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Oxalate oxidase is an enzyme that degrades oxalate and is used in commercial urinary assays to measure oxalate levels. The objective of this study was to establish an enhanced expression system for secretion and purification of oxalate oxidase using Pichia pastoris. A codon optimized synthetic oxalate oxidase gene derived from Hordeum vulgare (barley) was generated and cloned into the pPICZα expression vector downstream of the N-terminal alpha factor secretion signal peptide sequence and used for expression in P. pastoris X-33 strain. A novel chimeric signal peptide consisting of the pre-OST1 sequence fused to pro-αpp8 containing several amino acid substitutions was also generated to enhance secretion. Active enzyme was purified to greater than 90% purity using Q-Sepharose anion exchange chromatography. The purified oxalate oxidase enzyme had an estimated Km value of 256μM, and activity was determined to be 10U/mg. We have developed an enhanced oxalate oxidase expression system and method for purification.

Idiopathic calcium oxalate (CaOx) stones often develop attached to Randall's plaque present on kidney papillary surfaces. Similar to the plaques formed during vascular calcification, Randall's plaques consist of calcium phosphate crystals mixed with an organic matrix that is rich in proteins, such as inter-α-trypsin inhibitor, as well as lipids, and includes membrane-bound vesicles or exosomes, collagen fibres and other components of the extracellular matrix. Kidney tissue surrounding Randall's plaques is associated with the presence of classically activated, pro-inflammatory macrophages (also termed M1) and downregulation of alternatively activated, anti-inflammatory macrophages (also termed M2). In animal models, crystal deposition in the kidneys has been associated with the production of reactive oxygen species, inflammasome activation and increased expression of molecules implicated in the inflammatory cascade, including osteopontin, matrix Gla protein and fetuin A (also known as α2-HS-glycoprotein). Many of these molecules, including osteopontin and matrix Gla protein, are well known inhibitors of vascular calcification. We propose that conditions of urine supersaturation promote kidney damage by inducing the production of reactive oxygen species and oxidative stress, and that the ensuing inflammatory immune response promotes Randall's plaque initiation and calcium stone formation.

Introduction:Based on 2010 American Urological Association recommendations our practice transitioned from sterile to high level disinfection flexible cystoscope reprocessing and from steril...

Purpose of review The aim of the article is to review studies on bone health and oxalate metabolism/therapeutics in the obese rodent model of Roux-en-Y gastric bypass (RYGB) and examine pathways to decrease procedural morbidity. Recent findings Compared with controls, RYGB rodents have up to 40-fold more fat in their stool (steatorrhea) which positively correlates to increased urinary oxalate. These unabsorbed intestinal fatty acids bind calcium and prevent gut calcium oxalate formation, increasing soluble luminal oxalate availability and absorption (enteric hyperoxaluria). When intraluminal fecal fat exceeded about 175 mg/24 h in our model, more paracellular and transcellular oxalate transport across the distal colon occurred. Increasing dietary calcium and colonization with Oxalobacter formigenes reduced hyperoxaluria, whereas vitamin B6 supplementation did not. RYGB animals, when severely calcium deficient, had bone mineral density loss that could not be rescued with vitamin D supplementation. Summary The findings of hyperoxaluria, steatorrhea, and decreased bone mineral density are seen in both human and rodent RYGB. Our model suggests that a low-fat, low-oxalate diet combined with calcium supplementation can decrease urinary oxalate and improve skeletal bone health. Our model is a useful tool to study renal and bone RYGB effects. Studies of longer duration are required to further evaluate mechanisms of disease and durability of therapeutics.

INTRODUCTION AND OBJECTIVE:Existing animal models of renal oxalate excretion utilize either gut or peritoneal cavity for oxalate absorption. Ex vivo renal perfusion is an established tool for graft...

INTRODUCTION AND OBJECTIVE:24-hour urinary oxalate testing is a key component of comprehensive metabolic evaluation, yet it cannot measure transient spikes in oxalate concentration such as followin...

In vitro experiments demonstrate calcium oxalate (CaOx) supersaturation (SS) drives CaOx nucleation and growth. We investigated the link between 24-hour urine SS CaOx and in vivo stone growth through a natural history, imaging study.Using an institutional review board-approved database, we sought80% CaOx stone formers who prior to stone intervention obtained 2 separate computerized tomography (CT) scans with at least one 24-hour urine collection between scans. Two blinded reviewers calculated bilateral 3-dimensional stone volume using the Visage 7® region of interest pen tool. CT volume difference was divided by time between scans, and SS CaOx was grouped into low (5), medium (5-10) and high risk (10). Statistical significance between groups was assessed by Kruskal-Wallis test.We identified 80 individuals with stone growth measured by 3-dimensional CT (mean ∼7 months between studies). Inter-reviewer reliability of CT volume measurement was well correlated (0.98, Gwet's AC2), and an arbitrator was only needed in 13/160 (8%) cases. Median stone volume growth/year was 15%, 71% and 177% for low, medium and high risk groups, respectively (p0.001). Despite inter-individual variation, best fit of mean SS CaOx vs stone volume growth was moderately correlated (Spearman's rho=0.53, p0.001).In a population of pure CaOx stone formers, increased 24-hour SS CaOx risk was associated with increased in vivo stone growth. Further investigations using CT volumetric stone growth may allow for the noninvasive study of stone growth modulators, improved stone risk prediction and development of a kidney stone simulator.

