Fellowship training in endourology: Impact on percutaneous nephrolithotomy access patterns.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) remains the treatment of choice for kidney stones larger than 2 cm. Few studies have examined the reasons why some urologists obtain their own PCNL access while others prefer to have interventional radiology (IR) obtain access. The objective of this study was to investigate what factors influence this decision. METHODS: A survey was posted to the American Urological Association's (AUA) Young Urologist Community. Descriptive statistics and exploratory analyses were used to summarize practice trends and motivating factors. RESULTS: All 99 respondents began practicing within the past 11 years. Ninety-two currently perform PCNLs and 47% of them obtain their own access. Endourology fellowship-trained physicians were more likely to currently obtain their own access (75%) compared to urologists who completed non-endourology fellowships (75% vs. 23%, p=0.58) and non-fellowship-trained urologists (75% vs. 45%, p=0.01). Logging >50 cases during training also predicted physicians obtaining their own access and having a larger annual number of PCNL cases. The most common motivator for obtaining one's own access was preference to control their own access point (95%). CONCLUSIONS: Urologist-obtained PCNL access was associated with greater training experience (endourology fellowship) and current annual PCNL case volume. Urologist-reported factors that influenced the decision to obtain one's own access include control of access, comfort level, and both physician and patient convenience. By identifying the factors that influence practice patterns, we may better address barriers, improve education to make urologistobtained PCNL access feasible even without fellowship training, and ultimately improve outcomes and quality of care.

Thirty-day hospital revisits after prostate brachytherapy: who is at risk?

BACKGROUND: Transperineal prostate brachytherapy is a common outpatient procedure for the treatment of prostate cancer. Whereas long-term morbidity and toxicities are widely published, rates of short-term complications leading to hospital revisits have not been well described. MATERIALS AND METHODS: Patients who underwent brachytherapy for prostate cancer in an ambulatory setting were identified in the Healthcare Cost and Utilization Project State Ambulatory Surgery Database for California between 2007 and 2011. Emergency department (ED) visits and inpatient admissions within 30 days of treatment were determined from the California Healthcare Cost and Utilization Project State Emergency Department Database and State Inpatient Database, respectively. RESULTS: Between 2007 and 2011, 9,042 patients underwent brachytherapy for prostate cancer. Within 30 days postoperatively, 543 (6.0%) patients experienced 674 hospital encounters. ED visits comprised most encounters (68.7%) at a median of 7 days (interquartile range 2-16) after surgery. Inpatient hospitalizations occurred on 155 of 674 visits (23.0%) at a median of 12 days (interquartile range 5-20). Common presenting diagnoses included urinary retention, malfunctioning catheter, hematuria, and urinary tract infection. Logistic regression demonstrated advanced age {65-75 years: odds ratio [OR], 1.3 [95% confidence interval (CI) 1.06-1.60, P = 0.01]; >75 years: OR 1.5 [95% CI 1.18-1.97, P = 0.001]}, inpatient admission within 90 days before surgery [OR 2.68 (95% CI 1.8-4.0, P < 0.001)], and ED visit within 180 days before surgery [OR 1.63 (95% CI 1.4-1.89, P < 0.001)] as factors that increased the risk of hospital-based evaluation after outpatient brachytherapy. Charlson comorbidity score did not influence risk. CONCLUSIONS: ED visits and inpatient admissions are not uncommon after prostate brachytherapy. Risk of revisit is higher in elderly patients and those who have had recent inpatient or ED encounters.

The LACE Score as a Tool to Identify Radical Cystectomy Patients at Increased Risk of 90-Day Readmission and Mortality.

INTRODUCTION: Radical cystectomy for bladder cancer is associated with high rates of readmission. We investigated the LACE score, a validated prediction tool for readmission and mortality, in the radical cystectomy population. MATERIALS & METHODS: Patients who underwent radical cystectomy for bladder cancer were identified by ICD-9 codes from the Healthcare Cost and Utilization Project State Inpatient Database for California years 2007-2010. The LACE score was calculated as previously described, with components of L: length of stay, A: acuity of admission, C: comorbidity, and E: number of emergency department visits within 6 months preceding surgery. RESULTS: Of 3,470 radical cystectomy patients, 638 (18.4%) experienced 90-day readmission, and 160 (4.6%) 90-day mortality. At a previously validated "high-risk" LACE score ≥ 10, patients experienced an increased risk of 90-day readmission (22.8 vs. 17.7%, p = 0.002) and mortality (9.1 vs. 3.5%, p < 0.001). On adjusted multivariable analysis, "high risk" patients by LACE score had increased 90-day odds of readmission (adjusted OR = 1.24, 95% CI: 0.99-1.54, p = 0.050) and mortality (adjusted OR = 2.09, 95% CI: 1.47-2.99, p < 0.001). CONCLUSION: The LACE score reasonably identifies patients at risk for 90-day mortality following radical cystectomy, but only poorly predicts readmission. Providers may use the LACE score to target high-risk patients for closer follow-up or intervention.

