Venanzio Valenza - Academia.edu (original) (raw)

Papers by Venanzio Valenza

Journal of Translational Medicine, Apr 17, 2018

Background: Recurrent pregnancy loss (RPL) occurs in 3-5% in about 30% of cases no cause can be f... more Background: Recurrent pregnancy loss (RPL) occurs in 3-5% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation. Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent 51 Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20 healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1β and IL-18 by ELISA, respectively. Results: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS (P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial expression of Nalp-3, caspase-1 and IL-1β was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001, respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women. Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers, potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis. Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and pregnancy outcome.

This chapter is designed to clarify the role of Nuclear Medicine in the clinical decision-making ... more This chapter is designed to clarify the role of Nuclear Medicine in the clinical decision-making process of non-oncological diseases. It presents a number of typical cases referring to one or a group of diseases. Being diverse in scope, the cases provide relevant information on the usefulness of nuclear medicine examinations in clinical practice. In particular, individual cases focus on common neurological, cardiological, skeletal and gastrointestinal disorders. Moreover, joint inflammation/infection, lymphatic disease and endocrinological disorders are reported.

Digestive and Liver Disease, 2021

BACKGROUND Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated w... more BACKGROUND Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated with insulin resistance, and its association with metabolically associated fatty liver disease (MAFLD) has never been explored in prospective studies. The aim of this study was to assess the clinical features of MAFLD in DM1 patients. METHODS We investigated the prevalence and the diagnostic features of MAFLD in a cohort of 29 outpatient fully characterized DM1 patients; afterward, we compared the selected cohort of DM1-MAFLD individuals with a propensity-matched cohort of non-DM1-MAFLD RESULTS: 13/29 (44.83%) DM1 patients received a clinical diagnosis of MAFLD. Compared to DM1 patients with normal liver, DM1-MAFLD individuals showed a higher male prevalence (p = 0.008), BMI (p = 0.014), HOMA score (p = 0.012), and GGT levels (p = 0.050). The statistical comparison showed that the DM1-MAFLD group had a more severe MAFLD according to the FIB4 score than non-DM1-MAFLD patients. This association of a more severe form of liver disease with DM1 remained significant after logistic regression analysis (OR: 6.12, 95% CI 1.44- 26.55).

Current Radiopharmaceuticals, 2022

Introduction: Pulmonary embolism (PE) can be diagnosed by perfusion lung scintigra-phy using huma... more Introduction: Pulmonary embolism (PE) can be diagnosed by perfusion lung scintigra-phy using human albumin macroaggregates labelled 99mTc (99mTc-MAA). When PE is suspected, subcutaneous Low Molecular Weight Heparin (LMWH) should be administered even before the results of the PE diagnostic flowchart. In our study, we aimed to evaluate a possible interaction (in vitro interference) between 99mTc-MAA and LMWH. Materials and Methods: The reconstitution of MAA kit was performed according to the manufac-turer's instruction. After labelling, we carried out the following preparations: a standard dose of 99mTc-MAA alone, as control; 99mTc-MAA and enoxaparin at different ratios. According to the manufacturer's instruction, the radiochemical purity was performed and evaluated immediately (T0), after 15 and 30 minutes after incubation (T15 and T30). Results: We compared the radiochemical purity of 99mTc-MAA with: (i) radiochemical purity of 99mTc-MAA and enoxaparin (11 ratio), (ii) radi...

Digestive and Liver Disease, 2017

is satisfactory in 92% of patients and significantly affects the overall satisfaction. Regarding ... more is satisfactory in 92% of patients and significantly affects the overall satisfaction. Regarding the information received before the examination, the satisfaction is of 92%, while it comes down to 85% for those received after: both have a significant impact (p<0.001) on overall satisfaction. All other parameters analyzed don't impact significantly on overall satisfaction. Altogether more than 94% of patients is satisfied or fully satisfied for examination, so that the 96% would return at our Unit or would recommend to other people. Conclusions: The data collected with this study have enable to highlight aspects that influence customer satisfaction of outpatients undergoing endoscopic examinations at our Operative Unit: the survey confirms the importance of logistic and social skills than those technicians.

