Drug-induced liver injury is a significant and still unresolved clinical problem. Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical d...Drug-induced liver injury is a significant and still unresolved clinical problem. Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development. Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites. Aging, preexisting liver disease, enzyme induction or inhibition, genetic variances, local 02 supply and, above all, the intrinsic molecular properties of the drug may affect this process. Necrotic death follows antioxidant consumption and oxidation of intracellular proteins, which determine increased permeability of mitochondrial membranes, loss of potential, decreased ATP synthesis, inhibition of Ca^2＋-dependent ATPase, reduced capability to sequester Ca^2＋ within mitochondria, and membrane bleb formation. Conversely, activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis. Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage. Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis, in which different HLA genotypes might play a major role. This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage. Future perspectives including new frontiers for research are discussed.展开更多
AIM:To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus(HCMV)and Epstein-Barr virus(EBV)infection in inflammatory bowel disease(IBD).METHODS:A cohort of 40 IBD patients(17 refractor...AIM:To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus(HCMV)and Epstein-Barr virus(EBV)infection in inflammatory bowel disease(IBD).METHODS:A cohort of 40 IBD patients(17 refractory)and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest.Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry,and correlations with clinical and endoscopic indexes of activity,and risk factors were investigated.RESULTS:All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as comparedto 13/23(56.5%)non-refractory and 13/40(32.5%)controls.The median DNA value was significantly higher in refractory(HCMV 286 and EBV 5.440 copies/105cells)than in non-refractory(HCMV 0 and EBV 6copies/105 cells;P<0.05 and<0.001)IBD patients and controls(HCMV and EBV 0 copies/105 cells;P<0.001 for both).Refractory patients showed DNA peak values≥103 copies/105 cells in diseased mucosa in comparison to non-diseased mucosa(P<0.0121 for HCMV and<0.0004 for EBV),while non-refractory patients and controls invariably displayed levels below this threshold,thus allowing us to differentiate viral colitis from mucosal infection.Moreover,the mucosal load positively correlated with the values found in the peripheral blood,whilst no correlation with the number of positive cells at immunohistochemistry was found.Steroid use was identified as a significant risk factor for both HCMV(P=0.018)and EBV(P=0.002)colitis.Finally,a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis,whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications.CONCLUSION:Viral colitis appeared to contribute to mucosal lesions in refractory IBD,and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.展开更多
This article discusses a practical, evidence-based approach to the diagnosis and management of liver cirrhosis by focusing on etiology, severity, presence of complications, and potential home-managed treatments. Relev...This article discusses a practical, evidence-based approach to the diagnosis and management of liver cirrhosis by focusing on etiology, severity, presence of complications, and potential home-managed treatments. Relevant literature from 1985 to 2010 (PubMed) was reviewed. The search criteria were peer-reviewed full papers published in English using the following MESH headings alone or in combination: "ascites", "liver fibrosis", "cirrhosis", "chronic hepatitis", "chronic liver disease", "decompensated cirrhosis", "hepatic encephalopathy", "hypertransaminasemia", "liver transplantation" and "portal hypertension". Forty-nine papers were selected based on the highest quality of evidence for each section and type (original, randomized controlled trial, guideline, and review article), with respect to specialist setting (Gastroenterology, Hepatology, and Internal Medicine) and primary care. Liver cirrhosis from any cause represents an emerging health issue due to the increasing prevalence of the disease and its complications worldwide. Primary care physicians play a key role in early identification of risk factors, in the management of patients for improving quality and length of life, and for preventing complications. Specialists, by contrast, should guide specific treatments, especially in the case of complications and for selecting patient candidates for liver transplantation. An integrated approach between specialists and primary care physicians is essential for providing better outcomes and appropriate home care for patients with liver cirrhosis.展开更多
Coronavirus disease 2019(COVID-19)is,at present,one of the most relevant global health problems.In the literature hepatic alterations have been described in COVID-19 patients,and they are mainly represented by worseni...Coronavirus disease 2019(COVID-19)is,at present,one of the most relevant global health problems.In the literature hepatic alterations have been described in COVID-19 patients,and they are mainly represented by worsening of underlying chronic liver disease leading to hepatic decompensation and liver failure with higher mortality.Several potential mechanisms used by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)to cause liver damage have been hypothesized.COVID-19 primary liver injury is less common than secondary liver injury.Most of the available data demonstrate how liver damage in SARSCo V-2 infection is likely due to systemic inflammation,and it is less likely mediated by a cytopathic effect directed on liver cells.Moreover,liver alterations could be caused by hypoxic injury and drugs(antibiotics and non-steroidal antiinflammatory drugs,remdesivir,tocilizumab,tofacitinib and dexamethasone).SARS-Co V-2 infection can induce multiple vascular district atherothrombosis by affecting simultaneously cerebral,coronary and peripheral vascular beds.Data in the literature highlight how the virus triggers an exaggerated immune response,which added to the cytopathic effect of the virus can induce endothelial damage and a prothrombotic dysregulation of hemostasis.This leads to a higher incidence of symptomatic and confirmed venous thrombosis and of pulmonary embolisms,especially in central,lobar or segmental pulmonary arteries,in COVID-19.There are currently fewer data for arterial thrombosis,while myocardial injury was identified in 7%-17%of patients hospitalized with SARS-Co V-2 infection and 22%-31%in the intensive care unit setting.Available data also revealed a