarker for the diagnostic and prognostic evaluation of hepatocellular carcinoma

Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.

Estimación de la perfusión de hígado e íleon terminal con microesferas coloreadas, comparando asistencias mecánicas circulatorias de flujo continuo y pulsátil

ObjectiveTo estimate blood flow in the small intestine and liver by administration of coloured microspheres in the left atrium, comparing this estimate with continuous flow perfusion and pulsatile flow, in order to confirm or reject hypoperfusion and hypoxia in these organs attributed to loss of pulse amplitude as the cause of Heyde's syndrome. Material and methodTwenty-two minipig pigs of both sexes weighing 29.5±9.6kg were implanted with 11 continuous and 11 pulsatile mechanical circulatory assist devices were implanted in 22 minipig. Haemodynamic and analytic parameter were measured. Liver and terminal ileum blood perfusión was estimated by administration of stained microspheres previus to circulatory support, at 30minutes of full assist and at 30minutes of partial assist. ResultsData were reported as percent of estimated perfusion at baseline. The study was performed by analysis of variance for repeated measures with a significance α of 0.05. In the liver, type of assistance (total or partial), type of pump (continuous or pulsatile) and the interaction between the 2had the following statistical significance: 0.518. 0.364 and 0.237 respectively. In the terminal ileum the results were: 0.264. 0.193 and 0.141.Analytically significant differences were observed in bilirubin level related to the continuous flow pump, as well as pH and urea. ConclusionsWe observed no significant differences in the estimation of perfusion in ileum and liver when comparing continuous flow and pulsatile flow CMA.

Deep-learning CT reconstruction in clinical scans of the abdomen: a systematic review and meta-analysis.

To perform a systematic literature review and meta-analysis of the two most common commercially available deep-learning algorithms for CT. We used PubMed, Scopus, Embase, and Web of Science to conduct systematic searches for studies assessing the most common commercially available deep-learning CT reconstruction algorithms: True Fidelity (TF) and Advanced intelligent Clear-IQ Engine (AiCE) in the abdomen of human participants since only these two algorithms currently have adequate published data for robust systematic analysis. Forty-four articles fulfilled inclusion criteria. 32 studies evaluated TF and 12 studies assessed AiCE. DLR algorithms produced images with significantly less noise (22-57.3% less than IR) but preserved a desirable noise texture with increased contrast-to-noise ratios and improved lesion detectability on conventional CT. These improvements with DLR were similarly noted in dual-energy CT which was only assessed for a single vendor. Reported radiation reduction potential was 35.1-78.5%. Nine studies assessed observer performance with the two dedicated liver lesion studies being performed on the same vendor reconstruction (TF). These two studies indicate preserved low contrast liver lesion detection (>5mm) at CTDIvol 6.8mGy (BMI 23.5kg/m2) to 12.2mGy (BMI 29kg/m2). If smaller lesion detection and improved lesion characterization is needed, a CTDIvol of 13.6-34.9mGy is needed in a normal weight to obese population. Mild signal loss and blurring have been reported at high DLR reconstruction strengths. Deep learning reconstructions significantly improve image quality in CT of the abdomen. Assessment of other dose levels and clinical indications is needed. Careful choice of radiation dose levels is necessary, particularly for small liver lesion assessment.

A gadoxetic-acid enhancement flux analysis of small liver nodules (≤2 cm) in patients at high risk of hepatocellular carcinoma

PurposeTo discriminate between benignities and hepatocellular carcinomas (HCCs) in patients at high risk of HCC using a novel enhancement flux analysis for gadoxetic-acid enhanced MRI. MethodThis study retrospectively collected 181 liver nodules in 156 patients at high risk of HCC who underwent gadoxetic acid-enhanced MRI examinations with following surgical resection from 1st August 2017 to 31st December 2021 as the training set; another 42 liver nodules in 36 patients were prospectively collected from 1st January 2022 to 1st October 2022 as the test set. The time-intensity curves (TICs) of liver nodules were formed with consecutive time points: 0 s, 20 s, 1 min, 2 min, 5 min, 10 min, 15 min, and 20 min since contrast injection. A novel enhancement flux analysis was applied by using a biexponential function fitting to distinguish benignities and HCC. Besides, previously published models including maximum enhancement ratio (ERmax), percentage signal ratio (PSR), and ERmax+PSR were compared. The areas under the receiver operating characteristic curves (AUCs) were compared among these methods. ResultsThe novel enhancement flux analysis showed the highest AUCs in the training set (0.897, 95%CI: 0.833–0.960) and the test set (0.859, 95%CI: 0.747–0.970) among all models. The AUCs of PSR, ERmax and ERmax+PSR were 0.801 (95%CI: 0.710–0.891), 0.620 (95%CI: 0.510–0.729), and 0.799 (95%CI: 0.709–0.889) in the training set, and were 0.701 (95%CI: 0.539–0.863), 0.529 (95%CI: 0.342–0.717), and 0.708 (95%CI: 0.549–0.867) in the test set. ConclusionsThe biexponential flux analysis for gadoxetic-acid enhanced MRI presents a better potential in accurate diagnosis of small HCC nodules.

