Folate levels in hepatocellular carcinoma patients with portal vein thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) occurs frequently in hepatocellular carcinoma (HCC) and is often diagnosed in the course of a routine patient evaluation and surveillance for liver cancer. The purpose of this study is to investigate the relationship between folate status and portal vein thrombosis. METHODS: HCC with PVT patients were 78, HCC without PVT were 60 and control subjects were 70 randomly selected. We evaluate serum and red blood cellular folate, homocysteine, alpha fetal protein cholesterol, triglycerides, prothrombin time. RESULTS: HCC patients with PVT showed lower levels of serum folate, respect HCC patients without PVT, with an average difference of 1.6 nmol/l p < 0.01 (95% CI - 2.54 to - 0.66), red cell folate 33.6 nmol/l p < 0.001 (95% CI - 43.64 to - 23.55) and albumin 0.29 g/dl p < 0.001 (95% CI - 0.42 to - 0.15); PVT patients displayed higher levels of bilirubin 0.53 mg/dl p < 0.001 (95% CI 0.23 to 0.78), INR 0.91 p < 0.001 (95% CI 0.72 to 1.09), γGT 7.9 IU/l (95% CI 4.14 to 11.65) and homocysteine 4.6 µmol/l p < 0.05 (95% CI 0.32 to 8.87) CONCLUSION: The low folate concentration and higher levels of homocysteine are associated with the loss of antithrombotic function, and with a more aggressive course of HCC and with a higher change of complications related to portal vein thrombosis.

Lipoprotein(a) in patients with hepatocellular carcinoma and portal vein thrombosis.

BACKGROUND: The mechanism for hypercoagulability in malignancy is not entirely understood. Although several studies report contrasting finding about the link between elevated plasma levels of the lipoprotein(a) [Lp(a)] and the possible recurrence of venous thromboembolism, we perform a study to evaluate the impact of the Lp(a) in the development of portal vein thromboembolism (PVT) in patients with HCC. METHODS: We compared 44 PVT patients with 50 healthy subjects and 50 HCC patients. RESULTS: The comparison between PVT patients and HCC showed in the former the mean value of serum lipoprotein levels was higher than 37.3 mg/dl (p = 0.000). The comparison between PVT versus healthy controls showed that in the former, mean value of serum lipoprotein levels was higher than 75 mg/dl (p = 0.000). The predictive value test of serum lipoprotein(a) on PVT was 0.72 and on HCC was 0.83. The odds ratio of lipoprotein(a) was 9.21 on PVT and 6.33 on HCC. CONCLUSION: Patients with PVT and HCC showed a statistical significant serum lipoprotein(a) level higher than the subjects with HCC and no PVT or the healthy subject. So we assume a role of lipoprotein(a) as predictor of venous thromboembolism in neoplastic patients.

Change in Coefficient of Fatigability Following Rapid, Repetitive Movement Training in Post-Stroke Spastic Paresis: A Prospective Open-Label Observational Study.

BACKGROUND: In post-stroke patients, the possibility of performing an active ankle dorsiflexion movement is favorable for the recovery of gait. Moreover, the fatigue due to repetitive active ankle dorsiflexion could reduce the speed gait. We assessed the change in coefficient of fatigability of active ankle dorsiflexion after a home-based self-rehabilitative procedure in post-stroke patients. METHODS: In a prospective open-label observational study conducted in 2 university hospitals, a home-based self-rehabilitation treatment comprising two 12-minute sessions per day (3 times per week for 3 months) was performed by 10 outpatients with post-stroke lower limb impairment. Each session consisted of three 1-minute series of repeated active ankle dorsiflexion efforts at maximal speed on the paretic side, each one followed by 3-minute bouts of triceps surae stretch. Coefficients of fatigability of dorsiflexion and 10-meter barefoot ambulation speed were evaluated at baseline and at the end of the program. RESULTS: At 3 months of follow-up, there was a decrease in the coefficients of fatigability of ankle dorsiflexion, both with knee flexed and extended (respectively from 8% to 2% and from 6% to 2%; P < .01), associated with an increase in comfortable ambulation speed (from .24 to .26 m/s; P < .05). CONCLUSIONS: The reduction of coefficient of fatigability of ankle dorsiflexion, together with walking speed improvement, suggested the effectiveness of self-rehabilitation using alternated periods of self-stretch and rapid alternating efforts in the paretic lower limb after stroke.