higher occurrence of stroke and more serious forms of peripheral arterial disease in COVID-19 patients.Hemostasis dysregulation is observed during the COVID-19 course.Lower platelet count,mildly increased prothrombin time and increased Ddimer are typical laboratory features of patients with severe SARS-Co V-2 infection,described as“COVID-19 associated coagulopathy.”These alterations are correlated to poor outcomes.Moreover,patients with severe SARS-Co V-2 infection are characterized by high levels of von Willebrand factor with subsequent ADAMTS13 deficiency and impaired fibrinolysis.Platelet hyperreactivity,hypercoagulability and hypofibrinolysis during SARS-Co V-2 infection induce a pathological state named as“immuno-thromboinflammation.”Finally,liver dysfunction and coagulopathy are often observed at the same time in patients with COVID-19.The hypothesis that liver dysfunction could be mediated by microvascular thrombosis has been supported by postmortem findings and extensive vascular portal and sinusoidal thrombosis observation.Other evidence has shown a correlation between coagulation and liver damage in COVID-19,underlined by the transaminase association with coagulopathy,identified through laboratory markers such as prothrombin time,international normalized ratio,fibrinogen,D-dimer,fibrin/fibrinogen degradation products and platelet count.Other possible mechanisms like immunogenesis of COVID-19 damage or massive pericyte activation with consequent vessel wall fibrosis have been suggested.展开更多
Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold stan...Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.展开更多
Nonalcoholic fatty liver disease(NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation, steatohe...Nonalcoholic fatty liver disease(NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.展开更多
The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. ...The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD.The effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes.In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.展开更多
Lemierre’s syndrome(LS)is an uncommon condition with oropharyngeal infections,internal jugular vein thrombosis,and systemic metastatic septic embolization as the main features.Fusobacterium species,a group of strictl...Lemierre’s syndrome(LS)is an uncommon condition with oropharyngeal infections,internal jugular vein thrombosis,and systemic metastatic septic embolization as the main features.Fusobacterium species,a group of strictly anaerobic Gram negative rod shaped bacteria,are advocated to be the main pathogen involved.We report a case of LS complicated by pulmonary embolism and pulmonary septic emboli that mimicked a neoplastic lung condition.A Medline search revealed 173 case reports of LS associated with internal jugular vein thrombosis that documented the type of microorganism.Data confirmed high prevalence in young males with Gram negative infections(83.2%).Pulmonary embolism was reported in 8.7% of cases mainly described in subjects with Gram positive infections(OR=9.786;95%CI:2.577-37.168,P=0.001),independently of age and gender.Only four fatal cases were reported.LS is an uncommon condition that could be complicated by pulmonary embolism,especially in subjects with Gram positive infections.展开更多
Patients with renal failure are at increased risk of cardiovascular events even at the earliest stages of disease. In addition to many classic cardiovascular risk factors, many conditions that are commonly identified ...Patients with renal failure are at increased risk of cardiovascular events even at the earliest stages of disease. In addition to many classic cardiovascular risk factors, many conditions that are commonly identified as emerging risk factors might contribute to occurrence of cardiovascular disease. Changes in circulating levels of many of these emerging risk factors have been demonstrated in patients with early stages of renal failure caused by different types of renal disease and have been associated with detection of cardiovascular complications. However, for most of these factors evidence of benefts of correction on cardiovascular outcome is missing. In this article, we comment on the role of lipoprotein（a） and prothrombotic factors as potential contributors to cardiovascular events in patients with early renal failure.展开更多
AIM: To investigate the possible association between Tako-tsubo cardiomyopathy(TTC)-a reversible clini-cal condition mimicking an acute myocardial infarction characterized by multifactorial pathophysiologic mecha-nism...AIM: To investigate the possible association between Tako-tsubo cardiomyopathy(TTC)-a reversible clini-cal condition mimicking an acute myocardial infarction characterized by multifactorial pathophysiologic mecha-nisms- and respiratory system diseases. METHODS: We systematically searched PubMed and EMBASE medical information sources, to identify the different triggering causes, limiting our search to ar-ticles in English. The search keywords were: "tako-tsubo cardiomyopathy", "takotsubo", "takotsubo cardiomyopa-thy", "broken heart syndrome", "stress-induced cardio-myopathy", "apical ballooning syndrome", and "ampulla cardiomyopathy in combination with respiratory dis-eases, lung, pulmonary disease. For each kind of dis-ease, we registered: author, year and country of study, patient sex, age, concurring situation, and outcome. RESULTS: Out of a total of 1725 articles found, we se-lected 37 papers reporting a total of 38 patients. As ex-pected, most patients were women(81.6%), mean age was 65 ± 10 years. Outcome was favorable in 100% of cases, and all the patients have been discharged un-eventfully in a few days. CONCLUSION: An association between respiratory diseases and TTC is likely to exist. Patients with severe respiratory diseases, due to the high dosages of β2-agonists used or to the need of invasive procedures, are highly exposed to the risk of developing TTC.展开更多
Idiopathic hypereosinophilic syndrome(HES) is a rare disorder characterized by peripheral eosinophilia exceeding 1500/mm3, a chronic course, absence of secondary causes, and signs and symptoms of eosinophil-mediated t...Idiopathic hypereosinophilic syndrome(HES) is a rare disorder characterized by peripheral eosinophilia exceeding 1500/mm3, a chronic course, absence of secondary causes, and signs and symptoms of eosinophil-mediated tissue injury. One of the best-characterized forms of HES is the one associated with FIP1L1-PDGFRA gene rearrangement, which was recently demonstrated as responsive to treatment with the small molecule kinase inhibitor drug, imatinib mesylate. Here, we describe the case of a 51-year-old male, whose symptoms satisfied the clinical criteria for HES with cutaneous and cardiac involvement and who also presented with vasculitic brain lesions and retroperitoneal bleeding. Molecular testing, including fluorescence in situ hybridization, of bone marrow and peripheral blood showed no evidence of PDGFR rearrangements. The patient was initially treated with high-dose steroid therapy and then with hydroxyurea, but proved unresponsive to both. Upon subsequent initiation of imatinib mesilate, the patient showed a dramatic improvement in eosinophil count and progressed rapidly through clinical recovery. Long-term follow-up confirmed the efficacy of treatment with low-dose imatinib and with no need of supplemental steroid treatment, notwithstanding the absence of PDGFR rearrangement.展开更多
Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations,with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts,lipids,and ...Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations,with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts,lipids,and nutrients,as well as destruction of membrane lipids and mitochondrial dysfunction.Both oxidative and nitrosative stress are associated with ongoing manifestations of the disease.In particular,abnormalities in nitric oxide metabolism and thiol oxidation already occur at early stages,thus leading to the hypothesis that these biochemical events play a pathogenic role in primary biliary cirrhosis.Moreover,the association of these metabolic abnormalities with the progression of the disease may indicate some biochemical parameters as early diagnostic markers of disease evolution,and may open up the potential for pharmacological intervention to inhibit intra-and extra-cellular stress events for resuming hepatocellular functions.The following paragraphs summarize the current knowledge by outlining molecular mechanisms of the disease related to these stress events.展开更多
Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, ap...Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, apart from ease of fatigue, minimal ankle oedema and hypotension. There is no accepted strategy for safely treating both hypercholesterolemia and analbuminemia in order to eventually decrease the atherosclerotic risk. We report a case of congenital analbuminemia(1.0 g/dL) in a 38-year-old male with hypercholesterolemia(range: 406-475 mg/dL) and severe arterial dysfunction [no brachial artery flow-mediated dilation(FMD)]. Long-term, cholesterol-lowering treatment with atorvastatin was associated with the appearance of peripheral edema. Twomonths of infusion with albumin improved FMD(7%) and reduced serum cholesterol(273 mg/dL), supporting the hypothesis of a compensatory role of hypercholesterolemia. Statin treatment, together with periodical albumin infusions, may contribute to the safe reduction of cardiovascular risk.展开更多
BACKGROUND: Partial porto-systemic shunts have been popularized because of reported low rate of mortality and morbidity (especially encephalopathy, liver failure and oc- clusion). To further investigate these assumpti...BACKGROUND: Partial porto-systemic shunts have been popularized because of reported low rate of mortality and morbidity (especially encephalopathy, liver failure and oc- clusion). To further investigate these assumptions, we ret- rospectively reviewed the results of partial porta-caval shunts performed at different stages of liver disease. METHODS: Twenty-nine cirrhotic patients underwent a partial porta-caval shunt with a ringed polytetrafluoroethy- lene interposition prosthesis of 8-mm ( 20 patients) or 10- mm (9 patients) in diameter. Pre- and post-shunt porta- caval pressure was measured in all patients. Twelve patients (41.4%) belonged to Child A, 11 Child B (37.9%), and 6 Child C (20.7%). Eleven patients (37.9%) suffered from hepatic encephalopathy preoperatively. Twelve patients (41%) were operated on in emergency/urgency. RESULTS: Porta-caval pressure gradient, reduced signifi- cantly using either 8- or 10-mm prosthesis. The overall ear- ly mortality and morbidity were 13. 8% and 48% respec- tively. The early mortality and morbidity were different be- tween patients of Child A and B when compared to those of Child C (0 vs 66.6% and 34.8% vs 66.6% respectively). No patient re-bled early from varices. The overall late mor- tality and morbidity were 40% and 64% respectively. Shunt thrombosis and stenosis took place in 16% and 8% of the two groups of patients respectively; variceal re-bleeding oc- curred in 4 patients (16%). Encephalopathy occurred post- operatively in 5 patients (20%), acute in 3 patients (12%), and chronic in 2 (8%). The actuarial survival rate at 3 and 5 years was 92% and 75% for patients of Child A, 70% and 60% for patients of Child B, and 0% for patients of Child C. CONCLUSIONS: Our results indicate that partial porta-ca- val shunt with a small diameter interposition H-graft is an effective procedure for the treatment of variceal bleeding, as well as for the prevention of re-bleeding in patients of Child A and those of Child B, as an elective or emergency/ urgency procedure, with a low rate of complications and encephalopathy. This technique could be used safely in pa- tients with good liver function but they should be moni- tored closely because of the risk of shunt occlusion.展开更多
AIM: To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.
AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was ev...AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo L.RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earliest(6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES.CONCLUSION Ada treatment, upon multidisciplinary(gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQo L in patients affected by ES.展开更多
BACKGROUND Type 1 diabetes originates from gene-environment interactions,with increasing incidence over time.AIM To identify correlates of childhood type 1 diabetes in European countries using an ecological approach.S...BACKGROUND Type 1 diabetes originates from gene-environment interactions,with increasing incidence over time.AIM To identify correlates of childhood type 1 diabetes in European countries using an ecological approach.Several environmental variables potentially influencing the onset of type 1 diabetes have been previously evaluated.However,the relationships between epidemiologic data and exposure to toxic airborne molecules are scarcely studied.METHODS We employed an ecological model to explore,in a wide time period(1990-2018),associations between type 1 diabetes incidence in 19 European countries(systematic literature review)and the nationwide production of five widely diffused air pollutants:particulate matter<10μm(PM10),nitrogen oxides(NO),non-methane volatile organic compounds(VOCs),sulphur oxide(SO2),and ammonia.RESULTS Data confirm a raising incidence of type 1 diabetes in 18 