Digestive and Liver Disease, 2016

Introduction: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive disease with... more Introduction: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive disease with almost absent LAL activity, characterized by massive microvesicular steatosis evolving to cirrhosis and liver failure. Milder reductions in LAL function have been recently described in patients with NAFLD. Aim: We aimed to determine LAL activity in a population of patients with cryptogenic cirrhosis. Materials and methods: Consecutive patients with cryptogenic cirrhosis were enrolled. Two age/sex-matched control groups were selected: patients with cirrhosis of known etiology; healthy subjects undergoing medicine checkups. LAL activity was dosed with dried-blood technique using the inhibitor Lalistat-2. Results: Sixty patients with cryptogenic cirrhosis, 80 patients with cirrhosis from other etiology (HCV: 45; alcohol: 23; HBV: 7; autoimmune: 5), and 80 healthy subjects were enrolled. Patients with cryptogenic cirrhosis had a mean BMI of 31.1 ± 7.9 kg/m 2 and a high prevalence of diabetes (66%), consistent with a prevalent metabolic etiology. LAL activity was strongly reduced in patients with cryptogenic cirrhosis with respect to healthy subjects (0.64 ± 0.29 vs 1.05 ± 0.42 nmol/spot/h, p < 0.001), but similarly reduced also in other cirrhotics (0.63 ± 0.33 nmol/spot/h; p < 0.001 vs healthy subjects; p = 0.5 vs cryptogenic cirrhotics). In the entire cirrhotic group, LAL activity was not correlated with age, sex, or Child-Pugh class, but directly correlated with platelet number (=0.43; p < 0.001), and inversely with spleen volume (cm 2) (= −0.22; p = 0.01), and presence of oesophageal varices (= −0.19; p < 0.05). Conclusions: LAL activity is severely reduced in cirrhosis of any etiology, and the impaired LAL function is possibly implicated in severe alterations of cholesterol metabolism characterizing cirrhosis (cellular membrane stability; biliary acid and sex hormone metabolism, etc.). Determinants of reduced LAL activity are likely epigenetic/post-transcriptional factors not tightly dependent on liver function but possibly associated with portal hypertension.

Digestive and Liver Disease, 2016

Nuclear Medicine Textbook, 2019

This chapter is designed to clarify the role of Nuclear Medicine in the clinical decision-making ... more This chapter is designed to clarify the role of Nuclear Medicine in the clinical decision-making process of non-oncological diseases. It presents a number of typical cases referring to one or a group of diseases. Being diverse in scope, the cases provide relevant information on the usefulness of nuclear medicine examinations in clinical practice. In particular, individual cases focus on common neurological, cardiological, skeletal and gastrointestinal disorders. Moreover, joint inflammation/infection, lymphatic disease and endocrinological disorders are reported.

Clinical Nuclear Medicine, 2018

A 47-year-old man, with a history of anabolic steroid abuse, developed hepatic adenomatosis and m... more A 47-year-old man, with a history of anabolic steroid abuse, developed hepatic adenomatosis and multifocal hepatocellular carcinoma. He underwent ultrasound and CT follow-up, showing multiple solid and fluid hepatic lesions. Consequently, hospitalization was required because of high fever (up to 39°C), weakness, and anorexia. An abdominal CT scan revealed an enlargement of one of the intrahepatic fluid collections. Biochemical and microbiological analyses of a fluid sample showed bilirubin and bile acids as well as Streptococcus cristatus and Enterobacter cloacae. Thus, the patient underwent 99m Tc-trimethylbromo-iminodiacetic acid scintigraphy, demonstrating bile collection in the lesion with a flow from a bile duct.

