Exophytic condyloma: are they as benign as we think?

AIM: As the understanding of anal dysplasia continues to develop, controversy remains regarding treatment of these lesions. The purpose of this study was to evaluate lesion type (flat vs exophytic) and the association between morphology and dysplasia. METHODS: This was a single-centre retrospective analysis of a prospectively collected pathological database of patients > 17 years old who underwent operative excision/biopsies for presumed anal condyloma or dysplasia from 2009 to 2018. The analysis includes comparisons between patient factors, phenotype and grade of dysplasia. RESULTS: Sixty-nine patients had 423 lesions. The mean age of the study population was 48.2 years. 62.3% were men and 46.4% of patients were black. 47.8% of patients were human immunodeficiency virus (HIV) positive and 39.1% were men who have sex with men (MSM). There were 176 (41.6%) flat lesions and 234 (55.3%) exophytic lesions. Exophytic lesions were 2.5-fold more likely to be associated with a higher grade of dysplasia than flat lesions (OR 2.63, 95% CI 1.09-6.32). Neither lesion type nor dysplasia severity was associated with human papillomavirus, lesion location or patient characteristics, including race, MSM or HIV status. DISCUSSION: Exophytic lesions were more than twice as likely to have advanced dysplasia compared with flat lesions. A clearer understanding of the association between gross lesion appearance and dysplasia will allow more appropriate counselling of patients and the development of better screening and treatment guidelines for anal condylomata and dysplasia.

Detrimental role of hyperuricemia on the cardio-reno-vascular system.

A bulk of evidence now exists that links gout with adverse cardiovascular (CV) outcomes. However, continuing doubt remains as to whether hyperuricemia can be truly considered an independent major CV risk factor. In fact, many gouty patients who develop major CV and renal events also possess several traditional CV risk factors, the presence of which can potentially confound any relationship between gout and adverse CV events. This paper reviews the available evidence to determine whether sufficient proof exists from biological, epidemiological and clinical trial studies to support a causal relationship between gout and major CV and renal events. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.

Aldosterone to active Renin ratio as screening test for primary aldosteronism: reproducibility and influence of orthostasis and salt loading.

Measurement of the aldosterone to active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but several sampling conditions impact on the AARR. We aimed to evaluate the reproducibility and the influence of orthostasis and salt loading on the AARR. The Graz Endocrine Causes of Hypertension (GECOH) study is a diagnostic accuracy study among hypertensive patients at a tertiary care centre in Graz, Austria. With a median interval of 4 weeks we determined the AARR under standardized sampling conditions twice in the sitting position, after 1h in the supine position, and after a salt infusion test (SIT). We identified 9 patients with PA and 151 patients with essential hypertension (EH). The Pearson correlation coefficient between both AARR measurements in the sitting position was 0.79 (p<0.001). In EH, recumbency was associated with a significant decrease of aldosterone and, to a lesser extent, of renin, thus lowering the AARR as compared to the sitting position (p<0.001 for all). In PA, recumbency had only minor effects, but it increased the rate of false negative AARR. SIT suppressed the AARR and its components in EH, whereas in PA only renin was slightly decreased. AARR has a good intra-individual reproducibility and decreases during recumbency. These results suggest that a single AARR determination in the sitting position is a reliable screening tool for PA.

Mineralocorticoid receptor blockade-a novel approach to fight hyperkalaemia in chronic kidney disease.

Hyperkalaemia continues to be a major hazard of mineralocorticoid receptor blockade in an effort to retard the progression of chronic kidney disease (CKD). In cardiac patients on mineralocorticoid receptor blockade, RLY-5016 which captures K(+) in the colon has been effective in reducing the risk of hyperkalaemia. This compound might be useful in CKD as well.

Apolipoprotein A-IV concentrations and clinical outcomes in haemodialysis patients with type 2 diabetes mellitus--a post hoc analysis of the 4D Study.

