112 results on '"Rosanna Villani"'
Search Results
2. Prevalence and clinical relevance of liver dysfunction after thoracic surgery: a retrospective study
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Rosanna Villani, Domenico Loizzi, Antonia Federica Sacco, Lucia Mirabella, Mariateresa Santoliquido, Diletta Mongiello, Francesco Sollitto, and Gaetano Serviddio
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Medicine ,Science - Abstract
Abstract Postoperative elevation of serum aminotransferase or alkaline phosphatase levels after liver and heart surgeries has been widely reported. The prevalence and clinical significance of hypertransaminasemia/liver dysfunction after thoracic surgery remains largely unknown. Significant differences in surgical procedures between thoracic and extra-thoracic surgeries may suggest different risks of liver dysfunction. We retrospectively analyzed data from 224 consecutive patients who underwent thoracic surgery. Liver function tests were recorded the day before surgery, 12 h, 1 day, 5, and 10 days after the surgical procedure. Patients were studied to identify the frequency of hypertransaminasemia and/or hyperbilirubinemia and/or increase of INR levels. 37,5% of patients showed an increase in serum alanine aminotransferase (ALT) level after thoracic surgery, whereas an increase in gamma glutamyl transferase (GGT) serum levels of any grade was observed in 53,6% of patients. Approximately 83% of patients who experienced an increase in the serum GGT or ALT levels showed a grade 1 or 2 change. Operative time was associated with hypertransaminasemia in the univariate and multivariate analyses, whereas the use of metformin was associated with a lower risk of ALT increase.
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- 2023
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3. Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer’s Disease
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Hina Kanwal, Moris Sangineto, Martina Ciarnelli, Pasqualina Castaldo, Rosanna Villani, Antonino Davide Romano, Gaetano Serviddio, and Tommaso Cassano
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neurodegenerative diseases ,Alzheimer’s disease ,endocannabinoid system ,fatty acid amide hydrolase (FAAH) ,monoacylglycerol (MAGL) ,cannabinoid receptors (CB1R ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Alzheimer’s disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD.
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- 2024
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4. Metabolic reprogramming in inflammatory microglia indicates a potential way of targeting inflammation in Alzheimer's disease
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Moris Sangineto, Martina Ciarnelli, Tommaso Cassano, Antonio Radesco, Archana Moola, Vidyasagar Naik Bukke, Antonino Romano, Rosanna Villani, Hina Kanwal, Nazzareno Capitanio, Loren Duda, Carlo Avolio, and Gaetano Serviddio
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Immunometabolism ,Alzheimer's disease ,Microglia ,Dimethyl malonate ,Macrophage ,Bioenergetics ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Microglia activation drives the pro-inflammatory activity in the early stages of Alzheimer's disease (AD). However, the mechanistic basis is elusive, and the hypothesis of targeting microglia to prevent AD onset is little explored. Here, we demonstrated that upon LPS exposure, microglia shift towards an energetic phenotype characterised by high glycolysis and high mitochondrial respiration with dysfunction. Although the activity of electron transport chain (ETC) complexes is boosted by LPS, this is mostly devoted to the generation of reactive oxygen species. We showed that by inhibiting succinate dehydrogenase (SDH) with dimethyl malonate (DMM), it is possible to modulate the LPS-induced metabolic rewiring, facilitating an anti-inflammatory phenotype. DMM improves mitochondrial function in a direct way and by reducing LPS-induced mitochondrial biogenesis. Moreover, the block of SDH with DMM inhibits the recruitment of hypoxia inducible-factor 1 α (HIF-1α), which mediates the induction of glycolysis and cytokine expression. Similar bioenergetic alterations were observed in the microglia isolated from AD mice (3xTg-AD), which present high levels of circulating LPS and brain toll-like receptor4 (TLR4). Moreover, this well-established model of AD was used to show a potential effect of SDH inhibition in vivo as DMM administration abrogated brain inflammation and modulated the microglia metabolic alterations of 3xTg-AD mice. The RNA-sequencing analysis from a public dataset confirmed the consistent transcription of genes encoding for ETC subunits in the microglia of AD mice (5xFAD). In conclusion, TLR4 activation promotes metabolic changes and the pro-inflammatory activity in microglia, and SDH might represent a promising therapeutic target to prevent AD development.
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- 2023
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5. Pseudocirrhosis and portal hypertension in patients with metastatic cancers: a systematic review and meta-analysis
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Rosanna Villani, Francesca Di Cosimo, Moris Sangineto, Antonino Davide Romano, and Gaetano Serviddio
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Medicine ,Science - Abstract
Abstract Pseudocirrhosis is a clinical and radiological entity mimicking liver cirrhosis in patients without a history of chronic liver disease. We performed a systematic review and meta-analysis of the current literature to evaluate the state-of-the-art and investigate the epidemiology and clinical features of pseudocirrhosis. We searched PubMed, Web of Science and Scopus for literature published until February 28, 2022. We included in the final analysis 62 articles (N = 389 patients): 51 case reports (N = 64 patients), 5 case series (N = 35 patients) and 6 observational studies (N = 290 patients). About 80% of patients included in the case reports and case series had breast cancer. Most patients had at least one clinical sign of portal hypertension and ascites was the most common clinical manifestation of portal hypertension. The median time from pseudocirrhosis to death was 2 months (IQR 1–7 months). Alkylating agents and antimitotics were the most common classes of anticancer drugs reported in our study population. Notably, about 70% of patients received three or more anticancer drugs. Finally, pseudocirrhosis is a condition that occurs in patients with hepatic metastases and may have a negative impact on survival and clinical management of patients because of the potential development of portal hypertension and its complications.
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- 2022
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6. High prevalence of false positive SARS-CoV2 serology in a cohort of patients with liver autoimmune diseases
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Maria Giulia Cornacchia, Moris Sangineto, Rosanna Villani, Francesco Cavallone, Giuseppe Di Gioia, Paola Cicciomessere, and Gaetano Serviddio
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chronic liver disease ,liver autoimmune disease ,sars-cov2 ,covid-19 ,serology ,autoantibodies ,Other systems of medicine ,RZ201-999 - Abstract
Aim: Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases. Methods: From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up. Results: The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Notably, among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. Moreover, the presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as its prevalence is not different between negative and false positive cases. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP). Conclusions: Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category.
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- 2021
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7. Serum lipid profile in HCV patients treated with direct-acting antivirals: a systematic review and meta-analysis
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Rosanna Villani, Francesca Di Cosimo, Antonino Davide Romano, Moris Sangineto, and Gaetano Serviddio
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Medicine ,Science - Abstract
Abstract Although direct-acting antivirals are very effective and safe drugs, several authors have reported the alteration of lipid profile during and after anti-HCV therapy suggesting a potential impact on the risk of cardiovascular events. We performed a systematic review and meta-analysis of observational studies to investigate the magnitude and temporal trend of lipid profile changes in DAA treated patients. All selected studies included data on lipid profile before starting therapy and at least one follow-up assessment during or after antiviral treatment. We identified 14 studies (N = 1537 patients) after removing duplicates. Pooled data showed an increase in total cholesterol 4 weeks after starting therapy (+ 15.86 mg/dl; 95% CI + 9.68 to 22.05; p
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- 2021
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8. Inhibition of nuclear factor (erythroid-derived 2)-like 2 promotes hepatic progenitor cell activation and differentiation
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Francesco Bellanti, Giorgia di Bello, Giuseppina Iannelli, Giuseppe Pannone, Maria Carmela Pedicillo, Luke Boulter, Wei-Yu Lu, Rosanna Tamborra, Rosanna Villani, Gianluigi Vendemiale, Stuart J. Forbes, and Gaetano Serviddio
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Medicine - Abstract
Abstract The stem cell ability to self-renew and lead regeneration relies on the balance of complex signals in their microenvironment. The identification of modulators of hepatic progenitor cell (HPC) activation is determinant for liver regeneration and may improve cell transplantation for end-stage liver disease. This investigation used different models to point out the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) as a key regulator of the HPC fate. We initially proved that in vivo models of biliary epithelial cells (BECs)/HPC activation show hepatic oxidative stress, which activates primary BECs/HPCs in vitro. NRF2 downregulation and silencing were associated with morphological, phenotypic, and functional modifications distinctive of differentiated cells. Furthermore, NRF2 activation in the biliary tract repressed the ductular reaction in injured liver. To definitely assess the importance of NRF2 in HPC biology, we applied a xenograft model by inhibiting NRF2 in the human derived HepaRG cell line and transplanting into SCID/beige mice administered with anti-Fas antibody to induce hepatocellular apoptosis; this resulted in effective human hepatocyte repopulation with reduced liver injury. To conclude, NRF2 inhibition leads to the activation and differentiation of liver progenitors. This redox-dependent transcription factor represents a potential target to regulate the commitment of undifferentiated hepatic progenitors into specific lineages.
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- 2021
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9. Effects of Ultramicronized Palmitoylethanolamide on Mitochondrial Bioenergetics, Cerebral Metabolism, and Glutamatergic Transmission: An Integrated Approach in a Triple Transgenic Mouse Model of Alzheimer's Disease
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Francesco Bellanti, Vidyasagar Naik Bukke, Archana Moola, Rosanna Villani, Caterina Scuderi, Luca Steardo, Gianmauro Palombelli, Rossella Canese, Sarah Beggiato, Mario Altamura, Gianluigi Vendemiale, Gaetano Serviddio, and Tommaso Cassano
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glutamate ,mitochondria ,hippocampus ,frontal cortex ,microdialysis ,Alzheimer's disease ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The therapeutic potential of ultramicronized palmitoylethanolamide (um-PEA) was investigated in young (6-month-old) and adult (12-month-old) 3 × Tg-AD mice, which received um-PEA for 3 months via a subcutaneous delivery system. Mitochondrial bioenergetics, ATP homeostasis, and magnetic resonance imaging/magnetic resonance spectroscopy were evaluated in the frontal cortex (FC) and hippocampus (HIPP) at the end of um-PEA treatment. Glutamate release was investigated by in vivo microdialysis in the ventral HIPP (vHIPP). We demonstrated that chronic um-PEA treatment ameliorates the decrease in the complex-I respiration rate and the FoF1-ATPase (complex V) activity, as well as ATP content depletion in the cortical mitochondria. Otherwise, the impairment in mitochondrial bioenergetics and the release of glutamate after depolarization was not ameliorated by um-PEA treatment in the HIPP of both young and adult 3 × Tg-AD mice. Moreover, progressive age- and pathology-related changes were observed in the cortical and hippocampal metabolism that closely mimic the alterations observed in the human AD brain; these metabolic alterations were not affected by chronic um-PEA treatment. These findings confirm that the HIPP is the most affected area by AD-like pathology and demonstrate that um-PEA counteracts mitochondrial dysfunctions and helps rescue brain energy metabolism in the FC, but not in the HIPP.
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- 2022
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10. Temporal profile of SARS-CoV-2 viral load in posterior nasopharyngeal samples: Analysis of 944 patients in Apulia, Italy
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Moris Sangineto, Fabio Arena, Rosella De Nittis, Rosanna Villani, Crescenzio Gallo, and Gaetano Serviddio
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COVID-19 ,Coronavirus ,Pandemic ,SARS-CoV-2 ,Viral load ,RT-PCR ,Infectious and parasitic diseases ,RC109-216 - Abstract
Objectives: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has heavily impacted Italy. The government's restriction measures have attenuated the burden on hospitals. The association of high viral replication with disease severity suggests the potential for lower viral load in milder clinical presentations. Methods: The reverse-transcription-polymerase-chain-reaction (RT-PCR) profile of 944 consecutive, non-replicate, positive retropharyngeal swabs was collected from 3 March to 8 June 2020 to investigate the temporal profile of SARS-CoV-2 viral load in the region of Capitanata, Apulia. Cycle threshold (Ct) values of 3 targets (N [nucleocapsid protein], E [envelope protein] and RdRP [RNA-dependent RNA-polymerase]) were analysed. Results: The median Ct values of the 3 targets increased considerably over the study period, showing a progressive and constant weekly change. The negative detection rate of E and RdRP increased over time. These data suggest that SARS-CoV-2 viral load progressively decreased along the outbreak course. During the first epidemic peak (March and April) the viral load among patients >80-years was significantly higher than for younger subjects. However, in May this age-dependent difference disappeared, underlying viral load reduction in the elderly. Conclusions: An attenuation of viral transmission or pathogenicity during the epidemic course is suggested, likely due to restriction measures, although viral factors might also be considered.