out of 19 explored countries.The average difference(last vs first report,all countries)was+6.9×100000/year,with values ranging from-1.4(Germany)to+16.6(Sweden)per 100000/year.Although the overall production of pollutants decreased progressively from 1990 to 2018,type 1 diabetes incidence was positively associated with the nationwide emissions of PM10,VOCs,and NO but not with those of SO2 and ammonia.Type 1 diabetes incidence was significantly higher in countries with high emissions than in those with low emissions of PM10(27.5±2.4 vs 14.6±2.4×100000 residents,respectively),VOCs(24.5±4.4 vs 13.2±1.7×100000 residents,respectively),and NO(26.6±3 vs 13.4±2.4×100000 residents,respectively),but not of SO2 or ammonia.CONCLUSION Evidence justify further studies to explore better links between long-term air quality and type 1 diabetes onset at the individual level,which should include exposures during pregnancy.In this respect,type 1 diabetes could be,at least in part,a preventable condition.Thus,primary prevention policies acting through a marked abatement of pollutant emissions might attenuate future type 1 diabetes incidence throughout Europe.展开更多
Chronic hepatitis B is usually a benign disease in Caucasian children;however,the long-term prognosis remains unsettled.This report describes the results of a 29-year longitudinal study including 99 white children wit...Chronic hepatitis B is usually a benign disease in Caucasian children;however,the long-term prognosis remains unsettled.This report describes the results of a 29-year longitudinal study including 99 white children with chronic hepatitis B,mainly acquired horizontally:91 were hepatitis B e antigen(HBeAg)-positive(4 had cirrhosis),and 8 were HBeAg negative at presentation.Of the 91 HBeAg-positive children,89 underwent HBeAg seroconversion after a mean period of 5.2 ±4.0 years and were included in the study.Of the 85 children without cirrhosis,one had HBeAg-negative hepatitis and the other 84 became inactive carriers.During a mean follow-up of 14.5 ±6.1 years after HBeAg seroclearance,4 carriers experienced reactivation,and 3 of them had HBeAg-negative hepatitis at the last follow-up.Of the 8 initially HBeAg-negative children,2 had HBeAg-negative hepatitis,and 6 were inactive carriers.Of the 4 children with cirrhosis,2 had hepatocellular carcinoma(HCC)and remained alive and 2 lost the histological features of cirrhosis in adulthood.Two patients with HBeAg-negative hepatitis and 1 with cirrhosis had experienced drug abuse.At the end of follow-up,15 of the 89 initially HBeAg-positive patients and 2 of 8 initially HBeAg-negative children had cleared hepatitis B surface antigen.In conclusion,the overall prognosis for chronic hepatitis B in horizontally infected Caucasian children is favorable;however,some patients progress to HCC and HBeAg-negative hepatitis.Long-term monitoring is important,as is counseling on cofactors of liver damage,such as alcohol and drug abuse.展开更多
Recently, it has been suggested that primary aldosteronism(PA) is associated with a variety of cardiac,vascular, metabolic, and renal sequelae that reflect the capability of elevated aldosterone to induce organ damage...Recently, it has been suggested that primary aldosteronism(PA) is associated with a variety of cardiac,vascular, metabolic, and renal sequelae that reflect the capability of elevated aldosterone to induce organ damage beyond that induced by hypertension itself. The evidence supporting of these views has been obtained from experiments conducted in rodents and clinica studies conducted in patients with this endocrine disorder. It has been suggested that untoward effects of high-salt intake are dependent on activation of mineralocorticoid receptors that might result from increased oxidative stress and changes in the intracellular redox potential. Unilateral adrenalectomy or treatment with mineralocorticoid receptor antagonists are the current options for treating an aldosterone-producing adrena adenoma or idiopathic adrenal hyperplasia. Treatments are largely effective in correcting hypertension and hypokalemia, and currently available information on their capability to prevent deterioration of renal function indicates that surgery and medical treatment are equallybeneficial in the long term. This editorial review will focus on the renal aspects of PA and highlights the role of the kidney as a key determinant of both adaptation to aldosterone-induced volume retention and response of blood pressure to treatment.展开更多
AIM：To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS： Forty-two consecutive patients transplanted for he...AIM：To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS： Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis （CH） B after LT was classified as minimal, mild, moderate or severe. RESULTS： HBV recurred in 7/42 （16.6%） patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg＋/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients （7.1%）, minimal/non-specific changes were observed in 18 （64.2%）, and at least 1 biopsy showed CH in the remaining 8 （28.5%）. Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg＋ or HBsAg- liver diseases.CONCLUSION： Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.展开更多
文摘Drug-induced liver injury is a significant and still unresolved clinical problem. Limitations to knowledge about the mechanisms of toxicity render incomplete the detection of hepatotoxic potential during preclinical development. Several xenobiotics are lipophilic substances and their transformation into hydrophilic compounds by the cytochrome P-450 system results in production of toxic metabolites. Aging, preexisting liver disease, enzyme induction or inhibition, genetic variances, local 02 supply and, above all, the intrinsic molecular properties of the drug may affect this process. Necrotic death follows antioxidant consumption and oxidation of intracellular proteins, which determine increased permeability of mitochondrial membranes, loss of potential, decreased ATP synthesis, inhibition of Ca^2＋-dependent ATPase, reduced capability to sequester Ca^2＋ within mitochondria, and membrane bleb formation. Conversely, activation of nucleases and energetic participation of mitochondria are the main intracellular mechanisms that lead to apoptosis. Non-parenchymal hepatic cells are inducers of hepatocellular injury and targets for damage. Activation of the immune system promotes idiosyncratic reactions that result in hepatic necrosis or cholestasis, in which different HLA genotypes might play a major role. This review focuses on current knowledge of the mechanisms of drug-induced liver injury and recent advances on newly discovered mechanisms of liver damage. Future perspectives including new frontiers for research are discussed.
