Aurelio Sonzogni - Academia.edu (original) (raw)

Papers by Aurelio Sonzogni

Journal of Hepatology, 2013

93 AUTOIMMUNE ACUTE LIVER FAILURE IN CHILDREN: CLINICAL CLUES AND A NEW DIAGNOSTIC SCORE A. Di Gi... more 93 AUTOIMMUNE ACUTE LIVER FAILURE IN CHILDREN: CLINICAL CLUES AND A NEW DIAGNOSTIC SCORE A. Di Giorgio, M. Bravi, E. Bonanomi, G. Alessio, A. Sonzogni, M. Colledan, L. D’Antiga. Paediatric Liver, GI and Transplantation, Paediatric Intensive Care, Laboratory Medicine, Transplant Pathology, General Surgery and Transplantation, Ospedali Riuniti Bergamo, Bergamo, Italy E-mail: ldantiga@ospedaliriuniti.bergamo.it

Digestive and Liver Disease, 2012

Nature Communications, 2015

Journal of Applied Physiology, 2021

Hypothesizing that the non-aerated lung fraction as evaluated by the quantitative analysis of the... more Hypothesizing that the non-aerated lung fraction as evaluated by the quantitative analysis of the lung computed tomography (CT) equals shunt (VA/Q = 0), we used a computational approach to estimate the magnitude of the ventilation–perfusion mismatch in severe COVID-19. The results show that a severe hyperperfusion of poorly ventilated lung region is likely the cause of the hypoxemia observed. The extensive microthrombosis of the pulmonary circulation may represent the pathophysiological mechanism of such VA/Q distribution.

Hepatology International, 2019

Objectives and study Various degrees of biliary changes are considered to be part of the histolog... more Objectives and study Various degrees of biliary changes are considered to be part of the histological picture of children with pediatrics autoimmune liver disease (AILD), but the literature is scarce and confusing. We aimed to describe the characteristics of children with AILD (autoimmune hepatitis, AIH, and autoimmune sclerosing cholangitis, ASC) focusing on the prevalence and type of biliary abnormalities on initial biopsy to see whether ASC was predictable on histological ground. Methods The files of children diagnosed with AILD were reviewed. The Ishak score was used to grade inflammation and fibrosis on biopsy; a biliary score was built to grade bile duct injury. Demographic, laboratory and histological features at diagnosis were reported and compared between the two groups (AIH vs ASC). Results Forty-one patients were diagnosed with AIH (n = 24), ASC (n = 13) and PSC (n = 4) between 2009 and 2018. Twentynine patients [F = 76%, AIH = 20, ASC = 9, median age at diagnosis 11.7 (range 2.2-17.8)] were included in the study; 12 (4 with PSC) were excluded. Prevalence of inflammatory bowel disease was higher in ASC group (56% vs 10% in AIH, p < 0.05). On histology 17% had cirrhosis. The grade of biliopathy with AILD was moderate in 72% and severe in 31%, and overall more prominent in ASC (p = 0.031). The inflammation of the bile ducts was classified as "multifocal" or "diffuse" mainly in ASC patients (89% vs 45% in AIH, p = 0.043). Periductular fibrosis was reported in 52% of AILD patients, with a higher mean score in ASC group (p < 0.05). However, ductular reaction, biliary metaplasia and granulomatous cholangitis were equally reported in AIH and ASC, providing no clear-cut for the distinction of the two entities in the global histological evaluation. Conclusions Majority of patients with pediatrics AILD have "moderate" or "severe" features of biliopathy; AIH and ASC are not easily distinguishable on histological ground at diagnosis, and therefore, the cholangiogram remains the only effective tool to differentiate patients with AIH from those with ASC. Further prospective studies are needed to better define histological biliary features in AILD, assess if the biliopathy responds to immunosuppressive treatment and evaluate its impact on long-term outcome.