Postoperative bone loss and increased fracture risk associated with Roux-en-Y gastric bypass (RYGB) have been attributed to vitamin D/calcium malabsorption and resultant secondary hyperparathyroidism (HPT). Adequate vitamin D supplementation (VDS), particularly in an older female population, reduces incidence of secondary HPT but the effect on bone loss and fracture risk remains unclear. To investigate whether VDS corrects the RYGB bone phenotype, 41 obese adult female rats were randomized to RYGB with 1000 IU (R1000) or 5000 IU (R5000) vitamin D/kg food or a sham surgical procedure with either paired (PF) or ad libitum (AL) feeding. Bone turnover markers, urinary calcium/creatinine ratio (CCR), and serum calciotropic and gut hormones were assessed throughout a 14-week postoperative period. Femurs were analyzed by micro-computed tomography (μCT), three-point bending test, and histomorphometry. 1000 IU animals had low 25‑hydroxyvitamin D (25(OH)D), high serum parathyroid hormone (PTH), and very low urine CCR levels. 5000 IU corrected the 25(OH)D and secondary HPT but did not increase urine CCR or serum levels of 1,25‑dihydroxyvitamin D (1,25(OH)D) significantly between RYGB groups. Compared to sham animals at 14 weeks, RYGB animals had significantly higher serum osteocalcin (OCN) and C-terminal telopeptide (CTX) levels. The gut hormone peptide tyrosine tyrosine hormone (PYY) was higher in the RYGB groups, and leptin was lower. μCT and biomechanical testing revealed RYGB females had decreased cortical and trabecular bone volume and weaker, stiffer bone than controls. Histomorphometry showed decreased bone volume and increased osteoid volume with increased mineral apposition rate in RYGB compared to controls. No differences in bone phenotype were identified between 1000 IU and 5000 IU groups, and osteoclast numbers were comparable across all four groups. Thus, in our model, 5000 IU VDS corrected vitamin D deficiency and secondary HPT but did not rescue RYGB mineralization rate nor the osteomalacia phenotype. Longer studies in this model are required to evaluate durability of these detrimental effects. Our findings not only underscore the importance of lifelong repletion of both calcium and vitamin D but also suggest that additional factors affect skeletal health in this population.

OBJECTIVE To determine if medical therapy affects long-term clinical outcomes in uric acid stone formers (UASF). METHODS We identified 53 UASF who had complete stone clearance following stone procedure by computed tomography (CT) and had ≥1 postoperative 24-hour urine collection and a clinical follow-up ≥6 months with a surveillance CT scan. Patients were divided into "adherent to medical therapy" (compliance with potassium citrate ± allopurinol verified by computerized pharmacy data) or nonadherent groups. Primary outcomes were CT stone recurrence rate and need for surgical stone intervention. RESULTS We found 28 of 53 (53%) adherent and 25 of 53 (47%) nonadherent individuals (14 declined medication, 11 intolerant). With median follow-up of 24 months, no significant differences were noted between groups in regards to stone recurrence (32%; P = .99) or in 24-hour urine pH compared to baseline or follow-up (range 5.46-5.62; P = 0.06). Adherent patients, however, had smaller CT stone recurrence sizes (6.3 ± 3.8 vs 11.8 ± 6.2 mm, P = .02), were 28% less likely to require stone surgery compared to those without therapy (P

Background The obturator nerve runs along the posterolateral walls of the bladder and electrosurgical stimulation in this region can result in adductor spasm which can occur suddenly and unexpectedly with potentially catastrophic results. Methods Sixty patients were prospectively randomized to receive either a single-injection ultrasound-guided obturator nerve block (ONB) or intravenous rocuronium after induction of general anesthesia (i.e., neuromuscular block [NMB]). The primary objective was to compare the incidence of adductor spasm during posterolateral bladder tumor resection when ONB or NMB was used. Secondary objectives included assessment of fall risk and incidence of adverse events. Results Five patients in the ONB group and six in the NMB group had nonlateral wall lesions. One patient in the ONB group suffered a cardiac arrest after induction of general anesthesia. Of the remaining 48 patients, six (10.2%) experienced adductor spasm. Most of these patients were in the NMB group (5/24, 20.8%), with only one patient (1/24, 4.2%) experiencing obturator reflex in the ONB group; this difference was not statistically significant (P=0.19). Patients in the ONB group had a greater decrease in mean hip adductor strength. Our study population was found to be at high risk of falls before surgery. There were no statistically significant group differences in the Timed Up and Go test, with time to perform the test increasing in both groups. Conclusions Both techniques are safe and efficacious for preventing adductor spasm. Our data and experience suggest that the ONB is relatively easy to perform and should be considered in patients with posterolateral bladder tumors.