基金Supported by(in part)Fondazione IRCCS Policlinico San Matteo(Progetto di Ricerca Corrente)entitled:"Studio della espressione del recettore per i prodotti finali della glicosilazione avanzata(RAGE)nelle Malattie Infiammatorie Croniche Intestinali",No.08064409
文摘AIM:To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus(HCMV)and Epstein-Barr virus(EBV)infection in inflammatory bowel disease(IBD).METHODS:A cohort of 40 IBD patients(17 refractory)and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest.Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry,and correlations with clinical and endoscopic indexes of activity,and risk factors were investigated.RESULTS:All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as comparedto 13/23(56.5%)non-refractory and 13/40(32.5%)controls.The median DNA value was significantly higher in refractory(HCMV 286 and EBV 5.440 copies/105cells)than in non-refractory(HCMV 0 and EBV 6copies/105 cells;P<0.05 and<0.001)IBD patients and controls(HCMV and EBV 0 copies/105 cells;P<0.001 for both).Refractory patients showed DNA peak values≥103 copies/105 cells in diseased mucosa in comparison to non-diseased mucosa(P<0.0121 for HCMV and<0.0004 for EBV),while non-refractory patients and controls invariably displayed levels below this threshold,thus allowing us to differentiate viral colitis from mucosal infection.Moreover,the mucosal load positively correlated with the values found in the peripheral blood,whilst no correlation with the number of positive cells at immunohistochemistry was found.Steroid use was identified as a significant risk factor for both HCMV(P=0.018)and EBV(P=0.002)colitis.Finally,a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis,whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications.CONCLUSION:Viral colitis appeared to contribute to mucosal lesions in refractory IBD,and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.
文摘This article discusses a practical, evidence-based approach to the diagnosis and management of liver cirrhosis by focusing on etiology, severity, presence of complications, and potential home-managed treatments. Relevant literature from 1985 to 2010 (PubMed) was reviewed. The search criteria were peer-reviewed full papers published in English using the following MESH headings alone or in combination: "ascites", "liver fibrosis", "cirrhosis", "chronic hepatitis", "chronic liver disease", "decompensated cirrhosis", "hepatic encephalopathy", "hypertransaminasemia", "liver transplantation" and "portal hypertension". Forty-nine papers were selected based on the highest quality of evidence for each section and type (original, randomized controlled trial, guideline, and review article), with respect to specialist setting (Gastroenterology, Hepatology, and Internal Medicine) and primary care. Liver cirrhosis from any cause represents an emerging health issue due to the increasing prevalence of the disease and its complications worldwide. Primary care physicians play a key role in early identification of risk factors, in the management of patients for improving quality and length of life, and for preventing complications. Specialists, by contrast, should guide specific treatments, especially in the case of complications and for selecting patient candidates for liver transplantation. An integrated approach between specialists and primary care physicians is essential for providing better outcomes and appropriate home care for patients with liver cirrhosis.
文摘Coronavirus disease 2019(COVID-19)is,at present,one of the most relevant global health problems.In the literature hepatic alterations have been described in COVID-19 patients,and they are mainly represented by worsening of underlying chronic liver disease leading to hepatic decompensation and liver failure with higher mortality.Several potential mechanisms used by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)to cause liver damage have been hypothesized.COVID-19 primary liver injury is less common than secondary liver injury.Most of the available data demonstrate how liver damage in SARSCo V-2 infection is likely due to systemic inflammation,and it is less likely mediated by a cytopathic effect directed on liver cells.Moreover,liver alterations could be caused by hypoxic injury and drugs(antibiotics and non-steroidal antiinflammatory drugs,remdesivir,tocilizumab,tofacitinib and dexamethasone).SARS-Co V-2 infection can induce multiple vascular district atherothrombosis by affecting simultaneously cerebral,coronary and peripheral vascular beds.Data in the literature highlight how the virus triggers an exaggerated immune response,which added to the cytopathic effect of the virus can induce endothelial damage and a prothrombotic dysregulation of hemostasis.This leads to a higher incidence of symptomatic and confirmed venous thrombosis and of pulmonary embolisms,especially in central,lobar or segmental pulmonary arteries,in COVID-19.There are currently fewer data for arterial thrombosis,while myocardial injury was identified in 7%-17%of patients hospitalized with SARS-Co V-2 infection and 22%-31%in the intensive care unit setting.Available data also revealed a higher occurrence of stroke and more serious forms of peripheral arterial disease in COVID-19 patients.Hemostasis dysregulation is observed during the COVID-19 course.Lower platelet count,mildly increased prothrombin time and increased Ddimer are typical laboratory features of patients with severe SARS-Co V-2 infection,described as“COVID-19 associated coagulopathy.”These alterations are correlated to poor outcomes.Moreover,patients with severe SARS-Co V-2 infection are characterized by high levels of von Willebrand factor with subsequent ADAMTS13 deficiency and impaired fibrinolysis.Platelet hyperreactivity,hypercoagulability and hypofibrinolysis during SARS-Co V-2 infection induce a pathological state named as“immuno-thromboinflammation.”Finally,liver dysfunction and coagulopathy are often observed at the same time in patients with COVID-19.The hypothesis that liver dysfunction could be mediated by microvascular thrombosis has been supported by postmortem findings and extensive vascular portal and sinusoidal thrombosis observation.Other evidence has shown a correlation between coagulation and liver damage in COVID-19,underlined by the transaminase association with coagulopathy,identified through laboratory markers such as prothrombin time,international normalized ratio,fibrinogen,D-dimer,fibrin/fibrinogen degradation products and platelet count.Other possible mechanisms like immunogenesis of COVID-19 damage or massive pericyte activation with consequent vessel wall fibrosis have been suggested.
基金Supported by (in part) research grants from the Italian Ministry of University and Research (No. FIRB 2003 RBAU01RANB002)the Italian National Research Council (short-term mobility grant 2005)+2 种基金the University of Bari (grants No. ORBA09XZZT and No. ORBA08YHKX) (to Portincasa P)University of Bari (No. DR11598-2009)the National Institutes of Health (US Public Health Service) (research grants No. DK54012 and No. DK73917) (to Wang DQH)
文摘Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.
