Characteristics and outcomes of ureteroscopic treatment in 2650 patients with impacted ureteral stones.

PURPOSE: To describe stone-free rates and complications of ureteroscopic treatment for impacted compared with non-impacted ureteral stones and evaluate predictive variables for impaction. METHODS: The Clinical Research Office of the Endourological Society prospectively collected 1 consecutive year of data from 114 centers worldwide. Patients eligible for inclusion were patients treated with ureteroscopy for ureteral stones. Patient characteristics, treatment details, and outcomes were compared with regard to stone impaction. Logistic regression analyses were conducted to explore predictive variables for ureteral stone impaction and to analyse the effect of impaction on outcomes. RESULTS: Of the 8543 treated patients, 2650 (31%) had impacted and 5893 (69%) non-impacted stones. The stone-free rate was 87.1% for impacted stones, which is lower compared with 92.7% for non-impacted stones (p < 0.001). Intra-operative complication rates were higher for impacted stones (7.9 versus 3.0%, p < 0.001). Significantly higher ureteral perforation- and avulsion rates were reported in the impacted stone group compared with the non-impacted stone group. No association between stone impaction and post-operative complications could be shown. Female gender, ASA-score >1, prior stone treatment, positive pre-operative urine culture, and larger stones showed to be predictive variables for stone impaction. CONCLUSIONS: Ureteroscopic treatment for impacted stones is associated with lower stone-free rates and higher intra-operative complication rates compared with treatment for non-impacted stones. The predictive variables for the presence of stone impaction may contribute to the identification of stone impaction during the diagnostic process. Moreover, identification of stone impaction may aid the selection of the optimal treatment modality.

Same Session Bilateral Ureteroscopy for Multiple Stones: Results from the CROES URS Global Study.

PURPOSE: This study presents a comparison of the international experience with ipsilateral and bilateral ureteroscopy for multiple, bilateral ureteral and renal stones vs single stone treatment. Patient and treatment characteristics and outcomes were compared. MATERIALS AND METHODS: The CROES (Clinical Research Office of the Endourological Society) Ureteroscopy Global Study includes 114 centers in 32 countries. Patients undergoing bilateral ureteroscopy, ipsilateral ureteroscopy for multiple stones and ureteroscopy for a single stone were examined from January 2010 to October 2012. Intraoperative characteristics and postoperative outcomes were identified for each patient. Inverse probability weighted regression adjustment analyses were done to compare outcomes independent of differences among centers and patient characteristics. RESULTS: The CROES Ureteroscopy Global Study consists of 11,885 patients. A total of 2,153 patients (18.7%) were treated for multiple stones, of whom 1,880 (87.3%) and 273 (12.7%) underwent ipsilateral and bilateral ureteroscopy, respectively. Inverse probability weighted regression adjustment models for bilateral vs ipsilateral ureteroscopy and multiple vs single stone treatments showed that patients with bilateral ureteroscopy and multiple stone treatments had lower stone-free rates, higher re-treatment rates and longer operative times compared to patients who underwent ipsilateral ureteroscopy and single stone treatment. There was no difference in complication rates among bilateral, ipsilateral and single stone ureteroscopy. CONCLUSIONS: This study presents a large series of patients who underwent bilateral and ipsilateral ureteroscopy. Our findings suggest a decrease in stone-free rates, increased re-treatment rates, increased operative times and longer hospital stay in patients treated for multiple stones. The treatment of multiple stones and bilateral ureteroscopy are safe compared to single stone treatment and ipsilateral ureteroscopy, respectively.

Comparison of multiplex platforms for cytokine assessments and their potential use for biomarker profiling in multiple sclerosis.