Journal of Men's Health

Background: Single Photon Emission Computed Tomography (SPECT) could be used to avoid the non-aff... more Background: Single Photon Emission Computed Tomography (SPECT) could be used to avoid the non-affected perfusion areas in patients with non-small-cell lung cancer (NSCLC) and to potentially reduce lung toxicity. The aim of this study is to compare dosimetric differences between two different 3D-conformal treatment plans, with and without CT/SPECT contribution. Methods: Simulation Computed tomography (CT) scans were accurately co-registered with SPECT scans and three different areas, based on SPECT intensity perfusion, were contoured: low perfusion (LP), medium perfusion (MP) and high perfusion (HP). Two different 3D-conformal plans, with co-planar and nonco-planar fields, were generated; one without SPECT information (anatomic plan), and one using the perfusion area identified with functional imaging (functional plan). Results: 9 patients were planned and a total of 18 plans were available for analysis. Anatomical and functional plans resulted in comparable planning target volume (PTV) coverage. In the functional plans, a significant reduction of dose in high perfusion areas was reported. The reduction of HP-V20 Gy values ranged from 15% to 8% (p = 0.046), the ipsiHP-V20 Gy from 38% to 22% (p = 0.028) and ipsiHP-Dmean reduction from 16 Gy to 12 Gy (p = 0.039). No significant differences in other organs at risk (OARs) metrics were reported between anatomical and functional plans. Conclusions: Despite the few cases reported, the strength of our study lies in the reported benefit of functional lung information in 3D conformal radiation planning, without compromising target coverage or worsening dose distribution to the OARs. There is an urgent need for prospective clinical and randomized trials in order to define the role of lung functional imaging in reducing toxicity in clinical practice.

Clinical Nuclear Medicine, 2021

Dysphagia, 2020

Dysphagia is common in tracheostomized patients who underwent head and neck surgery for cancer tr... more Dysphagia is common in tracheostomized patients who underwent head and neck surgery for cancer treatment. The objective of this study was to evaluate, by means of oropharyngoesophageal scintigraphy (OPES), the impact of an occluded tracheal tube (TT) on swallowing in patients treated for head and neck cancer before hospital discharge, to provide further information to the benefit of out-patient care management. From October 2018 to November 2019, we enrolled 19 tracheostomized patients (6 females and 13 males; mean age 61 years) who underwent primary surgical resection of head and neck tumor and swallowing rehabilitation during hospitalization. All subjects underwent a double-standard OPES, one with occluded tracheal tube and the other without TT, with their tracheal stoma being closed directly by a plaster. For each study, we assessed and compared the following quantitative parameters: oral transit time (OTTsec), pharyngeal transit time (PTTsec), esophageal transit time (ETTsec), o...

Journal of Translational Medicine, 2019

Journal of Hepatology, 2013

of AI increased according to severity of liver disease (25, 44, and 73% in Child–Pugh class A, B,... more of AI increased according to severity of liver disease (25, 44, and 73% in Child–Pugh class A, B, and C respectively; p = 0.047). There were negative correlations between Child–Pugh score and both basal cortisol (g = −0.377, p = 0.007) and peak cortisol levels (g = −0.373, p < 0.005) (Figure). Conclusions: In this study, AI was frequent in stable cirrhotic patients without infections or hemodynamic instability. AI was not related to the etiology of cirrhosis or alcohol consumption, either. AI tended to be associated with only severity of liver disease.

PLOS ONE, 2020

Background Liver cirrhosis has been known to be associated with increased intestinal permeability... more Background Liver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections. Methods LT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid (51 Cr-EDTA). Results The median 51 Cr-EDTA excretion was found to be higher in 35 LT recipients as compared with that in the healthy controls [4.77% (2.79-6.03) vs. 2.07% (1.57-2.42), p<0.0001], and comparable to that in the cirrhotic patients [3.69% (2.34-6.57), p = 0.445]. 51 Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections [infection/no infection: 4.97% (3.14-7.03) vs 4.62% (2.79-5.82), p = 0.938]. Conclusion LT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted.