文摘Nonalcoholic fatty liver disease(NAFLD) is currently recognized as one of the most common causes of chronic liver disease. It involves a spectrum of conditionsthat include pure steatosis without inflammation, steatohepatitis, fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes and, thus, oxidative stress, which is followed by inflammatory response. However, NAFLD pathogenesis is still largely unknown and has been extensively investigated. Although life style modification with the aim of losing weight has been advocated to treat this disorder, its effectiveness is limited; additionally, there is no specific pharmacologic treatment until nowadays. Recent evidence suggests that the gut microbiota may play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. Differences in gut microbiota between NAFLD patients and lean individuals as well as presence of small intestinal bacterial overgrowth in NAFLD subjects have been demonstrated. Furthermore, some data indicate that the immunoregulatory effects of probiotics may be beneficial in NAFLD treatment as they modulate the intestinal microbiota; improve epithelial barrier function and strengthen the intestinal wall decreasing its permeability; reduce bacterial translocation and endotoxemia; improve intestinal inflammation; and reduce oxidative and inflammatory liver damage. In this article, we review the clinical trials on the use of probiotics in the treatment of NAFLD and discuss the effects of these agents and their efficacy as an emerging therapeutic resource to treat NAFLD patients.
基金Supported by the Brazilian research foundations Fundacao de Amparo à Pesquisa do Estado do Rio de Janeiro--FAPERJ,No.E26/202.781/2017Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq,No.302401/2016-4
文摘The chronic inflammatory process underlying inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, derives from the interplay of several components in a genetically susceptible host. These components include environmental elements and gut microbiota a dysbiosis. For decades, immune abnormalities have been investigated as critically important in IBD pathogenesis, and attempts to develop effective therapies have predominantly targeted the immune system. Nevertheless, immune events represent only one of the constituents contributing to IBD pathogenesis within the context of the complex cellular and molecular network underlying chronic intestinal inflammation. These factors need to be appreciated within the milieu of nonimmune components. Damage-associated molecular patterns (DAMPs), which are essentially endogenous stress proteins expressed or released as a result of cell or tissue damage, have been shown to act as direct proinflammatory mediators. Excessive or persistent signalling mediated by such molecules can underlie several chronic inflammatory disorders, including IBD. The release of endogenous DAMPs amplifies the inflammatory response driven by immune and non-immune cells and promotes epigenetic reprogramming in IBD.The effects determine pathologic changes,which may sustain chronic intestinal inflammation and also underlie specific disease phenotypes.In addition to highlighting the potential use of DAMPs such as calprotectin as biomarkers,research on DAMPs may reveal novel mechanistic associations in IBD pathogenesis and is expected to uncover putative therapeutic targets.
文摘Lemierre’s syndrome(LS)is an uncommon condition with oropharyngeal infections,internal jugular vein thrombosis,and systemic metastatic septic embolization as the main features.Fusobacterium species,a group of strictly anaerobic Gram negative rod shaped bacteria,are advocated to be the main pathogen involved.We report a case of LS complicated by pulmonary embolism and pulmonary septic emboli that mimicked a neoplastic lung condition.A Medline search revealed 173 case reports of LS associated with internal jugular vein thrombosis that documented the type of microorganism.Data confirmed high prevalence in young males with Gram negative infections(83.2%).Pulmonary embolism was reported in 8.7% of cases mainly described in subjects with Gram positive infections(OR=9.786;95%CI:2.577-37.168,P=0.001),independently of age and gender.Only four fatal cases were reported.LS is an uncommon condition that could be complicated by pulmonary embolism,especially in subjects with Gram positive infections.
基金Supported by A European Cooperation in the field of Scientific and Technical Research(COST-BM1301)grant(to Catena C)a generous contribution of the Pier Silverio Nassimbeni Foundation(to Catena C and Sechi LA)
文摘Patients with renal failure are at increased risk of cardiovascular events even at the earliest stages of disease. In addition to many classic cardiovascular risk factors, many conditions that are commonly identified as emerging risk factors might contribute to occurrence of cardiovascular disease. Changes in circulating levels of many of these emerging risk factors have been demonstrated in patients with early stages of renal failure caused by different types of renal disease and have been associated with detection of cardiovascular complications. However, for most of these factors evidence of benefts of correction on cardiovascular outcome is missing. In this article, we comment on the role of lipoprotein（a） and prothrombotic factors as potential contributors to cardiovascular events in patients with early renal failure.
基金Supported by A scientific grant(FAR–Fondo Ateneo Ricerca)from the University of Ferrara,Italy(in part)
文摘AIM: To investigate the possible association between Tako-tsubo cardiomyopathy(TTC)-a reversible clini-cal condition mimicking an acute myocardial infarction characterized by multifactorial pathophysiologic mecha-nisms- and respiratory system diseases. METHODS: We systematically searched PubMed and EMBASE medical information sources, to identify the different triggering causes, limiting our search to ar-ticles in English. The search keywords were: "tako-tsubo cardiomyopathy", "takotsubo", "takotsubo cardiomyopa-thy", "broken heart syndrome", "stress-induced cardio-myopathy", "apical ballooning syndrome", and "ampulla cardiomyopathy in combination with respiratory dis-eases, lung, pulmonary disease. For each kind of dis-ease, we registered: author, year and country of study, patient sex, age, concurring situation, and outcome. RESULTS: Out of a total of 1725 articles found, we se-lected 37 papers reporting a total of 38 patients. As ex-pected, most patients were women(81.6%), mean age was 65 ± 10 years. Outcome was favorable in 100% of cases, and all the patients have been discharged un-eventfully in a few days. CONCLUSION: An association between respiratory diseases and TTC is likely to exist. Patients with severe respiratory diseases, due to the high dosages of β2-agonists used or to the need of invasive procedures, are highly exposed to the risk of developing TTC.
