Disease In High-risk Patients Research Articles

Condylomata acuminata of HIV-positive men may harbour focal areas of dysplasia: relevant implications for the management of human papillomavirus-induced disease in high-risk patients.

Condylomata acuminata of HIV-positive men may harbour focal areas of dysplasia: relevant implications for the management of human papillomavirus-induced disease in high-risk patients.

What is the fate of the cholecystostomy tube following percutaneous cholecystostomy?

Cholecystectomy is the preferred treatment for acute cholecystitis with percutaneous cholecystostomy (PC) considered an alternative therapy in severely debilitated patients. The aim of this study was to evaluate the efficacy and outcomes of PC at a tertiary referral center. We retrospectively reviewed all patients that had undergone PC from 2000 to 2014. Data collected included baseline demographics, comorbidities, details of PC placement and management, and post-procedure outcomes. The Charlson comorbidity index (CCI) was calculated for all patients at the time of PC. Four hundred and twenty-four patients underwent PC placement from 2000 to 2014, and a total of 380 patients had long-term data available for review. Within this cohort, 223 (58.7%) of the patients were male. The mean age at the time of PC placement was 65.3±14.2years of age, and the mean CCI was 3.2±2.1 for all patients. One hundred and twenty-five (32.9%) patients went on to have a cholecystectomy following PC placement. Comparison of patients who underwent PC followed by surgical intervention revealed that they were significantly younger (p=0.0054) and had a lower CCI (p<0.0001) compared to those who underwent PC alone. PC placement appears to be a viable, long-term alternative to cholecystectomy for the management of biliary disease in high-risk patients. Old and frail patients benefit the most, and in this cohort PC may be the definitive treatment.

The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes

Sodium glucose cotransporter 2 (SGLT2) inhibition lowers HbA1c, systolic BP (SBP) and weight in patients with type 2 diabetes and reduces renal hyperfiltration associated with type 1 diabetes, suggesting decreased intraglomerular hypertension. As lowering HbA1c, SBP, weight and intraglomerular pressure is associated with anti-albuminuric effects in diabetes, we hypothesised that SGLT2 inhibition would reduce the urine albumin-to-creatinine ratio (UACR) to a clinically meaningful extent. We examined the effect of the SGLT2 inhibitor empagliflozin on UACR by pooling data from patients with type 2 diabetes and prevalent microalbuminuria (UACR = 30-300mg/g; n = 636) or macroalbuminuria (UACR > 300mg/g; n = 215) who participated in one of five phase III randomised clinical trials. Primary assessment was defined as percentage change in geometric mean UACR from baseline to week 24. After controlling for clinical confounders including baseline log-transformed UACR, HbA1c, SBP and estimated GFR (according to the Modification of Diet in Renal Disease [MDRD] formula), treatment with empagliflozin significantly reduced UACR in patients with microalbuminuria (-32% vs placebo; p < 0.001) or macroalbuminuria (-41% vs placebo; p < 0.001). Intriguingly, in regression models, most of the UACR-lowering effect with empagliflozin was not explained by SGLT2 inhibition-related improvements in HbA1c, SBP or weight. In patients with type 2 diabetes and either micro- or macroalbuminuria, empagliflozin reduced UACR by a clinically meaningful amount. This effect was largely independent of the known metabolic or systemic haemodynamic effects of this drug class. Our results further support a direct renal effect of SGLT2 inhibitors. Prospective studies are needed to explore the potential of this intervention to alter the course of kidney disease in high-risk patients with diabetes. Clinicaltrials.gov NCT01177813 (study 1); NCT01159600 (study 2); NCT01159600 (study 3); NCT01210001 (study 4); and NCT01164501 (study 5).

Branched versus fenestrated endografts for endovascular repair of aortic arch lesions

