Abstract Background The development of sub-clinical organ damage precedes and predicts the occurrence of cardiovascular (CV) events in hypertensive as well as in obese patients. Aim and methods We ...investigated the prevalence and clinical correlates of organ damage (OD), namely carotid atherosclerosis (US scan) and urine albumin to creatinine ratio (three non-consecutive first morning samples) in a group of 164 obese patients and in an age- and gender-matched group of non-obese hypertensive patients. Results There was a significantly greater prevalence and severity of OD in obese patients as compared to non-obese hypertensive patients. In particular obese patients more frequently had microalbuminuria (16 vs7%, χ2 5.8, P = 0.0157) and carotid abnormalities (53 vs 10%, χ2 69.5, P < 0.0001) as well as higher urinary albumin excretion rate (−0.05 ± 0.52 vs −0.28 ± 0.43log ACR, P < 0.0001) and carotid intima-media thickness (0.955 ± 0.224 vs 0.681 ± 0.171, <0.0001). Notably, the coexistence of hypertension and obesity did not entail a greater prevalence and severity of OD. Moreover, after adjusting for potentially confounding factors including blood pressure levels, diagnosis of diabetes, and lipid profile, morbidly obese patients showed a 5-fold, and 22-fold higher risk of having microalbuminuria, and carotid atherosclerosis, respectively. Conclusions Sub-clinical OD is highly prevalent in obese patients, even in the absence of high blood pressure. Hypertension and obesity seem to exert an independent, possibly non-additive role on the occurrence of organ damage.
The role of serum uric acid as an independent risk factor for cardiovascular and renal morbidity is controversial. A better understanding of its relationship with preclinical organ damage may help ...clarify the mechanism(s) implicated in the development of early cardiovascular disease. We evaluated the association between uric acid and the presence and degree of target organ damage in 425 (265 males, 160 females) middle-aged, untreated patients with essential hypertension. Left ventricular mass index and carotid intima-media thickness were assessed by ultrasound scan. Albuminuria was measured as the albumin to creatinine ratio in 3 nonconsecutive first morning urine samples. Overall, patients with target organ damage had significantly higher levels of serum uric acid as compared with those without it (presence versus absence of left ventricular hypertrophy, P=0.04; carotid abnormalities, P<0.05; microalbuminuria, P<0.004; and at least 1 versus no organ damage, P<0.03). In women, the occurrence and severity of each target organ damage we examined increased progressively from the lower to the upper serum uric acid tertiles (P<0.01). After adjustment for body mass index, age, creatinine clearance, and high-density lipoprotein cholesterol, each standard deviation increase in serum uric acid entailed a 75% higher risk of having cardiac hypertrophy and a 2-times greater risk of having carotid abnormalities. These results support the role of serum uric acid as an independent, modifiable marker of cardiovascular damage.
Abstract
Background
Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of gastrointestinal tract: the inflammatory damage increases the risk of developing preneoplastic and ...neoplastic conditions. Therefore, a good agreement between pathologists in the detection of preneoplastic lesion is essential in the management of IBD patients, in order to decrease the risk of progression towards neoplastic lesions. An agreement study on 4 pathologists and 38 cases of dysplasia demonstrated a fair agreement (k=0.4).1 A similar study demonstrated that the lowest level of agreement in the category indefinite for dysplasia (κ = 0.251).
Methods
The study consisted of a survey about diagnostic agreement in a series of preneoplastic lesions of IBD-affected patients, based on digital images. The occurrence of the disease and the occurrence of dysplasia were considered in the study. The study enclosed biopsy specimens from 30 colonoscopies and 1 surgical specimen, related to 20 patients with a clinical pattern of IBD from 4 reference centres in Italy. Digital slides were uploaded in an open-source learning platform. For each endoscopy, sampling sites with similar morphology were aggregated in 54 ‘blocks’, and a series of close-ended questions about (A) the occurrence of IBD (active, in remission, absent, not evaluable) and (B) the evidence of dysplasia (LG, HG, absent, undefined) have been submitted for every block. For each case, a final comprehensive evaluation about (1) the occurrence of IBD (present, absent, unsuitable for assessment), (2) the disease classification (ulcerative colitis, Crohn’s disease, unfit for differential diagnosis, not possible for lack of clinical data), (3) the occurrence of IBD-related dysplasia (IBD with dysplasia, dysplasia not IBD-related, dysplasia untestable, absent) and (4) the classification of dysplasia (sporadic adenoma, ALM, DALM, unclassifiable) were provided. Twenty gastrointestinal pathologists from as many centres in Italy were enrolled.