文摘Idiopathic hypereosinophilic syndrome(HES) is a rare disorder characterized by peripheral eosinophilia exceeding 1500/mm3, a chronic course, absence of secondary causes, and signs and symptoms of eosinophil-mediated tissue injury. One of the best-characterized forms of HES is the one associated with FIP1L1-PDGFRA gene rearrangement, which was recently demonstrated as responsive to treatment with the small molecule kinase inhibitor drug, imatinib mesylate. Here, we describe the case of a 51-year-old male, whose symptoms satisfied the clinical criteria for HES with cutaneous and cardiac involvement and who also presented with vasculitic brain lesions and retroperitoneal bleeding. Molecular testing, including fluorescence in situ hybridization, of bone marrow and peripheral blood showed no evidence of PDGFR rearrangements. The patient was initially treated with high-dose steroid therapy and then with hydroxyurea, but proved unresponsive to both. Upon subsequent initiation of imatinib mesilate, the patient showed a dramatic improvement in eosinophil count and progressed rapidly through clinical recovery. Long-term follow-up confirmed the efficacy of treatment with low-dose imatinib and with no need of supplemental steroid treatment, notwithstanding the absence of PDGFR rearrangement.
文摘Primary biliary cirrhosis is a multifactor autoimmune disease characterized by hepatic and systemic manifestations,with immune system dysregulation and abnormalities in the hepatic metabolism of bile salts,lipids,and nutrients,as well as destruction of membrane lipids and mitochondrial dysfunction.Both oxidative and nitrosative stress are associated with ongoing manifestations of the disease.In particular,abnormalities in nitric oxide metabolism and thiol oxidation already occur at early stages,thus leading to the hypothesis that these biochemical events play a pathogenic role in primary biliary cirrhosis.Moreover,the association of these metabolic abnormalities with the progression of the disease may indicate some biochemical parameters as early diagnostic markers of disease evolution,and may open up the potential for pharmacological intervention to inhibit intra-and extra-cellular stress events for resuming hepatocellular functions.The following paragraphs summarize the current knowledge by outlining molecular mechanisms of the disease related to these stress events.
文摘Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, apart from ease of fatigue, minimal ankle oedema and hypotension. There is no accepted strategy for safely treating both hypercholesterolemia and analbuminemia in order to eventually decrease the atherosclerotic risk. We report a case of congenital analbuminemia(1.0 g/dL) in a 38-year-old male with hypercholesterolemia(range: 406-475 mg/dL) and severe arterial dysfunction [no brachial artery flow-mediated dilation(FMD)]. Long-term, cholesterol-lowering treatment with atorvastatin was associated with the appearance of peripheral edema. Twomonths of infusion with albumin improved FMD(7%) and reduced serum cholesterol(273 mg/dL), supporting the hypothesis of a compensatory role of hypercholesterolemia. Statin treatment, together with periodical albumin infusions, may contribute to the safe reduction of cardiovascular risk.
文摘BACKGROUND: Partial porto-systemic shunts have been popularized because of reported low rate of mortality and morbidity (especially encephalopathy, liver failure and oc- clusion). To further investigate these assumptions, we ret- rospectively reviewed the results of partial porta-caval shunts performed at different stages of liver disease. METHODS: Twenty-nine cirrhotic patients underwent a partial porta-caval shunt with a ringed polytetrafluoroethy- lene interposition prosthesis of 8-mm ( 20 patients) or 10- mm (9 patients) in diameter. Pre- and post-shunt porta- caval pressure was measured in all patients. Twelve patients (41.4%) belonged to Child A, 11 Child B (37.9%), and 6 Child C (20.7%). Eleven patients (37.9%) suffered from hepatic encephalopathy preoperatively. Twelve patients (41%) were operated on in emergency/urgency. RESULTS: Porta-caval pressure gradient, reduced signifi- cantly using either 8- or 10-mm prosthesis. The overall ear- ly mortality and morbidity were 13. 8% and 48% respec- tively. The early mortality and morbidity were different be- tween patients of Child A and B when compared to those of Child C (0 vs 66.6% and 34.8% vs 66.6% respectively). No patient re-bled early from varices. The overall late mor- tality and morbidity were 40% and 64% respectively. Shunt thrombosis and stenosis took place in 16% and 8% of the two groups of patients respectively; variceal re-bleeding oc- curred in 4 patients (16%). Encephalopathy occurred post- operatively in 5 patients (20%), acute in 3 patients (12%), and chronic in 2 (8%). The actuarial survival rate at 3 and 5 years was 92% and 75% for patients of Child A, 70% and 60% for patients of Child B, and 0% for patients of Child C. CONCLUSIONS: Our results indicate that partial porta-ca- val shunt with a small diameter interposition H-graft is an effective procedure for the treatment of variceal bleeding, as well as for the prevention of re-bleeding in patients of Child A and those of Child B, as an elective or emergency/ urgency procedure, with a low rate of complications and encephalopathy. This technique could be used safely in pa- tients with good liver function but they should be moni- tored closely because of the risk of shunt occlusion.
文摘AIM: To evaluate the most cost-effectiveness strategy for preventing variceal growth and bleeding in patients with cirrhosis and small esophageal varices.
文摘AIM To report adalimumab(Ada) efficacy on articulargastrointestinal disease and health-related quality of life(HRQo L) in patients with enteropathic spondyloarthritis(ES).METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes(PROs) of the HRQo L questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor(TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests:(1) Ankylosing Spondylitis Disease Activity ScoreC-Reactive Protein(ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), Bath Ankylosing Spondylitis Functional Index(BASFI) and Bath Ankylosing Spondylitis Metrology Index(BASMI) for articular activity;(2) Inflammatory Bowel Disease Questionnaire(IBDQ), Crohn's Disease Activity Index(CDAI) and partial Mayo(p Mayo) score for gastrointestinal symptoms and activity; and(3) Health Assessment Questionnaire(HAQ), Patient Global Assessment(PGA) and Short Form-36 health survey(SF-36) questionnaires for PROs of the HRQo L.RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQo L scores, showed a significant improvement having been achieved at the earliest(6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES.CONCLUSION Ada treatment, upon multidisciplinary(gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQo L in patients affected by ES.