Frontiers in Neurology, 2020

Myotonic dystrophy type 1 (DM1, MIM #160900), the most common muscular dystrophy among adults, is... more Myotonic dystrophy type 1 (DM1, MIM #160900), the most common muscular dystrophy among adults, is a multisystem disorder, which affects, besides the skeletal muscle, several other tissues and/or organs, including the gastrointestinal apparatus, with manifestations that frequently affect the quality of life of DM1 patients. So far, only few, mainly retrospective studies evaluated this specific topic in DM1, so we performed a perspective study, enrolling 61 DM1 patients who underwent an extensive diagnostic protocol, including administration of the Gastrointestinal Symptom Rating Scale (GSRS), a validated patient-reported questionnaire about GI symptoms, laboratory tests, liver US scan, and an intestinal permeability assay, in order to characterize frequency and assess correlations regarding specific gastrointestinal manifestations with demographic or other DM1-related features. Our results in our DM1 cohort confirm the high frequency of various gastrointestinal manifestations, with the most frequent being constipation (45.9%). γGT levels were pathologically increased in 65% of DM1 patients and GPT in 29.82%; liver ultrasound studies showed steatosis in 34.4% of patients. Significantly, 91.22% of DM1 patients showed signs of altered intestinal permeability at the specific assay. We documented a gender-related prevalence and severity of gastrointestinal manifestations in DM1 females compared to DM1 males, while males showed higher serum GPT and γGT levels than females. Correlation studies documented a direct correlation between severity of muscle weakness estimated by MIRS score and γGT and alkaline phosphatase levels, suggesting their potential use as biomarkers of muscle disease severity in DM1.

Journal of the American College of Cardiology, 2014

background: Gut micro-flora is associated with systemic inflammation in several conditions and wi... more background: Gut micro-flora is associated with systemic inflammation in several conditions and with heart damage in shock and sepsis. In normal conditions commensals of intestinal mucosa induce a self-limiting inflammatory process, without tissue damage, resulting in a state of immunological tolerance. Conversely, their translocation into the blood stream may cause an inflammatory reaction, triggering the transcription of a variety of cytokines (CYT), chemokines, acute-phase proteins and cell adhesion molecules. We hypothesized a role of the gut micro-flora translocation in the pathogenesis of coronary atherosclerosis and in atherosclerotic plaque instability. methods: we studied 22 patients (pts) with coronary artery disease (CAD), normal ejection fraction and without alteration in gastrointestinal or colonic transit and motility. Each pts underwent 51Cr-EDTA test to investigate gut permeability (GP). Elimination in the urine of 51Cr-EDTA is expressed as a fraction of the orally administered dose. We considered normal GP a value < 3.5% according to literature. In 10 of these 22 pts blood samples were also collected to assess the systemic inflammatory pattern by multiplex CYT assay for 11 different CYT. results: 17 out of 22 pts (77%) presented an alteration of GP, 8 pts with Acute Coronary Syndrome (ACS)and 9 pts with stable angina (SA), without significant differences between the two groups (6.05% vs 6.97%, p=ns). Only 5 pts presented a normal GP (p<0.033). GP was altered in 6 out of the 10 pts tested for CYT. We found differences in CYT levels between altered vs normal GP only for 3 cytokines: IL-6 (promotes gut wall recovery favouring a normal GP) showed a strong inverse relation with GP (r=0.903, p= 0.001). VEGF (promotes plaque stability) was higher in pts with normal GP (35,82±110,56 pmol/ml vs 57,168±46,56 pmol/ml; p=0.09); while GM-CSF (enhances leukocyte infiltration) was higher in pts with altered GP (105,77 ± 58,77 pmol/ml vs 59,80 ± 18,40 pmol/ml; p=0.067). Conclusions: Our preliminary data suggest that altered GP is common in pts with CAD and may have a role in atherosclerosis and is associated with an altered balance of pro-inflammatory cytokines.

