Hepatocellular Carcinoma and Associated Clinical Features in Latino and Caucasian Patients from a Single Center.

INTRODUCTION AND AIM:Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and has seen a rapid increase in incidence in the United States. Racial and ethnic differences in HCC incidence have been observed, with Latinos showing the greatest increase over the past four decades, highlighting a concerning health disparity. The goal of the present study was to compare the clinical features at the time of diagnosis of HCC in Latino and Caucasian patients. MATERIAL AND METHODS:We retrospectively screened a total of 556 charts of Latino and Caucasian patients with HCC. RESULTS:The mean age of HCC diagnosis was not significantly different between Latinos and Caucasians, but Latinos presented with higher body mass index (BMI). Rates of hypertension, diabetes, and hyperlipidemia were similar in the two groups. The most common etiology of liver disease was alcohol drinking in Latinos, and chronic hepatitis C in Caucasian patients. Non-Alcoholic Steatohepatitis (NASH) was the associated diagnosis in 8.6% of Latinos and 4.7% of Caucasians. Interestingly, alpha-fetoprotein (AFP) levels at time of diagnosis were higher in Latino patients compared to Caucasians, but this difference was evident only in male patients. Multifocal HCC was slightly more frequent in Latinos, but the two groups had similar cancerous vascular invasion. Latino patients also presented with higher rates of both ascites and hepatic encephalopathy. CONCLUSION:Latino and Caucasian patients with HCC present with a different profile of etiologies, but cancer features appear to be more severe in Latinos

Aberrant Hepatic Methionine Metabolism and Gene Methylation in the Pathogenesis and Treatment of Alcoholic Steatohepatitis

The pathogenesis of alcoholic steatohepatitis (ASH) involves ethanol-induced aberrations in hepatic methionine metabolism that decrease levels of S-adenosylmethionine (SAM), a compound which regulates the synthesis of the antioxidant glutathione and is the principal methyl donor in the epigenetic regulation of genes relevant to liver injury. The present paper describes the effects of ethanol on the hepatic methionine cycle, followed by evidence for the central role of reduced SAM in the pathogenesis of ASH according to clinical data and experiments in ethanol-fed animals and in cell models. The efficacy of supplemental SAM in the prevention of ASH in animal models and in the clinical treatment of ASH will be discussed

Clinical features of alcoholic hepatitis in latinos and caucasians: A single center experience.

AimTo study differences of presentation, management, and prognosis of alcoholic hepatitis in Latinos compared to Caucasians.MethodsWe retrospectively screened 876 charts of Caucasian and Latino patients who were evaluated at University of California Davis Medical Center between 1/1/2002-12/31/2014 with the diagnosis of alcoholic liver disease. We identified and collected data on 137 Caucasians and 64 Latinos who met criteria for alcoholic hepatitis, including chronic history of heavy alcohol use, at least one episode of jaundice with bilirubin ≥ 3.0 or coagulopathy, new onset of liver decompensation or acute liver decompensation in known cirrhosis within 12 wk of last drink.ResultsThe mean age at presentation of alcoholic hepatitis was not significantly different between Latinos and Caucasians. There was significant lower rate of overall substance abuse in Caucasians compared to Latinos and Latinos had a higher rate of methamphetamine abuse (12.5% vs 0.7%) compared to Caucasians. Latinos had a higher mean number of hospitalizations (5.3 ± 5.6 vs 2.7 ± 2.7, P = 0.001) and mean Emergency Department visits (9.5 ± 10.8 vs 4.5 ± 4.1, P = 0.017) for alcohol related issues and complications compared to Caucasians. There was significantly higher rate of complications of portal hypertension including gastrointestinal bleeding (79.7% vs 45.3%, P < 0.001), spontaneous bacterial peritonitis (26.6% vs 9.5%, P = 0.003), and encephalopathy (81.2% vs 55.5%, P = 0.001) in Latinos compared to Caucasians.ConclusionLatinos have significant higher rates of utilization of acute care services for manifestations alcoholic hepatitis and complications suggesting poor access to outpatient care

Dysregulated Choline, Methionine, and Aromatic Amino Acid Metabolism in Patients with Wilson Disease: Exploratory Metabolomic Profiling and Implications for Hepatic and Neurologic Phenotypes.