Silybin supplementation during HCV therapy with pegylated interferon-α plus ribavirin reduces depression and anxiety and increases work ability.

BACKGROUND: Hepatitis C virus infection and interferon treatment are often associated with anxiety, depressive symptoms and poor health-related quality of life. To evaluate the Silybin-vitamin E-phospholipids complex effect on work ability and whether health related factors (anxiety and depression) were associated with work ability in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b (Peg-IFN) and Ribavirin (RBV). METHODS: Thirty-one patients (Group A) with chronic hepatitis and other 31 subjects in Group B were recruited in a randomized, prospective, placebo controlled, double blind clinical trial. Group A received 1.5 mg/kg per week of Peg-IFN plus RBV and placebo, while Group B received the same dosage of Peg-IFN plus RBV plus association of Silybin 94 mg + vitamin E 30 mg + phospholipids 194 mg in pills for 12 months. All subjects underwent to laboratory exams and questionnaires to evaluate depression (Beck Depression Inventory - BDI), anxiety (State-trait anxiety inventory - STAI) and work ability (Work ability Index - WAI). RESULTS: The comparison between group A and group B showed significant differences after 6 months in ALT (P < 0.001), and viremia (P < 0.05), after 12 months in ALT (P < 0.001), and AST (P < 0.001), at follow up in AST (P < 0.05), and ALT (P < 0.001). Significant difference were observed after 1 month in WAI (p < 0.001) and BDI (P < 0.05), after 6 months in WAI (P < 0.05) and STAI (P < 0.05), after 12 months and at follow up in WAI, STAI and BDI (p < 0.01). CONCLUSIONS: The supplementation with Silybin-vitamin E -phospholipids complex increased work ability and reduced depression and anxiety in patients treated with Peg-IFN and RBV. TRIAL REGISTRATION: NCT01957319 , First received: September 25, 2013. Last updated: September 30, 2013 (retrospectively registered).

What is changing in indications and treatment of hepatic hemangiomas. A review.

Hepatic cavernous hemangioma accounts for 73% of all benign liver tumors with a frequency of 0.4-7.3% at autopsy and is the second most common tumor seen in the liver after metastases. Patients affected by hemangioma usually have their tumor diagnosed by ultrasound abdominal examination for a not well defined pain, but pain persist after treatment of the hemangioma. The causes of pain can be various gastrointestinal pathologies including cholelithiasis and peptic ulcer disease.The malignant trasformation is practically inexistent. Different imaging modalities are used to diagnosis liver hemangioma including ultrasonography, computed tomography (CT), magnetic resonance (MR) imaging, and less frequently scintigraphy, positronemission tomography combined with CT (PET/CT) and angiography. Imaging-guided biopsy of hemangioma is usually not resorted to except in extremely atypical cases. The right indications for surgery remain rupture, intratumoral bleeding, Kasabach-Merritt syndrome and organ or vessels compression (gastric outlet obstruction, Budd-Chiari syndrome, etc.) represents the valid indication for surgery and at the same time they are all complications of the tumor itself. The size of the tumor do not represent a valid indication for treatment. Liver hemangiomas, when indication exist, have to be treated firstly by surgery (hepatic resection or enucleation, open, laproscopic or robotic), but in the recent years other therapies like liver transplantation, radiofrequency ablation, radiotherapy, trans-arterial embolization, and chemotherapy have been applied.

Evaluation of AMCase and CHIT-1 expression in monocyte macrophages lineage.

Acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT-1) are two active chitinases expressed in humans. The chitinase activity of AMCase was found to be causative in allergic inflammation and its expression was found to be induced by interleukin-13. CHIT1-1 is expressed by phagocytic cells and extremely high levels are seen in lysosomal storage diseases. Despite that AMCase expression in the inflammation is under investigation, little is known regarding its regulation during macrophages' full maturation and polarization. In this study, we compared AMCase and CHIT-1 modulation during monocyte to macrophage transition and polarization. Gene expression analysis was investigated by real-time PCR from mRNA of human monocytes obtained from buffy coat of healthy volunteers, from mRNA of polarized to classically activated macrophages (or M1), obtained by interferon (IFN)-γ and lipopolysaccharide (LPS) treatment, and from mRNA of alternatively activated macrophages (or M2) obtained by interleukin (IL)-4 exposure. Our results showed that the expression of AMCase and CHIT-1 were differently modulated in HMMs at different stage of maturation. The behavior of these two active chitinase suggests that in the immune response their role is complementary.

Systemic therapies in hepatocellular carcinoma: present and future.

Hepatocellular carcinoma (HCC) is now the third leading cause of cancer deathsworldwide and is generally presented at an advanced stage, limiting patients' quality of life. The conventional cytotoxic systemic therapy has proved to be ineffective in HCC, since its induction several decades ago. Today it is possible to use our knowledge of molecular hepatocarcinogenesis to provide a targeted therapy. Sorafenib has demonstrated large improvements in overall survival in HCC. This review describes the molecular mechanisms and potential therapeutic targets, focusing on sorafenib, sunitinib, tivantinib, antiangiogenic agents, and current and future immunotherapies. Thus, it will be necessary in the future to classify HCCs into subgroups according to their genomic and proteomic profiling. The identification of key molecules/receptors/signaling pathways and the assessment of their relevance as potential targets will be the main future challenge potentially influencing response to therapy. Defining molecular targeted agents that are effective for a specific HCC subgroup will hopefully lead to personalized therapy.

Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis.

BACKGROUND: Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis (NASH). Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota. AIMS: To evaluate the effects of Bifidobacterium longum with fructo-oligosaccharides (Fos) in the treatment of NASH. METHODS: A total of 66 patients were randomly and equally divided into two groups receiving Bifidobacterium longum with Fos and lifestyle modification (i.e., diet and exercise) versus lifestyle modification alone. The following variables were assessed at -4 (beginning of the dietary lead-in period), 0 (randomization), 6, 12, 18, and 24 weeks: aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, albumin, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting plasma glucose, insulin, C-peptide, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, homeostasis model assessment of insulin resistance (HOMA-IR), and serum endotoxins. Liver biopsies were performed at entry and repeated after 24 weeks of treatment. RESULTS: At the end of study period, we observed that the Bifidobacterium longum with Fos and lifestyle modification group versus the lifestyle modification alone group showed significant differences in the AST -69.6 versus -45.9 IU/mL (P < 0.05), LDL cholesterol -0.84 versus -0.18 mmol/L (P < 0.001), CRP -2.9 versus -0.7 mg/L (P < 0.05), TNF-α -0.45 versus -0.12 ng/mL (P < 0.001), HOMA-IR -1.1 versus -0.6 (P < 0.001), serum endotoxin -45.2 versus -30.6 pg/mL (P < 0.001), steatosis (P < 0.05), and the NASH activity index (P < 0.05). CONCLUSIONS: Bifidobacterium longum with Fos and lifestyle modification, when compared to lifestyle modification alone, significantly reduces TNF-α, CRP, serum AST levels, HOMA-IR, serum endotoxin, steatosis, and the NASH activity index.

Potential role of probiotics on colorectal cancer prevention.

BACKGROUND: Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. DISCUSSION: Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention. SUMMARY: Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host's immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.

Centenarians and supercentenarians: a black swan. Emerging social, medical and surgical problems.

The Black Swan Theory was described by Nassim Nicholas Taleb in his book "The Black Swan". This theory refers to "high-impact, hard-to-predict, and rare events beyond the realm of normal expectations". According to Taleb's criteria, a Black Swan Event is a surprise, it has a major impact and after the fact, the event is rationalized by hindsight, as if it had been expected. For most of human history centenarians were a rare and unpredictable phenomenon. The improvements of the social-environmental conditions, of medical care, and the quality of life caused a general improvement of the health status of the population and a consequent reduction of the overall morbidity and mortality, resulting in an overall increase of life expectancy. The study of centenarians and supercentenarians had the objective to consider this black swan and to evaluate the health, welfare, social and economic consequences of this phenomenon.

