Abstract Background and aims The independent role of serum uric acid (SUA) as a marker of cardio-renal risk is debated. The aim of this study was to assess the relationship between SUA, metabolic ...syndrome (MS), and other cardiovascular (CV) risk factors in an Italian population of hypertensive patients with a high prevalence of diabetes. Methods and results A total of 2429 patients (mean age 62 ± 11 years) among those enrolled in the I-DEMAND study were stratified on the basis of SUA gender specific quartiles. MS was defined according to the NCEP-ATP III criteria, chronic kidney disease (CKD) as an estimated GFR (CKD-Epi) <60 ml/min/1.73 m2 or as the presence of microalbuminuria (albumin-to-creatinine ratio ≥2.5 mg/mmol in men and ≥3.5 mg/mmol in women). The prevalence of MS, CKD, and positive history for CV events was 72%, 43%, and 20%, respectively. SUA levels correlated with the presence of MS, its components, signs of renal damage and worse CV risk profile. Multivariate logistic regression analysis revealed that SUA was associated with a positive history of CV events and high Framingham risk score even after adjusting for MS and its components (OR 1.10, 95% CI 1.03–1.18; P = 0.0060; OR 1.28, 95% CI 1.15–1.42; P < 0.0001). These associations were stronger in patients without diabetes and with normal renal function. Conclusions Mild hyperuricemia is a strong, independent marker of MS and high cardio-renal risk profile in hypertensive patients under specialist care. Intervention trials are needed to investigate whether the reduction of SUA levels favorably impacts outcome in patients at high CV risk.
Background
Crohn’s disease (CD) and ulcerative colitis, two forms of inflammatory bowel disease (IBD), are chronic and relapsing conditions of the gastrointestinal tract both characterized by long ...lasting chronic inflammation and increased risk of dysplasia and colorectal cancer (CRC). The aim of our study was to evaluate the interobserver agreement about IBD-associated dysplasia among pathologists belonging to the Italian Group for Inflammatory Bowel Diseases (IG-IBD P).
Methods
The present multicenter survey was performed using telepathology, supported by an open source E-learning platform. Biopsy specimens from 30 colonoscopies and from 20 patients were included. The glass slides of any case, including clinical and endoscopic data, were digitalized and uploaded on the E-learning platform. All the digital slides were grouped in 54 diagnostic “blocks”. Blinded histopathological evaluation on all the digital slides was performed by 20 gastrointestinal pathologists. Closed-ended questions about (1) the occurrence of IBD; (2) the classification of IBD (as UC or CD); (3) the presence of active versus quiescent disease; (4) the presence of dysplasia; (5) the possible association of dysplasia with the sites of disease (dysplasia-associated lesion or mass—DALM vs adenoma-like mass—ALM); (6) the grading of dysplasia according to the ECCO guidelines (negative, indefinite, low grade, high grade categories) and (7) the presence of associated serrated features, were proposed in each case. Inter-observer agreement was evaluated by mean agreement percentage and kappa statistic, when suitable.
Results
The diagnosis of IBD was confirmed in 19 of 20 patients, 17 of 19 being classified as UC, 2 as CD. The mean interobserver agreement percentages about (1) the evidence of IBD, (2) the presence of either UC or CD and (3) the activity grading resulted to be 80%, 69% and 86%, respectively. Dysplasia was detected in 8/20 patients, with moderate agreement between pathologists (mean 72%,
k
0.48). Particularly, low grade dysplasia was found in 13 biopsies (combined
k
0.38), whereas high grade dysplasia in 8 (combined
k
0.47). When the endoscopic and histopathological data were combined, features consistent with DALM were found in 6 of 20 patients with low grade dysplasia and those consistent with ALM in 2 patients with low grade dysplasia in a single biopsy (mean agreement: 86%). An associated serrated pattern was discovered in 4 patients (7 biopsies).
Conclusions
Our study showed moderate interobserver agreement about the histopathological detection and classification of IBD-associated dysplasia. Further efforts should be undertaken to integrate the histopathological data with both the ancillary tests and molecular investigations.
Metabolic syndrome (MS) has been shown to predict cardiovascular events in hypertension. Recently, a new four-group left ventricular (LV) hypertrophy classification based on both LV dilatation and ...concentricity was proposed. This classification has been shown to provide a more accurate prediction of cardiovascular events, suggesting that the presence of LV dilatation may add prognostic information. We investigated the relationship between MS and the new classification of LV geometry in patients with primary hypertension. A total of 372 untreated hypertensive patients were studied. Four different patterns of LV hypertrophy (eccentric nondilated, eccentric dilated, concentric nondilated and concentric dilated hypertrophy) were identified by echocardiography. A modified National Cholesterol Education Program definition for MS was used, with body mass index replacing waist circumference. The overall prevalence of MS and LV hypertrophy (LVH) was 29% and 61%, respectively. Patients with MS showed a higher prevalence of LVH (P=0.0281) and dilated LV geometries, namely eccentric dilated and concentric dilated hypertrophy (P=0.0075). Moreover, patients with MS showed higher LV end-diastolic volume (P=0.0005) and prevalence of increased LV end-diastolic volume (P=0.0068). The prevalence of LV chamber dilatation increased progressively with the number of components of MS (P=0.0191). Logistic regression analysis showed that the presence of MS entails a three times higher risk of having LV chamber dilatation even after adjusting for several potential confounding factors. MS is associated with LV dilatation in hypertension. These findings may, in part, explain the unfavourable prognosis observed in patients with MS.