Endovascular repair of the aortic arch represents a formidable challenge because of aortic diameter, angulation, elasticity, and greater distance to the femoral access vessels. Whereas both fenestrated and branched endografts have been customized to accommodate complex pathologic processes of the arch, no data comparing the techniques are available. The aim of this study was to compare the outcomes of custom-made fenestrated vs branched thoracic endovascular aortic repair (fTEVAR vs bTEVAR). This was a single-center, retrospective comparative study of all consecutive patients treated with fTEVAR and bTEVAR for aortic arch diseases. All patients were considered unsuitable for open surgical therapy and treated with customized stent grafts (Cook Medical, Bloomington, Ind). Within 42months, 29 patients underwent fTEVAR and bTEVAR (66± 9years; nine female patients). The fTEVAR patients (n= 15) had no differences in comorbidities compared with the bTEVAR patients (n= 14). Dissection or postdissection aneurysm was the indication in 6 of 15 fTEVARs and 5 of 14 bTEVARs (40% vs 36%; P= NS); the remaining procedures were performed for aneurysms. Six (40%) fTEVAR patients underwent previous cervical debranching compared with all bTEVAR patients. In all patients with bTEVAR, two arch vessels were targeted (innominate, 13; left carotid artery, 14; left subclavian artery, 1), whereas fTEVAR targeted 1.6± 0.5 arch vessels (bovine trunk, 4; innominate artery, 1; left carotid artery, 10; left subclavian artery, 9). Technical success was achieved in all but one case of a fenestrated endograft that was displaced, resulting in major stroke and death of the patient. Strokes occurred in two fTEVAR patients and one bTEVAR patient (P= NS). The 30-day mortality was 20% in the fTEVAR patients (n= 3) vs 0% in the bTEVAR patients (P= NS). The causes of early mortality were major stroke (n= 1), access complication (n= 1), and myocardial infarction (n= 1). Mean follow-up was 8 (1-35) and 10 (2-22) months for fTEVAR and bTEVAR, respectively. No branch occlusions occurred, and two patients underwent coil embolization for endoleaks (P= NS). One patient was readmitted with infected branched endograft 4months after intervention and has so far been successfully treated with aneurysm sac drainage and antibiotics. There was one late nonaneurysm-related death in each group. Both fTEVAR and bTEVAR are feasible for the treatment of aortic arch diseases in high-risk patients. Results are promising, although fTEVAR was associated with higher mortality in this early experience. bTEVAR was more commonly used in Ishimaru zone0.

IP219. When Antegrade Access Fails: Utilization of Retrograde Arterial Access in the Management of Infrainguinal Occlusive Disease Is a Safe and Feasible Strategy

The objective of this review is to describe technical success and short-term outcomes after a retrograde approach for infrainguinal therapeutic revascularization. Retrograde access techniques allow entry into the distal target vessel to aid in recanalization of occlusions when endovascular antegrade access fails. A lower extremity intervention vascular registry was queried to identify patients in whom a retrograde access was performed when a tibial, popliteal, or superficial femoral artery (SFA) occlusion could not be managed through an antegrade approach. Demographics, surgical indication, comorbidities, rates of procedural success, limb salvage rates, periprocedural complications, and mortality were collected. Access of the tibial, peroneal, pedal, or popliteal artery was obtained after anesthetizing the skin with a micropuncture sheath under ultrasound. Lesions successfully crossed were then treated either directly via the retrograde access or via subintimal arterial flossing with antegrade-retrograde intervention. From February 2012 to August 2015, 51 cases were identified (19 office and 32 hospital) in which a retrograde access was performed. Preoperative indications included Rutherford 3 (6), Rutherford 4 (12), and Rutherford 5 (33). Technical success rate was 86% (44 of 51). Technical failures were due to inability to cross the lesion or to connect with the antegrade access. Of these failures, two required below-knee amputation (BKA), four remained chronic Rutherford 5, but with healing wounds, and one died. A variety of tibial (23) and SFA/popliteal (56) lesions were treated via percutaneous angioplasty (PTA) alone (29), atherectomy (27), or with PTA/stent (26). At follow-up, there was a 73% overall improvement rate in clinical status as measured by Rutherford score. Three intraoperative crossing complications occurred. All complications were repaired successfully with stents, except one posterior tibial perforation that did not lead to limb compromise. At 60 days postprocedure, five major amputations (three below- and two above-knee amputations) had occurred. One BKA was the result of wet gangrene. The patient later developed a stump infection, underwent a knee disarticulation, and ultimately died secondary to sepsis for a 2% mortality rate. Retrograde approach for extensive infrainguinal occlusive disease in high-risk patients for limb salvage is a safe and feasible strategy with excellent limb-salvage and complication rates at follow-up. This technique can be expanded to both office and hospital locations offering an endovascular option for revascularization to patients who are not otherwise bypass candidates for limb salvage.

MP73-18 EXTERNAL VALIDATION OF PREOPERATIVE AST/ALT (DE-RITIS) RATIO AS A PROGNOSTIC INDICATOR IN LOCALIZED AND METASTATIC RENAL CELL CARCINOMA