Chest, 2018

Background. The deficiency of α 1-antitrypsin (AAT) is secondary to misfolding and polymerization... more Background. The deficiency of α 1-antitrypsin (AAT) is secondary to misfolding and polymerization of the abnormal Z-AAT in liver cells and is associated with lung emphysema. Alveolar macrophages (AM) produce AAT, however it is not known if Z-AAT can polymerize in AM, further decreasing lung AAT and promoting lung inflammation. Aims. To investigate if AAT polymerizes in human AM and to study the possible relation between polymerization and degree of lung inflammation. Methods. Immunohistochemical analysis with 2C1 monoclonal antibody specific for polymerized

Circulation, 2020

Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs... more Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs Guagliumi, Virmani, and Finn), who respond to the information, sharing their reasoning with the reader (regular type). A discussion by the authors follows. Patient presentation: A 43-year-old woman complained of abrupt onset of chest pain, which started while she was assisting her husband who had just been hospitalized for coronavirus disease 2019 (COVID-19) interstitial pneumonia. A 12-lead ECG performed 2 hours after symptom onset documented an ST-segment elevation in the inferior and lateral leads (Figure 1A). She was transferred to our hub center for urgent coronary angiography and primary percutaneous coronary intervention. On admission, she was awake, complaining of persistent chest pain. She reported neither fever nor dyspnea in previous days but a transient episode of angina the day before. She was hypotensive and tachycardic (systolic blood pressure, 70 mm Hg; heart rate, 130 bpm). Coffee ground emesis was present. While she was breathing room air, her So 2 was 100%, Pao 2 /Fio 2 ratio was normal, and lactate was moderately increased to 4.39 mmol/L. Focused echocardiography examination revealed severe left ventricular dysfunction (ejection fraction, 25%) with global hypokinesia and inferior and lateral akinesia (Figure 1C and Movie I in the Data Supplement). A moderate pericardial effusion (13 mm) without signs of cardiac tamponade was observed. Blood test documented normal white and red cell counts, mild acute kidney and liver injury, and slightly increased highsensitivity C-reactive protein (1.4 mg/dL). The international normalized ratio and partial thromboplastin time were in normal range. High-sensitivity troponin I was 11 795 ng/L (Figure 2). Dr Guagliumi: Clinical suspicion for COVID-19 was very high given the clinical history of exposure. Very little is known about the nature of how COVID-19 infection causes injury to the heart, but the differential diagnosis at this point with ST-segment elevations and chest pain included epicardial coronary thrombosis in the inferior (likely right coronary artery) territory, myocarditis-induced electrocardiographic changes, coronary spasm, and acute pericarditis. Given the clinical history of chest pain in a relatively young woman with no coronary risk factors and marked increase of troponin, suspicion was high for myocarditis, but an acute coronary syndrome was important to rule out. Patient presentation (continued): Emergency coronary angiography showed normal epicardial coronary vessels with TIMI (Thrombolysis in Myocardial Infarction) grade 2 flow in the left anterior descending artery and intense, persistent myocardial blush in the distal right coronary artery

SSRN Electronic Journal, 2022

World Journal of Gastroenterology, 2021

BACKGROUND Intestinal ischemia has been described in case reports of patients with severe acute r... more BACKGROUND Intestinal ischemia has been described in case reports of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (coronavirus disease 19, COVID-19). AIM To define the clinical and histological, characteristics, as well as the outcome of ischemic gastrointestinal manifestations of SARS-CoV-2 infection. METHODS A structured retrospective collection was promoted among three tertiary referral centres during the first wave of the pandemic in northern Italy. Clinical, radiological, endoscopic and histological data of patients hospitalized for COVID-19 between March 1st and May 30th were reviewed. The diagnosis was established by consecutive analysis of all abdominal computed tomography (CT) scans performed. RESULTS Among 2929 patients, 21 (0.7%) showed gastrointestinal ischemic manifestations either as presenting symptom or during hospitalization. Abdominal CT showed bowel distention in 6 patients while signs of colitis/enteritis in 12. Three patient...

Pediatric Hepatology and Liver Transplantation, 2019

In spite of significant improvements, availability, and deeper knowledge of many tools of investi... more In spite of significant improvements, availability, and deeper knowledge of many tools of investigation in liver transplanted patients (US, angiography, cholangiography, CT, and MRI), liver biopsy maintains a central role in the diagnosis and management of early and late postsurgery complications. Information arising from liver biopsy interpretation may be crucial for clinical decisions and therapy arrangements, but, to reach this goal, tissue samples must be representative, processed properly, and carefully evaluated by committed pathologists in order to discover significant histological pictures. Continuous and detailed communications between hepatologists and pathologists are necessary to obtain correct diagnostic details from this unique powerful procedure. Biochemical liver tests are associated with poor sensitivity and specificity in the diagnosis of graft dysfunction and usually provide only limited information about the target and the severity of graft damage. Moreover proto...