Celiac Disease (CeD) is an immune-mediated inflammatory disorder of the small intestine, affecting genetically susceptible individuals when exposed to gluten. Small intestinal biopsy interpretation ...has been the "gold standard" for celiac disease (CeD) for over 50 years. Despite today's availability of sensitive and specific serological tests, the histopathological features from mucosal biopsy play a key role in diagnosing when CeD is suspected. Such a diagnostic approach requires a multidisciplinary team to optimize both tissue sampling and interpretation via the interaction between the pathologist and the gastroenterologist. Pathologists of the Italian Group of Gastrointestinal Pathology (GIPAD-SIAPEC), together with a member (TR) of the Italian Society of Technicians (AITIC) and an expert gastroenterologist (CC), provide position statements as a practical tool for reading and interpreting the report. Moreover, a position statement was formulated about the recently described condition known as Non-Celiac Gluten Sensitivity (NCGS). Within such a diagnostic setting, both the architectural abnormalities of the duodenal mucosa, namely glandular hyperplasia, and villous atrophy and the number of intraepithelial T-lymphocytes should be well highlighted. Ancillary tests such as anti-CD3 stain are useful for an accurate count of the intraepithelial T lymphocytes when CeD or NCGS is suspected. Moreover, anti-CD3 and anti-CD8 stains are recommended in patients not responding to the gluten-free diet (GFD) to confirm a diagnosis of Refractory Celiac Disease (RCeD). Diagnostic clues about the differential diagnosis of both CeD and RCeD have also been rendered.
Hyperhomocysteinemia is considered a risk factor in arterial and venous thrombosis. The mechanism by which homocysteine (HCy) supports athereothrombosis is still unknown and may be multifactorial. ...Earlier in vitro studies demonstrated that HCy induced arachidonic acid release and increased thromboxane B2 (TXB2) formation. In this work, we found that HCy stimulated the rapid and sustained phosphorylation of platelet p38 mitogen‐activated protein kinase (p38 MAPK). The effect was time‐ and dose‐dependent. The HCy effect on p38 MAPK phosphorylation was prevented by N‐acetyl‐l‐cysteine and iloprost and was partially inhibited by nordihydroguaiaretic acid. Moreover, the incubation of platelets with HCy led to the phosphorylation of cytosolic phospholipase A2 (cPLA2). In addition HCy promoted cPLA2 activation, assessed as arachidonic acid release. The cPLA2 phosphorylation and activation were both impaired by the inhibition of p38 MAPK through SB203580. This effect was not complete, reaching at the most the 50% of the total. In FURA 2‐loaded platelets, HCy induced a dose‐dependent intracellular calcium rise suggesting that the calcium elevation promoted by HCy could participate in the cPLA2 activation, leading to arachidonic acid release and TXB2 formation. In conclusion, our data provide insight into the mechanisms of platelet activation induced by HCy, suggesting that the p38 MAPK/cPLA2 pathway could play a relevant role in platelet hyperactivity described in hyperhomocysteinemia.
Metabolic syndrome (MS) has recently been shown to be a forerunner of chronic kidney disease (CKD). Microalbuminuria (MA) is associated with both MS and CKD. This study aimed to prospectively ...investigate the relationship among MA, MS and renal outcome in non-diabetic patients with primary hypertension. A total of 790 hypertensive patients enrolled in the MAGIC study between 1993 and 1997 (mean age 49.3±10.7 years) were included in the analysis. Renal outcome was defined as the first hospitalization with a diagnosis of CKD. At baseline, 146 (19%) and 60 (7.6%) patients met MS and MA criteria, respectively. A total of 20 patients (2.5%) concomitantly showed MS and MA. After a median follow-up of 11.6 years (interquartile range 3.2 years), renal end point was reached in 15.8% of patients with MS and in 8.9% of those without it (P=0.0087). The incidence of renal events increased progressively starting from patients with neither MS nor MA, to patients with only one of these abnormalities and then to those with both. Significant interaction was observed between MS and MA. Patients with concomitant occurrence of MS and MA at baseline showed a greater than fivefold risk of renal outcome, as compared with patients with neither of these two risk factors (hazard ratio 5.46; 95% confidence interval 2.34-12.75). This risk became even higher when data were adjusted for potential confounders. MS and MA are independent and interactive predictors of renal outcome in non-diabetic patients with primary hypertension.
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Objectives. Hypertensive patients with metabolic syndrome (MS) are at greater risk for cardiovascular disease. To get a better understanding of the pathophysiology underlying this association, we ...evaluated the relationship between MS and subclinical organ damage in essential hypertensive patients.
Design and setting. A total of 354 untreated, nondiabetic patients with primary hypertension were included in the study. A modified ATP III definition for MS was used, with body mass index replacing waist circumference. Albuminuria was measured as albumin to creatinine ratio, left ventricular mass index (LVMI) was assessed by echocardiography and carotid abnormalities by ultrasonography.
Results. The prevalence of MS was 25%. Patients with MS were more likely to be smokers (P = 0.004) and had higher serum uric acid levels (P = 0.004). Moreover, they showed higher urinary albumin excretion (P = 0.0004) and LVMI (P = 0.0006), increased intima‐media thickness (P = 0.045), as well as higher prevalence of microalbuminuria (P = 0.03) and left ventricular hypertrophy (LVH; P = 0.003). After adjusting for age, gender and duration of hypertension, we found that the presence of MS entails a twofold greater risk for microalbuminuria (P = 0.04), LVH (P = 0.003) and carotid abnormalities (P < 0.05). When patients were stratified according to the number of components of MS, albuminuria (P = 0.002) and LVMI (P = 0.005) increased progressively across categories.
Conclusions. Metabolic syndrome is associated with subclinical organ damage in nondiabetic, essential hypertensive patients. These data may, in part, explain the high cardiovascular morbidity and mortality that is observed in hypertensive patients with MS.
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