Purpose of review In addition to traditional risk factors such as low urine volume or hypercalciuria, emerging data suggest that calcium oxalate (CaOx), one of the most common mineral complexes in the urine, elicits a strong immunologic response. This review highlights those studies and projects how future therapies may be directed for kidney stone prevention. Recent findings Over the last 2 years, several groups have studied the response of the immune system to CaOx crystals using cell culture and animal models. Dominguez et al. found that CaOx crystals were recognized by monocytes through an lipopolysaccharide-mediated mechanism, leading to M1 'inflammatory' macrophage phenotype. Patel et al. proposed excessive oxalate-mediated reactive oxygen species within macrophage mitochondria may impair their ability to properly clear stones. Two other groups developed mouse models (an androgen receptor knock-out and an overexpression of Sirtuin 3 protein) and demonstrated increased renal anti-inflammatory macrophage differentiation and decreased CaOx deposition in experimental compared with controls. Anders et al. fed hyperoxaluric mice 1,3-butanediol, which blocks an inflammatory form of cell death called NLRP3 inflammasome and found less intrarenal oxidative damage and higher anti-inflammatory renal infiltrates in experimentals. Finally, monocytes exposed to CaOx crystals followed by hydroxyapatite had reduced inflammatory cytokine and chemokine production compared with those without hydroxyapatite, suggesting that Randall's plaque may play a role in dampening M1-mediatiated CaOx inflammation. Summary By modulating the immune response, immunotherapy could provide the means to prevent stone recurrences in certain individuals. The promotion of M2 over M1 macrophages and inhibition of inflammation could prevent the cascade that leads to CaOx nucleation. Future therapies may target the ability of macrophages to degrade CaOx crystals to prevent stones.

Urine pH is critical for net acid and solute excretion, but the genetic factors that contribute to its regulation are incompletely understood. Methods: We tested the association of single nucleotide polymorphisms (SNPs) from 16 genes related to ammonia (NH3) metabolism (15 biological candidates selected a priori, 1 selected from a previous genome-wide association study analysis) to that of 24-hour urine pH in 2493 individuals of European descent across 2 different cohorts using linear regression, adjusting for age, sex, and body mass index. Results: Of 2871 total SNPs in these genes, 13 SNPs in ATP6V0A4 (a4 subunit of hydrogen− adenosine triphosphatase), SLC9A3 (sodium/hydrogen exchanger, isoform 3), and RHCG (Rhesus C glycoprotein), and 12 SNPs from insulin-like growth factor binding protein 7 (IGFBP7) had a meta-analysis P value

Background Hyperoxaluria and oxalate kidney stones frequently develop after Roux-en-Y gastric bypass (RYGB). Oxalobacter formigenes can degrade ingested oxalate. Objectives Examine the effect of O. formigenes wild rat strain (OXWR) colonization on urinary oxalate excretion and intestinal oxalate transport in a hyperoxaluric RYGB model. Setting Basic Science Laboratory, United States. Methods At 21 weeks of age, 28 obese male Sprague-Dawley rats survived Sham (n = 10) or RYGB (n = 18) surgery and were maintained on a 1.5% potassium oxalate, 40% fat diet. At 12 weeks postoperatively, half the animals in each group were gavaged with OXWR. At 16 weeks, percent dietary fat content was lowered to 10%. Urine and stool were collected weekly to determine oxalate and colonization status, respectively. At week 20, [14 C]-oxalate fluxes and electrical parameters were measured in vitro across isolated distal colon and jejunal (Roux limb) tissue mounted in Ussing Chambers. Results RYGB animals lost 22% total weight while Shams gained 5%. On a moderate oxalate diet, urinary oxalate excretion was 4-fold higher in RYGB than Sham controls. OXWR colonization, obtained in all gavaged animals, reduced urinary oxalate excretion 74% in RYGB and 39% in Sham and was further augmented by lowering the percentage of dietary fat. Finally, OXWR colonization significantly enhanced basal net colonic oxalate secretion in both groups. Conclusions In our model, OXWR lowered urinary oxalate by luminal oxalate degradation in concert with promotion of enteric oxalate elimination. Trials of O. formigenes colonization and low-fat diet are warranted in calcium oxalate stone formers with gastric bypass and resistant hyperoxaluria.

INTRODUCTION AND OBJECTIVES:Absorptive hypercalciuria, or excessive gut absorption of dietary calcium, is the most commonly identified metabolic cause of calcium-based renal stones. Since intestina...

INTRODUCTION AND OBJECTIVES:Urinary oxalate, an integral part of the 24-hour urine stone profile, is used to calculate mineral supersaturations and estimate kidney stone risk. The goal of our labor...

INTRODUCTION AND OBJECTIVES:In vitro studies have shown that calcium oxalate supersaturation (CaOX SS) principally drives CaOX stone formation and growth. As this has not been previously validated ...

