Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology 2023 Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Antiplatelet therapy (APT) is the foundation of treatment and prevention of atherothrombotic events in patients with atherosclerotic cardiovascular disease. Selecting the optimal APT strategies to reduce major adverse cardiovascular events, while balancing bleeding risk, requires ongoing review of clinical trials. Appended, the focused update of the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the use of APT provides recommendations on the following topics: (1) use of acetylsalicylic acid in primary prevention of atherosclerotic cardiovascular disease; (2) dual APT (DAPT) duration after percutaneous coronary intervention (PCI) in patients at high bleeding risk; (3) potent DAPT (P2Y12 inhibitor) choice in patients who present with an acute coronary syndrome (ACS) and possible DAPT de-escalation strategies after PCI; (4) choice and duration of DAPT in ACS patients who are medically treated without revascularization; (5) pretreatment with DAPT (P2Y12 inhibitor) before elective or nonelective coronary angiography; (6) perioperative and longer-term APT management in patients who require coronary artery bypass grafting surgery; and (7) use of APT in patients with atrial fibrillation who require oral anticoagulation after PCI or medically managed ACS. These recommendations are all on the basis of systematic reviews and meta-analyses conducted as part of the development of these guidelines, provided in the Supplementary Material.

Atherosclerotic plaque regression in homozygous familial hypercholesterolaemia: a case report of a long-term lipid-lowering therapy involving LDL-receptor-independent mechanisms.

Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare and life-threatening genetic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels, important xanthomatosis and increased risk of premature atherosclerotic cardiovascular disease. Management of HoFH at an early stage is recommended but conventional lipid-lowering therapies (LLTs) dependent on the LDL-receptor for clearance of LDL particles, are usually not sufficient. However, agents acting independently of the LDL-receptor, such as inhibitors of microsomal triglyceride transfer protein (MTP) or angiopoietin-like protein 3 (ANGPTL3), administered in combination, on top of standard-of-care LLT constitute a promising therapy for HoFH. Case summary: The present case describes a long-term (>10 years) follow-up of a 52-year-old woman with severe HoFH, who was treated with conventional lipid-lowering medications (i.e. statins and ezetimibe) for several years before experiencing the risks and benefits that were encountered with the use of LDL-receptor-independent agents (MTP and ANGPTL3 inhibitors). This combination therapy demonstrated a good long-term safety and efficacy profile, while continuous monitoring of hepatic enzymes (sometimes requiring dose adjustments) and fat accumulation is recommended when using lomitapide. Discussion: Treating this HoFH patient with an LLT involving the combination of MTP and ANGPTL3 LDL-receptor-independent inhibitors (lomitapide and evinacumab, respectively) showed remarkable improvement in LDL-C levels, disappearance of xanthomatosis and regression in atherosclerotic plaques. In addition to safety and efficacy, one should question the affordability and access hurdle that emerging combination of expensive therapies might constitute in the future for the payers. These challenges could eventually limit the clinical use of those innovative treatments despite their clinical benefit.

Risk Prediction Tool for Assessing the Probability of Death or Myocardial Infarction in Patients With Stable Coronary Artery Disease.

Several risk scores in acute coronary syndromes are available, but few models exist for stable coronary artery disease to guide decision-making and prognosis. A multivariate model was developed using 23 baseline candidate variables from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Therapy EvaluationTrial (n = 2,287 patients). Discrimination of the model was evaluated by the concordance c-index. The procedure was validated using 100 random half samples. We identified 9 independent predictors of death or myocardial infarction (MI) during a 5-year follow-up. The following predictors and points contributing to the risk score were: heart failure (3), number of diseased coronary arteries (1 for each vessel), diabetes (1), age (1 for each 15 years ≥ age 45), previous revascularization (1), current smoking (1), female (1), previous MI (1), and high-density lipoprotein cholesterol (1: 31 to 40 mg/dL; 2: <30 mg/dL). The risk tool had a potential range from 0 to 15, corresponding to 5-year event rates of 5.8% to 56%. C-indices ranged from 0.67 for the full data set to 0.62 for the validating subsamples. Respective observed versus predicted 5-year event rates for 3 predefined risk strata revealed: 30% had a low-risk score of 0 to 3 (9.3% vs 9.3%, or 1.9%/year); 59% had an intermediate-risk score of 4-6 (18.0% vs 18.1%, or 3.6%/year); and 11% had a high-risk score of 7-11 (36% vs 36.5%, or 7.2%/year). This stable coronary artery disease risk score permitted a prognostic assessment of 5-year probability of death or MI with an approximate 4-fold range in event rates from the lowest (9.3%) to the highest (36%) terciles, thus enabling better clinical practice decisions that allow physicians to tailor the intensity of treatment to the level of risk.