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- 2021
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11. Liver Ultrasound Elastography in Non-Alcoholic Fatty Liver Disease: A State-of-the-Art Summary
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Rosanna Villani, Pierluigi Lupo, Moris Sangineto, Antonino Davide Romano, and Gaetano Serviddio
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liver ,ultrasound ,elastography ,NAFLD ,steatosis ,steatohepatitis ,Medicine (General) ,R5-920 - Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic disease which is currently the most common hepatic disorder affecting up to 38% of the general population with differences according to age, country, ethnicity and sex. Both genetic and acquired risk factors such as a high-calorie diet or high intake of saturated fats have been associated with obesity, diabetes and, finally, NAFLD. A liver biopsy has always been considered essential for the diagnosis of NAFLD; however, due to several limitations such as the potential occurrence of major complications, sampling variability and the poor repeatability in clinical practice, it is considered an imperfect option for the evaluation of liver fibrosis over time. For these reasons, a non-invasive assessment by serum biomarkers and the quantification of liver stiffness is becoming the new frontier in the management of patients with NAFLD and liver fibrosis. We present a state-of-the-art summary addressing the methods for the non-invasive evaluation of liver fibrosis in NAFLD patients, particularly the ultrasound-based techniques (transient elastography, ARFI techniques and strain elastography) and their optimal cut-off values for the staging of liver fibrosis.
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- 2023
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12. A Review on Biological Effects of Ultrasounds: Key Messages for Clinicians
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Carla Maria Irene Quarato, Donato Lacedonia, Michela Salvemini, Giulia Tuccari, Grazia Mastrodonato, Rosanna Villani, Lucia Angela Fiore, Giulia Scioscia, Antonio Mirijello, Annarita Saponara, and Marco Sperandeo
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ultrasound ,diagnostic imaging ,heating ,cavitation ,radiation force ,biological effects ,Medicine (General) ,R5-920 - Abstract
Ultrasound (US) is acoustic energy that interacts with human tissues, thus, producing bioeffects that may be hazardous, especially in sensitive organs (i.e., brain, eye, heart, lung, and digestive tract) and embryos/fetuses. Two basic mechanisms of US interaction with biological systems have been identified: thermal and non-thermal. As a result, thermal and mechanical indexes have been developed to provide a means of assessing the potential for biological effects from exposure to diagnostic US. The main aims of this paper were to describe the models and assumptions used to estimate the “safety” of acoustic outputs and indices and to summarize the current state of knowledge about US-induced effects on living systems deriving from in vitro models and in vivo experiments on animals. This review work has made it possible to highlight the limits associated with the use of the estimated safety values of thermal and mechanical indices relating above all to the use of new US technologies, such as contrast-enhanced ultrasound (CEUS) and acoustic radiation force impulse (ARFI) shear wave elastography (SWE). US for diagnostic and research purposes has been officially declared safe, and no harmful biological effects in humans have yet been demonstrated with new imaging modalities; however, physicians should be adequately informed on the potential risks of biological effects. US exposure, according to the ALARA (As Low As Reasonably Achievable) principle, should be as low as reasonably possible.
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- 2023
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13. Contrast-Enhanced Ultrasound in Distinguishing between Malignant and Benign Peripheral Pulmonary Consolidations: The Debated Utility of the Contrast Enhancement Arrival Time
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Carla Maria Irene Quarato, Beatrice Feragalli, Donato Lacedonia, Gaetano Rea, Giulia Scioscia, Evaristo Maiello, Concetta Di Micco, Cristina Borelli, Antonio Mirijello, Paolo Graziano, Lucia Dimitri, Rosanna Villani, and Marco Sperandeo
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contrast enhanced ultrasound ,arrival time ,lung ultrasound ,peripheral pulmonary lesions ,diagnostic accuracy ,Medicine (General) ,R5-920 - Abstract
Background. Limited studies and observations conducted on a too small number of patients prevent determining the actual clinical utility of pulmonary contrast-enhanced ultrasound (CEUS). The aim of the present study was to examine the efficacy of contrast enhancement (CE) arrival time (AT) and other dynamic CEUS findings for differentiating between malignant and benign peripheral lung lesions. Methods. 317 inpatients and outpatients (215 men, 102 women; mean age: 52 years) with peripheral pulmonary lesions were included in the study and underwent pulmonary CEUS. Patients were examined in a sitting position after receiving an intravenous injection of 4.8 mL of sulfur hexafluoride microbubbles stabilized by a phospholipid shell as ultrasound contrast agent (SonoVue—Bracco; Milan, Italy). Each lesion was observed for at least 5 min in real-time and the following temporal characteristics of enhancement were detected: the arrival time (AT) of microbubbles in the target lesion; the enhancement pattern; the wash-out time (WOT) of microbubbles. Results were then compared in light of the definitive diagnosis of community acquired pneumonia (CAP) or malignancies, which was not known at the time of CEUS examination. All malignant cases were diagnosed by histological results, while pneumonia was diagnosed on the basis of clinical and radiological follow-up, laboratory findings and, in some cases, histology. Results. CE AT has not been shown to differ between benign and malignant peripheral pulmonary lesions. The overall diagnostic accuracy and sensibility of a CE AT cut-off value < 10 s in discriminating benign lesions were low (diagnostic accuracy: 47.6%; sensibility: 5.3%). Poor results were also obtained in the sub-analysis of small (mean diameter < 3 cm) and large (mean diameter > 3 cm) lesions. No differences were recorded in the type of CE pattern showed between benign and malignant peripheral pulmonary lesions. In benign lesions we observed a higher frequency of delayed CE wash-out time (WOT) > 300 s. Anyhow, a CE WOT cut-off value > 300 s showed low diagnostic accuracy (53.6%) and sensibility (16.5%) in discriminating between pneumonias and malignancies. Similar results were also obtained in the sub-analysis by lesion size. Squamous cell carcinomas showed a more delayed CE AT compared to other histopathology subtypes. However, such a difference was statistically significant with undifferentiated lung carcinomas. Conclusions. Due to an overlap of CEUS timings and patterns, dynamic CEUS parameters cannot effectively differentiate between benign and malignant peripheral pulmonary lesions. Chest CT remains the gold standard for lesion characterization and the eventual identification of other pneumonic non-subpleural localizations. Furthermore, in the case of malignancy, a chest CT is always needed for staging purposes.
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- 2023
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14. Temporary Botulinum Immobilization of Residuum Muscles for Facilitation of the Initial Ingrowth of Skin to the Porous Skin and Bone Integrated Pylon in the Technology of Direct Skeletal Attachment: Large Animal Model
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Zachary Bohart, Charles Cassidy, David Merrill, Mario Villani, Rosanna Villani, Leo Cappabianca, and Mark Pitkin
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direct skeletal attachment ,porcine model ,skin immobilization ,botulinum injections ,osseointegration ,body-implant interface ,Other systems of medicine ,RZ201-999 ,Medical technology ,R855-855.5 - Abstract
Enhancing the technology of bone-anchored limb prosthetics, we present a modified porcine model for developing an infection-free integration between the skin and a percutaneous bone implant. The deeply porous Skin and Bone Integrated Pylon (SBIP) presented an infection-free skin-implant interface both after implantation into the dorsum and after implantation into the residuum after below-knee amputation. However, deep ingrowth of skin into the porous cladding of the SBIP was achieved better in the dorsal procedure, while implantation to the residuum sometimes developed a stoma, probably due to the high mobility of the skin and soft tissues in the pig's thigh. Uncontrolled high skin mobility during the first week after implantation constituted a limitation for the porcine animal model, which we tried to address in the current study. As our previous studies showed that casting of the leg residuum did not sufficiently limit the skin's movement around the implant, we tested a modified protocol of the implantation, which included injection of botulinum toxin into the thigh muscles. During the course of the study, we identified proper botulinum toxin componentry, dosage, and the period after injections to achieve a maximal effect of immobilization of the muscles affecting skin movements. To verify the immobilization, we used kinetic data on the asymmetry of loading during gait with the Strideway System, Tekscan, Inc., Boston, MA, USA. We found that injections in the four muscles of the distal thigh of the left hind leg with MYOBLOC® (rimabotulinumtoxinB; 5,000 units/muscle) were sufficient to provide noticeable immobilization by the fourth week after the procedure. This conclusion was made based on the analysis of the dynamics of asymmetry in vertical ground reactions on the injected (left hind) and uninvolved (right hind) legs during gait over an instrumented walkway.
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- 2022
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15. Genetic Polymorphisms and Clinical Features in Diabetic Patients With Fatty Liver: Results From a Single-Center Experience in Southern Italy
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Rosanna Villani, Grazia Pia Magnati, Giuseppe De Girolamo, Moris Sangineto, Antonino Davide Romano, Tommaso Cassano, and Gaetano Serviddio
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diabetes ,NAFLD ,SNPs ,fatty liver ,polymorphisms ,Medicine (General) ,R5-920 - Abstract
Genetic background may be involved in the promotion and progression of non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that the single nucleotide polymorphisms (SNPs) may be associated with the specific clinical features in the patients with hepatic steatosis; however, data on the patients with diabetes from Southern Italy are lacking. We enrolled 454 patients and 260 of them had type 2 diabetes. We studied the PNPLA3 rs738409, LPIN1 rs13412852, KLF6 rs3750861, SOD2 rs4880, TM6SF2 rs58542926, and ZNF624 rs12603226 SNPs and their distribution in the study population. Lipid profile, liver stiffness, and kidney function were also studied to understand the potential role of the SNPs in the development of clinical phenotypes. No differences were observed in the distribution of polymorphisms between the diabetic and non-diabetic subjects. Carriers of risk allele G for PNPLA3 rs738409 SNP showed a lower mean value of serum triglycerides and a higher liver stiffness. Risk allele for KLF6 rs3750861 and SOD2 rs4880 polymorphism had a lower estimated glomerular filtration rate (eGFR) value, whereas no differences in the glucose and glycated hemoglobin level were observed in the subgroups by the different genotypes. Genetic polymorphisms are useful to identify the patients at higher risk of development of liver fibrosis and lower eGFR values in the patients with diabetes and NAFLD. Their use in clinical practice may help the clinicians to identify the patients who require a more strict follow-up program.
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- 2021
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16. Assessing the impact of COVID-19 on liver cancer management (CERO-19)
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Sergio Muñoz-Martínez, Victor Sapena, Alejandro Forner, Jean-Charles Nault, Gonzalo Sapisochin, Lorenza Rimassa, Bruno Sangro, Jordi Bruix, Marco Sanduzzi-Zamparelli, Wacław Hołówko, Mohamed El Kassas, Tudor Mocan, Mohamed Bouattour, Philippe Merle, Frederik J.H. Hoogwater, Saleh A. Alqahtani, Helen L. Reeves, David J. Pinato, Emmanouil Giorgakis, Tim Meyer, Gerda Elisabeth Villadsen, Henning Wege, Massimiliano Salati, Beatriz Mínguez, Giovan Giuseppe Di Costanzo, Christoph Roderburg, Frank Tacke, María Varela, Peter R. Galle, Mario Reis Alvares-da-Silva, Jörg Trojan, John Bridgewater, Giuseppe Cabibbo, Christian Toso, Anja Lachenmayer, Andrea Casadei-Gardini, Hidenori Toyoda, Tom Lüdde, Rosanna Villani, Ana María Matilla Peña, Cassia Regina Guedes Leal, Monica Ronzoni, Manuel Delgado, Christie Perelló, Sonia Pascual, José Luis Lledó, Josepmaria Argemi, Bristi Basu, Leonardo da Fonseca, Juan Acevedo, Alexander R. Siebenhüner, Chiara Braconi, Brandon M. Meyers, Alessandro Granito, Margarita Sala, Carlos Rodríguez-Lope, Lorraine Blaise, Manuel Romero-Gómez, Federico Piñero, Dhanny Gomez, Vivianne Mello, Rogerio Camargo Pinheiro Alves, Alex França, Fernanda Branco, Giovanni Brandi, Gustavo Pereira, Susanna Coll, Maria Guarino, Carlos Benítez, Maria Margarita Anders, Juan C. Bandi, Mercedes Vergara, Mariona Calvo, Markus Peck-Radosavljevic, Ignacio García-Juárez, Vincenzo Cardinale, Mar Lozano, Martina Gambato, Stefano Okolicsanyi, Dalia Morales-Arraez, Alessandra Elvevi, Alberto E. Muñoz, Alberto Lué, Massimo Iavarone, and Maria Reig
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COVID-19 ,Hepatocellular carcinoma ,Cholangiocarcinoma ,Liver cancer ,Management ,Clinical trials ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. Methods: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. Results: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). Conclusions: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. Lay summary: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.
