Smoking as a risk factor for autoimmune liver disease: what we can learn from primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the immune-mediated destruction of biliary epithelial cells in small intrahepatic bile ducts. The disease is characterised by circulating anti-mitochondrial antibodies (AMA) as well as disease specific anti-nuclear antibodies (ANA), cholestatic liver biochemistry, and characteristic histology. The disease primarily affects middle-aged females, and its incidence is apparently increasing worldwide. Epidemiological studies have indicated several risk factors for the development of PBC, with family history of PBC, recurrent urinary tract infection, and smoking being the most widely cited. Smoking has been implicated as a risk factor in several autoimmune diseases, including the liver, by complex mechanisms involving the endocrine and immunological systems to name a few. Studies of smoking in liver disease have also shown that smoking may progress the disease towards fibrosis and subsequent cirrhosis. This review will examine the literature surrounding smoking as a risk factor for PBC, as well as a potential factor in the progression of fibrosis in PBC patients

Preclinical atherosclerosis and metabolic syndrome increase cardio- and cerebrovascular events rate: a 20-year follow up

BACKGROUND: Intima-media thickness (IMT) is a validated marker of preclinical atherosclerosis and a predictor of cardiovascular events. PATIENTS: We studied a population of 529 asymptomatic patients (age 62\u2009\ub1\u200912.8 years), divided into two groups of subjects with and without Metabolic Syndrome (MetS). METHODS: All patients, at baseline, have had a carotid ultrasound evaluation and classified in two subgroups: the first one without atherosclerotic lesions and the second one with preclinical atherosclerosis (increased IMT or asymptomatic carotid plaque). Cardiovascular endpoints were investigated in a 20-years follow-up. RESULTS: There were 242 cardiovascular events: 144 among patients with MetS and 98 among in healthy controls (57.4% vs. 35.2%; P\u2009<\u20090.0001). 63 events occurred in patients with normal carotid arteries, while 179 events occurred in patients with preclinical atherosclerosis (31.8% vs. 54.1%; P\u2009<\u20090.0001). Of the 144 total events occurred in patients with MetS, 36 happened in the subgroup with normal carotid arteries and 108 in the subgroup with preclinical atherosclerosis (45% vs. 63.15%; P\u2009=\u20090.009). 98 events occurred in patients without MetS, of which 27 in the subgroup with normal carotid arteries and 71 in the subgroup with preclinical atherosclerosis (22.88% vs. 44.37%; P\u2009=\u20090.0003). In addition, considering the 63 total events occurred in patients without atherosclerotic lesions, 36 events were recorded in the subgroup with MetS and 27 events in the subgroup without MetS (45% vs. 22.88%; P\u2009=\u20090.0019). Finally, in 179 total events recorded in patients with preclinical carotid atherosclerosis, 108 happened in the subgroup with MetS and 71 happened in the subgroup without MetS (63.15% vs. 44.37%; P\u2009=\u20090.0009). The Kaplan-Meier function showed an improved survival in patients without atherosclerotic lesions compared with patients with carotid ultrasound alterations (P\u2009=\u20090.01, HR: 0.7366, CI: 0.5479 to 0.9904). CONCLUSIONS: Preclinical atherosclerosis leads to an increased risk of cardiovascular events, especially if it is associated with MetS

Behaviour of the plasma concentration of gelatinases and their tissue inhibitors in subjects with venous leg ulcers.

Venous leg ulcers are common in subjects with chronic venous insufficiency. The increased intraluminal pressure causes alteration of the skin microcirculation, leukocyte activation and release of proteolytic enzymes leading to ulceration. An impaired expression and activity of matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) might influence extracellular matrix degradation and deposition in chronic venous ulcers with the failure of the healing process. Our aim was to evaluate plasma concentration of gelatinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in subjects with venous leg ulcers before and after the compression therapy. We enrolled 36 subjects (12 men and 24 women, mean age 67.38 ± 12.7 yrs) with non-infected venous leg ulcers (CEAP C6), which underwent a color Duplex scan examination of the veins and arteries of the inferior limbs and were treated with a multi-layer bandaging system. The ulcer healing was obtained in 23 subjects only (9 men and 14 women). We evaluated, on fasting venous blood, the plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 using ELISA kit, before and after the treatment. We observed a significant increase in plasma concentration of gelatinases and their inhibitors and in MMP-2/TIMP-2 ratio in subjects with leg ulcers in comparison with normal controls. In subjects with healed ulcers we found a decrease in MMP-9 and TIMP-1 levels and in MMP-2/TIMP-2 ratio compared to the baseline values, although higher levels of all the examined parameters in comparison with normal controls. In conclusion, plasma MMPs profile is impaired in subjects with venous leg ulcers and it improves after the healing, persisting anyway altered in respect to healthy controls

