Mitochondrial dysfunction is associated with the severity of liver fibrosis in patients after the Fontan operation.

The gold standard for determining the severity of liver disease in Fontan patients is now liver biopsy. Since it is an invasive procedure, this study determined the possibility of applying mitochondrial function from isolated peripheral blood mononuclear cells (PBMCs) as a non-invasive indicator of liver fibrosis. Fontan patients (n = 37) without known liver disease were analysed cross-sectionally. Patients were classified according to their histology using the METAVIR score as follows; F0/F1-no/mild fibrosis; F2-moderate fibrosis; and F3/F4-cirrhosis. Peripheral blood mononuclear cells were assessed for mitochondrial activity and apoptosis. This study did not find any significant differences in cardiac function among the groups according to liver histology. Interestingly, our findings indicated a significant decrease in maximal respiration and spare respiratory capacity, in both the moderate (F2) and cirrhosis (F3/F4) groups compared with the group without significant fibrosis (F0/F1). Moreover, the cirrhosis group exhibited higher levels of apoptosis and lower levels of live cells, compared with both the moderate and no significant fibrosis groups. In conclusion, the degree of liver fibrosis in Fontan patients is strongly correlated with mitochondrial dysfunction in PBMCs. Mitochondrial function and apoptosis could potentially serve as novel markers for tracking the progression of liver fibrosis in these patients.

Risk factors of worsening kidney function and mortality in patients with renal vein thrombosis: a retrospective study.

BACKGROUND: The outcome of renal vein thrombosis, in particular as for the long-term impact on kidney function, is not fully known. We aimed to study the natural course and outcomes of patients with renal vein thrombosis, in a large, single-center cohort. METHODS: A single-center retrospective cohort study including patients who were diagnosed with renal vein thrombosis between January 2006 and September 2021 was analyzed. The main outcomes analyzed were worsening kidney function, defined as a decrease in eGFR of at least 40% from baseline, and all-cause mortality. RESULTS: Eighty-seven patients were included, 56.3% were female, median age was 57 years. Malignancy was the most common cause of renal vein thrombosis (60.9%), followed by post-surgery and trauma (16.1%) and nephrotic syndrome (12.6%). At initial presentation, 65.5% of the patients were asymptomatic; the main signs and symptoms were gross hematuria (20.7%), flank pain (18.4%), and flank tenderness (9.2%). During follow-up, 18 (21.4%) patients experienced worsening kidney function and 57 (65.5%) died. Multivariable analyses showed that the risk of worsening kidney function was higher in patients with nephrotic syndrome (hazard ratio [HR] 18.41; 95% confidence interval [CI], 1.57-216.04), body weight ≥ 60 kg (HR 4.82; 95% CI 1.43-16.32), and malignancy (HR 9.10; 95% CI 1.05-78.63). Symptomatic acute renal vein thrombosis was associated with a lower risk of worsening kidney function compared to asymptomatic or symptomatic chronic renal vein thrombosis (HR 0.12; 95% CI 0.01-0.96). Malignancy (HR 5.45; 95% CI 2.58-11.54), age ≥ 75 years (HR 3.44; 95% CI 1.49-7.93), and serum albumin < 3.0 g/dL (HR 2.88; 95% CI 1.65-5.05) were associated with an increased mortality risk. CONCLUSION: Renal vein thrombosis is associated with a high rate of worsening kidney function and mortality. It is crucial to promptly identify patients at high risk and initiate early treatment to prevent negative outcomes.

Prediction of survival and analysis of prognostic factors for hepatocellular carcinoma: a 20-year of imaging diagnosis in Upper Northern Thailand.