BACKGROUND: The levels of pro and anti-inflammatory cytokines can be altered in different autoimmune pathologies, such as multiple sclerosis (MS). It is likely that cytokines in bodily fluids can provide a good reflection of ongoing disease patho-physiology. In this study we aimed to validate multiplex cytokine platforms and evaluate whether these cytokines are differentially expressed in MS. METHODS: Assay validation for simultaneous quantification of IL-1ß, IL-6, IL-8 and TNF-α in serum and CSF were performed using both the Luminex-xMAP (Luminex) and Meso Scale Discovery (MSD) platforms. Next, the relation of the pro-inflammatory cytokine 4-plex with disease progression, symptoms and subtypes was studied in paired serum and CSF of MS patients (n=56), and compared with healthy controls (n=203), with the use of the MSD-platform. RESULTS: The MSD-platform showed overall better assay characteristics such as, sensitivity, recovery and linearity compared to the Luminex for the 4-plex cytokines in CSF and serum. IL-6, IL-8 and TNF-α (p<0.001) levels were significantly increased in MS serum compared to healthy controls. Moreover, serum IL-1ß levels correlated with expanded disability status scale (EDSS) scores (r=-0.34, p<0.05). Additionally, IL-6 and IL-8 CSF levels were both significantly decreased in MS patients compared to non-inflammatory neurological disease controls. Noteworthy, higher IL-8 CSF levels than IL-8 serum levels were observed for MS patients, indicating intrathecal activation of macrophages in MS. CONCLUSION: We have demonstrated that the pro-inflammatory 4-plex kit of the MSD-platform shows better assay characteristics in comparison with Luminex kit for quantification of these cytokines in serum and CSF. Overall, the increased levels of IL-6, IL-8 and TNF-α in serum of MS patients compared to healthy controls, support the use of multiple cytokines for future MS biomarker and disease progression research.

The Influence of Body Mass Index on Outcomes in Ureteroscopy: Results from the Clinical Research Office of Endourological Society URS Global Study.

INTRODUCTION: Although ureteroscopy (URS) has been established as a viable treatment for stones in obese patients, its safety and success has not been fully elucidated. The current study describes the worldwide prevalence of obesity in patients with urolithiasis and examines trends in URS outcomes, safety, and efficacy. METHODS: This study utilized the Clinical Research Office of the Endourological Society (CROES) URS Global Study, which was a prospective, multicenter study including 11,885 patients treated with URS for urinary stones at 1 of 114 urology departments across 32 countries. The relationship between body mass index (BMI), diabetes, and creatinine, with retreatment, stone-free rates, complications, and long hospital stay, was examined with a multivariate logistic regression analyses. RESULTS: Of the 10,099 URS patients with BMI data, 17.4% were obese and 2.2% were super obese. Overall, 86.7% patients were stone free and 16.8% required retreatment. Higher BMI was associated with lower stone-free rates, and any deviation from normal weight was associated with higher retreatment rates. In multivariate analysis controlling for several variables including stone size, the association between BMI and lower stone-free rates with higher retreatment rates persisted. Intraoperative complications occurred in 518 (5.1%) patients, and 343 (3.4%) experienced a postoperative complication. Postoperative complications were more frequent in the underweight and super obese subjects, and there was no relationship between BMI and intraoperative complications. DISCUSSION: Although URS for stone disease was found to be an overall safe procedure for obese and super obese patients, efficacy of the procedure may be lower compared with normal-weight subjects and higher retreatment rates may be necessary.

Sleep quality and duration are related to microvascular function: the Amsterdam Growth and Health Longitudinal Study.

Sleep and sleep disorders are related to cardiovascular disease, and microvascular function is an early cardiovascular disease marker. Therefore, the relationship of sleep (measured in sleep quality and duration) with microvascular function was examined in healthy adults. Sleep quality was assessed with the validated Sleep Wake Experience List (SWEL) questionnaire. Duration of sleep was self-reported in an additional question. Microvascular function was measured using nailfold capillaroscopy. Linear regression analyses were used to examine the relationship between sleep and microvascular function. Potential confounders included physical activity, smoking, blood pressure, body mass index and several biochemical parameters. Analyses were performed in 259 participants (116 men). For women reporting insufficient (<7 h) sleep duration, microvascular function (post-ischaemic capillary recruitment) was significantly lower (b = -11.17; P = 0.04) compared to women reporting sufficient sleep duration. There was no relationship between sleep quality and microvascular function in females. In males, a trend towards lower capillary recruitment was found in those reporting a combination of poor sleep quality and insufficient duration (b = -7.54; P = 0.09), compared to those reporting good sleep quality as well as sufficient duration. This study suggests an association between sleep and microvascular function. Which aspects of sleep exactly affect microvascular function, and if indeed the association is different between males and females in other samples, needs further research.

Serum leptin is not altered nor related to cognitive decline in Alzheimer's disease.