Journal of Translational Medicine, Apr 17, 2018

Background: Recurrent pregnancy loss (RPL) occurs in 3-5% in about 30% of cases no cause can be f... more Background: Recurrent pregnancy loss (RPL) occurs in 3-5% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation. Methods: 70 women with idiopathic RPL and 30 healthy women were recruited at the Recurrent Pregnancy Loss Outpatient Unit of the Gemelli Hospital of Rome from March 2013 to February 2017. Enrolled women underwent 51 Cr-ethylene-diamine-tetraacetic acid absorption test to evaluate intestinal permeability. Sera obtained from enrolled women were analysed for lipopolysaccharide (LPS) by ELISA. Anxiety and depression state were evaluated by administering STAI-Y and Zung-SDS tests, respectively. Of all recruited individuals, 35 women with idiopathic RPL and 20 healthy controls accepted to undergo diagnostic hysteroscopy and endometrial biopsy. Endometrial lysates were investigated for inflammasome Nalp-3 by Western blot analysis, and caspase-1, IL-1β and IL-18 by ELISA, respectively. Results: Higher prevalence of abnormal intestinal permeability (P < 0.0001), increased circulating levels of LPS (P < 0.05), anxiety (P < 0.05) and depression (P < 0.05) were observed in RLP women compared to controls. Endometrial expression of Nalp-3, caspase-1 and IL-1β was significantly increased in RPL group (P < 0.0001; P < 0.05 and P < 0.001, respectively). IL-18 endometrial levels were not found to be higher in RPL cases. Statistically significant association between higher intestinal permeability and abnormally increased expression of endometrial Nalp-3, was observed in RPL (P < 0.01). Furthermore, higher LPS serum levels, a bacterial-derived activator of Nalp-3 complex, was shown to be statistically associated to abnormal endometrial expression of Nalp-3 inflammasome (P < 0.01) in RPL women. Conclusions: In women with RLP, leaky gut might occur and allow passage into circulation of immune triggers, potentially able to elicit endometrial innate immune response and, thus, to contribute to miscarriage pathogenesis. Diagnosis and treatment of intestinal disorders underlying leaky gut might improve endometrial environment and pregnancy outcome.

This chapter is designed to clarify the role of Nuclear Medicine in the clinical decision-making ... more This chapter is designed to clarify the role of Nuclear Medicine in the clinical decision-making process of non-oncological diseases. It presents a number of typical cases referring to one or a group of diseases. Being diverse in scope, the cases provide relevant information on the usefulness of nuclear medicine examinations in clinical practice. In particular, individual cases focus on common neurological, cardiological, skeletal and gastrointestinal disorders. Moreover, joint inflammation/infection, lymphatic disease and endocrinological disorders are reported.

Digestive and Liver Disease, 2021

BACKGROUND Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated w... more BACKGROUND Myotonic dystrophy type 1 (DM1) is a rare inherited neuromuscular disease associated with insulin resistance, and its association with metabolically associated fatty liver disease (MAFLD) has never been explored in prospective studies. The aim of this study was to assess the clinical features of MAFLD in DM1 patients. METHODS We investigated the prevalence and the diagnostic features of MAFLD in a cohort of 29 outpatient fully characterized DM1 patients; afterward, we compared the selected cohort of DM1-MAFLD individuals with a propensity-matched cohort of non-DM1-MAFLD RESULTS: 13/29 (44.83%) DM1 patients received a clinical diagnosis of MAFLD. Compared to DM1 patients with normal liver, DM1-MAFLD individuals showed a higher male prevalence (p = 0.008), BMI (p = 0.014), HOMA score (p = 0.012), and GGT levels (p = 0.050). The statistical comparison showed that the DM1-MAFLD group had a more severe MAFLD according to the FIB4 score than non-DM1-MAFLD patients. This association of a more severe form of liver disease with DM1 remained significant after logistic regression analysis (OR: 6.12, 95% CI 1.44- 26.55).

Current Radiopharmaceuticals, 2022

Introduction: Pulmonary embolism (PE) can be diagnosed by perfusion lung scintigra-phy using huma... more Introduction: Pulmonary embolism (PE) can be diagnosed by perfusion lung scintigra-phy using human albumin macroaggregates labelled 99mTc (99mTc-MAA). When PE is suspected, subcutaneous Low Molecular Weight Heparin (LMWH) should be administered even before the results of the PE diagnostic flowchart. In our study, we aimed to evaluate a possible interaction (in vitro interference) between 99mTc-MAA and LMWH. Materials and Methods: The reconstitution of MAA kit was performed according to the manufac-turer's instruction. After labelling, we carried out the following preparations: a standard dose of 99mTc-MAA alone, as control; 99mTc-MAA and enoxaparin at different ratios. According to the manufacturer's instruction, the radiochemical purity was performed and evaluated immediately (T0), after 15 and 30 minutes after incubation (T15 and T30). Results: We compared the radiochemical purity of 99mTc-MAA with: (i) radiochemical purity of 99mTc-MAA and enoxaparin (11 ratio), (ii) radi...