BACKGROUND: To evaluate survival rates of hepatocellular carcinoma (HCC), the Chiang Mai Cancer Registry provided characteristics data of 6276 HCC patients diagnosed between 1998-2020 based on evolution of imaging diagnosis. Evolution can be separated into four cohorts, namely, cohort 1 (1990-2005) when we had ultrasound (US) and single-phase computed tomography (CT), cohort 2 (2006-2009) when one multi-phase CT and one magnetic resonance imaging (MRI) were added, cohort 3 (2010-2015) when MRI with LI-RADS was added, and finally, cohort 4 (2016-2020) when two upgraded MRIs with LI-RADS were added. METHODS: Cox proportional hazard models were used to determine the relation between death and risk factors including methods of imagining diagnosis, gender, age of diagnosis, tumor stages, history of smoking and alcohol-use, while Kaplan-Meier curves were used to calculate survival rates. RESULTS: The median age of diagnosis was 57.0 years (IQR: 50.0-65.0) and the median survival time was 5.8 months (IQR: 1.9-26.8) during the follow-up period. In the univariable analysis, all factors were all associated with a higher risk of death in HCC patients except age of diagnosis. In a multivariable analysis, elderly age at diagnosis, regional and metastatic stages and advanced methods of imagining diagnosis during cohorts 2 and 3 were independently associated with the risk of death in HCC patients. The survival rate of patients diagnosed during cohort 4 was significantly higher than the other cohorts. CONCLUSION: As a significantly increasing survival rate of HCC patients in cohort 4, advanced methods of diagnostic imaging can be a part of the recommendation to diagnose HCC.

Prediction microvascular invasion of hepatocellular carcinoma based on tumour margin enhancing pattern in multiphase computed tomography images.

Purpose: The presence of microvascular invasion of hepatocellular carcinoma has a significantly decreased outcome following hepatectomy or liver transplantation. Currently, it is still based on histological examination. Identification of microvascular invasion by using pre-operative imaging is important for the decision-making of surgeons and interventional radiologists. Aim of the study was to predict the microvascular invasion of hepatocellular carcinoma based on tumour margin enhancement of pre-operative multiphase computed tomography (CT) images. Material and methods: Fifty-three patients with hepatocellular carcinoma, who underwent pre-operative multiphase CT scans, were included in this study. Tumour margin enhancing patterns were analysed in the late arterial phase, portovenous phase, and delay phase. The CT features including peritumoral enhancement, arterial rim-enhancement, presence of daughter nodules, complete capsule enhancement in portovenous/delay phase, and nodular capsule enhancement in portovenous/delay phase were reviewed with calculations for sensitivity and specificity. Univariate analysis and multivariate analysis were used to identify predictive features for microvascular invasion (MVI). Results: In the late arterial phase, peritumoral enhancement or the presence of daughter nodules were not predictors for MVI. Nodular capsule enhancement in the portovenous phase and delay phase were independent predictors for MVI with odds ratios of 29.25 and 33.09, respectively. The sensitivity and specificity for incomplete/nodular capsule enhancement in the portovenous phase were 69.23% and 96.86%, respectively. The sensitivity and specificity for incomplete/nodular capsule enhancement in the delay phase were 71.79% and 96.86%, respectively. Conclusion: Nodular capsule enhancement in the portovenous phase or delay phase was a good predictor for MVI.

Investigating Up-to-Seven Criteria and APRI (AST Platelet Ratio) as Prognostic Factors in Intermediate-Stage Hepatocellular Carcinoma Patients Who Received Transarterial Chemoembolization.

BACKGROUND: Transarterial chemoembolization (TACE) is one of the locoregional treatments for intermediate-stage hepatocellular carcinoma (HCC). Multidetector computed tomography (MDCT) is a widely used diagnostic tool for HCC. It can also evaluate tumor size, tumor number, and tumor invasion. This study aimed to determine the median survival time in intermediate-stage HCC patients who underwent TACE and to find out  prognostic factors influencing patients' survival time after TACE. METHODS: A computerized search of medical record database in Maharaj Nakorn ChiangMai Hospital from January 2016 to December 2019 revealed 187 intermediate-stage HCC patients who received TACE as the first-line treatment. RESULTS: The median survival time of patients in this study was 9.9 months (95% CI: 8.3-11.6). The patients with aspartate aminotransferase-to-platelet ratio (APRI) less than 0.5 had a significantly better median survival time as compared with patients with APRI ratio more than 0.5; (13.2 months versus 9.9 months, p-value < 0.05). Univariate and multivariate Cox regression analysis demonstrated that tumor number > 7 and tumor size > 5 centimeters (cm) could be considered as independent parameters predicting poor overall survival time in the sufferers (HR 2.64 95%CI 1.68-4.15 and HR 2.38 95%CI 1.32-4.31, respectively). CONCLUSION: Based on our findings, patients with intermediate-stage HCC who received TACE had a lower median survival time compared to previous studies. However, we identified APRI less than 0.5, tumor size less than 5 cm, and tumor number less than 7 as prognostic factors improving survival time in intermediate-stage HCC patients.