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- 2021
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17. Risk of Statin-Induced Hypertransaminasemia
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Rosanna Villani, MD, PhD, Eliano Pio Navarese, MD, PhD, Francesco Cavallone, MD, Jacek Kubica, MD, PhD, Francesco Bellanti, MD, PhD, Antonio Facciorusso, MD, Gianluigi Vendemiale, MD, and Gaetano Serviddio, MD
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Medicine (General) ,R5-920 - Abstract
Objective: To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia. Patients and Methods: We performed a systematic review of electronic databases and included articles published between January 1, 1965, and April 10, 2017. Randomized clinical trials (RCTs) comparing statins vs placebo were included. Odds ratios (ORs) were pooled in random-effect meta-analyses according to established methods recommended by the Cochrane Collaboration. Results: Seventy-three eligible RCTs, comprising 123,051 patients, were identified. Statins associated with a significantly risk of hypertransaminasemia (OR 1.45; 95% confidence interval [CI], 1.24-1.69; P
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- 2019
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18. Tocilizumab and liver injury in patients with COVID-19
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Gaetano Serviddio, Rosanna Villani, Giovanni Stallone, Giulia Scioscia, Maria Pia Foschino-Barbaro, and Donato Lacedonia
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Current mortality rate in patients with COVID-19 disease is about 2%, whereas 5% of patients require admission to the intensive care unit. It is assumed that interleukin (IL)-6 may be involved in the pathogenesis of severe COVID-19 infections; therefore, in the absence of a specific antiviral therapy, some authors have suggested that tocilizumab – a drug used to block the signal transduction pathway of IL-6 – could have beneficial effects in the management of severe COVID-19 disease. However, mild-to-moderate elevation in transaminases and drug-induced liver injury have been observed in patients treated with tocilizumab. We present seven cases of patients with elevated liver enzymes [up to five times the upper limit of normal (ULN)] at baseline who received tocilizumab for life-threatening COVID-19 disease. All patients had no history of liver or pulmonary disease and were admitted for acute hypoxemic respiratory failure, dyspnea and fever due to COVID-19 bilateral pneumonia. IL-6 was available in six patients, and was significantly increased particularly in those with severe impairment of lung function. All patients received tocilizumab (8 mg/kg/day) for two consecutive days because of lack of improvement after hydroxychloroquine, azithromycin and lopinavir/ritonavir treatment. After tocilizumab administration, clinical condition rapidly improved and liver function test normalized within 3 weeks of treatment. Tocilizumab may be effective for the treatment of severe COVID-19 disease, even in patients with elevated liver function tests. Further studies are needed to evaluate the impact of tocilizumab use on liver function tests in patients with pre-existing chronic liver disease.
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- 2020
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19. From Cannabis sativa to Cannabidiol: Promising Therapeutic Candidate for the Treatment of Neurodegenerative Diseases
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Tommaso Cassano, Rosanna Villani, Lorenzo Pace, Antonio Carbone, Vidyasagar Naik Bukke, Stanislaw Orkisz, Carlo Avolio, and Gaetano Serviddio
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Cannabis sativa ,oxidative stress ,phytocannabinoids ,cannabidiol ,Alzheimer's disease ,Parkinson's disease ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Cannabis sativa, commonly known as marijuana, contains a pool of secondary plant metabolites with therapeutic effects. Besides Δ9-tetrahydrocannabinol that is the principal psychoactive constituent of Cannabis, cannabidiol (CBD) is the most abundant nonpsychoactive phytocannabinoid and may represent a prototype for anti-inflammatory drug development for human pathologies where both the inflammation and oxidative stress (OS) play an important role to their etiology and progression. To this regard, Alzheimer's disease (AD), Parkinson's disease (PD), the most common neurodegenerative disorders, are characterized by extensive oxidative damage to different biological substrates that can cause cell death by different pathways. Most cases of neurodegenerative diseases have a complex etiology with a variety of factors contributing to the progression of the neurodegenerative processes; therefore, promising treatment strategies should simultaneously target multiple substrates in order to stop and/or slow down the neurodegeneration. In this context, CBD, which interacts with the eCB system, but has also cannabinoid receptor-independent mechanism, might be a good candidate as a prototype for anti-oxidant drug development for the major neurodegenerative disorders, such as PD and AD. This review summarizes the multiple molecular pathways that underlie the positive effects of CBD, which may have a considerable impact on the progression of the major neurodegenerative disorders.
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- 2020
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20. Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression
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Francesco Bellanti, Rosanna Villani, Rosanna Tamborra, Maria Blonda, Giuseppina Iannelli, Giorgia di Bello, Antonio Facciorusso, Giuseppe Poli, Luigi Iuliano, Carlo Avolio, Gianluigi Vendemiale, and Gaetano Serviddio
- Subjects
Oxysterols ,Non-alcoholic fatty liver disease ,Mitochondria ,Cholesterol excess ,Fatty acids ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury.
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- 2018
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21. Pharmacological and Toxicological Effects of Phytocannabinoids and Recreational Synthetic Cannabinoids: Increasing Risk of Public Health
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Vidyasagar Naik Bukke, Moola Archana, Rosanna Villani, Gaetano Serviddio, and Tommaso Cassano
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synthetic cannabinoids ,phytocannabinoids ,Cannabis sativa ,schedule 1 drugs ,spice ,K2 ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Synthetic Cannabinoids (CBs) are a novel class of psychoactive substances that have rapidly evolved around the world with the addition of diverse structural modifications to existing molecules which produce new structural analogues that can be associated with serious adverse health effects. Synthetic CBs represent the largest class of drugs detected by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) with a total of 207 substances identified from 2008 to October 2020, and 9 compounds being reported for the first time. Synthetic CBs are sprayed on natural harmless herbs with an aim to mimic the euphoric effect of Cannabis. They are sold under different brand names including Black mamba, spice, K2, Bombay Blue, etc. As these synthetic CBs act as full agonists at the CB receptors, they are much more potent than natural Cannabis and have been increasingly associated with acute to chronic intoxications and death. Due to their potential toxicity and abuse, the US government has listed some synthetic CBs under schedule 1 classification. The present review aims to provide a focused overview of the literature concerning the development of synthetic CBs, their abuse, and potential toxicological effects including renal toxicity, respiratory depression, hyperemesis syndrome, cardiovascular effects, and a range of effects on brain function.
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- 2021
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22. Pharmacological Treatment of Depression in Alzheimer’s Disease: A Challenging Task
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Tommaso Cassano, Silvio Calcagnini, Antonio Carbone, Vidyasagar Naik Bukke, Stanislaw Orkisz, Rosanna Villani, Adele Romano, Carlo Avolio, and Silvana Gaetani
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Alzheimer’s disease ,depression ,amyloid-β peptide ,tricyclic antidepressants ,selective serotonin reuptake inhibitors ,serotonin ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Besides the memory impairment, Alzheimer’s disease (AD) is often complicated by neuropsychiatric symptoms also known as behavioral and psychological symptoms of dementia, which occur in one-third of patients at an early stage of the disease. Although the relationship between depressive disorders and AD is debated, the question if depression is a prodromal symptom preceding cognitive deficits or an independent risk factor for AD is still unclear. Moreover, there is growing evidence reporting that conventional antidepressants are not effective in depression associated with AD and, therefore, there is an urgent need to understand the neurobiological mechanism underlying the resistance to the antidepressants. Another important question that remains to be addressed is whether the antidepressant treatment is able to modulate the levels of amyloid-β peptide (Aβ), which is a key pathological hallmark in AD. The present review summarizes the present knowledge on the link between depression and AD with a focus on the resistance of antidepressant therapies in AD patients. Finally, we have briefly outlined the preclinical and clinical evidences behind the possible mechanisms by which antidepressants modulate Aβ pathology. To our opinion, understanding the cellular processes that regulate Aβ levels may provide greater insight into the disease pathogenesis and might be helpful in designing novel selective and effective therapy against depression in AD.
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- 2019
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23. A Novel Nutraceuticals Mixture Improves Liver Steatosis by Preventing Oxidative Stress and Mitochondrial Dysfunction in a NAFLD Model
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Moris Sangineto, Vidyasagar Naik Bukke, Francesco Bellanti, Rosanna Tamborra, Archana Moola, Loren Duda, Rosanna Villani, Antonino Davide Romano, and Gaetano Serviddio
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non-alcoholic fatty liver disease ,nutraceutical ,mitochondria ,micronutrients ,steatosis ,oxidative stress ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease globally, and represents a health care burden as treatment options are very scarce. The reason behind the NAFLD progression to non-alcoholic steatohepatitis (NASH) is not completely understood. Recently, the deficiency of micronutrients (e.g., vitamins, minerals, and other elements) has been suggested as crucial in NAFLD progression, such that recent studies reported the potential hepatic antioxidant properties of micronutrients supplementation. However, very little is known. Here we have explored the potential beneficial effects of dietary supplementation with FLINAX, a novel mixture of nutraceuticals (i.e., vitamin E, vitamin D3, olive dry-extract, cinnamon dry-extract and fish oil) in a NAFLD model characterized by oxidative stress and mitochondrial function impairment. Steatosis was firstly induced in Wistar rats by feeding with a high-fat/high-cholesterol diet for 4 weeks, and following this the rats were divided into two groups. One group (n = 8) was treated for 2 weeks with a normal chow-diet, while a second group (n = 8) was fed with a chow-diet supplemented with 2% FLINAX. Along with the entire experiment (6 weeks), a third group of rats was fed with a chow-diet only as control. Statistical analysis was performed with Student’s T test or one-way ANOVA followed by post-hoc Bonferroni test when appropriate. Steatosis, oxidative stress and mitochondrial respiratory chain (RC) complexes activity were analyzed in liver tissues. The dietary supplementation with FLINAX significantly improved hepatic steatosis and lipid accumulation compared to untreated rats. The mRNA and protein levels analysis showed that CPT1A and CPT2 were up-regulated by FLINAX, suggesting the enhancement of fatty acids oxidation (FAO). Important lipoperoxidation markers (i.e., HNE- and MDA-protein adducts) and the quantity of total mitochondrial oxidized proteins were significantly lower in FLINAX-treated rats. Intriguingly, FLINAX restored the mitochondrial function, stimulating the activity of mitochondrial RC complexes (i.e., I, II, III and ATP-synthase) and counteracting the peroxide production from pyruvate/malate (complex I) and succinate (complex II). Therefore, the supplementation with FLINAX reprogrammed the cellular energy homeostasis by restoring the efficiency of mitochondrial function, with a consequent improvement in steatosis.
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- 2021
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24. Immunity as Cornerstone of Non-Alcoholic Fatty Liver Disease: The Contribution of Oxidative Stress in the Disease Progression
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Marcello Dallio, Moris Sangineto, Mario Romeo, Rosanna Villani, Antonino Davide Romano, Carmelina Loguercio, Gaetano Serviddio, and Alessandro Federico
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non-alcoholic fatty liver disease ,trained immunity ,oxidative stress ,hepatocellular carcinoma ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and has become the major cause of chronic liver disease, especially in western countries. NAFLD encompasses a wide spectrum of hepatic histological alterations, from simple steatosis to steatohepatitis and cirrhosis with a potential development of hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is characterized by lobular inflammation and fibrosis. Several studies reported that insulin resistance, redox unbalance, inflammation, and lipid metabolism dysregulation are involved in NAFLD progression. However, the mechanisms beyond the evolution of simple steatosis to NASH are not clearly understood yet. Recent findings suggest that different oxidized products, such as lipids, cholesterol, aldehydes and other macromolecules could drive the inflammation onset. On the other hand, new evidence indicates innate and adaptive immunity activation as the driving force in establishing liver inflammation and fibrosis. In this review, we discuss how immunity, triggered by oxidative products and promoting in turn oxidative stress in a vicious cycle, fuels NAFLD progression. Furthermore, we explored the emerging importance of immune cell metabolism in determining inflammation, describing the potential application of trained immune discoveries in the NASH pathological context.
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- 2021
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25. Effects of dietary fatty acids and cholesterol excess on liver injury: A lipidomic approach
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Gaetano Serviddio, Francesco Bellanti, Rosanna Villani, Rosanna Tamborra, Chiara Zerbinati, Maria Blonda, Marco Ciacciarelli, Giuseppe Poli, Gianluigi Vendemiale, and Luigi Iuliano
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Oxysterols ,Non-alcoholic fatty liver disease ,Cholesterol excess ,Fatty acids ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Lipid accumulation is the hallmark of Non-alcoholic Fatty Liver Disease (NAFLD) and has been suggested to play a role in promoting fatty liver inflammation. Previous findings indicate that during oxidative stress conditions excess cholesterol autoxidizes to oxysterols. To date, the role of oxysterols and their potential interaction with fatty acids accumulation in NASH pathogenesis remains little investigated. We used the nutritional model of high fatty acids (HFA), high cholesterol (HCh) or high fat and high cholesterol (HFA+FCh) diets and explored by a lipidomic approach, the blood and liver distribution of fatty acids and oxysterols in response to dietary manipulation. We observed that HFA or HCh diets induced fatty liver without inflammation, which was otherwise observed only after supplementation of HFA+HCh. Very interestingly, the combination model was associated with a specific oxysterol fingerprint. The present work provides a complete analysis of the change in lipids and oxysterols profile induced by different lipid dietary model and their association with histological alteration of the liver. This study allows the generation of interesting hypotheses on the role of interaction of lipid and cholesterol metabolites in the liver injury during NAFLD development and progression. Moreover, the changes in the concentration and quality of oxysterols induced by a combination diet suggest a novel potential pathogenic mechanism in the progression from simple steatosis to steatohepatitis.