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging I1 Apr 2016MP73-18 EXTERNAL VALIDATION OF PREOPERATIVE AST/ALT (DE-RITIS) RATIO AS A PROGNOSTIC INDICATOR IN LOCALIZED AND METASTATIC RENAL CELL CARCINOMA Dattatraya Patil, Rishi Sekar, Jeff Pearl, Yoram baum, Kathryn Wehrmeyer, Mersiha Torlak, Mehrdad Alemozaffar, Christopher Filson, Kenneth Ogan, and Viraj Master Dattatraya PatilDattatraya Patil More articles by this author , Rishi SekarRishi Sekar More articles by this author , Jeff PearlJeff Pearl More articles by this author , Yoram baumYoram baum More articles by this author , Kathryn WehrmeyerKathryn Wehrmeyer More articles by this author , Mersiha TorlakMersiha Torlak More articles by this author , Mehrdad AlemozaffarMehrdad Alemozaffar More articles by this author , Christopher FilsonChristopher Filson More articles by this author , Kenneth OganKenneth Ogan More articles by this author , and Viraj MasterViraj Master More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1673AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A recent European cohort study showed the De-Ritis ratio, defined as the ratio of preoperative aspartate aminotransferase (AST) to alanine aminotransferase (ALT), as an independent predictor of overall and recurrence-free survival in localized renal cell carcinoma (RCC). In this study, we perform an external validation of the De-Ritis ratio as a prognostic indicator in a distinct cohort of patients with localized as well as metastatic RCC. METHODS Patients that underwent nephrectomy for localized and metastatic RCC between 2001 and 2014 with available laboratory values within one week prior to the surgery were queried from the Emory Nephrectomy Database. After sensitivity-specificity trade-off analysis, De-Ritis ratio of 1.2 was used as an optimal threshold to divide subjects into high and low subgroups. Prognostic value of the De-Ritis ratio was used for further analysis with Kaplan-Meier and Cox proportional survival regression models. RESULTS In a cohort of 451 patients, an elevated DeRitis ratio (AST/ALT≥1.2) was associated with statistically significant reduction in overall survival (log-rank, p=0.0023) and recurrence-free survival (log-rank, p=0.0395). On multivariate survival analysis, De-Ritis ratio was shown to be an independent and significant predictor of overall survival (HR=1.91, p=0.002) and recurrence-free survival (HR=2.13, p=0.014) as seen in Table 1. CONCLUSIONS Elevated De-Ritis ratio (AST/ALT≥1.2) is an independent and significant predictor of overall and recurrence-free survival and is capable of differentiating high-risk disease in patients with localized as well as metastatic RCC. These findings are consistent with a previous study investigating the De-Ritis ratio in a European cohort, and further validates its prognostic ability in a geographically distinct cohort including patients who presented with metastatic disease. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e967 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Dattatraya Patil More articles by this author Rishi Sekar More articles by this author Jeff Pearl More articles by this author Yoram baum More articles by this author Kathryn Wehrmeyer More articles by this author Mersiha Torlak More articles by this author Mehrdad Alemozaffar More articles by this author Christopher Filson More articles by this author Kenneth Ogan More articles by this author Viraj Master More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP02-19 BIOMARKERS OF BIOCHEMICAL (BCR) AND CLINICAL RECURRENCE (CR) IN PROSTATE CANCER (PCA) FOLLOWING RADICAL PROSTATECTOMY (RP) – PERFORMANCE OF A 17-GENE GENOMIC PROSTATE SCORE (GPS) AND TESTS FOR PTEN LOSS.

