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To elucidate regional trends of infectious complications following transrectal ultrasound prostate biopsy (TRUS-PB) from a national, privately-insured database.Using Market Scan, we identified all men who underwent TRUS-PB from 2010 to 2015. Infectious complications (UTI, prostatitis, sepsis) occurring 30 days after the prostate biopsy from emergency room (ER) visits or hospital admissions constituted the primary outcomes. We analyzed unadjusted and adjusted rates of infectious complications from ER visits and hospital admissions per 100 prostate biopsies by state. Multivariable logistic regression analyses were used to identify patient covariates associated with infectious complications.During the study interval, we identified 193,490 patients who underwent TRUS-PB. The mean age was 57.6 years (SD: 5.0). Over time the unadjusted national rates of infectious complications remained similar from 0.4 ER visits per 100 prostate biopsies in 2010 -0.2 in 2015 (P = 0.83), and 1.2 hospital admissions per 100 prostate biopsies in 2010 to 1.1 in 2015 (P= 0.58). Connecticut had the lowest unadjusted infectious complication rate per 100 biopsies at 0.64, whereas West Virginia had the highest at 2.34. Multivariable analysis revealed higher Elixhauser status and patient age were associated with higher odds of infectious complications (P0.05).While rates of infectious complications attributable to prostate biopsies remain relatively stable, significant variation exists at the state level regarding this adverse outcome.

INTRODUCTION AND OBJECTIVE:Chronic orchialgia continues to be a challenge for urologists to treat and for patients to live with. Currently, conservative treatment (rest, anti-inflammatory drugs, ph...

INTRODUCTION AND OBJECTIVE:Clinical practice guidelines recommend antibiotic prophylaxis for transrectal prostate biopsy. However, infectious complications following biopsy have been an emerging co...

Introduction: Chronic orchialgia continues to be a challenge for urologists to treat and for patients to live with. Currently, conservative treatment (rest, anti-inflammatory drugs, physic...

With growing support of perioperative chemotherapy for upper tract urothelial carcinoma (UTUC), current biopsy methods are challenging, and little is known as to the degree to which patients would appropriately receive neoadjuvant chemotherapy (NAC) from biopsy alone. Herein, we sought to assess the rates of appropriate clinical use of NAC and identify clinicopathologic factors associated with aggressive UTUC amongst patients undergoing radical nephroureterectomy (RNU) for clinically localized disease.From 2004 to 2013, we identified all treatment naïve patients diagnosed with clinically localized, high grade UTUC (cTa-4Nx) who underwent RNU from the National Cancer Database (NCDB). Pathologic criteria for NAC (pT2-4N0,x; pTanyN1) from RNU represented the primary outcome. Bivariate and multivariable analyses were utilized to identify covariates associated with primary outcome to determine appropriate use of NAC.During the study interval, 5,362 patients were diagnosed with clinically localized UTUC and underwent RNU. Overall, 49.1% of patients presented with an unknown primary tumor stage (Tx) and 24.5% had invasive UTUC from biopsy. On multivariable analysis, upper tract tumor size was associated with invasive UTUC eligible for NAC (all P0.05). Amongst patients with cTx UTUC from biopsy, half of patients had pathologic noninvasive UTUC (pTa,is,1) from RNU and would be overtreated with NAC.Significant uncertainty persists in assigning primary upper tract tumor depth and represents a key barrier to widespread implementation of NAC for patients with high grade UTUC. Further research is needed to more accurately determine clinical criteria to identify patients for NAC.

Pediatric urolithiasis is on the rise globally and incidence rates have risen by 6-10% annually over the past couple of decades. Given the increasing incidence, high likelihood of recurrence, and long life expectancy of children, the use of ionizing radiation in the diagnosis, management, and follow up of pediatric urolithiasis has been scrutinized recently and many institutions and organizations have emphasized the use of non-ionizing imaging modality such as ultrasound. This review examines the use of ultrasound in the diagnosis and treatment of pediatric urolithiasis. Specifically, the role of ultrasound in shockwave lithotripsy, percutaneous nephrolithotomy, and, more recently, ureteroscopy will be examined.

Rationale: The density of native (preexisting) collaterals varies widely and is a significant determinant of variation in severity of stroke, myocardial infarction, and peripheral artery disease. However, little is known about mechanisms responsible for formation of the collateral circulation in healthy tissues. Objective: We previously found that variation in vascular endothelial growth factor (VEGF) expression causes differences in collateral density of newborn and adult mice. Herein, we sought to determine mechanisms of collaterogenesis in the embryo and the role of VEGF in this process. Methods and Results: Pial collaterals begin forming between embryonic day 13.5 and 14.5 as sprout-like extensions from arterioles of existing cerebral artery trees. Global VEGF-A overexpressing mice ( Vegf hi/+ ) formed more, and Vegf lo/+ formed fewer, collaterals during embryogenesis, in association with differences in vascular patterning. Conditional global reduction of Vegf or Flk1 only during collaterogenesis significantly reduced collateral formation, but now without affecting vascular patterning, and the effects remained in adulthood. Endothelial-specific Vegf reduction had no effect on collaterogenesis. Endothelial-specific reduction of a disintegrin-and-metalloprotease-domain-10 ( Adam10 ) and inhibition of γ-secretase increased collateral formation, consistent with their roles in VEGF-induced Notch1 activation and suppression of prosprouting signals. Endothelial-specific knockdown of Adam17 reduced collateral formation, consistent with its roles in endothelial cell migration and embryonic vascular stabilization, but not in activation of ligand-bound Notch1. These effects also remained in adulthood. Conclusions: Formation of pial collaterals occurs during a narrow developmental window via a sprouting angiogenesis-like mechanism, requires paracrine VEGF stimulation of fetal liver kinase 1-Notch signaling, and adult collateral number is dependent on embryonic collaterogenesis.