Results
325 of the 400 tests were successfully concluded.
Agreement values
overall agreement
mean k value 0.59
evidence of IBD in the cases
k value not assessable for excess of concordant answers
differential diagnosis SPORADIC ADENOMA / DALM / ALM
k value not assessable for excess of concordant answers
evidence of dysplasia in the cases
mean k value 0,37
overall evidence of dysplasia in blocks
mean k value 0.42
Conclusion
A preliminary data analysis demonstrated a good agreement about the occurrence of IBD, and a lower agreement about the occurrence of dysplasia and its classification in IBD. Analysis of the correlation between agreement and clinical-histologic parameters could provide interesting spotlights on diagnostic algorithms in this field.
A reduction in renal function is associated with high cardiovascular morbidity and mortality in hypertension. The aim of the present study was to investigate the relationship between creatinine ...clearance and subclinical organ damage in 957 never previously treated, middle-aged patients with primary hypertension. Renal function was estimated by means of the serum creatinine level using the Cockcroft-Gault formula; left ventricular hypertrophy (LVH) was determined according to electrocardiographic criteria; and retinal vascular changes were evaluated by direct ophthalmoscopy. Creatinine clearance was, on the average, 83+/-21.2 ml/min, and the prevalence of LVH and retinopathy was 13 and 49%, respectively. Creatinine clearance was inversely related to the duration of disease (r=-0.132, P<0.0001), systolic blood pressure (r=-0.110, P=0.001), serum glucose (r=-0.090, P=0.007), total cholesterol (r=-0.196, P<0.0001), and LDL-cholesterol (r=-0.196, P<0.0001). Patients in the lower quintile of creatinine clearance showed a higher prevalence of electrocardiogram (ECG) determined LVH (P=0.04), as well as retinal changes (P=0.02). The risk of having LVH or retinal vascular changes increases significantly with each s.d. decrease in creatinine clearance, regardless of traditional cardiovascular risk factors. Moreover, patients with ECG-determined LVH and retinal changes showed lower creatinine clearance as compared to those with lesser degrees of target organ involvement (P<0.01). In conclusion, a mild reduction in creatinine clearance is associated with preclinical end-organ damage in patients with normal creatinine and primary hypertension. These data may help explain the high cardiovascular mortality observed in patients with renal dysfunction. Routine evaluation of creatinine clearance could be useful for identifying patients at higher cardiovascular risk.
A theory is presented for the evaluation of the different terms of the pressure gradient force, when mesoscale flow is driven by a sensible heat source in the planetary boundary layer (PBL), or by an ...elevated confined heat source. By accessing the relative importance of each contribution, specific solution techniques for mesoscale atmospheric flows can be adopted. When the hydrostatic contribution dominates, the spatial variation of the vertical temperature profile can be used to uniquely define the horizontal pressure gradient force.
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.
The Notch signaling has been implicated in the regulation of self-renewal of adult stem cells and differentiation of precursors along a specific cell lineage, in normal embryonic development and ...organogenesis. There is also evidence that signaling through Notch receptors regulate cell proliferation and cell survival in several types of cancer, with opposing results depending on tissue context. No data are available in the literature concerning modulation of the expression of Notch receptors, and their ligands, in human cutaneous malignant melanoma. Here, we have investigated, for the first time, the expression of Notch-1, Notch-2, Jagged-1, Jagged-2 and Delta-like 1 proteins, by immunohistochemistry, in a series of benign and malignant human melanocytic lesions: five common melanocytic nevi, five ‘dysplastic nevi' and 20 melanomas (five in situ, five T1–T2, five T3–T4 and five metastatic melanomas). We found that the expression of Notch-1 and Notch-2, as well as Notch ligands, was upregulated in ‘dysplastic nevi' and melanomas as compared with common melanocytic nevi. These results indicate that the activation of Notch may represent an early event in melanocytic tumor growth and upregulation of Notch signaling may sustain tumor progression.
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