Gadoxetate-Enhanced MRI as a Diagnostic Tool in the Management of Hepatocellular Carcinoma: Report from a 2020 Asia-Pacific Multidisciplinary Expert Meeting.

Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.

Automatic hemorrhage segmentation on head CT scan for traumatic brain injury using 3D deep learning model.

The most common cause of long-term disability and death in young adults is a traumatic brain injury. The decision for surgical intervention for craniotomy is dependent on the injury type and the patient's neurologic exam. The potential subtypes of intracranial hemorrhage that may necessitate surgical intervention include subdural hemorrhage, epidural hemorrhage, and intraparenchymal hemorrhage. We proposed a novel automatic method for segmenting the hemorrhage subtypes on a CT scan by integrated CT scan with bone window as input of a deep learning model. Brain CT scans were collected from adult patients and annotated regions of subdural hemorrhage, epidural hemorrhage, and intraparenchymal hemorrhage by neuroradiologists. Their raw DICOM images were preprocessed by two different window settings i.e., subdural and bone windows. The collected CT scans were divided into two datasets namely training and test datasets. A deep-learning model was modified to segment regions of each hemorrhage subtype. The model is a three-dimensional convolutional neural network including four parallel pathways that process the input at different resolutions. It was trained by a training dataset. After the segmentation result was produced by the deep-learning model, it was then improved in the post-processing step. The size of the segmented lesion was considered, and a region-growing algorithm was applied. We evaluated the performance of the proposed method on the test dataset. The method reached the median Dice similarity coefficients higher than 0.37 for each hemorrhage subtype. The proposed method demonstrates higher Dice similarity coefficients and improved segmentation performance compared to previously published literature.

Extracellular vesicles as a new hope for diagnosis and therapeutic intervention for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer with a high mortality rate. Early diagnosis and treatment before tumor progression into an advanced stage is ideal. The current diagnosis of HCC is mainly based on imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging. These methods have some limitations including diagnosis in the case of very small tumors with atypical imaging patterns. Extracellular vesicles (EVs) are nanosized vesicles which have been shown to act as an important vector for cell-to-cell communication. In the past decade, EVs have been investigated with regard to their roles in HCC formation. Since these EVs contain biomolecular cargo such as nucleic acid, lipids, and proteins, it has been proposed that they could be a potential source of tumor biomarkers and a vector for therapeutic cargo. In this review, reports on the roles of HCC-derived EVs in tumorigenesis, and clinical investigations using circulating EVs as a biomarker for HCC and their potential diagnostic roles have been comprehensively summarized and discussed. In addition, findings from in vitro and in vivo reports investigating the potential roles of EVs as therapeutic interventions are also presented. These findings regarding the potential benefits of EVs will encourage further investigations and may allow us to devise novel strategies using EVs in the early diagnosis as well as for treatment of HCC in the future.

Classification of hepatocellular carcinoma and intrahepatic cholangiocarcinoma based on multi-phase CT scans.

Liver and bile duct cancers are leading causes of worldwide cancer death. The most common ones are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Influencing factors and prognosis of HCC and ICC are different. Precise classification of these two liver cancers is essential for treatment and prevention plans. The aim of this study is to develop a machine-based method that differentiates between the two types of liver cancers from multi-phase abdominal computerized tomography (CT) scans. The proposed method consists of two major steps. In the first step, the liver is segmented from the original images using a convolutional neural network model, together with task-specific pre-processing and post-processing techniques. In the second step, by looking at the intensity histograms of the segmented images, we extract features from regions that are discriminating between HCC and ICC, and use them as an input for classification using support vector machine model. By testing on a dataset of labeled multi-phase CT scans provided by Maharaj Nakorn Chiang Mai Hospital, Thailand, we have obtained 88% in classification accuracy. Our proposed method has a great potential in helping radiologists diagnosing liver cancer.