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2016MP02-19 BIOMARKERS OF BIOCHEMICAL (BCR) AND CLINICAL RECURRENCE (CR) IN PROSTATE CANCER (PCA) FOLLOWING RADICAL PROSTATECTOMY (RP) – PERFORMANCE OF A 17-GENE GENOMIC PROSTATE SCORE (GPS) AND TESTS FOR PTEN LOSS. Cristina Magi-Galluzzi, Michael Bonham, Athanasios Tsiatis, Sara Falzarano, Anne Dee, Tara Maddala, Dejan Knezevic, Phillip Febbo, H. Jeffrey Lawrence, and Eric Klein Cristina Magi-GalluzziCristina Magi-Galluzzi More articles by this author , Michael BonhamMichael Bonham More articles by this author , Athanasios TsiatisAthanasios Tsiatis More articles by this author , Sara FalzaranoSara Falzarano More articles by this author , Anne DeeAnne Dee More articles by this author , Tara MaddalaTara Maddala More articles by this author , Dejan KnezevicDejan Knezevic More articles by this author , Phillip FebboPhillip Febbo More articles by this author , H. Jeffrey LawrenceH. Jeffrey Lawrence More articles by this author , and Eric KleinEric Klein More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1891AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES PTEN loss by fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) has been reported in 20-60% of localized PCa and is viewed as an adverse prognostic factor. The GPS (scale 0-100) is an analytically and clinically validated RT-PCR assay that measures tumor aggressiveness in biopsies of men with early stage PCa. Gene selection for GPS was based on the strength of association between their expression and clinical outcomes and PTEN RNA expression was evaluated but not included in the GPS signature. The prognostic value of GPS and PTEN loss as determined by IHC and FISH in predicting cR and BCR after RP for clinically localized PCa was assessed. METHODS RPs from 441 AUA low, intermediate and high risk disease patients were used to develop GPS. PTEN status was assessed by FISH and IHC in 287 and 369 of these patients, respectively, using tissue microarrays. PTEN FISH loss was defined as hemizygous or homozygous deletion; PTEN IHC loss was defined as homogeneous loss of staining. GPS was generated using tumor RNA from microdissected RPs. Multivariable Cox models were used to analyze BCR and cR (defined as distant or local recurrence), and regression to the mean correction was used for GPS. RESULTS 38% of patients had PTEN loss by FISH and 25% by IHC, and evaluable patients were representative of the full cohort. While PTEN status by FISH or IHC was associated with BCR (p< 0.001) and cR (p<0.05) in univariate analysis, after adjusting for GPS, neither FISH nor IHC PTEN was a significant predictor of either BCR (p>0.05) or cR (p>0.1). Concordance between the 2 PTEN methodologies was 66% (p<0.001), whereas PTEN status and GPS were only weakly correlated (Spearman corr = 0.2 - FISH, 0.3 - IHC) and a broad range of overlapping GPS was observed in each PTEN category. GPS remained very strongly associated with cR and BCR after adjusting for PTEN [HR/20 units=CR 4.0 (95% CI 2.1, 7.6), BCR 2.1 (95% CI 1.3-3.3) by FISH; HR/20 units =CR 4.0 (2.3, 6.7), BCR 1.6 (95% CI 1.1-2.3) by IHC]. Of PTEN deleted cases (by FISH), 31% with the lowest GPS had <2% 10-year rate of cR. Of PTEN intact cases (by FISH), 29% with the highest GPS had a 14% 10-year rate of cR. CONCLUSIONS GPS is a significant predictor of BCR and cR following RP after adjustment for PTEN status assessed by FISH or IHC. PTEN is not a significant predictor of BCR or cR after adjustment for GPS. GPS can identify a group of PTEN loss patients with a very favorable prognosis and a group of PTEN intact patients with unfavorable prognosis. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e18 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Cristina Magi-Galluzzi More articles by this author Michael Bonham More articles by this author Athanasios Tsiatis More articles by this author Sara Falzarano More articles by this author Anne Dee More articles by this author Tara Maddala More articles by this author Dejan Knezevic More articles by this author Phillip Febbo More articles by this author H. Jeffrey Lawrence More articles by this author Eric Klein More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

External validation of preoperative AST/ALT (De-Ritis) ratio as a prognostic indicator in localized and metastatic renal cell carcinoma.

589 Background: Recently, the De-Ritis ratio, defined as the ratio of preoperative aspartate aminotransferase (AST) to alanine aminotransferase (ALT), was shown to be an independent predictor of overall and recurrence-free survival in a European cohort with localized renal cell carcinoma (RCC). In this study, we perform an external validation of the De-Ritis ratio as a prognostic indicator in a distinct cohort of patients with localized and metastatic RCC. Methods: Patients that underwent nephrectomy for localized and metastatic RCC between 2001 and 2014 with available laboratory values within one week of surgery were queried from the Emory Nephrectomy Database. De-Ritis ratio of 1.2 was used to divide subjects into high and low subgroups. Using clinical follow-up data, prognostic value of the De-Ritis ratio was analyzed using the Kaplan-Meier method and Cox proportional regression models. Results: In a cohort of 451 patients, an elevated De-Ritis ratio (AST/ALT ≥ 1.2) was associated with significantly decreased overall survival (log-rank, p=0.0023) and recurrence-free survival (Log-rank, p=0.0395). On multivariate analysis, De-Ritis ratio was shown to be an independent and significant predictor of overall survival (HR=0.52, p=0.002) and recurrence-free survival (HR=0.47, p=0.014) as seen in Table. Conclusions: Elevated De-Ritis ratio (AST/ALT ≥ 1.2) is an independent and significant predictor of overall and recurrence-free survival and is capable of differentiating high-risk disease in patients with localized and metastatic RCC. These findings are consistent with a previous study investigating the prognostic value of the De-Ritis ratio in a European cohort, and further validates its prognostic ability in a geographically distinct cohort including patients who presented with metastatic disease [Table: see text]

Characteristics of the Relationship of Kidney Dysfunction with Cardiovascular Disease in High Risk Patients with Diabetes.