Proper fluoroscopic education and protocols may reduce the patient radiation dose but few prospective studies in urology have been performed. Using optically stimulated luminescent dosimeters we tested whether fluoroscopy time and/or entrance skin dose would decrease after educational and radiation reduction protocols.At default manufacturer settings fluoroscopy time and entrance skin dose were prospectively measured using optically stimulated luminescent dosimeters in patients undergoing ureteroscopy, retrograde pyelogram/stent or percutaneous nephrolithotomy with access for stone disease. A validated radiation safety competency test was administered to urology faculty and residents before and after web based, hands-on fluoroscopy training. Default fluoroscopy settings were changed from continuous to intermittent pulse rate and from standard to half-dose output. Fluoroscopy time and entrance skin dose were then measured again.The cohorts of 44 pre-protocol and 50 post-protocol patients with stones were similarly matched. The change in mean fluoroscopy time and entrance skin dose from pre-protocol to post-protocol was -0.6 minutes and -11.6 mGy (33%) for percutaneous nephrolithotomy (p = 0.62 and0.001), 0.5 minutes and -0.1 mGy (34%) for ureteroscopy (p = 0.42 and 0.31), and 0.1 minute and -0.1 mGy (29%) for retrograde pyelogram/stent (p = 0.85 and 0.49, respectively). Urologist post-training test scores increased 30% from pretraining scores (p = 0.1).Radiation safety training protocols improved clinical knowledge but did not significantly alter fluoroscopy time. Changing equipment default settings to intermittent pulse rate (12 frames per second) and half-dose lowered the entrance skin dose by 30% across all endourology patients but most significantly during percutaneous nephrolithotomy. To limit patient radiation exposure fluoroscopy default settings should be decreased before all endourology procedures and image equipment manufacturers should consider lowering standard default renal settings.

Renal urolithiasis is a pathological condition common to a multitude of genetic, physiological and nutritional disorders, ranging from general hyperoxaluria to obesity. The concept of quickly dissolving renal uroliths via chemolysis, especially calcium-oxalate kidney stones, has long been a clinical goal, but yet to be achieved. Over the past 25 years, there has been a serious effort to examine the prospects of using plant and microbial oxalate-degrading enzymes known to catabolize oxalic acid and oxalate salts. While evidence is emerging that bacterial probiotics can reduce recurrent calcium-oxalate kidney stone disease by lowering systemic hyperoxaluria, the possible use of free oxalate-degrading enzyme therapy remains a challenge with several hurdles to overcome before reaching clinical practice.

Idiopathic stone formers often form calcium oxalate (CaOx) stones that are attached to calcium phosphate (CaP) deposits in the renal tissue, known as Randall’s plaques (RP). Plaques are suggested to originate in the renal tubular basement membrane and spread into the interstitial regions where collagen fibrils and vesicles become mineralized; if the epithelium is breached, the RP becomes overgrown with CaOx upon exposure to urine. We have developed a two-stage model system of CaP–CaOx composite stones, consisting of Stage (1) CaP mineralized plaque, followed by Stage (2) CaOx overgrowth into a stone. In our first paper in this series (Stage 1), osteopontin (and polyaspartate) were found to induce a non-classical mineralization of porcine kidney tissues, producing features that resemble RP. For the Stage 2 studies presented here, biomimetic RPs from Stage 1 were implanted into the bladders of rats. Hyperoxaluria was induced with ethylene glycol for comparison to controls (water). After 4 weeks, rats were sacrificed and the implants were analyzed using electron microscopy and X-ray microanalyses. Differences in crystal phase and morphologies based upon the macromolecules present in the biomimetic plaques suggest that the plaques have the capacity to modulate the crystallization reactions. As expected, mineral overgrowths on the implants switched from CaP (water) to CaOx (hyperoxaluric). The CaOx crystals were aggregated and mixed with organic material from the biomimetic RP, along with some amorphous and spherulitic CaOx near the “stone” surfaces, which seemed to have become compact and organized towards the periphery. This system was successful at inducing “stones” more similar to human idiopathic kidney stones than other published models.

Objective. To compare organ specific radiation dose and image quality in kidney stone patients scanned with standard CT reconstructed with filtered back projection (FBP-CT) to those scanned with low dose CT reconstructed with iterative techniques (IR-CT). Materials and Methods. Over a one-year study period, adult kidney stone patients were retrospectively netted to capture the use of noncontrasted, stone protocol CT in one of six institutional scanners (four FBP and two IR). To limit potential CT-unit use bias, scans were included only from days when all six scanners were functioning. Organ dose was calculated using volumetric CT dose index and patient effective body diameter through validated conversion equations derived from previous cadaveric, dosimetry studies. Board-certified radiologists, blinded to CT algorithm type, assessed stone characteristics, study noise, and image quality of both techniques. Results. FBP-CT (n=250) and IR-CT (n=90) groups were similar in regard to gender, race, body mass index (mean BMI = 30.3), and stone burden detected (mean size 5.4 ± 1.2 mm). Mean organ-specific dose (OSD) was 54-62% lower across all organs for IR-CT compared to FBP-CT with particularly reduced doses (up to 4.6-fold) noted in patients with normal BMI range. No differences were noted in radiological assessment of image quality or noise between the cohorts, and intrarater agreement was highly correlated for noise (AC2=0.873) and quality (AC2=0.874) between blinded radiologists. Conclusions. Image quality and stone burden assessment were maintained between standard FBP and low dose IR groups, but IR-CT decreased mean OSD by 50%. Both urologists and radiologists should advocate for low dose CT, utilizing reconstructive protocols like IR, to reduce radiation exposure in their stone formers who undergo multiple CTs.