Wilson disease (WD) is a genetic copper overload condition characterized by hepatic and neuropsychiatric symptoms with a not well-understood pathogenesis. Dysregulated methionine cycle is reported in animal models of WD, though not verified in humans. Choline is essential for lipid and methionine metabolism. Defects in neurotransmitters as acetylcholine, and biogenic amines are reported in WD; however, less is known about their circulating precursors. We aimed to study choline, methionine, aromatic amino acids, and phospholipids in serum of WD subjects. Hydrophilic interaction chromatography-quadrupole time-of-flight mass spectrometry was employed to profile serum of WD subjects categorized as hepatic, neurologic, and pre-clinical. Hepatic transcript levels of genes related to choline and methionine metabolism were verified in the Jackson Laboratory toxic milk mouse model of WD (tx-j). Compared to healthy subjects, choline, methionine, ornithine, proline, phenylalanine, tyrosine, and histidine were significantly elevated in WD, with marked alterations in phosphatidylcholines and reductions in sphingosine-1-phosphate, sphingomyelins, and acylcarnitines. In tx-j mice, choline, methionine, and phosphatidylcholine were similarly dysregulated. Elevated choline is a hallmark dysregulation in WD interconnected with alterations in methionine and phospholipid metabolism, which are relevant to hepatic steatosis. The elevated phenylalanine, tyrosine, and histidine carry implications for neurologic manifestations and are worth further investigation

Reversible Holmes Tremor due to Middle Cerebral Artery Giant Aneurysm

A 40-year-old man presented with a 6-month history of mild but worsening tremor of variable intensity. The patient had a focal, irregular, rest and action tremor of middle amplitude and low frequency (about 4 Hz), limited to his right arm with oscillatory motion around the elbow. It was present inconsistently at rest, particularly during emotional activation, and enhanced by posture maintenance. It was evoked by various positions and tasks. Particularly, the tremor was present during fine motor skills such as writing, and it was increased by drinking and shaving, showing a minimal intentional component. The patient also reported slight loss in manual dexterity in his right hand

<i>Tordylium apulum L.</i>: caratterizzazione dell'olio essenziale e valutazione dell'attività antimicrobica ed antiossidante

In questa sede vengono presentati i risultati della caratterizzazione dell'olio essenziale di Tordylium apulum L., una ombrellifera diffusa in tutto il bacino del Mediterraneo, in Europa continentale e in Asia Minore

Clinical signs and symptoms of Wilson disease in a real-world cohort of patients in the United States: a medical chart review study

IntroductionThere are limited data from the United States regarding the real-world signs and symptoms of Wilson disease (WD). This retrospective, observational medical chart review was conducted to identify real-world characteristics of patients with WD in the United States, as well as WD signs and symptoms at diagnosis and over time.MethodsDe-identified clinical data were abstracted from medical charts of US patients diagnosed with WD between January 1, 2012, and June 30, 2017. Hepatic, neurologic, and psychiatric biochemical findings, signs, and symptoms were characterized at diagnosis and follow-up/during treatment.ResultsIn total, 225 WD patients were included in the study. The mean (SD) age at diagnosis was 24.7 (9.8) years, and 65.3% were male. Median (Q1–Q3) follow-up after diagnosis was 39.5 (33.8–60.4) months. The most common disease presentation at WD diagnosis was combined neurologic/psychiatric and hepatic (52.9%), followed by neurologic/psychiatric (20.0%), hepatic (16.9%), and asymptomatic (10.2%). Common clinical characteristics at diagnosis were Kayser-Fleischer rings (77.2%), low ceruloplasmin levels (95.2%), high hepatic copper (97.8%), elevated 24-hour urinary copper excretion (90.2%), and abnormal liver function tests (38.7%–85.1%). At diagnosis, the most common biochemical findings or hepatic sign/symptoms were abnormal liver enzymes (50.7%), abdominal pain (16.6%), and fatigue (15.7%). The most common neurologic signs/symptoms were headache (18.3%), dysarthria (17.4%), and ataxia (17.0%). Common psychiatric signs/symptoms included anxiety/depression/other mood changes (36.2%), emotional lability (12.8%), and increased irritability/anger outbursts (9.2%). Prevalence of biochemical abnormalities or signs/symptoms among patients at diagnosis and after ~1-year follow-up were neurologic (60.1% and 44.0%), hepatic (69.6% and 37.8%), and psychiatric (53.7% and 37.6%), respectively. Common new onset symptoms at ~1-year post-WD diagnosis were abnormal liver enzymes (5.6%), headache (6.2%), and anxiety/depression/other mood changes (7.2%).ConclusionsThese real-world, descriptive data highlight the clinical complexity and heterogeneity of WD and the need for better education about diagnostic testing and multidisciplinary support. Although rare, the neurologic, psychiatric, and hepatic signs/symptoms of WD have a substantial clinical impact