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- 2016
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26. The Glucose Metabolic Pathway as A Potential Target for Therapeutics: Crucial Role of Glycosylation in Alzheimer’s Disease
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Vidyasagar Naik Bukke, Rosanna Villani, Moola Archana, Agata Wawrzyniak, Krzysztof Balawender, Stanislaw Orkisz, Luca Ferraro, Gaetano Serviddio, and Tommaso Cassano
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Alzheimer’s disease ,neurodegeneration ,post-translational modifications ,glycans ,glycosylation ,phosphorylation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Glucose uptake in the brain decreases because of normal aging but this decline is accelerated in Alzheimer’s disease (AD) patients. In fact, positron emission tomography (PET) studies have shown that metabolic reductions in AD patients occur decades before the onset of symptoms, suggesting that metabolic deficits may be an upstream event in at least some late-onset cases. A decrease in availability of glucose content induces a considerable impairment/downregulation of glycosylation, which is an important post-translational modification. Glycosylation is an important and highly regulated mechanism of secondary protein processing within cells and it plays a crucial role in modulating stability of proteins, as carbohydrates are important in achieving the proper three-dimensional conformation of glycoproteins. Moreover, glycosylation acts as a metabolic sensor that links glucose metabolism to normal neuronal functioning. All the proteins involved in β-amyloid (Aβ) precursor protein metabolism have been identified as candidates of glycosylation highlighting the possibility that Aβ metabolism could be regulated by their glycosylation. Within this framework, the present review aims to summarize the current understanding on the role of glycosylation in the etiopathology of AD, emphasizing the idea that glucose metabolic pathway may represent an alternative therapeutic option for targeting AD. From this perspective, the pharmacological modulation of glycosylation levels may represent a ‘sweet approach’ to treat AD targeting new mechanisms independent of the amyloid cascade and with comparable impacts in familial and sporadic AD.
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- 2020
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27. The Dual Role of Glutamatergic Neurotransmission in Alzheimer’s Disease: From Pathophysiology to Pharmacotherapy
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Vidyasagar Naik Bukke, Moola Archana, Rosanna Villani, Antonino Davide Romano, Agata Wawrzyniak, Krzysztof Balawender, Stanislaw Orkisz, Sarah Beggiato, Gaetano Serviddio, and Tommaso Cassano
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glutamate ,NMDA ,AMPA ,metabotropic receptors ,EAAT1/2 ,therapeutic targets ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Alzheimer’s disease (AD) is an age-related dementia and neurodegenerative disorder, characterized by Aβ and tau protein deposition impairing learning, memory and suppressing synaptic plasticity of neurons. Increasing evidence suggests that there is a link between the glucose and glutamate alterations with age that down-regulates glucose utilization reducing glutamate levels in AD patients. Deviations in brain energy metabolism reinforce the development of AD by hampering glutamate levels in the brain. Glutamate is a nonessential amino acid and the major excitatory neurotransmitter synthesized from glucose. Alterations in cerebral glucose and glutamate levels precede the deposition of Aβ plaques. In the brain, over 40% of neuronal synapses are glutamatergic and disturbances in glutamatergic function have been implicated in pathophysiology of AD. Nevertheless, targeting the glutamatergic system seems to be a promising strategy to develop novel, improved therapeutics for AD. Here, we review data supporting the involvement of the glutamatergic system in AD pathophysiology as well as the efficacy of glutamatergic agents in this neurodegenerative disorder. We also discuss exciting new prospects for the development of improved therapeutics for this devastating disorder.
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- 2020
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28. Molecular Aspects and Treatment of Iron Deficiency in the Elderly
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Antonino Davide Romano, Annalisa Paglia, Francesco Bellanti, Rosanna Villani, Moris Sangineto, Gianluigi Vendemiale, and Gaetano Serviddio
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iron deficiency anemia ,elderly ,nutritional status ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Iron deficiency (ID) is the most frequent nutritional deficiency in the whole population worldwide, and the second most common cause of anemia in the elderly. The prevalence of anemia is expecting to rise shortly, because of an ageing population. Even though WHO criteria define anemia as a hemoglobin serum concentration
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- 2020
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29. Two-Dimensional Shear Wave Elastography versus Transient Elastography: A Non-Invasive Comparison for the Assessment of Liver Fibrosis in Patients with Chronic Hepatitis C
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Rosanna Villani, Francesco Cavallone, Antonino Davide Romano, Francesco Bellanti, and Gaetano Serviddio
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liver fibrosis ,stiffness ,ElastQ ,2D-SWE ,chronic hepatitis C ,elastography ,Medicine (General) ,R5-920 - Abstract
In recent years, several non-invasive methods have been developed for staging liver fibrosis in patients with chronic hepatitis C. A 2D-Shear wave elastography (SWE) technique has been recently introduced on the EPIQ 7 US system (ElastQ), but its accuracy has not been validated in patients with chronic hepatitis C virus (HCV) infection. We enrolled 178 HCV patients to assess their liver fibrosis stage with ElastQ software using transient elastography as a reference standard. The best cut-off values to diagnose ≥ F2, ≥ F3, and F4 were 8.15, 10.31, and 12.65 KPa, respectively. Liver stiffness values had a positive correlation with transient elastography (r = 0.57; p < 0.001). The area under the receiver operating characteristics (AUROC) was 0.899 for ≥ F2 (moderate fibrosis), 0.900 for ≥ F3 (severe fibrosis), and 0.899 for cirrhosis. 2D-SWE has excellent accuracy in assessing liver fibrosis in patients with chronic hepatitis C and an excellent correlation with transient elastography.
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- 2020
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30. Analogs in the treatment of chronic hepatitis B: real life experience with tenofovir and entecavir
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Rosanna Villani, Roberta Forlano, Gianluigi Vendemiale, and Gaetano Serviddio
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Tenofovir ,Entecavir ,Chronic Hepatitis B ,Retrospective study ,Medicine (General) ,R5-920 - Abstract
INTRODUCTION: Tenofovir and entecavir are potent antiviral agents. By suppressing viral replication, they induce histological improvement and finally delay the progression of chronic hepatitis B and the development of complications. They are rarely associated with serious side effects. Our data from a real life experience support data from the literature and suggest some minimal difference that may be useful in tailoring therapy. PATIENTS AND METHODS: We retrospectively analyzed 54 patients affected by chronic hepatitis B (31 and 23 treated by entecavir and tenofovir, respectively). Eight patients were cirrhotic. At baseline and 4-12 and 24 weeks after starting therapy, biochemical and virological analysis were performed in all patients. Renal function tests (serum creatinine, creatinine clearance and blood urea), serum (calcium and phosphate blood level) and urine electrolyte were also studied. RESULTS: All the patients reached virological control within 24 weeks. Only in the group treated by tenofovir we observed a complete viral suppression within 12 weeks. Some patients treated with tenofovir showed increased creatinine clearance without serum creatinine alteration. No significant side effects were reported with the exception of one case of persistent headache in the entecavir group for which the drug was suspended. CONCLUSIONS: Entecavir and tenofovir are effective in suppressing viral replication in patients with chronic hepatitis B. Tenofovir is more potent than entecavir and viral replication is blocked within 12 weeks of therapy. Tenofovir administration is associated with slight increase of creatinine clearance without alteration of serum creatinine levels. The choice of one or the other should be made according to target and specific patients characteristics. In patients with high serum viral load where the complete and quick control of viral replication is the main target, tenofovir may represent the best choice.
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- 2015
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31. Molecular Mechanisms Involved in HCC Recurrence after Direct-Acting Antiviral Therapy
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Rosanna Villani, Gianluigi Vendemiale, and Gaetano Serviddio
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direct-acting antivirals ,hepatocellular carcinoma ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Chronic hepatitis C is associated with a high risk of developing hepatocellular carcinoma (HCC) because of a direct effect of the Hepatitis C Virus (HCV) proteins and an indirect oncogenic effect of chronic inflammation and impaired immune response. The treatment of chronic hepatitis C markedly reduces all-cause mortality; in fact, interferon-based treatment has shown a reduction of HCC incidence of more than 70%. The recent introduction of the highly effective direct-acting antivirals (DAAs) has completely changed the scenario of chronic hepatitis C (CHC) with rates of HCV cure over 90%. However, an unexpectedly high incidence of HCC recurrence was observed in patients after DAA treatment (27% versus 0.4–2% in patients who received interferon treatment). The mechanism that underlies the high rate of tumor relapse is currently unknown and is one of the main issues in hepatology. We reviewed the possible mechanisms involved in HCC recurrence after DAA treatment.
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- 2018
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32. DAAs Rapidly Reduce Inflammation but Increase Serum VEGF Level: A Rationale for Tumor Risk during Anti-HCV Treatment.
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Rosanna Villani, Antonio Facciorusso, Francesco Bellanti, Rosanna Tamborra, Annamaria Piscazzi, Matteo Landriscina, Gianluigi Vendemiale, and Gaetano Serviddio
- Subjects
Medicine ,Science - Abstract
Novel direct-acting antivirals (DAAs) have completely changed the panorama of hepatitis C due to their high efficacy and optimal safety profile. Unfortunately, an unexpectedly high rate of early recurrence of hepatocellular carcinoma has been reported within weeks of starting treatment, but the mechanism is not known.We monitored the serum level of vascular endothelial growth factor (VEGF) and changes in the pattern of circulating interleukins in 103 chronic hepatitis C patients during antiviral treatment with DAA-regimens. VEGF, epidermal growth factor (EGF), and several interleukins were assessed at baseline, during treatment, and after treatment. The biological effect of DAA-treated patient serum on human umbilical vein endothelial cell (HUVEC) proliferation was also confirmed.After 4 weeks of therapy, VEGF increased approximately 4-fold compared to baseline, remained elevated up to the end of treatment, and returned to the pre-treatment level after the end of therapy. In contrast, interleukin-10 and tumor necrosis factor-alpha significantly decreased during therapy, which was coincident with HCV clearance. The levels of both remained low after treatment. The addition of serum from patients collected during therapy induced HUVEC proliferation; however, this disappeared after the end of therapy.DAA administration induces an early increase in serum VEGF and a change in the inflammatory pattern, coinciding with HCV clearance. This may alter the balance between inflammatory and anti-inflammatory processes and modify the antitumor surveillance of the host. Fortunately, such modifications return reverse to normal after the end of treatment.
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- 2016
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33. Modulation of the Oxidative Stress and Lipid Peroxidation by Endocannabinoids and Their Lipid Analogues
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Cristina Anna Gallelli, Silvio Calcagnini, Adele Romano, Justyna Barbara Koczwara, Marialuisa de Ceglia, Donatella Dante, Rosanna Villani, Anna Maria Giudetti, Tommaso Cassano, and Silvana Gaetani
- Subjects
oxidative stress ,lipid peroxidation ,reactive aldehydes ,reactive oxygen and nitrogen species ,free radicals ,endocannabinoids ,cannabinoid receptors ,peroxisome proliferator-activated receptors ,transient receptor potential vanilloid ,G protein-coupled receptors ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Growing evidence supports the pivotal role played by oxidative stress in tissue injury development, thus resulting in several pathologies including cardiovascular, renal, neuropsychiatric, and neurodegenerative disorders, all characterized by an altered oxidative status. Reactive oxygen and nitrogen species and lipid peroxidation-derived reactive aldehydes including acrolein, malondialdehyde, and 4-hydroxy-2-nonenal, among others, are the main responsible for cellular and tissue damages occurring in redox-dependent processes. In this scenario, a link between the endocannabinoid system (ECS) and redox homeostasis impairment appears to be crucial. Anandamide and 2-arachidonoylglycerol, the best characterized endocannabinoids, are able to modulate the activity of several antioxidant enzymes through targeting the cannabinoid receptors type 1 and 2 as well as additional receptors such as the transient receptor potential vanilloid 1, the peroxisome proliferator-activated receptor alpha, and the orphan G protein-coupled receptors 18 and 55. Moreover, the endocannabinoids lipid analogues N-acylethanolamines showed to protect cell damage and death from reactive aldehydes-induced oxidative stress by restoring the intracellular oxidants-antioxidants balance. In this review, we will provide a better understanding of the main mechanisms triggered by the cross-talk between the oxidative stress and the ECS, focusing also on the enzymatic and non-enzymatic antioxidants as scavengers of reactive aldehydes and their toxic bioactive adducts.