We aimed at comparing the relationship of reduced estimated glomerular filtration rate (eGFR) with cardiovascular disease (CVD) and mortality between high risk patients with and without type 2 diabetes mellitus (T2DM). The cross-sectional study evaluated 16,298 participants (1,627 T2DM) acutely admitted to hospital. The longitudinal study comprised 7,508 patients (673 with diabetes and 6,835 without). eGFR was categorized into 6 stages from >90 to <15 mL/min/1.73 m2. Kidney dysfunction was defined by an eGFR < 60 mL/min/1.73 m2. Patients with T2D showed a higher prevalence of CVD (37.9% versus 23.6%; P < 0.001) and kidney dysfunction (25% versus 13.2%; P < 0.001) than in the general population. An association with CVD was found with eGFR stages from 30 to 90 mL/min/1.73 m2 in T2D and from <15 to 90 mL/min/1.73 m2 in general population, in whom the association of eGFR with coronary heart disease was in an inverse relationship (P < 0.01 for trend). Survival, in diabetes, was lower (P = 0.037) but not associated with kidney dysfunction. Conclusions. In a high risk population, patients admitted to hospital, the relationship of kidney function with CVD is different between T2D and the general population. Competing mortality and the presence of other major risk factors in diabetes may be responsible for this difference.

Prevalence of Chagas Disease in High-Risk Patients With Pacemaker in a United States-Based Clinic

Prevalence of Chagas Disease in High-Risk Patients With Pacemaker in a United States-Based Clinic

Increased Circulating Plasma Cells Predicts Poor Overall Survival in Symptomatic Plasma Cell Myeloma Patients

Abstract Backgrounds Flow cytometry can rapidly determine immunophenotypes of neoplastic plasma cells (PCs) and quantify PCs in patients with plasma cell myeloma. Flow cytometric immunophenotyping and quantification of neoplastic plasma cells is sensitive and reliable tool for diagnosis and disease monitoring in patients with monoclonal gammopathy. Circulating PCs (cPCs) in peripheral blood (PB) after autologous hematopoietic stem cell transplantation is a marker of high-risk disease in patients with plasma cell myeloma. We assessed the utility of quantification of cPCs using flow cytometry for risk stratification in newly diagnosed plasma cell myeloma patients in the era of novel agents. Methods PB and bone marrow (BM) aspirates of 85 newly diagnosed patients with symptomatic plasma cell myeloma from August 2013 to July 2014 were analyzed by five-color flow cytometry using monoclonal antibodies against CD45, CD19, CD56, CD38, and CD138. The gating strategy employed first used the expression of CD38 and CD138 to identify plasma cells among 100,000 to 200,000 events. cPCs in PB was determined according to the patient's specific immunophenotype of neoplastic PCs in BM. Results The median age of the patient population was 68 years (45~87) and 58% were female. Median follow-up duration was 19.2 months. Six out of 85 patients (7%) did not show cPCs. Among 79 patient (93%) who had detectable cPCs, the median cPCs was 0.09% (0.006~3.612%). Patients without cPCs or cPCs under 0.05% were assigned to low cPCs group (n=32, 38%) and others to high cPCs group (n=53, 62%) according to receiver operating characteristics analysis. High cPCs group showed higher level of BM neoplastic PCs detected by both methodologys of morphology and flow cytometry (P=0.002, 0.033, respectively), higher BM cellularity (P=0.011), higher serum M protein level (P=0.013), lower hemoglobin (P=0.008), and lower platelet level (P=0.034) than low cPCs group. High cPCs group was associated with adverse cytogenetics such as t(4;14) and monosomy 13 (P=0.008), and CD45 negative immunophenotype (P=0.007). In survival analysis, high cPCs presented shorter overall survival (OS) than low cPCs group (P=0.013) (Fig. 1). It was independent with patient age and cytogenetic risks (P =0.011). Conclusion By flow cytometry cPCs was detected in most symptomatic plasma cell myeloma patients. Increased cPCs ≥0.05% among PB leukocytes could be an independent prognostic factor showing adverse effect in overall survival in symptomatic plasma cell myeloma patients. Figure 1. Kaplan-Meier survival curve of patients with plasma cell myeloma who showed 0.05% or more circulating plasma cells in peripheral blood and patients with circulating plasma cells less than 0.05%. Figure 1. Kaplan-Meier survival curve of patients with plasma cell myeloma who showed 0.05% or more circulating plasma cells in peripheral blood and patients with circulating plasma cells less than 0.05%. Disclosures No relevant conflicts of interest to declare.