Pediatric Surgery International, 2021

The management of hepatic hemangioendothelioma (HHE) may be challenging. We aimed to review a lar... more The management of hepatic hemangioendothelioma (HHE) may be challenging. We aimed to review a large cohort of children who presented to our centers with symptomatic HHE in the last 16 years. We collected age at presentation, clinical features, histology, diagnostic process, management and outcome. Twenty seven patients (male/female 5/22), median age 13 days (1–1530) presented with hepatomegaly (24/27), cardiac failure (10/27), cutaneous hemangiomas (8/27), fever and anemia (6/27 each), vomiting (5/27), splenomegaly (4/27). The lesion was focal, multifocal, or diffuse in 9 patients of each group. The management included medical treatment (8/27), embolization (8/27), resection (3/27), observation (6/27), transplantation (2/27). After 16 months’ follow-up (30 days–11 years), 23/27 (85%) were alive. Diffuse lesions (4/4), cardiac failure (4/4), type II histology (4/4), age older than 6 months at diagnosis (3/4) predicted mortality (all p < 0.01). Histology showed type 1 lesion in 3/8, type 2 in 3/8, and type 3 in 2/8 with foci of angiosarcoma. Most patients with symptomatic HHE can be managed successfully with a combination of medical, radiological and surgical treatments. Patients with diffuse lesions, late presentation, cardiac failure and type II histology have a poor outcome. Diagnostic level IV. Therapeutic level IV.

Hepatology Research, 2021

Coronavirus disease (COVID‐19) is characterized by pneumonia with secondary damage to multiple or... more Coronavirus disease (COVID‐19) is characterized by pneumonia with secondary damage to multiple organs including the liver. Liver injury (elevated alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) often correlates with disease severity in COVID‐19 patients. The aim of this study is to identify pathological microthrombi in COVID‐19 patient livers by correlating their morphology with liver injury, and examine hyperfibrinogenemia and von Willebrand factor (vWF) as mechanisms of their formation.

Journal of pediatric gastroenterology and nutrition, Jan 6, 2017

2012 ESPGHAN guidelines allow to establish a celiac disease (CD) diagnosis without duodenal biops... more 2012 ESPGHAN guidelines allow to establish a celiac disease (CD) diagnosis without duodenal biopsy in symptomatic pediatric patients with anti-tissue transglutaminase (anti-tTG) titers > 10 times the upper limit of normal (ULN). For some years now, new chemiluminescence immunoassays have been made available: it is important to establish the clinical performance of anti-tTG and to determine the cut-off best suited to predict Marsh ≥ 2 in order to avoid gastrointestinal endoscopy not only in children, but also in the adult population. 2565 patients performed duodenal biopsy from July 2012 to September 2016; we selected all the patients who had undergone QUANTA Flash® anti-tTG IgA within +/- 3 months of duodenal biopsy and before the start of gluten free diet. 827 patients fulfilled the criteria for selection. Using a cut-off of 20 CU (Area Under the Curve: 0.995), sensitivity, specificity, positive and negative predictive value were 98.2%, 98.4%, 97.9% and 98.6%, respectively. For ...

Digestive and Liver Disease, 2012

Oncotarget, 2018

Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem ce... more Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT. We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge. 63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8±100,3 μmol/g vs 28,4±37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2±48,8 μmol/g vs 55,7±10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 μmol/g at follow up had DFO-based chelation therapy, versus 26% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48% vs 4%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1% vs 0,9% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy.