Centrin 2: a novel marker of mature and neoplastic human astrocytes

As microtubule organizing centers, centrosomes play a pivotal role in cell division as well as in neurodevelopment and neuronal maturation. Among centrosomal proteins, centrin-2 (CETN2) contributes also to DNA repair mechanisms which are fundamental to prevent genomic instability during neural stem cell pool expansion. Nevertheless, the expression profile of CETN2 in human neural stem cells and their progeny is currently unknown. To address this question, we interrogated a platform of human neuroepithelial stem (NES) cells derived from post-mortem developing brain or established from pluripotent cells, and demonstrated that while CETN2 retains its centrosomal location in proliferating NES cells, its expression pattern changes upon differentiation. In particular, we found that CETN2 is selectively expressed in mature astrocytes with a broad cytoplasmic distribution. We then extended our findings on human autoptic nervous tissue samples. We investigated CETN2 distribution in diverse anatomical areas along the rostro-caudal neuraxis and pointed out a peculiar topography of CETN2-labelled astrocytes in humans which was not appreciable in murine tissues, where CETN2 was mostly confined to ependymal cells. As prototypical condition with glial overproliferation, we also explored CETN2 expression in glioblastoma multiforme, reporting a focal concentration of CETN2 in neoplastic astrocytes. This study expands CETN2 localization beyond centrosomes and reveals a unique expression pattern which makes it eligible as a novel astrocytic molecular marker, thus opening new roads to glial biology and human neural conditions

The expression pattern of GDF15 in human brain changes during aging and in Alzheimer's disease

Introduction: Growth Differentiation Factor 15 (GDF15) is a mitochondrial-stress-responsive molecule whose expression strongly increases with aging and age-related diseases. However, its role in neurodegenerative diseases, including Alzheimer's disease (AD), is still debated. Methods: We have characterized the expression of GDF15 in brain samples from AD patients and non-demented subjects (controls) of different ages. Results: Although no difference in CSF levels of GDF15 was found between AD patients and controls, GDF15 was expressed in different brain areas and seems to be predominantly localized in neurons. The ratio between its mature and precursor form was higher in the frontal cortex of AD patients compared to age-matched controls (p &lt; 0.05). Moreover, this ratio was even higher for centenarians (p &lt; 0.01), indicating that aging also affects GDF15 expression and maturation. A lower expression of OXPHOS complexes I, III, and V in AD patients compared to controls was also noticed, and a positive correlation between GDF15 and IL-6 mRNA levels was observed. Finally, when GDF15 was silenced in vitro in dermal fibroblasts, a decrease in OXPHOS complexes transcript levels and an increase in IL-6 levels were observed. Discussion: Although GDF15 seems not to be a reliable CSF marker for AD, it is highly expressed in aging and AD brains, likely as a part of stress response aimed at counteracting mitochondrial dysfunction and neuroinflammation