文摘BACKGROUND Type 1 diabetes originates from gene-environment interactions,with increasing incidence over time.AIM To identify correlates of childhood type 1 diabetes in European countries using an ecological approach.Several environmental variables potentially influencing the onset of type 1 diabetes have been previously evaluated.However,the relationships between epidemiologic data and exposure to toxic airborne molecules are scarcely studied.METHODS We employed an ecological model to explore,in a wide time period(1990-2018),associations between type 1 diabetes incidence in 19 European countries(systematic literature review)and the nationwide production of five widely diffused air pollutants:particulate matter<10μm(PM10),nitrogen oxides(NO),non-methane volatile organic compounds(VOCs),sulphur oxide(SO2),and ammonia.RESULTS Data confirm a raising incidence of type 1 diabetes in 18 out of 19 explored countries.The average difference(last vs first report,all countries)was+6.9×100000/year,with values ranging from-1.4(Germany)to+16.6(Sweden)per 100000/year.Although the overall production of pollutants decreased progressively from 1990 to 2018,type 1 diabetes incidence was positively associated with the nationwide emissions of PM10,VOCs,and NO but not with those of SO2 and ammonia.Type 1 diabetes incidence was significantly higher in countries with high emissions than in those with low emissions of PM10(27.5±2.4 vs 14.6±2.4×100000 residents,respectively),VOCs(24.5±4.4 vs 13.2±1.7×100000 residents,respectively),and NO(26.6±3 vs 13.4±2.4×100000 residents,respectively),but not of SO2 or ammonia.CONCLUSION Evidence justify further studies to explore better links between long-term air quality and type 1 diabetes onset at the individual level,which should include exposures during pregnancy.In this respect,type 1 diabetes could be,at least in part,a preventable condition.Thus,primary prevention policies acting through a marked abatement of pollutant emissions might attenuate future type 1 diabetes incidence throughout Europe.
文摘Chronic hepatitis B is usually a benign disease in Caucasian children;however,the long-term prognosis remains unsettled.This report describes the results of a 29-year longitudinal study including 99 white children with chronic hepatitis B,mainly acquired horizontally:91 were hepatitis B e antigen(HBeAg)-positive(4 had cirrhosis),and 8 were HBeAg negative at presentation.Of the 91 HBeAg-positive children,89 underwent HBeAg seroconversion after a mean period of 5.2 ±4.0 years and were included in the study.Of the 85 children without cirrhosis,one had HBeAg-negative hepatitis and the other 84 became inactive carriers.During a mean follow-up of 14.5 ±6.1 years after HBeAg seroclearance,4 carriers experienced reactivation,and 3 of them had HBeAg-negative hepatitis at the last follow-up.Of the 8 initially HBeAg-negative children,2 had HBeAg-negative hepatitis,and 6 were inactive carriers.Of the 4 children with cirrhosis,2 had hepatocellular carcinoma(HCC)and remained alive and 2 lost the histological features of cirrhosis in adulthood.Two patients with HBeAg-negative hepatitis and 1 with cirrhosis had experienced drug abuse.At the end of follow-up,15 of the 89 initially HBeAg-positive patients and 2 of 8 initially HBeAg-negative children had cleared hepatitis B surface antigen.In conclusion,the overall prognosis for chronic hepatitis B in horizontally infected Caucasian children is favorable;however,some patients progress to HCC and HBeAg-negative hepatitis.Long-term monitoring is important,as is counseling on cofactors of liver damage,such as alcohol and drug abuse.
基金Supported by A research grant from the Italian Ministry of University(to Sechi LA and Catena C)a research grant from the PierS ilverio Nassimbeni Foundation
文摘Recently, it has been suggested that primary aldosteronism(PA) is associated with a variety of cardiac,vascular, metabolic, and renal sequelae that reflect the capability of elevated aldosterone to induce organ damage beyond that induced by hypertension itself. The evidence supporting of these views has been obtained from experiments conducted in rodents and clinica studies conducted in patients with this endocrine disorder. It has been suggested that untoward effects of high-salt intake are dependent on activation of mineralocorticoid receptors that might result from increased oxidative stress and changes in the intracellular redox potential. Unilateral adrenalectomy or treatment with mineralocorticoid receptor antagonists are the current options for treating an aldosterone-producing adrena adenoma or idiopathic adrenal hyperplasia. Treatments are largely effective in correcting hypertension and hypokalemia, and currently available information on their capability to prevent deterioration of renal function indicates that surgery and medical treatment are equallybeneficial in the long term. This editorial review will focus on the renal aspects of PA and highlights the role of the kidney as a key determinant of both adaptation to aldosterone-induced volume retention and response of blood pressure to treatment.
文摘AIM：To evaluate the long-term histological outcome of patients transplanted for HBV-related liver disease and given HBIg prophylaxis indefinitely after LT. METHODS： Forty-two consecutive patients transplanted for hepatitis B were prospectively studied. HBsAg, HBVDNA and liver function tests were evaluated in the serum 3, 6 and 12 mo after LT and then yearly. LB was obtained 6 and 12 mo after LT and yearly thereafter. Chronic hepatitis （CH） B after LT was classified as minimal, mild, moderate or severe. RESULTS： HBV recurred in 7/42 （16.6%） patients after 6-96 mo of follow-up. A hundred and eightyseven LB were evaluated. Four of 7 patients with graft reinfection, all with unknown HBV DNA status before LT, developed cirrhosis at 12-36 mo of follow-up. Of the 122 LB obtained from 28 HBsAg＋/HCV- recipients with no HBV recurrence after LT, all biopsies were completely normal in only 2 patients （7.1%）, minimal/non-specific changes were observed in 18 （64.2%）, and at least 1 biopsy showed CH in the remaining 8 （28.5%）. Twentynine LB obtained from 7 patients transplanted for HBVHCV cirrhosis and remaining HBsAg- after LT revealed recurrent CH-C. Actuarial survival was similar in patients with HBsAg＋ or HBsAg- liver diseases.CONCLUSION： Though protocol biopsies may enable the detection of graft dysfunction at an early stage, the risk of progression and the clinical significance of these findings remains to be determined.