International Journal of Molecular Sciences, 2022

Early post-transplant is the critical phase for the success of hematopoietic stem cell transplant... more Early post-transplant is the critical phase for the success of hematopoietic stem cell transplantation (HSCT). New viral infections and the reactivations associated with complete ablation of the recipient’s T-cell immunity and inefficient reconstitution of the donor-derived system represent the main risks of HSCT. To date, the pharmacological treatments for post-HSCT viral infection-related complications have many limitations. Adoptive cell therapy (ACT) represents a new pharmacological strategy, allowing us to reconstitute the immune response to infectious agents in the post-HSC period. To demonstrate the potential advantage of this novel immunotherapy strategy, we report three cases of pediatric patients and the respective central nervous system complications after donor lymphocyte infusion.

The Lancet Infectious Diseases, 2020

Liver International, 2020

SARS2‐CoV‐2 breakout in Italy caused a huge number of severely ill patients with a serious increa... more SARS2‐CoV‐2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post‐mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID‐19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS‐CoV‐2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS‐CoV‐2 triggers a series of reactions leading to striking vascular alterations.

Digestive and Liver Disease, 2015

A 60-year-old man recently returned from a motorcycle tour n the Romanian countryside, claimed wo... more A 60-year-old man recently returned from a motorcycle tour n the Romanian countryside, claimed worsening malaise, nauea, hyporexia and diarrhoea (2–3 bowel movements per day, ithout blood), unresponsive to symptomatic therapy, with conomitant weight loss of 5 kg. On admission, clinical history was egative, except for a two-year history of bronchial asthma, not equiring specific treatment. Laboratory tests showed eosinophilic

Journal of Hepatology, 2013

93 AUTOIMMUNE ACUTE LIVER FAILURE IN CHILDREN: CLINICAL CLUES AND A NEW DIAGNOSTIC SCORE A. Di Gi... more 93 AUTOIMMUNE ACUTE LIVER FAILURE IN CHILDREN: CLINICAL CLUES AND A NEW DIAGNOSTIC SCORE A. Di Giorgio, M. Bravi, E. Bonanomi, G. Alessio, A. Sonzogni, M. Colledan, L. D’Antiga. Paediatric Liver, GI and Transplantation, Paediatric Intensive Care, Laboratory Medicine, Transplant Pathology, General Surgery and Transplantation, Ospedali Riuniti Bergamo, Bergamo, Italy E-mail: ldantiga@ospedaliriuniti.bergamo.it

Digestive and Liver Disease, 2012

Nature Communications, 2015

Journal of Applied Physiology, 2021

Hypothesizing that the non-aerated lung fraction as evaluated by the quantitative analysis of the... more Hypothesizing that the non-aerated lung fraction as evaluated by the quantitative analysis of the lung computed tomography (CT) equals shunt (VA/Q = 0), we used a computational approach to estimate the magnitude of the ventilation–perfusion mismatch in severe COVID-19. The results show that a severe hyperperfusion of poorly ventilated lung region is likely the cause of the hypoxemia observed. The extensive microthrombosis of the pulmonary circulation may represent the pathophysiological mechanism of such VA/Q distribution.

Hepatology International, 2019

Objectives and study Various degrees of biliary changes are considered to be part of the histolog... more Objectives and study Various degrees of biliary changes are considered to be part of the histological picture of children with pediatrics autoimmune liver disease (AILD), but the literature is scarce and confusing. We aimed to describe the characteristics of children with AILD (autoimmune hepatitis, AIH, and autoimmune sclerosing cholangitis, ASC) focusing on the prevalence and type of biliary abnormalities on initial biopsy to see whether ASC was predictable on histological ground. Methods The files of children diagnosed with AILD were reviewed. The Ishak score was used to grade inflammation and fibrosis on biopsy; a biliary score was built to grade bile duct injury. Demographic, laboratory and histological features at diagnosis were reported and compared between the two groups (AIH vs ASC). Results Forty-one patients were diagnosed with AIH (n = 24), ASC (n = 13) and PSC (n = 4) between 2009 and 2018. Twentynine patients [F = 76%, AIH = 20, ASC = 9, median age at diagnosis 11.7 (range 2.2-17.8)] were included in the study; 12 (4 with PSC) were excluded. Prevalence of inflammatory bowel disease was higher in ASC group (56% vs 10% in AIH, p < 0.05). On histology 17% had cirrhosis. The grade of biliopathy with AILD was moderate in 72% and severe in 31%, and overall more prominent in ASC (p = 0.031). The inflammation of the bile ducts was classified as "multifocal" or "diffuse" mainly in ASC patients (89% vs 45% in AIH, p = 0.043). Periductular fibrosis was reported in 52% of AILD patients, with a higher mean score in ASC group (p < 0.05). However, ductular reaction, biliary metaplasia and granulomatous cholangitis were equally reported in AIH and ASC, providing no clear-cut for the distinction of the two entities in the global histological evaluation. Conclusions Majority of patients with pediatrics AILD have "moderate" or "severe" features of biliopathy; AIH and ASC are not easily distinguishable on histological ground at diagnosis, and therefore, the cholangiogram remains the only effective tool to differentiate patients with AIH from those with ASC. Further prospective studies are needed to better define histological biliary features in AILD, assess if the biliopathy responds to immunosuppressive treatment and evaluate its impact on long-term outcome.