Ultrasound Use in Diagnosis and Management of Venous Leg Ulcer.

Leg ulcers caused by venous diseases are effectively assessed by Doppler ultrasonography. The examination provides clear anatomical and physiological information for the diagnosis, treatment planning, and real-time guiding during the surgical treatment. Diagnostic Doppler ultrasonography assesses deep, superficial, and perforator veins, starting from patency assessment by direct visualization and simply compression test. The internal flow can be assessed by pulse wave analysis, which is used for rule out downstream flow obstruction and valvular incompetence. The venous valve function of deep, superficial, and perforator systems can be evaluated by measuring the time of the retrograde flow after flow augmentation performing in the upright position. At the end of the study, the venous map will be obtained and this map will guide clinicians to target treatment where the culprit is. The ultrasound technology has made a big shift in the treatment in the venous disease. In recent years, after the evolution and wide availability of ultrasound, newer treatment modalities have emerged for venous treatment. These include endovenous thermal ablation, endovenous adhesive closure, and ultrasound-guided foam sclerotherapy. Patients no longer require general anesthesia or hospitalization. Therefore utilization of duplex ultrasound has also surged and played an essential role in both diagnosis and therapy in venous ulcer. This article has dedicated to reviewing basic anatomy, the technique in diagnosis, and treatment.

Effect of sodium benzoate and chlorhexidine gluconate on a bio-thermoplastic elastomer made from thermoplastic starch-chitosan blended with epoxidized natural rubber.

Thermoplastic elastomer (TPE) was developed by blending thermoplastic starch (TPS) with rubber. Thermoplastic starch-chitosan (TPSC) was prepared by the solution mixing of cassava starch, chitosan (CTS) and glycerol in acidified water (lactic acid 1 wt%) at 80 °C follow by melt mixing at 130 °C. Sodium benzoate (BEN) and chlorhexidine gluconate (Cl) were added during the solution mixing as additives for antimicrobial properties. TPSC was melt-mixed with epoxidized natural rubber (ENR) (70/30 wt/wt). The tensile strength and elongation at break of the TPSC/ENR increased with the additive content. Elastic recovery was improved by the addition of Cl. A new peak in the FTIR data confirmed the reaction between the reactive functional groups of the CTS and the additives with the epoxy groups of ENR. These reactions and miscibility of the TPSC/ENR/additives blends improved the mechanical properties, elasticity, morphology, and antimicrobial properties of the blends.

Cardiorespiratory burden of brass neck coils placed on Kayan Karen long-neck women of Thailand.

There is only scarce information regarding the physiological and health impact of lifelong wearing of the neck brass coils in Karen Kayan women. The purpose of this study was to determine the influence of wearing brass neck coils on cardiorespiratory and cerebrovascular functions in long-neck Karen women. A total of 28 Karen women (aged 23-66 years) were studied. Fourteen Karen women who had been wearing neck brass coils were compared with 14 Karen women with no neck coils. We also studied 14 age-matched city-living controls. Radiographic examination of 2 older Karen women wearing neck coils showed low levels of the clavicles. There were no group differences in resting heart rate and brachial-ankle pulse wave velocity. Both systolic and diastolic blood pressure was greater and functional capacity was lower in both Karen women than city-living controls (all p < 0.05). Karen women wearing neck coils demonstrated lower flow-mediated dilation, lung functions, including forced vital capacity and forced expiratory volume during the first second, and cerebral blood flow velocity than Karen women without neck coils (all p < 0.05). Karen women wearing neck coils demonstrate reduced endothelial and pulmonary functions as well as cerebral perfusion compared with age-matched Karen women without neck coils living in the same villages. Brass neck coils worn by Karen women may elevate risks of developing cardiopulmonary and cerebrovascular diseases. Novelty Cerebral blood flow velocity and macrovascular and microvascular functions were lower in Karen wearing neck coils. There appears to be substantial burden of brass neck coils exerted on physiological systems in Karen women.