Summary Introduction Ureteroscopy has been shown to be a highly efficacious and safe modality for the treatment of pediatric urolithiasis. However, conventional ureteroscopy relies on fluoroscopy for intraoperative guidance, exposing both patient and operating room personnel to ionizing radiation. Pediatric urolithiasis patients are at a particularly increased risk from this radiation exposure. The use of ultrasound in place of fluoroscopy for intraoperative guidance has emerged as one modification that can reduce radiation exposure during ureteroscopy. Although ultrasound-guided ureteroscopy has been shown to be a safe, and effective approach to stone management in adults, there have been no studies to date utilizing this approach in children. Objective The aim was to describe our initial experience with ultrasound-guided ureteroscopy in children as a safe and feasible modality to manage pediatric urolithiasis. Study design A retrospective review of consecutive patients that underwent ultrasound-guided ureteroscopy by one pediatric urologist (A.K.S.) from 2014 to 2016 for symptomatic urolithiasis was performed. Patient data were extracted from our center's IRB-approved prospectively maintained database of all children with urolithiasis. Materials and methods Real-time ultrasonic guidance was provided by a pediatric uroradiology attending, with fluoroscopy available on standby. With the probe positioned on the patient's flank, ultrasound was used to visualize advancement of guidewire, dual-lumen catheter, and ureteroscope through the ureteral orifice and up to the renal pelvis (Figure). Stones were identified and removed via basket retrieval. At the conclusion of each case, ultrasonography was then used to confirm stent placement of indwelling double pigtail ureteral catheters. Results Eleven patients were identified that underwent 12 ultrasound-guided ureteroscopic procedures in an outpatient setting. Stones were accessed in various locations and were removed by basket retrieval. Laser calycostomy into calyceal diverticulum and balloon dilations of ureterovesical junction and calyceal infundibulum were also performed. There were Clavien grade I and II complications in four patients; all of which were related to pain control. Discussion To our knowledge, this is the first study reporting the successful use of ultrasound-guided ureteroscopy in children. The main limitation of this feasibility study is its small sample size. A larger series is needed to corroborate these findings and make them generalizable to a wider population. Conclusion This feasibility study accomplished its aim of demonstrating for the first time that ultrasound-guided ureteroscopy can be safely used in children to manage urolithiasis. Download : Download high-res image (198KB) Download : Download full-size image Figure . Intraoperative ultrasound showing guidewire (solid arrow) and ureteroscope (dotted arrow).

Liver eosinophilia has been associated with incidences of drug-induced liver injury (DILI) for more than 50 years, although its role in this disease has remained largely unknown. In this regard, it was recently shown that eosinophils played a pathogenic role in a mouse model of halothane-induced liver injury (HILI). However, the signaling events that drove hepatic expression of eosinophil-associated chemokines, eotaxins, eosinophil infiltration, and subsequent HILI were unclear. We now provide evidence implicating hepatic epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) and type 2 immunity, in particular, interleukin-4 (IL-4) production, in mediating hepatic eosinophilia and injury during HILI. TSLP was constitutively expressed by mouse hepatocytes and increased during HILI. Moreover, the severity of HILI was reduced in mice deficient in either the TSLP receptor (TSLPR) or IL-4 and was accompanied by decreases in serum levels of eotaxins and hepatic eosinophilia. Similarly, concanavalin A–induced liver injury, where type 2 cytokines and eosinophils play a significant role in its pathogenesis, was also reduced in TSLPR-deficient mice. Studies in vitro revealed that mouse and human hepatocytes produce TSLP and eotaxins in response to treatment with combinations of IL-4 and proinflammatory cytokines IL-1β and tumor necrosis factor alpha. Conclusion: This report provides the first evidence implicating roles for hepatic TSLP signaling, type 2 immunity, and eosinophilia in mediating liver injury caused by a drug. (Hepatology 2014;60:1741-1752)

Drug-induced liver injury (DILI) is a major health issue, as it remains difficult to predict which new drugs will cause injury and who will be susceptible to this disease. This is due in part to the lack of animal models and knowledge of susceptibility factors that predispose individuals to DILI. In this regard, liver eosinophilia has often been associated with DILI, although its role remains unclear. We decided to investigate this problem in a murine model of halothane-induced liver injury (HILI). When female Balb/cJ mice were administered halothane, eosinophils were detected by flow cytometry in the liver within 12 hours and increased thereafter proportionally to liver damage. Chemokines, eotaxin-1 (CCL11) and eotaxin-2 (CCL24), which are known to attract eosinophils, increased in response to halothane treatment. The severity of HILI was decreased significantly when the study was repeated in wildtype mice made deficient in eosinophils with a depleting antibody and in eosinophil lineage-ablated ΔdblGata−/− mice. Moreover, depletion of neutrophils by pretreating animals with Gr-1 antibody prior to halothane administration failed to reduce the severity of HILI at antibody concentrations that did not affect hepatic eosinophils. Immunohistochemical staining for the granule protein, major basic protein, revealed that eosinophils accumulated exclusively around areas of hepatocellular necrosis. Conclusion: Our findings indicate that eosinophils have a pathologic role in HILI in mice and suggest that they may contribute similarly in many clinical cases of DILI. (HEPATOLOGY 2013)