Chest, 2018

Background. The deficiency of α 1-antitrypsin (AAT) is secondary to misfolding and polymerization... more Background. The deficiency of α 1-antitrypsin (AAT) is secondary to misfolding and polymerization of the abnormal Z-AAT in liver cells and is associated with lung emphysema. Alveolar macrophages (AM) produce AAT, however it is not known if Z-AAT can polymerize in AM, further decreasing lung AAT and promoting lung inflammation. Aims. To investigate if AAT polymerizes in human AM and to study the possible relation between polymerization and degree of lung inflammation. Methods. Immunohistochemical analysis with 2C1 monoclonal antibody specific for polymerized

Circulation, 2020

Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs... more Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs Guagliumi, Virmani, and Finn), who respond to the information, sharing their reasoning with the reader (regular type). A discussion by the authors follows. Patient presentation: A 43-year-old woman complained of abrupt onset of chest pain, which started while she was assisting her husband who had just been hospitalized for coronavirus disease 2019 (COVID-19) interstitial pneumonia. A 12-lead ECG performed 2 hours after symptom onset documented an ST-segment elevation in the inferior and lateral leads (Figure 1A). She was transferred to our hub center for urgent coronary angiography and primary percutaneous coronary intervention. On admission, she was awake, complaining of persistent chest pain. She reported neither fever nor dyspnea in previous days but a transient episode of angina the day before. She was hypotensive and tachycardic (systolic blood pressure, 70 mm Hg; heart rate, 130 bpm). Coffee ground emesis was present. While she was breathing room air, her So 2 was 100%, Pao 2 /Fio 2 ratio was normal, and lactate was moderately increased to 4.39 mmol/L. Focused echocardiography examination revealed severe left ventricular dysfunction (ejection fraction, 25%) with global hypokinesia and inferior and lateral akinesia (Figure 1C and Movie I in the Data Supplement). A moderate pericardial effusion (13 mm) without signs of cardiac tamponade was observed. Blood test documented normal white and red cell counts, mild acute kidney and liver injury, and slightly increased highsensitivity C-reactive protein (1.4 mg/dL). The international normalized ratio and partial thromboplastin time were in normal range. High-sensitivity troponin I was 11 795 ng/L (Figure 2). Dr Guagliumi: Clinical suspicion for COVID-19 was very high given the clinical history of exposure. Very little is known about the nature of how COVID-19 infection causes injury to the heart, but the differential diagnosis at this point with ST-segment elevations and chest pain included epicardial coronary thrombosis in the inferior (likely right coronary artery) territory, myocarditis-induced electrocardiographic changes, coronary spasm, and acute pericarditis. Given the clinical history of chest pain in a relatively young woman with no coronary risk factors and marked increase of troponin, suspicion was high for myocarditis, but an acute coronary syndrome was important to rule out. Patient presentation (continued): Emergency coronary angiography showed normal epicardial coronary vessels with TIMI (Thrombolysis in Myocardial Infarction) grade 2 flow in the left anterior descending artery and intense, persistent myocardial blush in the distal right coronary artery