Risk and outcomes of invasive pneumococcal disease in adults with underlying conditions in the post-PCV7 era, The Netherlands

BackgroundImmunocompromising conditions and advanced age (≥65 years) are associated with a high risk for invasive pneumococcal disease (IPD). We investigated the risk and outcomes of IPD in adults with underlying conditions in the post-PCV7 era in The Netherlands. MethodsIPD data from 2008 to 2012 was obtained from the national pneumococcal surveillance system, covering 25% of the Dutch population. Population estimates of underlying conditions were derived from the primary care data (2012). IPD incidence in adults with immunocompromising conditions (high risk group) and non-immunocompromising comorbidities (medium risk group) were compared to the “normal risk group” without diagnosed comorbidities. Case-fatality and ICU admission in the different risk groups was analyzed by logistic regression. Serotype specific propensities to affect high risk group IPD patients were calculated. ResultsAdults with a high risk condition have a 18-fold (95% CI 15.6–21.2) and 3-fold (95% CI 2.6–3.9) higher risk compared to the normal risk group for IPD at age 18–64 years and 65 years and older, respectively. In case of a medium risk condition, the risk is 5-fold (95% CI 4.3–5.7) and 2-fold (95% CI 1.9–2.6) higher in age groups 18–64 and ≥65 years old. Likewise, IPD patients with a high or medium risk condition have a higher case-fatality (after adjustment for age, odds ratio: 2-fold (95% CI 1.5–3.5) and 1.4-fold (95% CI 1.0–2.1), respectively). Several serotypes (e.g. 6A, 6B, 23A and 23B) are associated with a significantly higher propensity to cause disease in high risk patients. ConclusionsThe risk for IPD and death in the post-PCV7 era has remained considerably high in adults and elderly with underlying conditions. The identification of serotypes with a high propensity to affect risk groups can be important for selecting (future) vaccine serotypes.

Abstract 13224: Which White Cell Subtypes Predict the Presence of Coronary Artery Disease in High Risk Patients Over 55 Years Old?

Introduction: Inflammation has an important role in initiation and progression of coronary artery disease (CAD). Different white cell count (WCC) subtypes may reflect different mechanisms of this complex disease, and may be valuable clinically in risk stratification and detection of patients with CAD. Studies on the correlation between WCC subtypes and CAD have yielded conflicting results. Hypothesis: We hypothesized that WCC subtypes are associated with the presence of CAD in high-risk patients over 55 years old. Methods: We analyzed 622 patients over the age of 55 from the BRAVEHEART and MINACS cohort who were referred for coronary angiogram at our institution. Univariate and multivariate logistic regression models were used to compare different WCC subtypes as predictors of presence of CAD, defined as ≥50% stenosis of 1 or more coronary arteries. We adjusted for age, sex and conventional cardiac risk factors. Results: On univariate analysis, patients with CAD had significantly more CVD risk factors compared to control patients. Markers associated with CAD were lower lymphocytes (tertile 2 OR 0.61, 95% CI 0.39-0.98, p=0.040, tertile 3 OR 0.70, 95% CI 0.44-1.12, p=0.139), and higher monocytes (tertile 3 OR 2.51, 95% CI 1.45-4.34, p=0.001), neutrophil-lymphocyte ratio (NLR) (OR 1.70, 95% CI 1.07-2.68, p=0.024), and monocyte-lymphocyte ratio (MLR) (tertile 3 OR 2.62, 95% CI 1.61-4.26, p&lt;0.001). After adjustment for CVD risk factors, lower lymphocytes (tertile 2 OR 0.40, 95% CI 0.22-0.73, p=0.003, tertile 3 OR 0.50, 95% CI 0.27-0.93, p=0.028), and higher monocytes (tertile 3 OR 2.38, 95% CI 1.23-4.61, p=0.010), NLR (tertile 3 OR 1.91, 95% CI 1.08-3.38, p=0.025), and MLR (tertile 3 OR 2.26, 95% CI 1.23-4.14, p=0.009) were associated with CAD. Conclusions: In high-risk patients over 55 years old, lower lymphocytes, and higher monocytes, NLR and MLR were associated with angiographically determined CAD independent of other risk factors. Monocytes and MLR were the strongest correlates of CAD in high-risk patients over 55. Whether these can be used as biomarkers of CAD in high risk patients warrants further study.

PTU-286 Success of prospective assessment for alcoholic liver disease in high risk patients: a well liver clinic model