Depression in older breast cancer survivors.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer among U.S. women .The 5-year survival rate for this tumour is nowadays 85%, and the 61% of these women are still alive at 15 years. When depression symptoms are present as a consequence of breast cancer treatments, they may interfere negatively with patients' quality of life. The aim of this study was to examine the effects of breast cancer treatment on the quality of life and the impact of depression on the health-related life. METHODS: We enrolled 173 women aged 65-75 years with early stage breast cancer diagnosed over the last 10 years, initially recruited to participate in a study examining heath-related quality of life in the first 5 years after breast cancer diagnosis. Participants were divided into four groups: 1) 46 breast cancer survivors (aged 65-70); 2) 62 women diagnosed with breast cancer (aged 65-69); 3) 32 women with recurrent breast cancer after 10 years (aged 66-75); 4) 30 women in good health status (aged 60-70). The Geriatric Depression Scale was used as a routine part of a comprehensive geriatric assessment. Collection of data for the application of instruments, such as sociodemographic variables (age, educational level, social state) and clinical date (stage and time of the disease and treatment), was carried out by trained researcher assistants. RESULTS: Our results demonstrated the correlation between depression and previous cancer experiences. In fact, in patients with cancer experience, the grade of depression was significantly higher compared to healthy subjects. Furthermore, we demonstrated that the patients with recurrent breast cancer were severely depressed compared to other groups. CONCLUSIONS: A high percentage of participants were identified as having emotional and/or well being problems. Further investigations on the cause of depression problems cancer-related are needed.

Elevated serum levels of Chromogranin A in hepatocellular carcinoma.

BACKGROUND: During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. METHODS: The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. RESULTS: The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). CONCLUSIONS: Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.

Serum Folate deficiency in HCV related Hepatocellular Carcinoma.

Nutritional and environmental factors had been reporting in the progression of hepatocellular carcinoma (HCC). In this study, we focused our intervention in the correlation between the folate status and the progression of HCC in patients with chronic virus C (HCV) infection. Nine-eight patients, HCV positive with HCC and one hundred of patients with HCV positive liver cirrhosis (LC) and one hundred patients with HCV positive chronic hepatitis (CHC) and one hundred control subjects were enrolled. The viremia for hepatitis C patients (HCV) was determined by HCV RNA with polymerase chain reaction. HCV was confirmed by HCV RNA or a positive anti-HCV test with chronic liver disease. The comparison of folate serum levels in HCC patients vs Liver Cirrhosis (LC) patients showed a significant decrease of 1.16 ng/ml P = 0.0006 (95% CI-1.925 to - 0.395), in HCC patients versus CHC a decrease of 1.40 ng/ml P < 0.0001 (95% CI-2.16 to - 0.63), in HCC vs controls a decrease of 3.80 ng/ml P < 0.0001 (95% CI-4.56 to - 3.03). The comparison of homocysteine Hcy serum levels showed a significant increase in HCC vs LC of 4 nmol/L (P < 0.0001, 95% CI 2.77 to 5.22) versus CHC of 9 nmol/L (P < 0.0001, 95% CI 7.78 to 10.22) and vs Controls 9.30 nmol/L (P < 0.0001, 95% CI 8.07 to 10.52). With progression of HCV infection from chronic hepatitis to cirrhosis, then to HCC development, serum folate levels are progressively decreasing together with a progressive increase in serum homocysteine levels reflecting its role in disease progress and carcinogenesis.

Acetyl-L-carnitine Slows the Progression from Prefrailty to Frailty in Older Subjects: A Randomized Interventional Clinical Trial.