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- 2018
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34. Hypoalbuminemia and Risk of Portal Vein Thrombosis in Cirrhosis
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Giuseppe, Palasciano, Felicia, D’Alitto, Ostilio, Palmieri Vincenzo, Daniela, Santovito, Dario, Di Michele, Giuseppe, Croce, David, Sacerdoti, Silvia, Brocco, Silvano, Fasolato, Lara, Cecchetto, Giancarlo, Bombonato, Michele, Bertoni, Tea, Restuccia, Paola, Andreozzi, Livia, Liguori Maria, Francesco, Perticone, Benedetto, Caroleo, Maria, Perticone, Orietta, Staltari, Roberto, Manfredini, Alfredo, De Giorgi, Maurizio, Averna, Antonina, Giammanco, Alessandro, Granito, Irene, Pettinari, Sara, Marinelli, Luigi, Bolondi, Lorenzo, Falsetti, Aldo, Salvi, Emanuele, Durante-Mangoni, Flavio, Cesaro, Vincenza, Farinaro, Enrico, Ragone, Ignazio, Morana, Angelo, Andriulli, Antonio, Ippolito, Angelo, Iacobellis, Grazia, Niro, Antonio, Merla, Giovanni, Raimondo, Sergio, Maimone, Irene, Cacciola, Doriana, Varvara, Davide, Drenaggi, Silvia, Staffolani, Antonio, Picardi, Umberto, Vespasiani-Gentilucci, Giovanni, Galati, Paolo, Gallo, Giovanni, Davì, Cosima, Schiavone, Francesca, Santilli, Claudio, Tana, Anna, Licata, Maurizio, Soresi, Battista, Bianchi Giovanni, Isabella, Carderi, Antonio, Pinto, Antonino, Tuttolomondo, Giovanni, Ferrari, Paolo, Gresele, Tiziana, Fierro, Olivia, Morelli, Giacomo, Laffi, Giulio, Romanelli Roberto, Umberto, Arena, Cristina, Stasi, Antonio, Gasbarrini, Matteo, Gargovich, Assunta, Zocco Maria, Laura, Riccardi, Elena, Ainora Maria, William, Capeci, Pio, Martino Giuseppe, Lorenzo, Nobili, Maurizio, Cavallo, Pierluigi, Frugiuele, Antonio, Greco, Antonello, Pietrangelo, Paolo, Ventura, Chiara, Cuoghi, Matteo, Marcacci, Gaetano, Serviddio, Gianluigi, Vendemiale, Rosanna, Villani, Ruggiero, Gargano, Gianpaolo, Vidili, Valentina, Di Cesare, Maristella, Masala, Giuseppe, Delitala, Pietro, Invernizzi, Giovanni, Di Minno, Antonella, Tufano, Francesco, Purrello, Graziella, Privitera, Alessandra, Forgione, Valentina, Curigliano, Marco, Senzolo, Kryssia Isabel, Rodríguez-Castro, Gianluigi, Giannelli, Carla, Serra, Sergio, Neri, Pietro, Pignataro, Mario, Rizzetto, Wilma, Debernardi Venon, Gianluca, Svegliati Baroni, Gaetano, Bergamaschi, Michela, Masotti, Filippo, Costanzo, Roberto, Corazza Gino, Hugh, Caldwell Stephen, Francesco, Angelico, Ben Maria, Del, Laura, Napoleone, Licia, Polimeni, Marco, Proietti, Valeria, Raparelli, Francesco, Romiti Giulio, Eleonora, Ruscio, Andrea, Severoni, Giovanni, Talerico, Filippo, Toriello, Annarita, Vestri, Cangemi, Roberto, Raparelli, Valeria, Talerico, Giovanni, Basili, Stefania, and Violi, Francesco
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- 2024
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35. Prevalence and risk factors for hospital-acquired anemia in internal medicine patients: learning from the 'less is more' perspective
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Rosanna Villani, Antonino Davide Romano, Roberta Rinaldi, Moris Sangineto, Mariateresa Santoliquido, Tommaso Cassano, and Gaetano Serviddio
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Emergency Medicine ,Internal Medicine - Abstract
Hospital-acquired anemia is defined as a new-onset anemia in hospitalized patients who have a normal hemoglobin level at admission. Its prevalence is unknown and most studies published on this topic have been conducted in intensive care unit patients with limited applicability to less acute settings, such as internal medicine wards. We conducted a retrospective study and enrolled 129 patients who were admitted to an Internal Medicine Unit between October 2021 and February 2022. The median value of phlebotomy during hospitalization was 46 ml (IQR 30–72 ml), whereas the median length of hospital stay was 9 days (IQR 5–13 days). The median value of hemoglobin reduction was −0.63 g/dl (p 85 ml had a hemoglobin reduction > 0.6 g/dl. 20.9% of patients developed anemia during the hospital stay (7% moderate and 13.9% mild). No cases of severe anemia were observed. The volume of blood drawn during the hospital stay and the Hb value on admission were the only two variables statistically associated with the development of anemia, whereas gender, age, and chronic diseases, such as diabetes, history of cancer, or heart failure, were not. Strategies, such as elimination of unnecessary laboratory tests and the use of smaller tubes for blood collection, are needed to reduce the volume of iatrogenic blood loss and avoid blood wastage occurring during hospitalization in internal medicine patients.
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- 2022
36. The impact of COVID-19 pandemic on well-being of Italian physicians: a report from the Italian Society of Internal Medicine (SIMI) national survey
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Giulio Francesco, Romiti, Leonardo, Bencivenga, Rosanna, Villani, Sebastiano, Cicco, Antonio, Cimellaro, Andrea, Dalbeni, Giovanni, Talerico, Antonello, Pietrangelo, Giorgio, Sesti, and Vincenzo, Zaccone
- Subjects
sars-cov-2 ,covid-19 ,well-being ,work-related stress ,Emergency Medicine ,Internal Medicine ,healthcare - Abstract
Over the past few years, COVID-19 pandemic has imposed a high toll worldwide, with a high burden of morbidity and mortality. Healthcare practitioners (HCPs) have been in the frontline since the beginning of the outbreak, and the high level of stress have affected their physical and mental status, as well as their relationships. We aimed at exploring the self-reported changes in comprehensive well-being in a cohort of Italian physicians. An online-based survey was administered to the members of the Italian Society of Internal Medicine (SIMI) between March and June 2021. The survey was based on 32 multiple-choice questions exploring self-reported physical and mental well-being, as well as changes in workloads, work-related feelings and physicians’ relationship with patients, colleagues and families. 228 physicians (mean age: 35.7 ± 9.8 years) participated in the survey; 120 (52.6%) were residents, 196 (86.0%) worked in COVID-19 units and 65 (28.5%) had COVID-19 during the pandemic. A significant proportion of respondents reported to have experience onset or worsening of physical and mental symptoms, with insomnia/sleep disorders (58.3%) and mood swings (47.8%) being the most common, respectively. The burden of physical and mental consequences was broadly higher among residents compared to specialists, with the former reporting more frequently an increase in the number of worked hours (p = 0.020) and being more frequently infected with COVID-19 (35.0% vs. 21.3, p = 0.032). Moreover, familiar and doctor–patient relationships were also considerably affected. Physicians have been suffering a wide spectrum of physical, mental and relational consequences during COVID-19 pandemic, with youngest doctors being more likely to present several physical and mental health symptoms. Further studies are needed to evaluate long-term consequences of COVID-19 pandemic on the well-being of HCPs, and potential preventive strategies.
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- 2022
37. Comparison of a Wireless Ultrasound Device with a High-End Ultrasound Machine in the Assessment of Pleuro-Pulmonary Diseases
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Carla Maria Irene Quarato, Lucia Angela Fiore, Donato Lacedonia, Giulia Scioscia, Michela Salvemini, Anela Hoxhallari, Rosanna Villani, Federica D’Agostino, Giulia Tuccari, Stefano Notarangelo, Antonio Mirijello, Salvatore De Cosmo, Evaristo Maiello, and Marco Sperandeo
- Abstract
Background. The newer wireless portable scanners seem to permit a quicker bedside ultrasound (US) assessment, shortening the transfer times of the portable US unit and without the hindering of connection cables. However, no substantial evidence is currently available regarding of the clinical effectiveness of such new generation devices. Objective. The aim of the current study was to evaluate the efficacy of a wireless US system with respect to a high-end US unit in a cohort of consecutive respiratory patients. Materials and Methods. This prospective observational study included a total of 72 respiratory patients admitted in the department of Internal Medicine. The US examination were independently performed by two experienced blinded examiners with a high-end Esaote MyLab-Twice scanner and a wireless double-head linear and convex probe OTE-L/C501CD. The findings resulting from the high-end US assessment and the wireless US examination were then compared each other. All the patients had a confirmation chest CT scan. Results. The high-end US machine identified 64 positive cases for pleuro-pulmonary alterations, in comparison to which the wireless US unit resulted in 13 false negative results. The respective overall sensitivity and specificity for the portable wireless US unit were of 79.69% and 100.00%, respectively. The resolution of the portable wireless US device was judged as good in 22 (31%) cases, affected by minor diagnostic limitations in 26 (36%) cases and affected by major diagnostic limitations in 24 (33%). The main diagnostic strength of the wireless probe was in the detection of pleural effusion (sensitivity 100%). The diagnostic sensitivity of the wireless probe in assessing abnormalities of the pleural line (67%), pulmonary subpleural consolidations (65%), pleural lesions (33%) and pericardial effusion (0%) was reduced. Conclusions. The newer wireless US probes may have clinical roles for the detection and management of pleural effusion when used by experienced examiners. However, sensitivity in detecting other pleuro-pulmonary pathologies is not comparable to high-end ultrasound machines.
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- 2023
38. The GLP-1 receptor agonist Exendin-4 modulates hippocampal NMDA-receptor signalling in aged rats and improves cognitive impairment in diabetic elderly patients
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Antonino Davide Romano, Rosanna Villani, Moris Sangineto, Tommaso Cassano, and Gaetano Serviddio
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Aging ,Geriatrics and Gerontology - Published
- 2022
39. Antihypertensive treatment changes and related clinical outcomes in older hospitalized patients
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Sebastiano, Cicco, D'Abbondanza, Marco, Proietti, Marco, Vincenzo, Zaccone, Chiara, Pes, Federica, Caradio, Mattioli, Massimo, Salvatore, Piano, Alberto Maria Marra, Alessandro, Nobili, Pier Mannuccio Mannucci, Antonello, Pietrangelo, Giorgio, Sesti, Elena, Buzzetti, Andrea, Salzano, Antonio, Cimellaro, Francesco, Perticone, Francesco, Violi, Gino Roberto Corazza, Salvatore, Corrao, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Alessio, Novella, Gabriella, Miglio, Alessia Antonella Galbussera, Ilaria, Ardoino, Prisco, Domenico, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Irene, Mattioli, Gianni, Biolo, Michela, Zanetti, Giacomo, Bartelloni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Pirro, Matteo, Lupattelli, Graziana, Bianconi, Vanessa, Alcidi, Riccardo, Giotta, Alessia, Massimo, R Mannarino, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Vincenza, Beneduce, Federica, Cacioppo, Giuseppe, Natoli, Salvatore, Mularo, Massimo, Raspanti, Christiano, Argano, Federica, Cavallaro, Marco, Zoli, Maria Laura Matacena, Giuseppe, Orio, Eleonora, Magnolfi, Serafini, Giovanni, Angelo, Simili, Mattia, Brunori, Ilaria, Lazzari, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Valeria Di Stefano, Simona, Leoni, Sonia, Seghezzi, Alessandra Danuto Di Mauro, Diletta, Maira, Marta, Mancarella, Tiziano, Lucchi, Paolo Dionigi Rossi, Marta, Clerici, Alessandra Danuta Di Mauro, Giulia, Bonini, Conti, Federica, Silvia, Prolo, Maddalena, Fabrizi, Miriana, Martelengo, Giulia, Vigani, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Lavinia, Pitotti, Donatella, Padula, Valentina, Antoci, Ginevra, Cambiè, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Giovanna, Leoncini, Jacopo, Alberto, Federico, Cattaneo, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Francesco, Cipollone, Maria Teresa Guagnano, Ilaria, Rossi, Emanuele, Valeriani, Damiani, D'Ardes, Lucia, Esposito, Simona, Sestili, Ermanno, Angelucci, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Antonella, Giorgi, Christian, Gracin, Giovanni, Imbimbo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Andrea, Volpini, Daniela, Lucente, Francesca, Manzoni, Annalisa, Pirozzi, Alberto, Zucchelli, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giuseppe, Bellelli, Maurizio, Corsi, Cesare, Antonucci, Chiara, Sidoli, Giulia, Principato, Alessandra, Bonfanti, Hajnalka, Szabo, Mazzola, Paolo, Piazzoli, Andrea, Franco, Arturi, Elena, Succurro, Bruno, Tassone, Federica, Giofrè, Maria Grazia Serra, Maria Antonietta Bleve, Antonio, Brucato, Teresa De Falco, Enrica, Negro, Martino, Brenna, Lucia, Trotta, Giovanni Lorenzo Squintani, Maria Luisa Randi, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Tancredi, Prandini, Francesco, Ratti, Chiara, Zurlo, Lorenzo, Cerruti, Elisabetta, Cosi, Roberto, Manfredini, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Ruana, Tiseo, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudia, Catalano, Irene Di Meo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Silvia, Schiavone, Alessio, Bragagni, Francesca Giulia Leoni, Valeria De Sando, Sara, Scarduelli, Michela, Cammarosano, Ilenia, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Carlo, Custodero, Giuseppe, Re, Andrea, Schilardi, Francesca, Loparco, Luigi, Fenoglio, Andrea, Falcetta, Alessia Valentina Giraudo, Salvatore, D'Aniano, Anna, L Fracanzani, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Felice, Cinque, Flora, Peyvandi, Raffaella, Rossio, Giulia, Colombo, Pasquale, Agosti, Erica, Pagliaro, Eleonora, Semproni, Canetta, Ciro, Valter, Monzani, Valeria, Savojardo, Giuliana, Ceriani, Christian, Folli, Giada, Pallini, Fabrizio, Montecucco, Luciano, Ottonello, Lara, Caserza, Giulia, Vischi, Salam, Kassem, Luca, Liberale, Nicola