Should oral medication dose be adjusted in Alzheimer’s disease?

AbstractBackgroundLittle is known about the absorption, distribution, metabolism and excretion (ADME) of both AD and non‐AD medicines currently used in people with AD. If drug disposition processes are altered in AD, individuals with AD may be at a greater risk of additional drug‐induced adverse effects, toxicity, or lack of effectiveness. Senescence Accelerated Mouse (SAMP8) is a naturally‐occurring mouse line that displays many characteristics identified in AD patients, and it is considered as a model of sporadic AD. The current study aims to assess if ADME is affected in SAMP8 mice.MethodWe utilized a proteomics approach to assess drug transporter and metabolising enzyme expression in the small intestine, liver, and kidney in SAMP8 mice. In addition, plasma concentrations of valsartan, digoxin, quetiapine (three model drugs selected based on proteome data) following oral administration in SAMP8 mice were assessed using LC‐MS. The morphological changes of small intestine, liver and kidney was evaluated using H&amp;E staining. The intestine permeability to these drugs was studied using Ussing chamber.ResultFollowing proteomic analysis, PCA plot indicated a clear separation between SAMP8 and SAMR1 intestine, liver and kidney tissue, with global functional analysis indicated altered drug metabolism in the small intestine and liver of SAMP8 mice. The oral pharmacokinetic study revealed a significant elevation in plasma exposure (i.e. AUC) to valsartan and digoxin but reduction to quetiapine in SAMP8 mice compared to their non‐AD control mice. When interpreted together with H&amp;E staining, ex vivo drug permeation study, and proteome data, the increase AUC to valsartan and digoxin is likely due to increased intestine leakiness. For digoxin, despite P‐glycoprotein expression was significantly increased in the small intestine, it failed to compensate the leaky gut. For quetiapine, the reduction in AUC in SAMP8 was due to increased hepatic metabolism, as increased levels of metabolites of quetiapine was detected in the plasma.ConclusionConsistent with our previous observation in APP/PS1 mice, drug disposition following oral administration was also noted in a mouse model of sporadic AD (SAMP8). Clinical study to evaluate altered ADME in people with AD should be considered to achieve precise medication use in people with AD.

Curcumin protects against bisphenol A-induced hepatic steatosis by inhibiting cholesterol absorption and synthesis inCD-1 mice.

Curcumin is a polyphenol extracted from the rhizome of turmeric, and our previous research showed that curcumin inhibited cholesterol absorption and had cholesterol-lowering effect. Bisphenol A (BPA), a common plasticizer, is widely used in the manufacture of food packaging and is associated with non-alcoholic fatty liver disease (NAFLD). We hypothesized that curcumin could protect against BPA-induced hepatic steatosis by inhibiting cholesterol absorption and synthesis. Male CD-1 mice fed BPA-contaminated diet with or without curcumin for 24 weeks were used to test our hypothesis. We found that chronic low-dose BPA exposure significantly increased the levels of serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol and the contents of liver TG and TC, resulting in liver fat accumulation and hepatic steatosis while curcumin supplementation could alleviate BPA-induced dyslipidemia and hepatic steatosis. Moreover, the anti-steatosis and cholesterol-lowering effects of curcumin against BPA coincided with a significant reduction in intestinal cholesterol absorption and liver cholesterol synthesis, which was modulated by suppressing the expression of sterol regulatory element-binding protein-2 (SREBP-2), Niemann-Pick C1-like 1 (NPC1L1), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in the small intestine and liver. In addition, the expression levels of liver lipogenic genes such as liver X receptor alpha (LXRα), SREBP-1c, acetyl-CoA carboxylase 1 (ACC1), and ACC2 were also markedly down-regulated by curcumin. Overall, our findings indicated that curcumin inhibited BPA-induced intestinal cholesterol absorption and liver cholesterol synthesis by suppressing SREBP-2, NPC1L1, and HMGCR expression, subsequently reducing liver cholesterol accumulation and fat synthesis, thereby preventing hepatic steatosis and NAFLD.