Roux-en-Y gastric bypass (RYGB) surgery is a popular and extremely effective procedure for sustained weight loss in the morbidly obese. However, hyperoxaluria and oxalate kidney stones frequently develop after RYGB and steatorrhea has been speculated to play a role. We examined the effects of RYGB and the role of dietary fat in an obese rat model by measuring fecal fat content and transmural oxalate fluxes across the distal colon compared to sham-operated controls (SHAM). Direct measurements of fecal fat content confirmed that RYGB on a 10 % fat diet excreted 40-fold more fecal fat than SHAM and, on a 40 % fat diet, RYGB excreted sevenfold more fecal fat than SHAM fed similarly. Results from the transport studies revealed a clear effect of high dietary fat (40 %) on colonic oxalate permeability and tissue conductance (G T) with comparable oxalate fluxes in RYGB and in SHAM. Administering a diet containing 10 % fat to both groups distinguished differences between RYGB and SHAM, revealing a 40 % increase in G T in RYGB and a reversal in the direction of net oxalate flux from absorption in SHAM to secretion in RYGB. These changes in colonic oxalate permeability were associated with a fourfold increase in urinary oxalate excretion in RYGB compared to SHAM. Therefore, oxalate solubility and permeability in the RYGB model are promoted by steatorrhea and result in enhanced passive oxalate absorption and hyperoxaluria. To our knowledge, these are the first measurements of intestinal oxalate transport in rats with RYGB.

The relationship between calcium oxalate kidney stone formation and inflammatory bowel disease (IBD) was first noted in two large retrospective case series from the 1960s. In over 1,400 patients with inflammatory bowel disease, 92 of 1,468 patients (6%) were identified to have developed renal stones, an occurrence that appeared as frequent as other systemic complications of this disease process [1, 2]. The mechanisms behind this high stone incidence were confirmed in the 1970s to be a complication of fat malabsorption and chronic diarrhea, which resulted in enteric hyperoxaluria, decreased urine citrate concentration and pH, and decreased urine volumes [3, 4]. Since those early descriptions, other malabsorptive intestinal disease states have also been added to the IBD/stone- associated list, including jejunoileal bypass (historical) and Roux-en-Y gastric bypass for obesity, chronic mesenteric ischemia, and small bowel ostomies [5, 6]. In general, patients with ileocolonic disease (9–17%) tend to be more commonly affected than those with ileal (6–8%) or colonic disease (3–5%) alone, and stone composition varies between calcium oxalate (malabsorptive diseases, ileocolonic Crohn’s disease) and uric acid (copious diarrhea, small bowel ostomies) depending on the disease state and amount of volume loss/diarrhea. This chapter will highlight the urinary abnormalities seen in modern bariatric surgical patients and in patients with the two most common forms of IBD (Crohn’s, ulcerative colitis) with a focus on the nutritional aspects that can be improved in these stone-forming populations.

Despite guidelines, routine 24-hour urine testing is completed in10% of high-risk, recurrent stone formers. Using surrogates for metabolic testing, such as key patient characteristics, could obviate the cost and burden of this test while providing information needed for proper stone prevention counseling.We performed a retrospective study of 392 consecutive patients from 2007 to 2014 with ≥2 lifetime stone episodes,70% calcium oxalate by mineral analysis, and ≥1 24-hour urine collection. We compared mean 24-hour urine values by age in decades. We used logistic regression and receiver operating characteristic (ROC) curve analysis to assess the predictive ability of age, gender, body mass index (BMI), and comorbidities to detect abnormal 24-hour urine parameters.The mean age of the cohort was 51 ± 16 years. Older age was associated with greater urinary oxalate (p-trend0.001), lower urinary uric acid (UA) (p-trend = 0.007), and lower urinary pH (p-trend0.001). A nonlinear association was noted between age and urinary calcium or citrate (calcium peaked at 40-49 years, p = 0.03; citrate nadired at 18-29 years, p = 0.001). ROC analysis of age, gender, and BMI to predict 24-hour urine abnormalities performed the best for hyperuricosuria (area under the curve [AUC] 0.816), hyperoxaluria (AUC 0.737), and hypocitraturia (AUC 0.740). Including diabetes mellitus or hypertension did not improve AUC significantly.In our recurrent calcium oxalate cohort, age significantly impacted urinary calcium, oxalate, citrate, and pH. Along with gender and BMI, age can be used to predict key 24-hour urine stone risk results. These data lay the foundation for a risk prediction tool, which could be a surrogate for 24-hour urine results in recurrent stone formers, who are unwilling or unable to complete metabolic testing. Further validation of these findings is needed in other stone populations.