SSRN Electronic Journal, 2022

World Journal of Gastroenterology, 2021

BACKGROUND Intestinal ischemia has been described in case reports of patients with severe acute r... more BACKGROUND Intestinal ischemia has been described in case reports of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (coronavirus disease 19, COVID-19). AIM To define the clinical and histological, characteristics, as well as the outcome of ischemic gastrointestinal manifestations of SARS-CoV-2 infection. METHODS A structured retrospective collection was promoted among three tertiary referral centres during the first wave of the pandemic in northern Italy. Clinical, radiological, endoscopic and histological data of patients hospitalized for COVID-19 between March 1st and May 30th were reviewed. The diagnosis was established by consecutive analysis of all abdominal computed tomography (CT) scans performed. RESULTS Among 2929 patients, 21 (0.7%) showed gastrointestinal ischemic manifestations either as presenting symptom or during hospitalization. Abdominal CT showed bowel distention in 6 patients while signs of colitis/enteritis in 12. Three patient...

Pediatric Hepatology and Liver Transplantation, 2019

In spite of significant improvements, availability, and deeper knowledge of many tools of investi... more In spite of significant improvements, availability, and deeper knowledge of many tools of investigation in liver transplanted patients (US, angiography, cholangiography, CT, and MRI), liver biopsy maintains a central role in the diagnosis and management of early and late postsurgery complications. Information arising from liver biopsy interpretation may be crucial for clinical decisions and therapy arrangements, but, to reach this goal, tissue samples must be representative, processed properly, and carefully evaluated by committed pathologists in order to discover significant histological pictures. Continuous and detailed communications between hepatologists and pathologists are necessary to obtain correct diagnostic details from this unique powerful procedure. Biochemical liver tests are associated with poor sensitivity and specificity in the diagnosis of graft dysfunction and usually provide only limited information about the target and the severity of graft damage. Moreover proto...

Pediatric Surgery International, 2021

The management of hepatic hemangioendothelioma (HHE) may be challenging. We aimed to review a lar... more The management of hepatic hemangioendothelioma (HHE) may be challenging. We aimed to review a large cohort of children who presented to our centers with symptomatic HHE in the last 16 years. We collected age at presentation, clinical features, histology, diagnostic process, management and outcome. Twenty seven patients (male/female 5/22), median age 13 days (1–1530) presented with hepatomegaly (24/27), cardiac failure (10/27), cutaneous hemangiomas (8/27), fever and anemia (6/27 each), vomiting (5/27), splenomegaly (4/27). The lesion was focal, multifocal, or diffuse in 9 patients of each group. The management included medical treatment (8/27), embolization (8/27), resection (3/27), observation (6/27), transplantation (2/27). After 16 months’ follow-up (30 days–11 years), 23/27 (85%) were alive. Diffuse lesions (4/4), cardiac failure (4/4), type II histology (4/4), age older than 6 months at diagnosis (3/4) predicted mortality (all p < 0.01). Histology showed type 1 lesion in 3/8, type 2 in 3/8, and type 3 in 2/8 with foci of angiosarcoma. Most patients with symptomatic HHE can be managed successfully with a combination of medical, radiological and surgical treatments. Patients with diffuse lesions, late presentation, cardiac failure and type II histology have a poor outcome. Diagnostic level IV. Therapeutic level IV.

Hepatology Research, 2021

Coronavirus disease (COVID‐19) is characterized by pneumonia with secondary damage to multiple or... more Coronavirus disease (COVID‐19) is characterized by pneumonia with secondary damage to multiple organs including the liver. Liver injury (elevated alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) often correlates with disease severity in COVID‐19 patients. The aim of this study is to identify pathological microthrombi in COVID‐19 patient livers by correlating their morphology with liver injury, and examine hyperfibrinogenemia and von Willebrand factor (vWF) as mechanisms of their formation.