BACKGROUND: Low plasma leptin levels can be a risk factor for Alzheimer's disease (AD) but the relation of leptin with disease progression in clinical AD is unknown. OBJECTIVE: The aim of this study was to investigate the relation between serum leptin concentrations and cognitive decline in clinical AD. METHODS: Serum leptin levels were analyzed in 295 non-obese subjects including healthy controls (n = 65), patients with subjective memory complaints (n = 99), patients with AD (n = 100), and patients with vascular dementia (n = 31). Leptin levels were related to hippocampal atrophy, baseline Mini-Mental State Examination (MMSE) scores and annual decline in MMSE measured over 2 years (range 0.4-4.5 years). RESULTS: Serum leptin levels were similar in AD patients compared to healthy controls and patients with subjective memory complaints. No correlation was observed between leptin concentrations and MMSE, annual change in MMSE during follow-up or atrophy. CONCLUSION: Serum leptin levels are not altered in this population of relatively young AD or vascular dementia patients (mean 60) compared to healthy and clinical control groups and were not related to cognitive decline. These results suggest that peripheral leptin levels do not play a role in evolution of AD pathology.

Body mass index is related to microvascular vasomotion, this is partly explained by adiponectin.

OBJECTIVE: obesity-related microvascular dysfunction, including alterations in rhythmic changes in vascular diameter, so-called 'vasomotion', may be important in the clustering of obesity with other cardiovascular risk factors. Adipokines have been suggested to play a role in obesity-related vascular dysfunction. Alterations in vasomotion have been found using extreme body mass index (BMI) phenotypes. Whether these alterations can be translated to the general population is unknown. The aim was to retrospectively investigate relationships between BMI, vasomotion and adipokines in a population-based cohort. METHODS: Adiposity, vasomotion, adiponectin and leptin were determined in 94 apparently healthy participants (age 42 years, 46 men, mean BMI 25·5 ± 3·8 kg/m(2) ) of the Amsterdam Growth and Health Longitudinal Study (AGHLS). Vasomotion was assessed via wavelet analysis of skin laser Doppler flowmetry (LDF). RESULTS: BMI was associated with the neurogenic domain of the vasomotion spectrum (ß -0·011, P = 0·046), adiponectin (ß -0·18, P = 0·028) and leptin (ß 2·22, P < 0·0001). Adiponectin was positively associated with the neurogenic domain of vasomotion (ß 0·016, P = 0·019). Leptin did not show any significant relationship with vasomotion. The association between BMI and the neurogenic domain of the vasomotion spectrum was partly explained by adiponectin. CONCLUSIONS: The association between adiposity and microvascular vasomotion also applies to the normal population and is partly explained by adiponectin.

Homocysteine levels are inversely associated with capillary density in men, not in premenopausal women.

BACKGROUND: Homocysteine is an independent predictor of cardiovascular risk. The mechanisms underlying this link are not fully elucidated. Whereas the role of vascular dysfunction in conduit arteries is extensively studied, the role of the microcirculation in this relationship is largely unexplored. We assessed the relationship between homocysteine levels and microvascular structure and function in a healthy, population-based cohort. MATERIALS AND METHODS: We cross-sectionally studied 260 participants (aged 42 years, 47% men) of the Amsterdam Growth and Health Longitudinal Study. Nailfold videocapillaroscopy was used to assess capillary density at baseline, during venous occlusion and during peak reactive hyperaemia. The relationship between tertiles of homocysteine and microvascular outcomes was evaluated using linear regression analyses, with adjustment for BMI and blood pressure. Stratified analyses were performed for men and women. RESULTS: In men, we observed a negative, nonlinear relationship between homocysteine and baseline capillary density, showing a lower capillary density in the highest tertile of homocysteine [adjusted B -8.65 capillaries/mm(2) (95%-CI: -16.05 to -1.25); P = 0.02]. In women, no significant associations were found between homocysteine and microvascular outcomes. CONCLUSIONS: In men, higher homocysteine levels are associated with a reduction in basal perfusion of skin capillaries. This finding provides a novel potential explanation for how homocysteine influences cardiovascular disease risk.

Cohort profile: the Amsterdam Growth and Health Longitudinal Study.