BACKGROUND: Ageing is characterized by a gradual decline in body function, representing the clinical situation called "frailty". Prefrailty is the intermediate stage between frailty and robust condition. L-carnitine (LC) plays an important role in energy production from long-chain fatty acids in mitochondria, and its serum level is lower in prefrail and frail subjects. OBJECTIVE: This study aims to evaluate the effect of Acetyl-L-carnitine (ALCAR) in pre-frail older patients. METHODS: We scheduled 3 months of treatment and then 3 months of follow-up. A total of 92 subjects were selected from May, 2009 to July, 2017, in a randomized, observational, double-blind, placebo-controlled study. We scheduled 3 months of treatment and then 3 months of follow-up. ALCAR (oral 1.5 g/bis in die - BID) or placebo groups were used. RESULTS: After the treatment, only the treated group displayed a decrease in C reactive protein (CRP) p < 0.001 and an increase in serum-free carnitine and acetylcarnitine (p < 0.05) in Mini-Mental state (MMSE) p < 0.0001 and 6-walking distance (p < 0.0001); ALCAR group vs. placebo group showed a decrease in HDL cholesterol and CRP (p < 0.01), an increase in MMSE score (p < 0.001) and in the 6-walking distance (p < 0.001). CONCLUSIONS: ALCAR treatment delays the incidence and severity of onset of degenerative disorders of the elderly in prefrail subjects with improvement in memory and cognitive processes.

Transcranial magnetic stimulation in Alzheimer's disease: a neurophysiological marker of cortical hyperexcitability.

Recently, neuropathological studies have shown an important motor cortex involvement in Alzheimer's disease (AD), even in its early stages, despite the lack of clinically evident motor deficit. Transcranial magnetic stimulation (TMS) studies have demonstrated that cortical excitability is enhanced in AD patients. This cortical hyperexcitability is believed to be a compensatory mechanism to execute voluntary movements, despite the progressive impairment of associative cortical areas. At present, it is not clear if these motor cortex excitability changes might be the expression of an involvement of intracortical excitatory glutamatergic circuits or an impairment of inhibitory cholinergic and, to a lesser extent, gabaergic activity. Although the main hypothesis for the pathogenesis of AD remains the degeneration of the basal forebrain cholinergic neurons, the development of specific TMS protocols, such as the paired-pulse TMS and the study of the short-latency afferent inhibition, points out the role of other neurotransmitters, such as gamma-amino-butyric acid, glutamate and dopamine. The potential therapeutic effect of repetitive TMS in restoring or compensating damaged cognitive functions, might become a possible rehabilitation tool in AD patients. Based on different patterns of cortical excitability, TMS may be useful in discriminating between physiological brain aging, mild cognitive impairment, AD and other dementing disorders. The present review provides a perspective of these TMS techniques by further understanding the role of different neurotransmission pathways and plastic remodelling of neuronal networks in the pathogenesis of AD.

A review of transcranial magnetic stimulation in vascular dementia.

Vascular dementia (VaD) is a clinical syndrome that encompasses a wide spectrum of cognitive disorders caused by cerebrovascular disease. The subcortical ischemic form of VaD is clinically homogeneous and a major cause of cognitive impairment in the elderly. Vascular lesions contribute to cognitive decline in neurodegenerative dementias, and VaD and Alzheimer's disease often coexist and share clinical features and multiple neurotransmission involvement. These similarities have led several investigators to use transcranial magnetic stimulation (TMS) to enucleate a neurophysiological profile of VaD. TMS studies have identified a pattern of cortical hyperexcitability probably related to the disruption of the integrity of white matter lesions due to cerebrovascular disease. The present review provides a perspective of these TMS techniques by further understanding the role of different neurotransmission pathways and plastic remodeling of neuronal networks in the pathogenesis of VaD.

Acetyl-L-carnitine reduces depression and improves quality of life in patients with minimal hepatic encephalopathy.

BACKGROUND: Minimal hepatic encephalopathy (MHE) represents a common complication present in well-compensated cirrhotic patients that impairs patients' daily functioning and health-related quality of life (HRQL). Acetyl-L-carnitine (ALC) has been shown to be useful in improving blood ammonia and cognitive functions in cirrhotic patients with MHE. OBJECTIVE: This study evaluated the effects of ALC treatment on HRQL and depression in patients with MHE. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study. Sixty-seven patients with MHE were recruited to the study. They were randomly assigned to two groups and received either 2 g acetyl-L-carnitine twice a day (n = 33) or placebo (n = 34) for 90 days. The primary efficacy measures were changes in aspartate aminotransferase, alanine aminotransferase, γ-glutamyl-transpeptidase, albumin, alkaline phosphatase, prothrombin time, and ammonia. Clinical and laboratory assessments, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. RESULTS: At the end of the study period, between the two groups, we observed a significant difference in physical function (p < 0.001), role physical (p < 0.001), general health (p < 0.001), social function (p < 0.05), role emotional (p < 0.05), mental health (p < 0.05), Beck Depression Inventory (p < 0.001), TMT-B s (p < 0.001), State Trait Inventory (p < 0.001), urea (p < 0.05), NH(4)(+) (p < 0.001), and bilirubin (p < 0.001). CONCLUSIONS: This study shows that ALC treatment is associated with significant improvement in patient energy levels, general functioning and well-being. The improvement of quality of life is associated with reduction of anxiety and depression.