Journal of pediatric gastroenterology and nutrition, Jan 6, 2017

2012 ESPGHAN guidelines allow to establish a celiac disease (CD) diagnosis without duodenal biops... more 2012 ESPGHAN guidelines allow to establish a celiac disease (CD) diagnosis without duodenal biopsy in symptomatic pediatric patients with anti-tissue transglutaminase (anti-tTG) titers > 10 times the upper limit of normal (ULN). For some years now, new chemiluminescence immunoassays have been made available: it is important to establish the clinical performance of anti-tTG and to determine the cut-off best suited to predict Marsh ≥ 2 in order to avoid gastrointestinal endoscopy not only in children, but also in the adult population. 2565 patients performed duodenal biopsy from July 2012 to September 2016; we selected all the patients who had undergone QUANTA Flash® anti-tTG IgA within +/- 3 months of duodenal biopsy and before the start of gluten free diet. 827 patients fulfilled the criteria for selection. Using a cut-off of 20 CU (Area Under the Curve: 0.995), sensitivity, specificity, positive and negative predictive value were 98.2%, 98.4%, 97.9% and 98.6%, respectively. For ...

Digestive and Liver Disease, 2012

Oncotarget, 2018

Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem ce... more Whereas many studies have addressed the risk of organ dysfunction following hematopoietic stem cell transplantation (HSCT), little is known about pancreatic susceptibility in this setting. We aimed to investigate the effect of iron overload (IO) and total body irradiation (TBI) on pancreatic function of children undergoing HSCT. We retrospectively evaluated children admitted between 2012-2016 fulfilling the following criteria: normal pancreatic iron concentration (PIC), regular pancreatic function before HSCT, availability of abdominal magnetic resonance imaging with gradient-recalled-echo sequences and a full set of biochemical markers of IO and pancreatic function performed before HSCT and at discharge. We divided the patients according to the use of TBI or myeloablative chemotherapy (MCHT) in the conditioning regimen. All patients with severe IO or moderate IO with a high risk of engraftment delay or transplantation-related complications underwent chelation therapy with deferoxamine (DFO) from the first day of conditioning to discharge. 63 patients had a HSCT in the study period, 13 did not fulfill the inclusion criteria; 50 (25 in each group) are included in the analysis, and did not show differences at baseline evaluation. At follow up testing the TBI group showed a significantly higher PIC (107,8±100,3 μmol/g vs 28,4±37,9 in MCHT group, p<0,0001). In the TBI group the patients who had DFO treatment had higher PIC (223,2±48,8 μmol/g vs 55,7±10,5 without DFO treatment, p<0,0001), and all patients having PIC >100 μmol/g at follow up had DFO-based chelation therapy, versus 26% of those with lower PIC (p<0,0001). The number of patients presenting exocrine pancreatic dysfunctions one month after transplantation was significantly higher in the TBI group (48% vs 4%; p<0.0001). The mean pancreatic volume reduction was significantly greater in the TBI group (39,1% vs 0,9% in the MCHT group; p<0,05), and was significantly worse on those who received DFO therapy.

International Journal of Molecular Sciences, 2022

Early post-transplant is the critical phase for the success of hematopoietic stem cell transplant... more Early post-transplant is the critical phase for the success of hematopoietic stem cell transplantation (HSCT). New viral infections and the reactivations associated with complete ablation of the recipient’s T-cell immunity and inefficient reconstitution of the donor-derived system represent the main risks of HSCT. To date, the pharmacological treatments for post-HSCT viral infection-related complications have many limitations. Adoptive cell therapy (ACT) represents a new pharmacological strategy, allowing us to reconstitute the immune response to infectious agents in the post-HSC period. To demonstrate the potential advantage of this novel immunotherapy strategy, we report three cases of pediatric patients and the respective central nervous system complications after donor lymphocyte infusion.

The Lancet Infectious Diseases, 2020

Liver International, 2020

SARS2‐CoV‐2 breakout in Italy caused a huge number of severely ill patients with a serious increa... more SARS2‐CoV‐2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post‐mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID‐19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS‐CoV‐2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS‐CoV‐2 triggers a series of reactions leading to striking vascular alterations.

Digestive and Liver Disease, 2015

A 60-year-old man recently returned from a motorcycle tour n the Romanian countryside, claimed wo... more A 60-year-old man recently returned from a motorcycle tour n the Romanian countryside, claimed worsening malaise, nauea, hyporexia and diarrhoea (2–3 bowel movements per day, ithout blood), unresponsive to symptomatic therapy, with conomitant weight loss of 5 kg. On admission, clinical history was egative, except for a two-year history of bronchial asthma, not equiring specific treatment. Laboratory tests showed eosinophilic