Digestive and Liver Disease, 2017

is satisfactory in 92% of patients and significantly affects the overall satisfaction. Regarding ... more is satisfactory in 92% of patients and significantly affects the overall satisfaction. Regarding the information received before the examination, the satisfaction is of 92%, while it comes down to 85% for those received after: both have a significant impact (p<0.001) on overall satisfaction. All other parameters analyzed don't impact significantly on overall satisfaction. Altogether more than 94% of patients is satisfied or fully satisfied for examination, so that the 96% would return at our Unit or would recommend to other people. Conclusions: The data collected with this study have enable to highlight aspects that influence customer satisfaction of outpatients undergoing endoscopic examinations at our Operative Unit: the survey confirms the importance of logistic and social skills than those technicians.

Digestive and Liver Disease, 2016

Introduction: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive disease with... more Introduction: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive disease with almost absent LAL activity, characterized by massive microvesicular steatosis evolving to cirrhosis and liver failure. Milder reductions in LAL function have been recently described in patients with NAFLD. Aim: We aimed to determine LAL activity in a population of patients with cryptogenic cirrhosis. Materials and methods: Consecutive patients with cryptogenic cirrhosis were enrolled. Two age/sex-matched control groups were selected: patients with cirrhosis of known etiology; healthy subjects undergoing medicine checkups. LAL activity was dosed with dried-blood technique using the inhibitor Lalistat-2. Results: Sixty patients with cryptogenic cirrhosis, 80 patients with cirrhosis from other etiology (HCV: 45; alcohol: 23; HBV: 7; autoimmune: 5), and 80 healthy subjects were enrolled. Patients with cryptogenic cirrhosis had a mean BMI of 31.1 ± 7.9 kg/m 2 and a high prevalence of diabetes (66%), consistent with a prevalent metabolic etiology. LAL activity was strongly reduced in patients with cryptogenic cirrhosis with respect to healthy subjects (0.64 ± 0.29 vs 1.05 ± 0.42 nmol/spot/h, p < 0.001), but similarly reduced also in other cirrhotics (0.63 ± 0.33 nmol/spot/h; p < 0.001 vs healthy subjects; p = 0.5 vs cryptogenic cirrhotics). In the entire cirrhotic group, LAL activity was not correlated with age, sex, or Child-Pugh class, but directly correlated with platelet number (=0.43; p < 0.001), and inversely with spleen volume (cm 2) (= −0.22; p = 0.01), and presence of oesophageal varices (= −0.19; p < 0.05). Conclusions: LAL activity is severely reduced in cirrhosis of any etiology, and the impaired LAL function is possibly implicated in severe alterations of cholesterol metabolism characterizing cirrhosis (cellular membrane stability; biliary acid and sex hormone metabolism, etc.). Determinants of reduced LAL activity are likely epigenetic/post-transcriptional factors not tightly dependent on liver function but possibly associated with portal hypertension.

Digestive and Liver Disease, 2016

Nuclear Medicine Textbook, 2019

This chapter is designed to clarify the role of Nuclear Medicine in the clinical decision-making ... more This chapter is designed to clarify the role of Nuclear Medicine in the clinical decision-making process of non-oncological diseases. It presents a number of typical cases referring to one or a group of diseases. Being diverse in scope, the cases provide relevant information on the usefulness of nuclear medicine examinations in clinical practice. In particular, individual cases focus on common neurological, cardiological, skeletal and gastrointestinal disorders. Moreover, joint inflammation/infection, lymphatic disease and endocrinological disorders are reported.

Clinical Nuclear Medicine, 2018

A 47-year-old man, with a history of anabolic steroid abuse, developed hepatic adenomatosis and m... more A 47-year-old man, with a history of anabolic steroid abuse, developed hepatic adenomatosis and multifocal hepatocellular carcinoma. He underwent ultrasound and CT follow-up, showing multiple solid and fluid hepatic lesions. Consequently, hospitalization was required because of high fever (up to 39°C), weakness, and anorexia. An abdominal CT scan revealed an enlargement of one of the intrahepatic fluid collections. Biochemical and microbiological analyses of a fluid sample showed bilirubin and bile acids as well as Streptococcus cristatus and Enterobacter cloacae. Thus, the patient underwent 99m Tc-trimethylbromo-iminodiacetic acid scintigraphy, demonstrating bile collection in the lesion with a flow from a bile duct.