Background The proposed revision to the Accreditation Council for Graduate Medical Education (ACGME) Common Program Requirements includes participation in real or simulated patient safety activities, such as root cause analysis (RCA).1 Because exposure to RCA may occur with low frequency, a mock RCA was developed and piloted for feasibility with Hematology/Oncology fellows. Objective To improve trainee knowledge of the goals and application of RCA in patient safety and quality improvement through a simulated experience. Methods A mock RCA was implemented with Hematology/Oncology fellows over two subsequent years. In small groups, they reviewed a case involving an adverse event and identified sources of harm. Additional details, in the form of provider interviews, were available upon request. Trainees identified the root cause(s) and proposed measurable changes. Teams presented proposals to peers and a panel representing hospital leadership. Feedback was provided. Trainees completed evaluations and were surveyed regarding their perceptions. Results Thirteen of 15 fellows completed the survey. Twelve of 13 (92%) fellows felt the mock RCA improved their comfort level for participation in a real RCA. Ten of 13 fellows (77%) reported increased awareness and likelihood of reporting near misses and/or adverse events following participation. More thorough patient care documentation following the session was reported by 8 of 13 (62%). Conclusion A pilot trial of a mock RCA with Hematology/Oncology fellows had high trainee satisfaction. Post-session surveys and informal interviews suggest trainees have reduced anxiety when faced with participation in a real RCA and have more interest in the process after participation.

Obesity is rampant across the spectrum of age, gender, and race in the Unites States. Paralleling this epidemic, kidney stone prevalence is also rising, affecting nearly 1 in 11 individuals. Bariatric surgical procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), are the most effective weight loss options for morbidly obese or severely obese individuals with comorbidities. A number of studies have linked kidney stone development to bariatric surgical history, particularly RYGB, which portends up to a threefold increase in calcium oxalate stone risk compared with age-matched, obese controls. Stone development after malabsorptive (RYGB) and restrictive (SG) bariatric procedures are driven primarily by alterations in 24-h urine profiles, such as increased urinary oxalate, decreased urine volume, and reduced urinary citrate levels-all of which have been linked to increased kidney stone risk. What clinical recommendations, if any, can be given to reduce kidney stone risk in bariatric kidney stone patients? This review provides not only updated stone incidence and 24-h urine data in this population, but also reassurance-the metabolic alterations that result from bariatric surgery can be successfully mitigated by increased provider awareness, patient education, and a combination of dietary and pharmacological adjustments.

Nature Reviews Disease Primers 2, 16008 (2016) In the version of the article originally published, a typographical error has now been corrected. The statement now reads: Exposure of vascular smooth muscle cells to high levels of calcium and phosphate triggers this transformation154,155, which activates bone morphogenetic proteins (BMPs) and WNT signalling pathways via upregulation of Runt-related transcription factor 2 (RUNX2) and msh homeobox 2 (MSX2) transcription factors156.

To establish the relationship between calcium nephrolithiasis, bone densitometry scoring, and bone mineral density (BMD) loss according to bone turnover markers (BTMs) and urinary metabolites.Patients with recurrent calcium nephrolithiasis and idiopathic fasting hypercalciuria (urinary calcium/creatinine ratio0.11) are more likely to have BMD loss that may lead to osteopenia or osteoporosis. In these patients, BTMs may be used as a surrogate for both bone health and stone recurrence. Suspect higher lithogenic states when calcium stone formers have serum beta-crosslaps (resorptive marker) greater than 0.311 ng/ml, serum osteocalcin (formative marker) greater than 13.2 ng/ml, and beta-crosslaps/osteocalcin ratio greater than 0.024.Patients with recurrent calcium nephrolithiasis and fasting hypercalciuria have a higher incidence of osteopenia and osteoporosis, measured by the dual-energy X-ray absorptiometry. These patients present not only with hypercalciuria and increased BTMs (mainly resorptive), but also up to 30% have hypocitraturia and increased urinary calcium/citrate ratio (0.25). On the basis of these results, a diagnostic algorithm was created, classifying hypercalciurics according to their fasting calcium/creatinine and calcium/citrate ratio. Medical therapy for these patients is aimed at improving the dietary habits (normocalcemic, low salt, low animal protein diet), prescribing combinations of potassium citrate, thiazides, and bisphosphonates, and correcting bone and urinary abnormalities that may lower future skeletal and kidney stone risk.

Positron-emission tomography/computed tomography (PET/CT) with fluorine-18 fluorodeoxyglucose (FDG) is used as first-line staging for patients with newly diagnosed non-small cell lung cancer (NSCLC). Our purpose was to review the accuracy of FDG-PET/CT to predict adrenal gland metastasis, explain the causes for false-positive PET, and provide a diagnostic algorithm.Two patients with incidentally discovered lung masses were found to have hypermetabolic adrenal activity by FDG-PET/CT with maximal standard uptake value (SUV) of 4.5 and 6.5. A MEDLINE search was performed on the topic of FDG-PET/CT, adrenal gland metastasis, and NSCLC. Literature was reviewed with regard to diagnosis, accuracy, outcomes, and alternative imaging or diagnostic strategies.Both patients underwent transabdominal laparoscopic adrenalectomy and were found to have nodular hyperplasia without evidence of adrenal tumor. A total of seven articles containing 343 patients were identified as having pertinent oncologic information for NSCLC patients with adrenal lesions. Sensitivity and specificity of PET/CT for distant metastasis was 94% and 85%, respectively, but only 13% (44/343) of these patients had histologically confirmed adrenal diagnoses. Based on this, a diagnostic algorithm was created to aid in decision making.Although PET/CT has high sensitivity and specificity for adrenal metastasis in the setting of NSCLC, adrenal biopsy or other secondary imaging should be considered to confirm the finding. Adrenalectomy in lieu of biopsy may have both diagnostic and therapeutic benefit in cases where the adrenal mass is ≥10 mm with high PET maximum SUV (≥3.1) and SUV ratios (2.5), where washout CT or chemical shift MRI is positive, or where percutaneous biopsy is deemed too difficult or unsafe.