Lucio Liberato, Tiziana, Tognin, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Maria Stella Pisciotta, Francesco Baffa Bellucci, Stefano, Buffelli, Camillo, Ferrandina, Francesca, Mazzeo, Elena, Spazzini, Giulia, Cono, Giulia, Cesaroni, Giuseppe, Montrucchio, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Carl, Margaria, Maura, Sanino, Ludovica, Perri, Luigina, Guasti, Francesca, Rotunno, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Roberto Davide Diprizio, Francesco, Dentali, Bertolotti, Marco, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Matteo, Galassi, Yasmine, Grassi, Alessio, Greco, Elena, Bigi, Pellegrini, Elisa, Laura, Orlandi, Giulia, Dondi, Lucia, Carulli, Angela, Sciacqua, Maria, Perticone, Rosa, Battaglia, Raffaele, Maio, Aleandra, Scozzafava, Valentino, Condoleo, Tania, Falbo, Lidia, Colangelo, Marco, Filice, Elvira, Clausi, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Ilaria, Benzoni, Andrea, Salvi, Leonardi, Roberto, Giampaolo, Damiani, Gianluca, Moroncini, William, Capeci, Giuseppe Pio Martino, Biondi, Lorenzo, Pietro, Pettinari, Monica, Ormas, Emanuele, Filippini, Devis, Benfaremo, Roberto, Romiti, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Alfio, Gennaro, Agostino, Gaudio, Samuele, Pignataro, Francesca, Mete, Miriam, Gino, Guido, Moreo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Roberta, Gonella, Domenico, Cerminara, Paolo, Setti, Chiara, Traversa, Camilla, Scarsi, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Marcello Giuseppe Maggio Gian Paolo Ceda, Simonetta, Morganti, Andrea, Artoni, Margherita, Grossi, Stefano Del Giacco, Davide, Firinu, Giulia, Costanzo, Giacomo, Argiolas, Giovanni, Paoletti, Francesca, Losa, Montalto, GIUSEPPE ALBERT, Anna, Licata, Filippo Alessandro Montalto, Francesco, Corica, Giorgio, Basile, Antonino, Catalano, Federica, Bellone, Concetto, Principato, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Tiziana, Meschi, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Giandomenico Nigro Imperiale, Sarah, Morellini, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Mattia, Bellan, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Tarquini, Roberto, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Volpi, Riccardo, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Federico, Napoli, Italia, Aiello, Teresa, Salvatore, Lucio, Monaco, Carmen, Ricozzi, Alberto, Pilotto, Ilaria, Indiano, Federica, Gandolfo, Franco Laghi Pasini, Pier Leopoldo Capecchi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Vittorio, Durante, Daniela, Tirotta, Giovanna, Eusebi, Cattaneo, Marco Natale, Amoruso, MARIA VALENTINA, Paola, Fracasso, Cristina, Fasolino, Moreno, Tresoldi, Enrica, Bozzolo, Sarah, Damanti, Massimo, Porta, Giuseppe, Armentaro, Maria Immacolata Arnone, Milena, Barone, Lorenzo, Bertolino, Sara, Bianco, Nicolò, Binello, Simona, Brancati, Agostino, Buonauro, William, Cordeddu, Curcio, Rosa, Andrea, Dalbeni, Salvatore, D'Agnano, Damiano, D'Ardes, Martina De Feo, Emilia, Donnarumma, Marco, Fei, Carmine Gabriele Gambino, Paolo, Giorgini, Lombardi, Rosa, Giuseppe, Miceli, Paola, Naccarato, Silvia, Noviello, Gaia, Olivieri, Roberta, Parente, Francesca Serena Pignataro, Sonia, Poma, Enrica, Porceddu, Pucci, Giacomo, Marco, Ricchio, Anna, Sabena, Marco, Salice, Claudia, Santarossa, Ambra, Savona, Caterina, Savrié, Roberto, Scicali, Mario, Stabile, Giovanni, Talerico, Michela, Talia, Eliezer Joseph Tassone, Thomas, Teatini, Elisabetta, Tombolini, Matteo, Traversa, Elia, Vettore, Alessandro, Vignal, Luca, Vilardi, Rosanna, Villani, Francesco, Vitale, Cicco, Sebastiano, D Abbondanza, Marco, Proietti, Marco, Zaccone, Vincenzo, Pes, Chiara, Caradio, Federica, Mattioli, Massimo, Piano, Salvatore, Marra, Alberto Maria, Nobili, Alessandro, Mannucci, Pier Mannuccio, Pietrangelo, Antonello, Sesti, Giorgio, Buzzetti, Elena, Salzano, Andrea, Cimellaro, Antonio, Antonio Cimellaro, Salvatore, Corrao, Mario, Barbagallo, Anna, Licata, Giuseppe, Montalto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, and Cimellaro, Antonio - Giovani Internisti Società Italiana di Medicina Interna (GIS-SIMI) and of the REPOSI Investigators
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cardiovascular events ,older patient ,hypertension ,antihypertensive drugs ,older patients ,survival ,Clinical Biochemistry ,antihypertensive drug ,General Medicine ,Biochemistry ,cardiovascular event - Abstract
Background: Hypertension management in older patients represents a challenge, particularly when hospitalized. Objective: The objective of this study is to investigate the determinants and related outcomes of antihypertensive drug prescription in a cohort of older hospitalized patients. Methods: A total of 5671 patients from REPOSI (a prospective multicentre observational register of older Italian in-patients from internal medicine or geriatric wards) were considered; 4377 (77.2%) were hypertensive. Minimum treatment (MT) for hypertension was defined according to the 2018 ESC guidelines [an angiotensin-converting-enzyme-inhibitor (ACE-I) or an angiotensin-receptor-blocker (ARB) with a calcium-channel-blocker (CCB) and/or a thiazide diuretic; if >80 years old, an ACE-I or ARB or CCB or thiazide diuretic]. Determinants of MT discontinuation at discharge were assessed. Study outcomes were any cause rehospitalization/all cause death, all-cause death, cardiovascular (CV) hospitalization/death, CV death, non-CV death, evaluated according to the presence of MT at discharge. Results: Hypertensive patients were older than normotensives, with a more impaired functional status, higher burden of comorbidity and polypharmacy. A total of 2233 patients were on MT at admission, 1766 were on MT at discharge. Discontinuation of MT was associated with the presence of comorbidities (lower odds for diabetes, higher odds for chronic kidney disease and dementia). An adjusted multivariable logistic regression analysis showed that MT for hypertension at discharge was associated with lower risk of all-cause death, all-cause death/hospitalization, CV death, CV death/hospitalization and non-CV death. Conclusions: Guidelines-suggested MT for hypertension at discharge is associated with a lower risk of adverse clinical outcomes. Nevertheless, changes in antihypertensive treatment still occur in a significant proportion of older hospitalized patients.
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- 2023
40. Eradication of <scp>HCV</scp> by direct antiviral agents restores mitochondrial function and energy homeostasis in peripheral blood mononuclear cells
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Rosanna Villani, Moris Sangineto, Paola Pontrelli, Francesco Bellanti, Vidyasagar N. Bukke, Archana Moola, Loreto Gesualdo, Gianluigi Vendemiale, Giuseppe Grandaliano, Giovanni Stallone, and Gaetano Serviddio
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Leukocytes, Mononuclear ,Genetics ,Humans ,Homeostasis ,Hepacivirus ,Antiviral Agents ,Hepatitis C ,Molecular Biology ,Biochemistry ,Mitochondria ,Biotechnology - Abstract
Hepatitis C virus (HCV) adopts several immune evasion mechanisms such as interfering with innate immunity or promoting T-cell exhaustion. However, the recent direct-antiviral agents (DAAs) rapidly eliminate the virus, and the repercussions in terms of immune system balance are unknown. Here we compared the PBMCs transcriptomic profile of patients with HCV chronic infection at baseline (T0) and 12 weeks after the end of the therapy (SVR12) with DAAs. 3862 genes were differently modulated, identifying oxidative phosphorylation as the top canonical pathway differentially activated. Therefore, we dissected PBMCs bioenergetic profile by analyzing mitochondrial respiration and glycolysis at 4 timepoints: T0, 4 weeks of therapy, end of therapy (EoT), and SVR12. Maximal and reserve respiratory capacity considerably increased at EoT, persisting until SVR12. Notably, over time a significant increase was observed in respiratory chain (RC) complexes protein levels and the enzymatic activity of complexes I, II, and IV. Mitochondrial-DNA integrity improved over time, and the expression of mitochondrial biogenesis key regulators such as TFAM, Nrf-1, and PPARGC1A significantly increased at SVR12; hence, RC complexes synthesis and mitochondrial respiration were supported after treatment. HCV clearance with DAAS profoundly changed PBMCs bioenergetic profile, suggesting the immunometabolism study as a new approach to the understanding of viral immune evasion mechanisms and host adaptations during infections and therapies.
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- 2022
41. High prevalence of false positive SARS-CoV2 serology in a cohort of patients with liver autoimmune diseases
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Paola Cicciomessere, Francesco Cavallone, Gaetano Serviddio, Giuseppe Di Gioia, Rosanna Villani, Maria Giulia Cornacchia, and Moris Sangineto
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medicine.medical_specialty ,High prevalence ,business.industry ,autoantibodies ,chronic liver disease ,serology ,Serology ,Other systems of medicine ,sars-cov2 ,liver autoimmune disease ,covid-19 ,Internal medicine ,Cohort ,Medicine ,business ,RZ201-999 - Abstract
Aim: Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) immunization in patients with autoimmune diseases is of particular concern to understand their response to the infection and to the vaccine. In fact, the immunological disorder and the immunosuppressive therapies could affect the serological response. SARS-CoV2 serological tests potentially provide this information, although they were rapidly commercialized with internal verifications. Here, we analysed the seroprevalence to SARS-CoV2 in a cohort of patients with liver autoimmune diseases. Methods: From May to December 2020, a cohort of patients affected by primary biliary cholangitis (PBC), autoimmune hepatitis (AIH) and PBC/AIH overlap syndrome were screened with reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal swabs, rapid antigenic test and chemiluminescent serological test during routine follow-up. Results: The analysis of 42 patients was carried out: 18 (42.85%) PBC, 12 (28.57%) AIH and 12 (28.57%) PBC/AIH overlap syndromes. Only 2 patients (4.76%) resulted positive to the RNA, antigen and antibody detection tests, hence affected by SARS-CoV2 infection. 14 subjects out of 40 negative cases presented a positive serology for SARS-CoV2 antibodies, hence with a false positivity in the 35% of cases without infection. Notably, among these, 6 (42.86%) patients presented only immunoglobulin (Ig)M positivity, 6 (42.86%) patients presented positivity for only IgG and 2 (14.28%) patients were positive to both IgM and IgG. Notably, the presence of autoantibodies did not correlate with the serological false positivity, highlighting that there is no cross-reactivity with autoantibodies. Moreover, the presence of polyclonal hypergammaglobulinemia did not interfere with the serological test as its prevalence is not different between negative and false positive cases. Interestingly, the patients with false positive serology showed higher levels of gamma-glutamyltransferase (GGT) and C-reactive protein (CRP). Conclusions: Patients with liver autoimmune diseases present a high rate of false positive SARS-CoV2 serology. Therefore, new strategies are needed to study the serological response in this patient category.
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- 2021
42. Effects of direct-acting antiviral agents on lipid and glucose profile in HCV patients with type 2 diabetes: A real-life Italian experience
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Andrea Dalbeni, Rosanna Villani, Michele Bevilacqua, Federica Sacco, Diego Faccincani, Filippo Cattazzo, Francesco Cavallone, Anna Mantovani, Vittoria Ceruti, Donatella Ieluzzi, Veronica Paon, Alessandro Mantovani, Gaetano Serviddio, and David Sacerdoti
- Subjects
cardiovascular risk factors ,hepatitis C virus ,Liver Cirrhosis ,direct-acting antiviral agents ,glucose profile ,lipid profile ,type 2 diabetes mellitus ,Antiviral Agents ,Cholesterol ,Glucose ,Hepacivirus ,Humans ,Lipids ,Prospective Studies ,Sustained Virologic Response ,Diabetes Mellitus, Type 2 ,Hepatitis C, Chronic ,Gastroenterology ,Hepatitis C ,Diabetes Mellitus ,Chronic ,Type 2 - Abstract
Hepatitis C virus (HCV) infection is associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The impact of HCV eradication on the metabolic profile in diabetic patients treated with direct-acting antiviral agents (DAAs) is not well defined. The aim of our study was to evaluate the effects of DAAs on a lipid and glucose profile in a cohort of diabetic patients with different liver fibrotic stages.T2DM patients with active HCV infection were consecutively enrolled in this prospective trial. Glycolipidic status was assessed, before starting DAA treatment (T0) and at 12 months after the beginning of treatment (T1). Liver fibrotic stage was assessed by FibroScan.In all, 131 patients were enrolled and all of them achieved a sustained virologic response. At baseline, no significant differences were found in lipid and glucose profiles in subgroup analysis by liver fibrosis, HCV genotype, and cardiovascular risk factors. At T1, total cholesterol and low-density lipoprotein cholesterol, but not triglycerides, significantly increased irrespective of liver fibrotic stage and baseline anthropometric and clinical profiles, while glycated hemoglobin significantly decreased only in F4 patients.HCV eradication in diabetic patients is associated with a worsening lipid profile that could impact future cardiovascular risk. A careful global monitoring of cardiovascular risk factors in all diabetic patients after HCV eradication is needed.