Journal of Men's Health

Background: Single Photon Emission Computed Tomography (SPECT) could be used to avoid the non-aff... more Background: Single Photon Emission Computed Tomography (SPECT) could be used to avoid the non-affected perfusion areas in patients with non-small-cell lung cancer (NSCLC) and to potentially reduce lung toxicity. The aim of this study is to compare dosimetric differences between two different 3D-conformal treatment plans, with and without CT/SPECT contribution. Methods: Simulation Computed tomography (CT) scans were accurately co-registered with SPECT scans and three different areas, based on SPECT intensity perfusion, were contoured: low perfusion (LP), medium perfusion (MP) and high perfusion (HP). Two different 3D-conformal plans, with co-planar and nonco-planar fields, were generated; one without SPECT information (anatomic plan), and one using the perfusion area identified with functional imaging (functional plan). Results: 9 patients were planned and a total of 18 plans were available for analysis. Anatomical and functional plans resulted in comparable planning target volume (PTV) coverage. In the functional plans, a significant reduction of dose in high perfusion areas was reported. The reduction of HP-V20 Gy values ranged from 15% to 8% (p = 0.046), the ipsiHP-V20 Gy from 38% to 22% (p = 0.028) and ipsiHP-Dmean reduction from 16 Gy to 12 Gy (p = 0.039). No significant differences in other organs at risk (OARs) metrics were reported between anatomical and functional plans. Conclusions: Despite the few cases reported, the strength of our study lies in the reported benefit of functional lung information in 3D conformal radiation planning, without compromising target coverage or worsening dose distribution to the OARs. There is an urgent need for prospective clinical and randomized trials in order to define the role of lung functional imaging in reducing toxicity in clinical practice.

Clinical Nuclear Medicine, 2021

Dysphagia, 2020

Dysphagia is common in tracheostomized patients who underwent head and neck surgery for cancer tr... more Dysphagia is common in tracheostomized patients who underwent head and neck surgery for cancer treatment. The objective of this study was to evaluate, by means of oropharyngoesophageal scintigraphy (OPES), the impact of an occluded tracheal tube (TT) on swallowing in patients treated for head and neck cancer before hospital discharge, to provide further information to the benefit of out-patient care management. From October 2018 to November 2019, we enrolled 19 tracheostomized patients (6 females and 13 males; mean age 61 years) who underwent primary surgical resection of head and neck tumor and swallowing rehabilitation during hospitalization. All subjects underwent a double-standard OPES, one with occluded tracheal tube and the other without TT, with their tracheal stoma being closed directly by a plaster. For each study, we assessed and compared the following quantitative parameters: oral transit time (OTTsec), pharyngeal transit time (PTTsec), esophageal transit time (ETTsec), o...

Journal of Translational Medicine, 2019

Journal of Hepatology, 2013

of AI increased according to severity of liver disease (25, 44, and 73% in Child–Pugh class A, B,... more of AI increased according to severity of liver disease (25, 44, and 73% in Child–Pugh class A, B, and C respectively; p = 0.047). There were negative correlations between Child–Pugh score and both basal cortisol (g = −0.377, p = 0.007) and peak cortisol levels (g = −0.373, p < 0.005) (Figure). Conclusions: In this study, AI was frequent in stable cirrhotic patients without infections or hemodynamic instability. AI was not related to the etiology of cirrhosis or alcohol consumption, either. AI tended to be associated with only severity of liver disease.

PLOS ONE, 2020

Background Liver cirrhosis has been known to be associated with increased intestinal permeability... more Background Liver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections. Methods LT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid (51 Cr-EDTA). Results The median 51 Cr-EDTA excretion was found to be higher in 35 LT recipients as compared with that in the healthy controls [4.77% (2.79-6.03) vs. 2.07% (1.57-2.42), p<0.0001], and comparable to that in the cirrhotic patients [3.69% (2.34-6.57), p = 0.445]. 51 Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections [infection/no infection: 4.97% (3.14-7.03) vs 4.62% (2.79-5.82), p = 0.938]. Conclusion LT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted.