BACKGROUND: Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and anti-oxidative plasma glycoprotein involved in reverse cholesterol transport. The aim of this study was to examine the association between apoA-IV and all-cause mortality, cardiovascular endpoints and parameters of protein-energy wasting and nutrition in haemodialysis patients. METHODS: This post hoc analysis was performed in the German Diabetes Dialysis Study (4D Study) evaluating atorvastatin in 1255 haemodialysis patients with type 2 diabetes mellitus, followed for a median of 4 years. The association between apoA-IV and relevant outcomes was analysed using Cox proportional hazards regression analyses. Body mass index (BMI) was used as a marker of protein-energy wasting. In addition, a definition of extended wasting was applied, combining median values of BMI, serum albumin, creatinine and sensitive C-reactive protein, to classify patients. RESULTS: Mean (±SD) apoA-IV concentration was 49.8 ± 14.2 mg dL(-1). Age- and gender-adjusted apoA-IV concentrations were strongly associated with the presence of congestive heart failure at baseline [odds ratio = 0.81, 95% confidence interval (CI) 0.74-0.88 per 10 mg dL(-1) increase; P < 0.001). During the prospective follow-up, the strongest association was found for all-cause mortality [hazard ratio (HR) = 0.89, 95% CI 0.85-0.95, P = 0.001), which was mainly because of patients with BMI > 23 kg m(-2) (HR = 0.87, 95% CI 0.82-0.94, P < 0.001) and those in the nonwasting group according to the extended definition (HR = 0.89, 95% CI 0.84-0.96, P = 0.001). This association remained significant after additionally adjusting for parameters associated with apoA-IV at baseline. Further associations were observed for sudden cardiac death. ApoA-IV was less strongly associated with atherogenic events such as myocardial infarction. CONCLUSIONS: Low apoA-IV levels seem to be a risk predictor of all-cause mortality and sudden cardiac death. This association might be modified by nutritional status.

Relationship between plasma aldosterone concentration and soluble cellular adhesion molecules in patients referred to coronary angiography.

OBJECTIVE: Evidence is emerging that aldosterone contributes to the development and progression of atherosclerosis and cardiovascular disease. Little is known, however, regarding an association between circulating aldosterone levels and soluble cellular adhesion molecules in humans. METHODS: We investigated the relationship between plasma aldosterone concentration (PAC) and soluble cellular adhesion molecules in a large cohort of patients referred to coronary angiography. After exclusion of patients with ongoing mineralocorticoid receptor blocker use, oral contraceptive or hormone replacement therapy, 1,733 patients (mean age: 62.5±10.8 years; 26.4%% women; mean PAC: 101.5±93.5 pg/mL) remained eligible for analyses. RESULTS: Pearson correlation analysis as well as age and gender adjusted partial correlation analysis revealed a positive association between PAC and soluble (s) E-, L- and P-selectin levels but not with sICAM-1 and sVCAM-1, respectively. In multivariate adjusted analyses of covariance (ANCOVA) sE- (p=0.026), sL- (p=0.049) and sP-selectin (p<0.001) levels increased steadily from the first (reference) to the third gender-specific tertile of PAC. No significant variation across PAC tertiles was found for sICAM-1 (p=0.767) and sVCAM1 (p=0.425) levels, respectively. Finally, multivariate regression analyses revealed circulating aldosterone as an important predictor for soluble selectin levels. CONCLUSION: Our findings in a large cohort of patients indicate that upregulation of selectins might represent a novel mechanism of aldosterone mediated development and progression of atherosclerosis. In view of aldosterone as a novel cardiovascular risk factor independent of angiotensin II, our findings warrant further interventional studies which should evaluate anti-atherosclerotic effects of aldosterone blocking treatment strategies in humans.

Glycated and carbamylated albumin are more "nephrotoxic" than unmodified albumin in the amphibian kidney.

There is increasing evidence that proteins in tubular fluid are "nephrotoxic." In vivo it is difficult to study protein loading of tubular epithelial cells in isolation, i.e., without concomitant glomerular damage or changes of renal hemodynamics, etc. Recently, a unique amphibian model has been described which takes advantage of the special anatomy of the amphibian kidney in which a subset of nephrons drains the peritoneal cavity (open nephrons) so that intraperitoneal injection of protein selectively causes protein storage in and peritubular fibrosis around open but not around closed tubules. There is an ongoing debate as to what degree albumin per se is nephrotoxic and whether modification of albumin alters its nephrotoxicity. We tested the hypothesis that carbamylation and glycation render albumin more nephrotoxic compared with native albumin and alternative albumin modifications, e.g., lipid oxidation and lipid depletion. Preparations of native and modified albumin were injected into the axolotl peritoneum. The kidneys were retrieved after 10 days and studied by light microscopy as well as by immunohistochemistry [transforming growth factor (TGF)-ß, PDGF, NF-κB, collagen I and IV, RAGE], nonradioactive in situ hybridization, and Western blotting. Two investigators unaware of the animal groups evaluated and scored renal histology. Compared with unmodified albumin, glycated and carbamylated albumin caused more pronounced protein storage. After no more than 10 days, selective peritubular fibrosis was seen around nephrons draining the peritoneal cavity (open nephrons), but not around closed nephrons. Additionally, more intense expression of RAGE, NF-κB, as well as PDGF, TGF-ß, EGF, ET-1, and others was noted by histochemistry and confirmed by RT-PCR for fibronectin and TGF-ß as well as nonradioactive in situ hybridization for TGF-ß and fibronectin. The data indicate that carbamylation and glycation increase the capacity of albumin to cause tubular cell damage and peritubular fibrosis.