Acetyl-L-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial.

The aim of this study was to investigate the effects of ALC treatment on cognitive functions in patients with severe hepatic encephalopathy. This was a randomized, double-blind, placebo-controlled study. 61 patients with severe hepatic encephalopathy were recruited to the study. The 2 groups received either 2 g ALC twice a day (n = 30) or placebo (n = 30) for 90 days. Clinical and laboratory assessment, psychometric tests and automated electroencephalogram (EEG) analysis were performed for all patients. At the end of the study period, between the 2 groups we observed a significant difference in Everyday Memory Questionnaire -23.9 vs 4.4 (p < 0.001), Logical Memory (Paragraph recall) test 22.3 vs 0.7 (p < 0.001), Trail Making Test A -7.5 vs -2.6 (p < 0.001), Trail Making Test B -10.5 vs -3.1 (p < 0.001), Controlled Oral Word Association Test 4.2 vs 0.5 (p < 0.001), Hooper test 2.6 vs 0.1 (p < 0.05), Judgement of line orientation 2.8 vs 0.3 (p < 0.001), Digit Cancellation time -24.5 vs -2.4 (p < 0.001), NH4⁺ 30.5 vs 13.5 (p < 0.001), prothrombin time 2 vs 2.4 (p < 0.05), alanine transaminase -10.7 vs -13.6 (p < 0.001). 88% of patients treated with ALC vs 72% of patients treated with placebo showed a significant improvement in EEG. The improvement of cognitive deficits, the reduction of ammonia, and the modification of EEG in patients treated with ALC suggest that ALC could represent a new tool in the treatment of severe hepatic encephalopathy.

The translational roadmap of the gut models, focusing on gut-on-chip.

It is difficult to model in vitro the intestine when seeking to include crosstalk with the gut microbiota, immune and neuroendocrine systems. Here we present a roadmap of the current models to facilitate the choice in preclinical and translational research with a focus on gut-on-chip. These micro physiological systems (MPS) are microfluidic devices that recapitulate in vitro the physiology of the intestine. We reviewed the gut-on-chips that had been developed in academia and industries as single chip and that have three main purpose: replicate the intestinal physiology, the intestinal pathological features, and for pharmacological tests.

Serum markers of hepatocellular carcinoma.

BACKGROUND: The hepatocellular carcinoma is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains intricate. METHODS: A literature search identified potential markers for hepatocellular carcinoma. These markers were analysed and justification was provided for these factors' inclusion to (or exclusion from) the markers of hepatocellular carcinoma (HCC). A search of the literature was made using cancer literature and the PubMed database for the following keywords: "markers and HCC," "Lens culinaris agglutinin reactive AFP (AFP-L3) and HCC," "Des-γ-carboxy prothrombin (DCP) and HCC," "Glypican-3 and HCC," "Chromogranin A and HCC," "Transforming growth factor ß1(TGF) and HCC," "α-l-fucosidase (AFU) and HCC," "Golgi protein-73 (GP73) and HCC," "Hepatocyte growth factor (HGF) and HCC," "Nervous growth factor (NGF) and HCC." CONCLUSIONS: Despite the large number of studies devoted to the immunohistochemistry of HCC, at the present time, the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. Given the poor response to current therapies, a better understanding of the molecular pathways active in this disease could potentially provide new targets for therapy. However, AFP shows a low sensitivity, therefore other biomarkers have been developed to make an early diagnosis and improve patients' prognosis.