Objective To investigate the efficacy and safety of alpha blockers in the treatment of patients with ureteric stones. Design Systematic review and meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Web of Science, Embase, LILACS, and Medline databases and scientific meeting abstracts to July 2016. Review methods Randomized controlled trials of alpha blockers compared with placebo or control for treatment of ureteric stones were eligible. Two team members independently extracted data from each included study. The primary outcome was the proportion of patients who passed their stone. Secondary outcomes were the time to passage; the number of pain episodes; and the proportions of patients who underwent surgery, required admission to hospital, and experienced an adverse event. Pooled risk ratios and 95% confidence intervals were calculated for the primary outcome with profile likelihood random effects models. Cochrane Collaboration’s tool for assessing risk of bias and the GRADE approach were used to evaluate the quality of evidence and summarize conclusions. Results 55 randomized controlled trials were included. There was moderate quality evidence that alpha blockers facilitate passage of ureteric stones (risk ratio 1.49, 95% confidence interval 1.39 to 1.61). Based on a priori subgroup analysis, there seemed to be no benefit to treatment with alpha blocker among patients with smaller ureteric stones (1.19, 1.00 to 1.48). Patients with larger stones treated with an alpha blocker, however, had a 57% higher risk of stone passage compared with controls (1.57, 1.17 to 2.27). The effect of alpha blockers was independent of stone location (1.48 (1.05 to 2.10) for upper or middle stones; 1.49 (1.38 to 1.63) for lower stones). Compared with controls, patients who received alpha blockers had significantly shorter times to stone passage (mean difference −3.79 days, −4.45 to −3.14; moderate quality evidence), fewer episodes of pain (−0.74 episodes, −1.28 to −0.21; low quality evidence), lower risks of surgical intervention (risk ratio 0.44, 0.37 to 0.52; moderate quality evidence), and lower risks of admission to hospital (0.37, 0.22 to 0.64; moderate quality evidence). The risk of a serious adverse event was similar between treatment and control groups (1.49, 0.24 to 9.35; low quality evidence). Conclusions Alpha blockers seem efficacious in the treatment of patients with ureteric stones who are amenable to conservative management. The greatest benefit might be among those with larger stones. These results support current guideline recommendations advocating a role for alpha blockers in patients with ureteric stones. Systematic review registration PROSPERO registration No CRD42015024169.

We determined the effect of dietary fat and oxalate on fecal fat excretion and urine parameters in a rat model of Roux-en-Y gastric bypass surgery.Diet induced obese Sprague-Dawley® rats underwent sham surgery as controls (16), or Roux-en-Y gastric bypass surgery (19). After recovery, rats had free access to a normal calcium, high fat (40%) diet with or without 1.5% potassium oxalate for 5 weeks and then a normal (10%) fat diet for 2 weeks. Stool and urine were collected after each period. Fecal fat was determined by gas chromatography and urine metabolites were evaluated by assay spectrophotometry.Daily fecal fat excretion remained low in controls on either diet. However, Roux-en-Y gastric bypass rats ingested a food quantity similar to that of controls but had eightfold higher fecal fat excretion (p0.001) and heavier stools (p = 0.02). Compared to controls, gastric bypass rats on the high fat diet with potassium oxalate had a fivefold increase in urine oxalate excretion (p0.001), while gastric bypass rats without potassium oxalate had a twofold increase in urine calcium (p0.01). Lowering dietary fat in gastric bypass rats with potassium oxalate led to a 50% decrease in oxalate excretion (p0.01), a 30% decrease in urine calcium and a 0.3 U increase in urine pH (p0.001).In this Roux-en-Y gastric bypass model high fat feeding resulted in steatorrhea, hyperoxaluria and low urine pH, which were partially reversible by lowering the dietary fat and oxalate content. Roux-en-Y gastric bypass rats on normal fat and no oxalate diets excreted twice as much oxalate as age matched, sham operated controls. Although Roux-en-Y gastric bypass hyperoxaluria appears primarily mediated by gut and diet, secondary causes of oxalogenesis from liver or other mechanisms deserve further exploration.

We identified epidemiological risk factors for the initial urinary tract infection in females of college age compared to age matched controls.We performed a prospective cohort study from July 2001 to January 2006 at the student health care facility at our institution. A total of 180 women experiencing a first urinary tract infection were compared to 80 asymptomatic women with no urinary tract infection history who served as controls. Urinalysis and urine culture were done at study enrollment. Questionnaires were used to obtain information on clinical symptoms and behaviors, including sexual and dietary practices, and alcohol consumption. Logistic regression was performed to identify potential risk factors in women who presented with an initial urinary tract infection compared with controls. Principal component analysis was then done to identify key sexual activity variables for multiple regression models.Urinary frequency and urgency were the most common urinary tract infection symptoms. Recent sexual activity was a significant risk factor for urinary tract infection with vaginal intercourse (p = 0.002) and the number of sexual partners in the last 2 weeks (p0.001) as the 2 primary variables. Alcohol consumption was associated with 2 of the 3 main principal components of sexual activity. Caffeinated beverage consumption also increased the risk of urinary tract infection (p0.04). Escherichia coli was the predominant pathogen isolated, followed by urease positive microbes.Recent sexual activity, the frequency of that activity and the number of sexual partners pose an increased risk of urinary tract infection. Alcohol consumption frequency and amount correlated with these behaviors.