Office and ambulatory pulse pressure--association with clinical characteristics and cardiovascular risk factors in normoalbuminuric patients with type 2 diabetes (ROADMAP study).

To investigate the association of office and ambulatory 24-h pulse pressure (PP) with clinical characteristics and cardiovascular risk factors in normoalbuminuric type 2 diabetic patients enrolled to the Randomised Olmesartan and Diabetes Microalbuminuria Prevention study, 4449 patients (2054 male and 2395 female; mean age 57.7±8.7 years) with type 2 diabetes, normoalbuminuria and at least one additional cardiovascular risk factor were included into the analysis. After adjustment by age, there were significant correlations between office PP and presence of hypertension (r=0.24; P<0.001), presence of cardiac and vascular disorders (r=0.17; P<0.001), metabolic syndrome (r=0.10; P<0.001), duration of diabetes (r=0.09; P<0.001), fasting blood glucose (r=0.08; P<0.001), albumin/creatinine ratio (r=0.07; P<0.001), insulin treatment, glycosylated haemoglobin (HbA1c), male gender and current smoking. In the subgroup of 1234 patients with ambulatory blood pressure measurement performed, ambulatory PP adjusted for office PP correlated with fasting blood glucose (r=0.16; P<0.001), metabolic syndrome (r=0.14; P<0.001), albumin/creatinine ratio (r=0.11; P<0.001) and indices of glycemic control (HbA1c: r=0.11; P<0.001). In this group of normoalbuminuric type 2 diabetic patients, office and ambulatory PP were associated with duration of diabetes, indices of glycemic control and cardiovascular risk factors. There was relationship between office and ambulatory PP and albuminuria even within normal albuminuria range.

Hypertension and kidney disease.

The relationship between chronic kidney disease and hypertension remains enigmatic and a matter of considerable clinical and academic interest, with evidence suggesting that hypertension is both a cause and a consequence of kidney disease. The kidney has a pivotal role in setting the blood pressure in any individual, and this is likely to be related to that individual's sensitivity to salt. The relationship between low birth weight and subsequent hypertension and kidney disease may be predicated on changes in post glomerular phenomena, including sodium transport, although there are differences observed between white and black populations, there being no such clear relationship demonstrable in the latter. Differences in vascular structure may account for some of this variation. There is , by way of example a considerable difference in the risk of death from cardiovascular disease between blacks and Caucasoid populations with renal disease, the former being at greater risk. International moves are now afoot to reduce dietary salt intake. Successful efforts to reduce blood pressure by these or by pharmacological means are likely to reduce death rates, although precise blood pressure targets remain an elusive concept. The possible role of non muscular heavy chain type II isoform A protein which is associated with non diabetic chronic kidney disease in subjects of African ancestry remains to be determined.

Cardiovascular disease in patients with chronic kidney disease–An update

In the recent past it has been increasingly recognized that even minor renal dysfunctioni sassociated (..) (AU)

Desde hace algún tiempo, se está reconociendo cada vez más que incluso una disfunción renal (..) (AU)

Determinants of urinary albumin excretion within the normal range in patients with type 2 diabetes: the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study.

AIMS/HYPOTHESIS: In contrast to microalbuminuric type 2 diabetic patients, the factors correlated with urinary albumin excretion are less well known in normoalbuminuric patients. This may be important because even within the normoalbuminuric range, higher rates of albuminuria are known to be associated with higher renal and cardiovascular risk. METHODS: At the time of screening for the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) Study, the urinary albumin/creatinine ratio (UACR) was 0.44 mg/mmol in 4,449 type 2 diabetic patients. The independent correlates of UACR were analysed. RESULTS: Independent correlates of UACR during baseline were (in descending order): night-time systolic BP (r(s) = 0.19); HbA(1c) (r(s) = 0.18); mean 24 h systolic BP (r(s) = 0.16); fasting blood glucose (r(s) = 0.16); night-time diastolic BP (r(s) = 0.12); office systolic BP, sitting (r(s) = 0.11), standing (r(s) = 0.10); estimated GFR (r(s) = 0.10); heart rate, sitting (r(s) = 0.10); haemoglobin (r(s) = -0.10); triacylglycerol (r(s) = 0.09); and uric acid (r(s) = -0.08; all p

[Paediatric simulation today and tomorrow. Perspectives and concepts]. / Kindersimulation heute und morgen. Perspektiven und Konzepte.