Biomarker profiling of plasma samples utilizing RANDOX biochip array technology.

RANDOX Biochip Array Technology offers an efficient, cost-effective method of measuring multiple analytes on a large number of samples in biologic fluids. This innovative technology has proven extremely useful in the profiling of markers in a number of different disease states. Biochip arrays have also shown promise in clinical trials, offering rapid evaluation of multiple markers and circulating levels of the analyte with only a small sample. This biochip technology has broad applications in clinical, pharmaceutical, toxicological, immunologic and microbiologic areas. This technique offers parallel profiling and will have great value in personalized and precision medicine. The aim of this manuscript is to explore the recent and future utility of biochips for profiling marker levels in different diseased populations using RANDOX's Biochip Array Technology.

Inflammatory and Metabolic Syndrome Biomarker Analysis of Vascular Outcomes in End-stage Renal Disease.

End-stage renal disease (ESRD) presents a complex syndrome in which inflammatory and metabolic processes contribute to disease progression and development of comorbid conditions. Over $1 trillion is spent globally on ESRD care. Plasma samples collected from 83 ESRD patients prior to hemodialysis were profiled for metabolic and inflammatory biomarker concentrations. Concentrations were compared between groups with and without history of stroke, acute coronary syndrome (ACS), congestive heart failure (CHF), and coronary artery disease (CAD). The 25 patients (30.1%) with history of stroke demonstrated decreased plasma interferon-γ levels (p = 0.042) and elevated plasma resistin, interleukin (IL)-1α, and leptin levels (p = 0.008, 0.021, 0.026, respectively) when compared with ESRD patients without history of stroke. The 14 patients (16.9%) with history of ACS demonstrated elevated plasma IL-6 levels (p = 0.040) when compared with ESRD patients without history of ACS. The 30 patients (36.1%) with history of CHF demonstrated decreased plasma leptin levels (p = 0.031) and elevated plasma IL-1ß levels (p = 0.042) when compared with ESRD patients without history of CHF. Finally, the 39 patients (47.0%) with history of CAD demonstrated elevated plasma IL-1α levels (p = 0.049) when compared with ESRD patients without history of CAD. Plasma biomarker concentration disturbances were observed in ESRD patients with history of stroke, ACS, CHF, and CAD when compared with ESRD patients without such history. Proinflammatory biomarker elevations were seen in stroke, ACS, CHF and CAD, while adipocytokine aberrations were observed in both stroke and CHF. These studies demonstrate that biomarker profiling of vascular comorbidities in ESRD may provide useful diagnostic and prognostic information in the management of ESRD patients.

Prevalence of metabolic syndrome in patients undergoing total joint arthroplasty and relevance of biomarkers.

BACKGROUND: Metabolic syndrome (MetS) is a collection of clinical conditions, including central obesity, hypertension, glucose intolerance and dyslipidemia. The long-term inflammatory and metabolic dysfunction associated with MetS may contribute to osteoarthritic processes leading up to total joint arthroplasty (TJA). The purpose of this study was to investigate levels of metabolic biomarkers and the prevalence of MetS in patients undergoing TJA. METHODS: Under IRB approval, citrated plasma samples were collected from 41 patients undergoing total hip and knee arthroplasty (THA/TKA) preoperatively and day 1 postoperatively. Control group consisted of 25 healthy human plasma samples (female and male, 18-35 years old) purchased from George King Biomedical Inc. (Overland Park, KS, USA). Samples were profiled for c-peptide, ferritin, IL-6, insulin, resistin, TNF-α, IL-1a, leptin, and PAI-1 using metabolic biochips purchased from RANDOX Co. (Antrim, Northern Ireland). NCEP/ATP III guidelines were used to evaluate which patients met MetS criteria. RESULTS: Levels of IL-6, resistin, TNF-a, IL-1a, leptin, and PAI-1 were significantly elevated in patients undergoing TJA compared to normal. C-peptide and insulin were both decreased in TJA compared to normal. No significance was found when comparing TJA to normal for ferritin. TNFα was significantly lower in TJA+MetS compared to TJA-MetS, while other biomarkers showed no difference in TJA±MetS populations. Insulin & c-peptide both showed a significant decrease in TJA-MetS compared to normal, but levels in TJA+MetS patients were not significantly different from controls. Resistin showed significant increases in TJA+MetS vs. normal, but not in TJA-MetS vs. normal. CONCLUSIONS: Overall, the differing metabolic profile seen in patients undergoing TJA suggest ongoing metabolic dysfunction. Insulin and c-peptide patterns among the different test groups hint toward a complex and dysfunctional metabolic process involved, with leptin and underlying insulin resistance playing a role. Increased resistin in TJA+MetS, but not in TJA-MetS, compared to normal, suggests that while elevated resistin levels may be associated with the osteoarthritic process, levels are further attenuated by MetS, which is highly prevalent in this population. Increased TNFα in TJA-MetS compared to TJA+MetS may be an artifact of differing sample populations or a true complication of the complex pathophysiology and medical regimen seen in patients with both OA and MetS. The lack of difference seen in the remaining biomarkers suggest that having MetS as a comorbidity does not contribute to the elevated levels seen in patients undergoing TJA.