Blood and urine oxalate determinations have been limited to the laboratory setting because of complex sample storage and processing methods as well as the need for color spectrophotometry and ion chromatography. We hypothesized that glucometer test strips, impregnated with glucose oxidase and dyes that measure secondary hydrogen peroxide production, could be infused with oxalate oxidase and produce enhanced color changes in the presence of oxalate. By increasing the amount of sodium oxalate in fresh blood, we found that glucometer-measured oxalate increased on a linear scale. In addition, oxalate levels in synthetic urine could be measured using a visual scale, suggesting that strip dwell time or oxalate/oxalate oxidase concentrations could be manipulated to enhance optimal sensitivity. Although further testing is necessary, this simple, first-generation oxometer may eventually allow point of care testing in the home or office, empowering patients with oxalate-based medical conditions and giving healthcare providers real-time oxalate feedback.

We investigated the association between sleep disordered breathing and erectile dysfunction in older men.We performed a cross-sectional analysis of community dwelling men age 67 years or older enrolled in the Osteoporotic Fractures in Men Sleep Study. Participants underwent overnight polysomnography (2003 to 2005) and completed sexual health questionnaires (2005 to 2006). We defined sleep disordered breathing using the apnea-hypopnea index or nocturnal hypoxemia. Erectile dysfunction was defined using the MMAS (Massachusetts Male Aging Study) scale and, in sexually active men, the International Index of Erectile Function. We used logistic regression to examine the association between sleep disordered breathing and erectile dysfunction.Mean participant age was 76±5 years. Of the 2,676 men completing the MMAS, 70% had moderate to complete erectile dysfunction. Among 1,099 sexually active men completing the IIEF-5 (5-item International Index of Erectile Function), 26% had moderate to severe erectile dysfunction. A higher apnea-hypopnea index was associated with greater odds of MMAS defined moderate to complete erectile dysfunction after adjusting for age and study site (OR 1.39, 95% CI 1.00-1.92 for severe sleep disordered breathing vs none, p trend=0.008), but not after further adjustment for body mass index, socioeconomic status and comorbidities (OR 1.05, 95% CI 0.75-1.49, p trend=0.452). Greater nocturnal hypoxemia was associated with increased odds of MMAS defined moderate to complete erectile dysfunction (unadjusted OR 1.36, 95% Cl 1.04-1.80 vs none) but this was attenuated after adjustment for age and study site (OR 1.24, 95% CI 0.92-1.66). Sleep disordered breathing was not associated with erectile dysfunction by 5-item International Index of Erectile Function.In this cross-sectional analysis in older men sleep disordered breathing was associated with higher odds of erectile dysfunction in unadjusted analyses that was largely explained by higher body mass index and increased comorbidity among men with sleep disordered breathing. Prospective studies accounting for obesity and multimorbidity would further clarify the association of sleep disordered breathing and erectile dysfunction.

Computerized tomography imaging is regularly used to assess stone HU values as a surrogate for stone composition and fragility. Techniques for measuring HU values are unstandardized, leading to high variability. We investigated several region of interest measurement strategies to quantify this variability.Patients from an institutional database who underwent preoperative computerized tomography, surgical stone extraction and stone composition analysis were identified. HU measurements were made of each patient stone using transverse/coronal slices in the abdominal/bone windows with 4 region of interest techniques, including 1) the maximum diameter region of interest, 2) the maximum diameter region of interest at all stone inclusive slices, 3) 2 equal-sized, nonoverlapping circular regions of interest and 4) 3 to 5 smaller nonoverlapping regions of interest randomly placed on the stone. Stones that were 80% or greater pure by composition were separately analyzed.A total of 172 patients were included in study. Mean ± SD stone size was 19.3 ± 15.6 mm. On subtype analysis 51 stones were calcium oxalate monohydrate, 9 were calcium oxalate dihydrate, 7 were calcium phosphate hydroxyapatite/brushite and 16 were uric acid. Mean HU values in the abdominal window for all stones identified by region of interest techniques 1 to 4 were 457 ± 253, 351 ± 210, 581 ± 363 and 587 ± 329, respectively. The distribution of means significantly differed across region of interest techniques, planes and windows when considering all stones together (p0.0001), stones with greater than 80% calcium oxalate dihydrate (p = 0.0113) and greater than 80% calcium oxalate monohydrate (p0.0001), and uric acid stones (p0.0001).HU values obtained to assess stone density vary depending on window, plane and region of interest technique. We recommend that clinicians select a single region of interest measurement technique and use it consistently to minimize interinstitutional variability.