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- 2022
43. Genetic Polymorphisms and Clinical Features in Diabetic Patients With Fatty Liver: Results From a Single-Center Experience in Southern Italy
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Moris Sangineto, Antonino Davide Romano, Giuseppe De Girolamo, Grazia Pia Magnati, Gaetano Serviddio, Rosanna Villani, and Tommaso Cassano
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Medicine (General) ,medicine.medical_specialty ,Single-nucleotide polymorphism ,Type 2 diabetes ,Gastroenterology ,chemistry.chemical_compound ,R5-920 ,NAFLD ,Internal medicine ,Diabetes mellitus ,Medicine ,Original Research ,fatty liver ,diabetes ,medicine.diagnostic_test ,business.industry ,Fatty liver ,General Medicine ,medicine.disease ,chemistry ,Population study ,Glycated hemoglobin ,polymorphisms ,business ,Lipid profile ,SNPs ,TM6SF2 - Abstract
Genetic background may be involved in the promotion and progression of non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that the single nucleotide polymorphisms (SNPs) may be associated with the specific clinical features in the patients with hepatic steatosis; however, data on the patients with diabetes from Southern Italy are lacking. We enrolled 454 patients and 260 of them had type 2 diabetes. We studied the PNPLA3 rs738409, LPIN1 rs13412852, KLF6 rs3750861, SOD2 rs4880, TM6SF2 rs58542926, and ZNF624 rs12603226 SNPs and their distribution in the study population. Lipid profile, liver stiffness, and kidney function were also studied to understand the potential role of the SNPs in the development of clinical phenotypes. No differences were observed in the distribution of polymorphisms between the diabetic and non-diabetic subjects. Carriers of risk allele G for PNPLA3 rs738409 SNP showed a lower mean value of serum triglycerides and a higher liver stiffness. Risk allele for KLF6 rs3750861 and SOD2 rs4880 polymorphism had a lower estimated glomerular filtration rate (eGFR) value, whereas no differences in the glucose and glycated hemoglobin level were observed in the subgroups by the different genotypes. Genetic polymorphisms are useful to identify the patients at higher risk of development of liver fibrosis and lower eGFR values in the patients with diabetes and NAFLD. Their use in clinical practice may help the clinicians to identify the patients who require a more strict follow-up program.
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- 2021
44. Liver fat content assessed by conventional B-mode ultrasound and metabolic profile in non-diabetic patients: Implications for clinical practice
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Rosanna Villani, Grazia Pia Magnati, Giulia Tuccari, Moris Sangineto, Antonino Davide Romano, Tommaso Cassano, and Gaetano Serviddio
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Radiological and Ultrasound Technology ,Radiology, Nuclear Medicine and imaging - Abstract
Introduction: Several studies have demonstrated a positive correlation between severe hepatic steatosis and metabolic alterations; however, few studies have addressed the potential association between different grades of steatosis and clinical patterns in a non-diabetic population. Methods: We conducted a cross-sectional study of 223 non-diabetic individuals. The severity of steatosis was assessed using B-mode ultrasound. We analyzed lipid and glucose profiles according to the severity of hepatic steatosis. Estimated glomerular filtration rate (eGFR) values were also recorded to investigate the potential impact of steatosis on kidney function. Results: Patients with steatosis were found to have higher insulinemia and mean values of fasting plasma glucose compared to patients without steatosis. A significant decrease in high-density lipoprotein level was observed only in patients with severe or moderate steatosis. All grades of steatosis were associated with increased triglyceride levels, which were more significant in severe steatosis. Subgroup analysis by body mass index demonstrated a significant difference between lean patients with steatosis and lean patients without steatosis for triglycerides (p = 0.002) and high-density lipoprotein levels (p = 0.019). Finally, patients diagnosed with steatosis demonstrated a higher prevalence of estimated glomerular filtration rate Conclusion: The degree of steatosis diagnosed at ultrasound may predict glucose or lipid metabolism disorders and a decline in kidney function in a non-diabetic population.
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- 2022
45. Serum lipid profile in HCV patients treated with direct-acting antivirals: a systematic review and meta-analysis
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Moris Sangineto, Rosanna Villani, Francesca Di Cosimo, Gaetano Serviddio, and Antonino Davide Romano
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0301 basic medicine ,Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Science ,DIRECT ACTING ANTIVIRALS ,Gastroenterology ,Antiviral Agents ,Article ,03 medical and health sciences ,0302 clinical medicine ,Chronic hepatitis ,Internal medicine ,medicine ,Humans ,Pooled data ,Antiviral treatment ,Viral hepatitis ,Triglycerides ,Aged ,Aged, 80 and over ,Potential impact ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Cholesterol, HDL ,Cholesterol, LDL ,Hepatitis C, Chronic ,Middle Aged ,Hepatitis C ,Lipids ,030104 developmental biology ,Meta-analysis ,Medicine ,030211 gastroenterology & hepatology ,Female ,Lipid profile ,business ,After treatment - Abstract
Although direct-acting antivirals are very effective and safe drugs, several authors have reported the alteration of lipid profile during and after anti-HCV therapy suggesting a potential impact on the risk of cardiovascular events. We performed a systematic review and meta-analysis of observational studies to investigate the magnitude and temporal trend of lipid profile changes in DAA treated patients. All selected studies included data on lipid profile before starting therapy and at least one follow-up assessment during or after antiviral treatment. We identified 14 studies (N = 1537 patients) after removing duplicates. Pooled data showed an increase in total cholesterol 4 weeks after starting therapy (+ 15.86 mg/dl; 95% CI + 9.68 to 22.05; p
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- 2021
46. Assessing the impact of COVID-19 on liver cancer management (CERO-19)
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Manuel Delgado, Mar Lozano, Alejandro Forner, Bruno Sangro, Alessandro Granito, Margarita Sala, Monica Ronzoni, Giuseppe Cabibbo, Frederik J H Hoogwater, José Luis Lledó, Rosanna Villani, Alessandra Elvevi, Lorenza Rimassa, Juan Acevedo, Mariona Calvo, Mercedes Vergara, Sergio Muñoz-Martínez, Jean-Charles Nault, Juan C. Bandi, Markus Peck-Radosavljevic, Brandon M. Meyers, Marco Sanduzzi-Zamparelli, Rogerio Alves, Saleh A. Alqahtani, Alberto E. Muñoz, Sonia Pascual, Alberto Lué, Josepmaria Argemi, Beatriz Minguez, Henning Wege, Giovan Giuseppe Di Costanzo, David J. Pinato, Victor Sapena, Maria Guarino, Stefano Okolicsanyi, Vivianne Mello, Martina Gambato, Susanna Coll, Carlos Benítez, Dhanny Gomez, Christoph Roderburg, Peter R. Galle, Bristi Basu, Federico Piñero, Cassia Leal, Frank Tacke, Christie Perelló, Tudor Mocan, Massimiliano Salati, Helen L. Reeves, Jörg Trojan, Vincenzo Cardinale, Mohamed El Kassas, Tom Lüdde, John Bridgewater, Mário Reis Álvares-da-Silva, Anja Lachenmayer, Giovanni Brandi, Alex Vianey Callado França, Mohamed Bouattour, Tim Meyer, Gerda Elisabeth Villadsen, M. Varela, Jordi Bruix, Dalia Morales-Arraez, Carlos Rodríguez-Lope, Christian Toso, Wacław Hołówko, Philippe Merle, Manuel Romero-Gómez, Ignacio García-Juárez, Fernanda Branco, Gonzalo Sapisochin, Chiara Braconi, Emmanouil Giorgakis, Hidenori Toyoda, Lorraine Blaise, Ana María Matilla Peña, Andrea Casadei-Gardini, Leonardo G Da Fonseca, Alexander Siebenhüner, Maria Reig, Gustavo Pereira, Massimo Iavarone, Maria Margarita Anders, Munoz-Martinez S., Sapena V., Forner A., Nault J.-C., Sapisochin G., Rimassa L., Sangro B., Bruix J., Sanduzzi-Zamparelli M., Holowko W., El Kassas M., Mocan T., Bouattour M., Merle P., Hoogwater F.J.H., Alqahtani S.A., Reeves H.L., Pinato D.J., Giorgakis E., Meyer T., Villadsen G.E., Wege H., Salati M., Minguez B., Di Costanzo G.G., Roderburg C., Tacke F., Varela M., Galle P.R., Alvares-da-Silva M.R., Trojan J., Bridgewater J., Cabibbo G., Toso C., Lachenmayer A., Casadei-Gardini A., Toyoda H., Ludde T., Villani R., Matilla Pena A.M., Guedes Leal C.R., Ronzoni M., Delgado M., Perello C., Pascual S., Lledo J.L., Argemi J., Basu B., da Fonseca L., Acevedo J., Siebenhuner A.R., Braconi C., Meyers B.M., Granito A., Sala M., Rodriguez-Lope C., Blaise L., Romero-Gomez M., Pinero F., Gomez D., Mello V., Pinheiro Alves R.C., Franca A., Branco F., Brandi G., Pereira G., Coll S., Guarino M., Benitez C., Anders M.M., Bandi J.C., Vergara M., Calvo M., Peck-Radosavljevic M., Garcia-Juarez I., Cardinale V., Lozano M., Gambato M., Okolicsanyi S., Morales-Arraez D., Elvevi A., Munoz A.E., Lue A., Iavarone M., Reig M., Basu, Bristi [0000-0002-3562-2868], Apollo - University of Cambridge Repository, Institut Català de la Salut, [Muñoz-Martínez S, Sapena V, Forner A] BCLC group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain. [Nault JC] Service d’hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France. Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris Nord, Paris, France. Centre de Recherche des Cordeliers, Inserm, Sorbonne Université, Université Paris, INSERM UMR 1138 Functional Genomics of Solid Tumors Laboratory, Paris, France. [Sapisochin G] Abdominal Transplant & HPB Surgical Oncology, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Canada. [Rimassa L] Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center – IRCCS, Rozzano, Milan, Italy. Department of Biomedical Sciences, Humanitas University, Milan, Italy. [Mínguez B] Unitat del Fetge, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Malalties hepàtiques, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Hepatocellular carcinoma ,LC ,medicine.medical_treatment ,diagnóstico::toma de decisiones clínicas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Nurses ,RC799-869 ,Liver transplantation ,Cholangiocarcinoma ,Clinical trials ,ENS-CCA ,Interquartile range ,Decisió, Presa de ,Pandemic ,Other subheadings::/diagnosis [Other subheadings] ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,CERO-19 ,Pandèmia de COVID-19, 2020 ,Immunology and Allergy ,iCCA, intrahepatic cholangiocarcinoma ,COVID-19, coronavirus disease 2019 ,Liver Cancer Outcome in the COVID-19-pandemic Project ,Settore MED/12 - Gastroenterologia ,ddc:617 ,IQR ,Gastroenterology ,BCLC, Barcelona Clinic Liver Cancer ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias hepáticas [ENFERMEDADES] ,Diseases of the digestive system. Gastroenterology ,Management ,Clinical Practice ,Clinical trial ,European Network for the Study of Cholangiocarcinoma ,Diagnosis::Clinical Decision-Making [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Fetge - Malalties - Diagnòstic ,Liver cancer ,PROGRESSION-FREE SURVIVAL ,Liver Cancer ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Otros calificadores::/diagnóstico [Otros calificadores] ,610 Medicine & health ,Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms [DISEASES] ,LT, liver transplantation ,Article ,Barcelona Clinic Liver Cancer ,Internal Medicine ,medicine ,ENS-CCA, European Network for the Study of Cholangiocarcinoma ,Hepatology ,business.industry ,CERO-19, Liver Cancer Outcome in the COVID-19-pandemic Project ,COVID-19 ,IQR, Interquartile range ,medicine.disease ,BCLC ,Emergency medicine ,Observational study ,610 Medizin und Gesundheit ,business ,HCC, hepatocellular carcinoma ,LC, liver cancer ,SARS-CoV-2, severe acute respiratory syndrome coronavirus-2 - Abstract
[Background & Aims] The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic., [Methods] An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave., [Results] Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37)., [Conclusions] The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making., [Lay summary] The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes.