<h3>Introduction</h3> Currently patients at high risk of developing alcoholic liver disease are given advice by health professionals, often only reach hepatology services once advanced cirrhosis or complications are seen. This out-dated system needs improvement to avoid an unprecedented increase in advanced liver disease. We aim to show that our new service of proactive assessment of at risk patients will allow earlier recognition of liver disease in this patient group. <h3>Method</h3> All eligible patients had no history of liver disease and had never seen gastroenterology/hepatology. Patients were referred from Alcohol Specialist Nurses (ASN), Alcohol Assertive Outreach Team (AAOT), Specialist Drug and Alcohol Services (SDAS) or GP after screening using Alcohol Use Disorders Identification Test (AUDIT), with a score ≥16 required. All patients were seen in community clinic by hepatology Advanced Nurse Practioner (ANP), undertaking full clinical assessment and Transient Elastrography (TE) using Fibroscan. Follow up: TE &lt;8 kPa – repeat in 12 months, TE 8–12 kPa – repeat in 6 months, TE 12–20 kPa – repeat in 3 months, TE &gt;20 kPa – refer to hepatology clinic. Any clinical concern regardless of TE score was also referred. All patients were seen between Nov 2013 and Feb 2015. <h3>Results</h3> 527 eligible patients, 387 male and 140 female. Ages ranged from 20–82, mean age 46.1. AUDIT scores range was 16–52, with 79.1% of patients scoring 26–40. 189 patients, 141 male and 48 female, were seen with the remainder failing to attend. 64 (33.8%) reported alcohol abstinence since referral, with a further 7 (3.6%) drinking &lt;21 U/week. 83 patients (43.9%) were high risk, still drinking &gt;50 U/week. TE scores were: &lt;8 kPa in 146 patients, 8–12 kPa in 19, 12–20 kPa in 10, &gt;20 kPa in 7, no result in 7. Those with higher AUDIT scores (26–40) were more likely to have abnormal TE (18.8% &gt;8 kPa) and 42.8% of TE &gt;20 kPa AUDIT was 36–40. 17 patients (8.9%) were referred to hepatology, 7 with TE &gt;20 kPa and 10 on clinical grounds. The remainder had follow up arranged appropriately. <h3>Conclusion</h3> Our new service identified a number of patients who would benefit from specialist hepatology input. Those not requiring specialist input yet may benefit long term from assessment but prospective data on follow up is still in its infancy. As expected, those at higher risk were more likely to have evidence of liver disease. In addition, more than 1/3 of patients involved in this service significantly reduced their alcohol intake. Methods into improving attendance rates needs to be investigated. Overall our service for prospective assessment of those at high risk of alcohol related liver disease is a dynamic new approach that we hope will lead to a greater emphasis on primary prevention. <h3>Disclosure of interest</h3> None Declared.

Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies.

Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css assessment after at least 7 days of therapy were eligible. The median Css in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3) and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P = 0.68). We conclude that the use of PCZ-tab was associated with higher Css and with the probability of achieving therapeutic goals without worsening of adverse effects.

Larger heads compensate for an increased risk of THA dislocation in high-risk patients

Dislocation is a devastating complication after total hip arthroplasty (THA) and occurs in 2-5% of primary THA cases and 5-10% of revision THA cases. Assuming correct implantation, dislocation risk can be reduced primarily by capsular repair and the use of larger prosthetic heads. However, larger heads are also associated with risks like accelerated wear or implant loosening, which is why heads with a maximum diameter of 36 mm are currently standard in primary THA. In cases with high dislocation risk, the use of 40 mm and 44 mm heads should be considered. This study aimed to quantify THA dislocation risk and retrospectively analyze the course of disease in high-risk patients treated with 40 mm or 44 mm femoral heads after primary or revision THA, concerning dislocation and other complications suffered. All patients with increased THA dislocation risk, treated from 2009-2014, were evaluated regarding dislocations. The cases with installation of 40 mm or 44 mm prosthetic heads were classified using a self-developed 5-level risk score and retrospectively analyzed. During the observation period, 288 THA interventions with increased dislocation risk were performed. In 278 cases with ball diameters ≤ 36 mm the dislocation rate was 15.1% (n=42). In 10 high dislocation-risk cases (3A to 4B according to recommended scoring system), 40 mm and 44 mm heads were used. After a 22.8 month mean follow-up, no THA dislocations were reported. Our results with 40 and 44 mm heads and the existing literature confirm much higher joint stability and, thus, significantly reduced dislocation risk with larger prosthetic heads in THA. Their use is, therefore, justified in high-risk patients and should be considered in future THA.