The Amsterdam Growth and Health Longitudinal Study (AGHLS) is a unique, multidisciplinary cohort study that was initially set up to examine growth and health among teenagers. Throughout the years, the AGHLS has aimed to answer research questions dealing with the relationships between the (natural) development of anthropometry, lifestyle and health from adolescence into adulthood. The AGHLS specifically focuses on anthropometrics, physical activity and fitness, cardiovascular disease risk, lifestyle, musculoskeletal health, psychological health and well-being. Besides this, many methodological issues related to the analysis of longitudinal data were also explored within the framework of the AGHLS. In 1976, students from two secondary schools from the greater Amsterdam area were included in the study. Between 1976 and 2006, 10 rounds of measurement were performed covering an age range between 13 and 43 years. The huge database collected so far has been primarily used to answer relevant research questions regarding the longitudinal relationship between lifestyle and health. Further information about the study can be obtained from the principal investigator Jos Twisk (jwr.twisk@vumc.nl), and up-to-date information on AGHLS can be found by visiting the website www.aggo.nl.

The relationship of body fatness and body fat distribution with microvascular recruitment: The Amsterdam Growth and Health Longitudinal Study.

INTRODUCTION: Microvascular function has been proposed to link body fatness to CVD and DM2. Current knowledge of these relationships is mainly based on studies in selected populations of extreme phenotypes. Whether these findings can be translated to the general population remains to be investigated. AIM: To assess the relationship of body fatness and body fat distribution with microvascular function in a healthy population-based cohort. METHODS: Body fatness parameters were obtained by anthropometry and whole-body dual-X-ray absorptiometry (DEXA) in 2000 and 2006. Microvascular recruitment (i.e., absolute increase in perfused capillaries after arterial occlusion, using nailfold capillaroscopy) was measured in 2006. Linear regression analysis was used to examine the relationship of (changes in) body fatness and body fat distribution with microvascular recruitment. RESULTS Data were available for 259 participants (116 men). Capillary density was higher in women than in men (difference 7.3/ mm(2); p < 0.05). In the total population, the relationship between total body fatness and microvascular recruitment was positive (ß = 0.43; p = 0.002), whereas a central pattern of fat distribution (trunk-over-total fatness) showed a negative relationship (ß = -26.2; p = 0.032) with microvascular recruitment. However, no association remained apparent after adjustment for gender. In addition, there was no relationship between 6-year changes in body fatness or fat distribution and microvascular recruitment. CONCLUSION: Women show higher capillary recruitment values than men. This study does not support a linear relationship between microvascular function and body fatness or body fat distribution within a population-based normal range.

Microvascular dysfunction: a potential mechanism in the pathogenesis of obesity-associated insulin resistance and hypertension.

The intertwined epidemics of obesity and related disorders such as hypertension, insulin resistance, type 2 diabetes, and subsequent cardiovascular disease pose a major public health challenge. To meet this challenge, we must understand the interplay between adipose tissue and the vasculature. Microvascular dysfunction is important not only in the development of obesity-related target-organ damage but also in the development of cardiovascular risk factors such as hypertension and insulin resistance. The present review examines the role of microvascular dysfunction as an explanation for the associations among obesity, hypertension, and impaired insulin-mediated glucose disposal. We also discuss communicative pathways from adipose tissue to the microcirculation.

Inflammation markers are associated with cardiovascular diseases risk in adolescents: the Young Hearts project 2000.

PURPOSE: The traditional approach for identifying subjects at risk from cardiovascular diseases (CVD) is to determine the extent of clustering of biological risk factors adjusted for lifestyle. Recently, markers of endothelial dysfunction and low grade inflammation, including high sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecules (sICAM), and soluble vascular adhesion molecules (sVCAM), have been included in the detection for high risk individuals. However, the relationship of these novel biomarkers with CVD risk in adolescents remains unclear. The purpose of this study, therefore, was to establish the association of hsCRP, sICAM, and sVCAM with CVD risk in an adolescent population. METHODS: Data from the Young Hearts 2000 cross-sectional cohort study, carried out in 1999-2001, were used. From a total of 2,017 male and female participants, 95 obese subjects were identified and matched according to age, sex, and cigarette smoking, with 95 overweight and 95 normal-weight adolescents. Clustered CVD risk was computed using a sum of Z-scores of biological risk factors. The relationship was described using multiple linear regression analyses. RESULTS: hsCRP, sICAM, and sVCAM showed significant associations with CVD risk. hsCRP and sICAM had a positive relation with CVD risk, whereas sVCAM showed an inverse relationship. In this study, lifestyle factors showed no relation with CVD risk. CONCLUSION: The results fit the hypothesized role of low grade inflammation and endothelial dysfunction in CVD risk in asymptomatic adolescents. The inverse relationship of VCAM, however, is hard to explain and indicates the complex mechanisms underlying CVD. Further research is needed to draw firm conclusions on the biomarkers used.