Frontiers in Neurology, 2020

Myotonic dystrophy type 1 (DM1, MIM #160900), the most common muscular dystrophy among adults, is... more Myotonic dystrophy type 1 (DM1, MIM #160900), the most common muscular dystrophy among adults, is a multisystem disorder, which affects, besides the skeletal muscle, several other tissues and/or organs, including the gastrointestinal apparatus, with manifestations that frequently affect the quality of life of DM1 patients. So far, only few, mainly retrospective studies evaluated this specific topic in DM1, so we performed a perspective study, enrolling 61 DM1 patients who underwent an extensive diagnostic protocol, including administration of the Gastrointestinal Symptom Rating Scale (GSRS), a validated patient-reported questionnaire about GI symptoms, laboratory tests, liver US scan, and an intestinal permeability assay, in order to characterize frequency and assess correlations regarding specific gastrointestinal manifestations with demographic or other DM1-related features. Our results in our DM1 cohort confirm the high frequency of various gastrointestinal manifestations, with the most frequent being constipation (45.9%). γGT levels were pathologically increased in 65% of DM1 patients and GPT in 29.82%; liver ultrasound studies showed steatosis in 34.4% of patients. Significantly, 91.22% of DM1 patients showed signs of altered intestinal permeability at the specific assay. We documented a gender-related prevalence and severity of gastrointestinal manifestations in DM1 females compared to DM1 males, while males showed higher serum GPT and γGT levels than females. Correlation studies documented a direct correlation between severity of muscle weakness estimated by MIRS score and γGT and alkaline phosphatase levels, suggesting their potential use as biomarkers of muscle disease severity in DM1.

Journal of the American College of Cardiology, 2014

background: Gut micro-flora is associated with systemic inflammation in several conditions and wi... more background: Gut micro-flora is associated with systemic inflammation in several conditions and with heart damage in shock and sepsis. In normal conditions commensals of intestinal mucosa induce a self-limiting inflammatory process, without tissue damage, resulting in a state of immunological tolerance. Conversely, their translocation into the blood stream may cause an inflammatory reaction, triggering the transcription of a variety of cytokines (CYT), chemokines, acute-phase proteins and cell adhesion molecules. We hypothesized a role of the gut micro-flora translocation in the pathogenesis of coronary atherosclerosis and in atherosclerotic plaque instability. methods: we studied 22 patients (pts) with coronary artery disease (CAD), normal ejection fraction and without alteration in gastrointestinal or colonic transit and motility. Each pts underwent 51Cr-EDTA test to investigate gut permeability (GP). Elimination in the urine of 51Cr-EDTA is expressed as a fraction of the orally administered dose. We considered normal GP a value < 3.5% according to literature. In 10 of these 22 pts blood samples were also collected to assess the systemic inflammatory pattern by multiplex CYT assay for 11 different CYT. results: 17 out of 22 pts (77%) presented an alteration of GP, 8 pts with Acute Coronary Syndrome (ACS)and 9 pts with stable angina (SA), without significant differences between the two groups (6.05% vs 6.97%, p=ns). Only 5 pts presented a normal GP (p<0.033). GP was altered in 6 out of the 10 pts tested for CYT. We found differences in CYT levels between altered vs normal GP only for 3 cytokines: IL-6 (promotes gut wall recovery favouring a normal GP) showed a strong inverse relation with GP (r=0.903, p= 0.001). VEGF (promotes plaque stability) was higher in pts with normal GP (35,82±110,56 pmol/ml vs 57,168±46,56 pmol/ml; p=0.09); while GM-CSF (enhances leukocyte infiltration) was higher in pts with altered GP (105,77 ± 58,77 pmol/ml vs 59,80 ± 18,40 pmol/ml; p=0.067). Conclusions: Our preliminary data suggest that altered GP is common in pts with CAD and may have a role in atherosclerosis and is associated with an altered balance of pro-inflammatory cytokines.