MP1-12 COMPARATIVE ANALYSIS OF AFRICAN AMERICAN AND EUROPEAN AMERICAN MEN USING A PROSTATE CANCER GENOMIC CLASSIFIER

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2015MP1-12 COMPARATIVE ANALYSIS OF AFRICAN AMERICAN AND EUROPEAN AMERICAN MEN USING A PROSTATE CANCER GENOMIC CLASSIFIER Michael Johnson, Voleak Choeurng, Kasra Yousefi, Elai Davicioni, Eric Klein, Robert Den, Adam Dicker, Ashley Ross, and Edward Schaeffer Michael JohnsonMichael Johnson More articles by this author , Voleak ChoeurngVoleak Choeurng More articles by this author , Kasra YousefiKasra Yousefi More articles by this author , Elai DavicioniElai Davicioni More articles by this author , Eric KleinEric Klein More articles by this author , Robert DenRobert Den More articles by this author , Adam DickerAdam Dicker More articles by this author , Ashley RossAshley Ross More articles by this author , and Edward SchaefferEdward Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.175AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) is a common malignancy with reported differences in clinical outcomes and tumor biology between African-American (AA) and European-American (EA) males. The Decipher genomic classifier (DGC) is a microarray-based tool to predict metastatic disease in high-risk patients following prostatectomy. In this study, we sought to determine the utility of DGC in identifying ancestry-based differences. We further compared these results to microarray-derived approximations of alternative genomic classifiers (1) Genomic Prostate Score (md-GPS) a biopsy-based predictor of adverse pathology (2) Cell Cycle Progression (md-CCP) a biopsy-based predictor of PCa-death and biochemical recurrence following radical prostatectomy. METHODS A total of 561 men (121 AA, 441 EA) were selected from four academic institutions. These patients underwent radical prostatectomy as primary treatment for prostate cancer between 1987 and 2012 and had not received neoadjuvant chemo- or radiation-therapy. Patients were divided based on reported ancestry and matched according to CAPRA-S risk category. Within each risk category, DGC was applied to each sample and compared to md-GPD and md-CCP. Mixed effects logistic regression was applied to identify differences between the ancestry-based cohorts. RESULTS DGC was able to detect a statistically significant genomic signature between AA and EA patients within the low and high-risk CAPRA-S cohorts (p = 0.01, 0.04, respectively). DGC did not identify a statistically significant difference within the intermediate risk cohort (p=0.94). md-GPS genomic signature only identified a difference within the high-risk cohort (low: p=0.77, intermediate: p=0.07, high: p=0.04). md-CCP failed to identify statistically different signatures in all cohorts (low: p=0.92, intermediate: p=0.18, high: p=0.97). CONCLUSIONS Genome-scale analyses of prostate cancer between males of AA and EA ancestries shows different genomic signatures, suggesting differing tumor biology. Further clinical and basic science studies should be performed to elucidate the functional and prognostic implications of these differences. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e5 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Johnson More articles by this author Voleak Choeurng More articles by this author Kasra Yousefi More articles by this author Elai Davicioni More articles by this author Eric Klein More articles by this author Robert Den More articles by this author Adam Dicker More articles by this author Ashley Ross More articles by this author Edward Schaeffer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Smoking pack years increase risk of coronary artery disease in high risk patients

(71% vs. 58%, p=0.07), who also reported greater pain (8-10 visual analogue scale) at onset (51% vs. 29%, p=0.002). The most commonly reported symptom for both genders was substernal or left-sided chest pain (74%), and more women reported jaw pain/discomfort (19% vs. 6%, p=0.004) and arm pain/discomfort (43% vs. 27%, p=0.03) than men. Overall, only 42 (37%) AMI patients thought their experience exactly matched what they previously thought experiencing a heart attack would be like, with no difference was noted between the sexes. Conclusion: For most patients experiencing AMIs the symptom experience was different to what they expected. Interventions to address the public’s perception of the heart attack experience are still needed, and these should address differences in symptoms between men and women.

Clinical Implications of Glucose Variability: Chronic Complications of Diabetes.

Glucose variability has been identified as a potential risk factor for diabetic complications; oxidative stress is widely regarded as the mechanism by which glycemic variability induces diabetic complications. However, there remains no generally accepted gold standard for assessing glucose variability. Representative indices for measuring intraday variability include calculation of the standard deviation along with the mean amplitude of glycemic excursions (MAGE). MAGE is used to measure major intraday excursions and is easily measured using continuous glucose monitoring systems. Despite a lack of randomized controlled trials, recent clinical data suggest that long-term glycemic variability, as determined by variability in hemoglobin A1c, may contribute to the development of microvascular complications. Intraday glycemic variability is also suggested to accelerate coronary artery disease in high-risk patients.

CASP8 SNP D302H (rs1045485) is associated with worse survival in MYCN-amplified neuroblastoma patients.

BackgroundNeuroblastoma is a pediatric cancer that exhibits a wide clinical spectrum ranging from spontaneous regression in low-risk patients to fatal disease in high-risk patients. The identification of single nucleotide polymorphisms (SNPs) may help explain the heterogeneity of neuroblastoma and assist in identifying patients at higher risk for poor survival. SNPs in the TP53 pathway are of special importance, as several studies have reported associations between TP53 pathway SNPs and cancer. Of note, less than 2% of neuroblastoma tumors have a TP53 mutation at diagnosis.Patients and MethodsWe selected 21 of the most frequently studied SNPs in the TP53 pathway and evaluated their association with outcome in 500 neuroblastoma patients using TaqMan allelic discrimination assays.Results and ConclusionWe investigated the impact of 21 SNPs on overall survival, event-free survival, age at diagnosis, MYCN status, and stage of the disease in 500 neuroblastoma patients. A missense SNP in exon 10 of the CASP8 gene SNP D302H was associated with worse overall and event-free survival in patients with MYCN-amplified neuroblastoma tumors.