Effect of erythropoietin stimulating agents on vascular endothelial growth factor levels in patients with end stage renal disease.

BACKGROUND: End stage renal disease (ESRD) is a debilitating disease that not only impacts quality of life, but also increases the risk of cardiovascular disease, stroke, and overall mortality. By improving our understanding of the molecular patterns seen in progression of chronic renal disease (CRD), we may be able to slow down and possibly even prevent progression renal failure. The vascular endothelial growth factor (VEGF) has been implicated as a major contributor to CRD disease progression, thus our aim was to profile the VEGF levels in patients with ESRD and to determine the effects of the erythropoietin stimulating agents (ESAs). METHODS: Under institution review board (IRB) approval, plasma samples were collected from 77 patients prior to hemodialysis and heparin administration. Normal human plasma samples (female & male, 18-35 years old) were purchased from George King Biomedical Inc (Overland Park, KS). All samples were stored at -80 °C. Inflammatory biochips were purchased from RANDOX (Co. Antrim, Northern Ireland) to test VEGF on 77 ESRD and 48 normal samples. RESULTS: The VEGF was significantly elevated in ESRD vs. normal (P<0.0001), ESRD+ESA vs. normal (P<0.0001), and ESRD-ESA vs. normal (P<0.0001). No difference was seen between ESRD+ESA and ESRD-ESA. Hemoglobin and free iron were significantly elevated in ESRD-ESA compared to ESRD+ESA (PHemoglobin=0.0007, PIron<0.0001). CONCLUSIONS: Our finding that VEGF was significantly elevated in ESRD vs. normal, aligns with the literature and suggests that VEGF may in fact play a key role in CRD progression. However, further studies to evaluate VEGF isomer levels are needed. While we saw lack of difference in VEGF levels between ESRD+ESA and ESRD-ESA, this may be due to the treatment algorithm used. Further investigation is warranted to determine whether the ESAs and hemoglobin levels show any influence on or crosstalk with the VEGF levels.

A Genome-wide RNAi Screen for Microtubule Bundle Formation and Lysosome Motility Regulation in Drosophila S2 Cells.

Long-distance intracellular transport of organelles, mRNA, and proteins ("cargo") occurs along the microtubule cytoskeleton by the action of kinesin and dynein motor proteins, but the vast network of factors involved in regulating intracellular cargo transport are still unknown. We capitalize on the Drosophila melanogaster S2 model cell system to monitor lysosome transport along microtubule bundles, which require enzymatically active kinesin-1 motor protein for their formation. We use an automated tracking program and a naive Bayesian classifier for the multivariate motility data to analyze 15,683 gene phenotypes and find 98 proteins involved in regulating lysosome motility along microtubules and 48 involved in the formation of microtubule filled processes in S2 cells. We identify innate immunity genes, ion channels, and signaling proteins having a role in lysosome motility regulation and find an unexpected relationship between the dynein motor, Rab7a, and lysosome motility regulation.

Prevalence of metabolic syndrome in patients with end stage renal disease and relevance of biomarkers.

BACKGROUND: As chronic kidney disease (CKD) and metabolic syndrome (MetS) share many of the same risk factors and similar inflammatory pathogenesis, multiple studies have suggested a correlation between CKD and MetS.. The purpose of this study is to investigate the prevalence of MetS in end stage renal disease (ESRD) patients. Furthermore, investigating metabolic biomarker levels in patients with ESRD may provide insight into the pathogenic processes and the development of associated comorbidities. METHODS: Under IRB approval, plasma samples were collected from 89 patients with ESRD prior to hemodialysis. Biochips purchased from RANDOX (Co. Antrim, Northern Ireland) were used to test C peptide, ferritin, IL-6, resistin, insulin, TNFα, IL-1α, leptin, PAI-1 on 82 ESRD and 17 normal samples. RESULTS: All biomarkers, except insulin, were significantly elevated in patients with ESRD, suggesting an ongoing inflammatory process. Patients with ESRD+MetS, as compared to ESRD-MetS, had significantly elevated leptin. Furthermore, ESRD+MetS vs. normal was significant for leptin, but ESRD-MetS vs. normal was not. ESRD+MetS and ESRD-MetS populations were not statistically different for all other biomarkers. CONCLUSION: These findings suggest elevated Leptin in ESRD may be attributed to MetS, which is highly prevalent in the ESRD population, rather than ESRD/CKD pathogenesis alone. Lack of a significant difference for all other biomarkers suggest biomarker elevation is due to ESRD pathogenesis, rather than due to MetS as a comorbidity.