The confrontation with critically ill newborns, infants and small children is rare and poses a particular challenge for the medical team. Confident technical and non-technical skills are essential for successful emergency treatment. Paediatric simulators facilitate a didactic infrastructure, linking textbook theory with experience-based practice. To summarize the current status of paediatric simulation in Germany, Austria and Switzerland an online survey of all associated centres was conducted. Paediatric simulation is currently available at 24 centres, which have 39 paediatric simulators available, including 8 for newborns, 26 for infants and 5 for children. A certain congruence of standards is detectable among these centres and most instructors have completed a specialized instructor training. Of the instructors 26% are specialized nursing personnel and 67% are physicians of which most are paediatricians and anaesthesiologists. Many centres (38%) operate solely by means of the enthusiastic dedication of the employees who organize various activities during their free time. Nearly all centres (92%) place particular emphasis on non-technical skills which include the interpersonal aspects of crisis resource management. Video-supported debriefing is considered to be the basis for effective training. Within the scope of the recently established PaedSim project the curricula of paediatric simulation courses should be more structured and internationally standardized, thereby increasing both efficacy and sustainability of these training programs.

Optimal blood pressure control versus additional immunosuppressive therapy in idiopathic membranous nephropathy - a retrospective analysis.

The treatment of idiopathic membranous nephropathy (MN) with nephrotic syndrome comprises immunosuppressive therapy and antihypertensive treatment with the blockade of the renin-angiotensin system (RAS). Given the relatively benign natural history of MN, an immunosuppressive-free therapeutic regimen should be considered as the primary treatment option. In a single-center, retrospective analysis we compared the outcome of 54 patients with biopsy-proven idiopathic MN 12, 24 and 60 months after initiation of therapy. All patients had RAS-blocking agents and 36 patients received additionally an immunosuppressive regimen. In both groups the patients initially had a nephrotic proteinuria (median 8.7 vs. 6.0 g/day, n.s.). Median blood pressure reduction was comparable after 12, 24 and 60 months in both groups. The median evolution of proteinuria during therapy after 12, 24 and 60 months was 3.4, 1.7 and 1.1 g/day in the group with immunosuppression compared to 3.0, 1.1 and 0.32 g/day in the non-immunosuppressive group. After 60 months no patient developed endstage renal failure. The number of severe side effects was significantly higher in patients with immunosuppression. Regarding renal function and reduction of proteinuria, patients with idiopathic MN treated without immunosuppressive therapy but with measures to ensure optimal blood pressure control and the full blockade of RAS had a similar outcome after 60 months as compared to patients who received additional immunosuppressive therapy.

The selective vitamin D receptor activator for albuminuria lowering (VITAL) study: study design and baseline characteristics.

BACKGROUND: Patients with diabetic nephropathy are at high risk for further progressive renal function loss. Treatments that decrease albuminuria have been linked with renal and cardiovascular protection. However, even when taking optimal treatment, residual renal and cardiovascular risk remains high which correlates with the magnitude of residual albuminuria. Use of vitamin D receptor activators, such as calcitriol and paricalcitol, is associated with improved sur- vival. A small study with paricalcitol showed reductions in albuminuria. The VITAL study tests the hypothesis whether paricalcitol persistently reduces albuminuria in diabetic subjects already receiving angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) therapy. METHODS: Randomization in this double-blind trial is equal allocation to paricalcitol 1 micro/day, 2 microg/day, or placebo. Inclusion criteria include: a diagnosis of type 2 diabetes, urinary albumin/creatinine ratio (UACR) between 100-3,000 mg/g, estimated glomerular filtration rate (eGFR) between 15-90 ml/min/1.73 m(2), serum calcium <9.8 mg/dl, and parathyroid hormone (PTH) between 35-500 pg/ml. RESULTS: Baseline characteristics of the 281 subjects are: 69% men, mean age 64.9 +/- 10.4 years, eGFR 40.7 +/- 16.7 ml/min, median UACR (interquartile range) 612.3 mg/g (281-1,181 mg/g) and PTH 98.4 +/- 63.8 pg/ml. CONCLUSION: This trial will be the first clinical test of the hypothesis that paricalcitol possesses pleiotropic effects and can modulate albuminuria in the setting of ACEI and/or ARB therapy. Results will have important clinical implications and are expected in November 2009.