Medical therapy for patients with subclinical and clinical carotid atherosclerosis

The management of carotid artery disease includes both modifications in life style as well treatment of vascular risk factors. However, strict risk factor modification, including improved antihypertensive therapy, lipid management, smoking cessation, and antiplatelet therapy, promise for reducing the vascular event rate in patients with carotid atherosclerosis. The best medical management for stroke prevention was highlighted in clinical practice guidelines issued jointly in 2006 by the American Heart Association and the American Stroke Association, and co-sponsored by the Council on Cardiovascular Radiology and Intervention and the American Academy of Neurology. Lowering blood pressure to a target below 120/80 mm Hg by life style interventions and antihypertensive treatment. Glucose control to near-normoglycemic levels (target hemoglobin A1C ≤7%) is recommended among diabetics to reduce micro-vascular complications and, with lesser certainty, macrovascular complications. The primary objective of this review is to summarize the current evidence and standards for the advanced diagnostic and management strategies used in asymptomatic and symptomatic patients with carotid atherosclerosis

Prediction of vascular events in subjects with subclinical atherosclerosis and the metabolic syndrome: the role of markers of inflammation.

AIM: The presence of the metabolic syndrome (MS) increases cardiovascular morbidity and mortality and we aimed to assess the outcome in subjects with the MS and subclinical atherosclerosis. METHODS: We followed-up for five years 339 Mediterranean subjects with asymptomatic carotid intima-media thickness >0.9 mm (men: 60%; age: 66±5 years), of whom 130 had the MS (men: 59%; age: 66±5 years), evaluating at baseline traditional cardiovascular risk factors (including male gender, older age, obesity, hypertension, diabetes, smoking, family history of cardiovascular diseases, dyslipidemia) and plasma levels of C-reactive protein and fibrinogen. RESULTS: Cardio- and cerebrovascular events were registered in the 29% of subjects with the MS and in the 20% of those without it and the presence of more criteria for the diagnosis of the MS was significantly associated with vascular morbidity and mortality. By multivariate analysis, including all baseline variables, independent predictive roles for the events were found for elevated markers of inflammation (OR 3.8), elevated fasting glucose (OR 2.1) and elevated triglycerides (OR 1.4). CONCLUSION: These findings confirm a worst vascular outcome in subjects with more criteria for the diagnosis of the MS and further suggest the need of future research to understand the combined role of inflammation and the MS in the progression from subclinical to clinical atherosclerosis

Childhood medical history and psychosis in adult life: Findings from the Bologna EU-GEI incidence and case–control study

Aim: To estimate the association between the inpatient admissions and Emergency Department (ED) visits before age of 18 years and adulthood-onset first-episode psychosis (FEP). Methods: We conducted a FEP incidence and case–control study and calculated the odds ratios (ORs) for incident FEP associated with inpatient admissions and ED visits prior to age of 18 years, adjusting our results for cannabis use, parental socio-economic class and childhood trauma. Results: In multivariate logistic regression analysis, odds of FEP increased significantly if the participant had a history of at least one inpatient admission (OR = 3.52; 95% confidence interval [95%CI] 1.07-11.54; P =.04) or at least one ED visit (OR = 8.93; 95%CI 2.41-33.14; P =.001) before age of 18. The associations remained significant adjusting for cannabis use, education, parental socio-economic class and childhood trauma. Conclusion: Consistently with the socio-neurodevelopmental model, we found a significant association between a positive history of hospital care in childhood and adulthood-onset psychosis