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- 2021
47. Inhibition of nuclear factor (erythroid-derived 2)-like 2 promotes hepatic progenitor cell activation and differentiation
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Giorgia di Bello, Maria Carmela Pedicillo, Giuseppe Pannone, Giuseppina Iannelli, Gianluigi Vendemiale, Rosanna Villani, Rosanna Tamborra, Luke Boulter, Francesco Bellanti, Stuart J. Forbes, Wei-Yu Lu, and Gaetano Serviddio
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0301 basic medicine ,Liver injury ,Chemistry ,Cellular differentiation ,Regeneration (biology) ,Biomedical Engineering ,Medicine (miscellaneous) ,Stem cells ,Cell Biology ,medicine.disease ,Article ,Liver regeneration ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Downregulation and upregulation ,030220 oncology & carcinogenesis ,medicine ,Medicine ,Progenitor cell ,Stem cell ,Transcription factor ,Developmental Biology - Abstract
The stem cell ability to self-renew and lead regeneration relies on the balance of complex signals in their microenvironment. The identification of modulators of hepatic progenitor cell (HPC) activation is determinant for liver regeneration and may improve cell transplantation for end-stage liver disease. This investigation used different models to point out the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) as a key regulator of the HPC fate. We initially proved that in vivo models of biliary epithelial cells (BECs)/HPC activation show hepatic oxidative stress, which activates primary BECs/HPCs in vitro. NRF2 downregulation and silencing were associated with morphological, phenotypic, and functional modifications distinctive of differentiated cells. Furthermore, NRF2 activation in the biliary tract repressed the ductular reaction in injured liver. To definitely assess the importance of NRF2 in HPC biology, we applied a xenograft model by inhibiting NRF2 in the human derived HepaRG cell line and transplanting into SCID/beige mice administered with anti-Fas antibody to induce hepatocellular apoptosis; this resulted in effective human hepatocyte repopulation with reduced liver injury. To conclude, NRF2 inhibition leads to the activation and differentiation of liver progenitors. This redox-dependent transcription factor represents a potential target to regulate the commitment of undifferentiated hepatic progenitors into specific lineages.
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- 2021
48. Risk of Statin-Induced Hypertransaminasemia
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Gianluigi Vendemiale, Francesco Cavallone, Jacek Kubica, Eliano Pio Navarese, Francesco Bellanti, Antonio Facciorusso, Gaetano Serviddio, and Rosanna Villani
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medicine.medical_specialty ,Statin ,medicine.drug_class ,Atorvastatin ,030204 cardiovascular system & hematology ,Placebo ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Medicine ,Rosuvastatin ,RCTs, randomized controlled trials ,030212 general & internal medicine ,lcsh:R5-920 ,business.industry ,nutritional and metabolic diseases ,Odds ratio ,Confidence interval ,Meta-analysis ,Original Article ,lipids (amino acids, peptides, and proteins) ,business ,lcsh:Medicine (General) ,medicine.drug ,ORs, odds ratios - Abstract
Objective: To assess the effect of statins compared with placebo on the risk of developing hypertransaminasemia. Patients and Methods: We performed a systematic review of electronic databases and included articles published between January 1, 1965, and April 10, 2017. Randomized clinical trials (RCTs) comparing statins vs placebo were included. Odds ratios (ORs) were pooled in random-effect meta-analyses according to established methods recommended by the Cochrane Collaboration. Results: Seventy-three eligible RCTs, comprising 123,051 patients, were identified. Statins associated with a significantly risk of hypertransaminasemia (OR 1.45; 95% confidence interval [CI], 1.24-1.69; P
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- 2019
49. A Novel Nutraceuticals Mixture Improves Liver Steatosis by Preventing Oxidative Stress and Mitochondrial Dysfunction in a NAFLD Model
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Archana Moola, Antonino Davide Romano, Gaetano Serviddio, Loren Duda, Francesco Bellanti, Rosanna Tamborra, Moris Sangineto, Vidyasagar Naik Bukke, and Rosanna Villani
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0301 basic medicine ,Vitamin ,Male ,medicine.medical_specialty ,Mitochondrial Diseases ,medicine.medical_treatment ,lcsh:TX341-641 ,Mitochondrion ,medicine.disease_cause ,Diet, High-Fat ,Article ,Cholesterol, Dietary ,Electron Transport ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,steatosis ,Animals ,oxidative stress ,Rats, Wistar ,Nutrition and Dietetics ,Chemistry ,Vitamin E ,Fatty liver ,non-alcoholic fatty liver disease ,medicine.disease ,Rats ,Fatty Liver ,mitochondria ,030104 developmental biology ,Mitochondrial respiratory chain ,Endocrinology ,micronutrients ,Dietary Supplements ,030211 gastroenterology & hepatology ,nutraceutical ,Steatohepatitis ,Steatosis ,lcsh:Nutrition. Foods and food supply ,Oxidative stress ,Food Science - Abstract
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease globally, and represents a health care burden as treatment options are very scarce. The reason behind the NAFLD progression to non-alcoholic steatohepatitis (NASH) is not completely understood. Recently, the deficiency of micronutrients (e.g., vitamins, minerals, and other elements) has been suggested as crucial in NAFLD progression, such that recent studies reported the potential hepatic antioxidant properties of micronutrients supplementation. However, very little is known. Here we have explored the potential beneficial effects of dietary supplementation with FLINAX, a novel mixture of nutraceuticals (i.e., vitamin E, vitamin D3, olive dry-extract, cinnamon dry-extract and fish oil) in a NAFLD model characterized by oxidative stress and mitochondrial function impairment. Steatosis was firstly induced in Wistar rats by feeding with a high-fat/high-cholesterol diet for 4 weeks, and following this the rats were divided into two groups. One group (n = 8) was treated for 2 weeks with a normal chow-diet, while a second group (n = 8) was fed with a chow-diet supplemented with 2% FLINAX. Along with the entire experiment (6 weeks), a third group of rats was fed with a chow-diet only as control. Statistical analysis was performed with Student’s T test or one-way ANOVA followed by post-hoc Bonferroni test when appropriate. Steatosis, oxidative stress and mitochondrial respiratory chain (RC) complexes activity were analyzed in liver tissues. The dietary supplementation with FLINAX significantly improved hepatic steatosis and lipid accumulation compared to untreated rats. The mRNA and protein levels analysis showed that CPT1A and CPT2 were up-regulated by FLINAX, suggesting the enhancement of fatty acids oxidation (FAO). Important lipoperoxidation markers (i.e., HNE- and MDA-protein adducts) and the quantity of total mitochondrial oxidized proteins were significantly lower in FLINAX-treated rats. Intriguingly, FLINAX restored the mitochondrial function, stimulating the activity of mitochondrial RC complexes (i.e., I, II, III and ATP-synthase) and counteracting the peroxide production from pyruvate/malate (complex I) and succinate (complex II). Therefore, the supplementation with FLINAX reprogrammed the cellular energy homeostasis by restoring the efficiency of mitochondrial function, with a consequent improvement in steatosis.
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- 2021
50. Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: An individual patient data meta-analysis
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Javier Crespo, Amit G. Singal, Pei-Chien Tsai, Giuseppe Cabibbo, Zoe Mariño, Alberto Zanetto, Elisabetta Degasperi, Xavier Forns, Pierre Nahon, Hiroko Nagata, Calogero Cammà, Francesco Paolo Russo, Mohamed El Kassas, Stefano Brillanti, Mina Nakagawa, Luisa Cavalletto, Tatsuya Minami, Giacomo Emanuele Maria Rizzo, Rob Bielen, Maria Reig, Liliana Chemello, Caitlin C. Murphy, Ming-Lung Yu, Mohamed Kohla, Sarah Shalaby, Gaetano Serviddio, Jose Luis Calleja, Angelo Sangiovanni, Ashraf Omar, Rosanna Villani, Franco Trevisani, Yasuhiro Asahina, Victor Sapena, Jean-François Dufour, Claudio Zavaglia, Fabio Conti, Jordi Bruix, Kévin Jean, Ciro Celsa, José Ríos, Hend Ibrahim Shousha, Nicolás Merchante, Stanislas Pol, C. Masetti, Marco Enea, Ferran Torres, Ryosuke Tateishi, Hidenori Toyoda, Universitat de Barcelona (UB), Università degli studi di Palermo - University of Palermo, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), The University of Tokyo (UTokyo), Università degli Studi di Milano [Milano] (UNIMI), University of Bologna, University of Milan, National Kaohsiung University of Science and Technology [Taiwan], Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Helwan University [Caire], Cairo University - Faculty of Medicine, Tokyo Medical and Dental University [Japan] (TMDU), University of Texas Southwestern Medical Center, National Liver Institute [Menoufia, Egypt], Menoufia University [Egypte], PoliclinicoTor Vergata - Fondatione PTV, Bern University Hospital [Berne] (Inselspital), Universita degli Studi di Padova, ANRS France Recherche Nord & sud Sida-hiv hépatites, Universidad de Cantabria [Santander], Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Università degli Studi di Foggia - University of Foggia, Hasselt University (UHasselt), Alma Mater Studiorum University of Bologna (UNIBO), The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors., Jean, Kevin/0000-0001-6462-7185, Tateishi, Ryosuke/0000-0003-3021-2517, Rios, Jose/0000-0002-0716-8784, Reig, Maria/0000-0002-5711-9534, Bruix, Jordi/0000-0002-9826-0753, Celsa, Ciro/0000-0002-5662-2162, Youssef, Naglaa/0000-0002-0368-1759, Torres, Ferran/0000-0002-7355-7913, Sapena, Victor/0000-0003-4379-6486, RUSSO, FRANCESCO PAOLO/0000-0003-4127-8941, Minami, Tatsuya/0000-0002-2918-892X, Rizzo, Giacomo Emanuele, Maria/0000-0001-9335-6740, Merchante, Nicolas/0000-0003-1120-8942, Crespo, Javier/0000-0001-8248-0172, SHALABY, SARAH/0000-0002-8700-6282, El Kassas, Mohamed/0000-0002-3396-6894, Sapena, Victor, Enea, Marco, Torres , Ferran, Celsa, Ciro, Rios, Jose, Rizzo, Giacomo Emanuele Maria, Nahon, Pierre, Marino, Zoe, Tateishi, Ryosuke, Minami, Tatsuya, Sangiovanni, Angelo, Forns, Xavier, Toyoda, Hidenori, Brillanti, Stefano, Conti, Fabio, Degasperi, Elisabetta, Yu, Ming-Lung, Tsai, Pei-Chien, Jean, Kevin, El Kassas, Mohamed, Shousha, Hend Ibrahim, Omar, Ashraf, Zavaglia, Claudio, Nagata, Hiroko, Nakagawa, Mina, Asahina, Yasuhiro, Singal, Amit G., Murphy, Caitlin, Kohla, Mohamed, Masetti, Chiara, Dufour, Jean-Francois, Merchante, Nicolas, Cavalletto, Luisa, Chemello, Liliana L. C., Pol, Stanislas, Crespo, Javier, Calleja, Jose Luis, Villani, Rosanna, Serviddio, Gaetano, Zanetto, Alberto, Shalaby, Sarah, Russo, Francesco Paolo, BIELEN, Rob, Trevisani, Franco, Camma, Calogero, Bruix, Jordi, Cabibbo, Giuseppe, Reig, Maria, Sapena V., Enea M., Torres F., Celsa C., Rios J., Rizzo G.E.M., Nahon P., Marino Z., Tateishi R., Minami T., Sangiovanni A., Forns X., Toyoda H., Brillanti S., Conti F., Degasperi E., Yu M.-L., Tsai P.-C., Jean K., El Kassas M., Shousha H.I., Omar A., Zavaglia C., Nagata H., Nakagawa M., Asahina Y., Singal A.G., Murphy C., Kohla M., Masetti C., Dufour J.-F., Merchante N., Cavalletto L., Chemello L.L.C., Pol S., Crespo J., Calleja J.L., Villani R., Serviddio G., Zanetto A., Shalaby S., Russo F.P., Bielen R., Trevisani F., Camma C., Bruix J., Cabibbo G., Reig M., Università degli Studi di Milano = University of Milan (UNIMI), University of Bologna/Università di Bologna, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Università degli Studi di Padova = University of Padua (Unipd), Università degli Studi di Foggia = University of Foggia (Unifg), and Cammà Calogero
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medicine.medical_specialty ,Carcinoma, Hepatocellular ,Cirrhosis ,Antiviral Agents ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,antiviral therapy ,medicine ,Humans ,Propensity Score ,hepatocellular carcinoma ,meta-analysis ,business.industry ,Liver Neoplasms ,Antiviral therapy ,Patient data ,medicine.disease ,3. Good health ,030220 oncology & carcinogenesis ,Meta-analysis ,Hepatocellular carcinoma ,Relative risk ,Cohort ,030211 gastroenterology & hepatology ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Neoplasm Recurrence, Local ,business ,Direct acting - Abstract
ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; pConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.
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- 2021
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