Metabolomic profiling in a Hedgehog Interacting Protein (Hhip) murine model of chronic obstructive pulmonary disease.

Genetic variants annotated to the hedgehog interacting protein (HHIP) are robustly associated with chronic obstructive pulmonary disease (COPD). Hhip haploinsufficiency in mice leads to increased susceptibility towards the development of emphysema following exposure to chronic cigarette smoke (CS). To explore the molecular pathways which contribute to increased susceptibility, we performed metabolomic profiling using high performance liquid chromatography tandem mass spectroscopy (LC/MS-MS) on plasma, urine, and lung tissue of Hhip +/- heterozygotes and wild type (Hhip +/+) C57/BL6 mice exposed to either room-air or CS for six months. Univariate comparisons between groups were made with a combined fold change ≥2 and Student's t-test p-value < 0.05 to denote significance; associations with mean alveolar chord length (MACL), a quantitative measure of emphysema, and gene-by-environment interactions were examined using empiric Bayes-mediated linear models. Decreased urinary excretion of cotinine despite comparable plasma levels was observed in Hhip +/- heterozygotes; a strong gene-by-smoking association was also observed. Correlations between MACL and markers of oxidative stress such as urinary methionine sulfoxide were observed in Hhip +/- but not in Hhip +/+ mice. Metabolite set enrichment analyses suggest reduced antioxidant capacity and alterations in macronutrient metabolism contribute to increased susceptibility to chronic CS-induced oxidative stress in Hhip haploinsufficiency states.

The predictive relationship between baseline insulin and glucose with subclinical carotid atherosclerosis after 5 years in a multi-ethnic cohort.

BACKGROUND AND AIMS: We aimed at exploring the relationship between baseline insulin and glucose and the progression of carotid atherosclerosis in a multi-ethnic cohort. METHODS: Males and females (n = 797) of European, Chinese, South Asian and Aboriginal origin were assessed as part of the Multicultural Community Health Assessment Trial (MCHAT) study for socio-demographics, smoking status, fasting insulin and glucose at baseline. IMT, plaque area and total area were assessed after 5 years. RESULTS: A total of 545 participants returned after 5 years for a follow-up assessment. Average age of the study participants was 47.5 (SD 8.9) years. At baseline, the median and interquartile range for insulin was 62.0 (49.5) pmol/L, and glucose was 5.2 (0.60) mmol/L. Baseline glucose and insulin predicted the 5-year progression of atherosclerosis in our models, after adjusting for covariates. We found significant insulin-ethnicity interactions in the IMT model (p = 0.044) with the slope of the relationship showing that for every percentage change in insulin the Europeans experienced 7.3% more increase in IMT at 5 years than the Aboriginals. In the plaque area and total area models, there were significant glucose-ethnicity interactions (p = 0.009 and p=0.016 respectively), with the slope showing a 101% and 121% increase for plaque area and total area, respectively, in Europeans, at 5 years per percent change in glucose at baseline. Logistic regression found a significant glucose-ethnicity interaction with the presence of plaques (OR = 0.31, p = 0.03) such that compared to the Europeans, the South Asians had a lower odds of developing plaque presence. Similarly, we found glucose-ethnicity interactions in the logistic regression when comparing the Chinese to the Europeans (OR = 0.2, p=0.005), with the Chinese being less likely to develop plaque presence. CONCLUSIONS: Ethnicity modifies the predictive relationship between insulin and glucose with sub-clinical indicators of carotid atherosclerosis but not consistently so.

Hhip haploinsufficiency sensitizes mice to age-related emphysema.

Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

A Chronic Obstructive Pulmonary Disease Susceptibility Gene, FAM13A, Regulates Protein Stability of ß-Catenin.

RATIONALE: A genetic locus within the FAM13A gene has been consistently associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies. However, the mechanisms by which FAM13A contributes to COPD susceptibility are unknown. OBJECTIVES: To determine the biologic function of FAM13A in human COPD and murine COPD models and discover the molecular mechanism by which FAM13A influences COPD susceptibility. METHODS: Fam13a null mice (Fam13a(-/-)) were generated and exposed to cigarette smoke. The lung inflammatory response and airspace size were assessed in Fam13a(-/-) and Fam13a(+/+) littermate control mice. Cellular localization of FAM13A protein and mRNA levels of FAM13A in COPD lungs were assessed using immunofluorescence, Western blotting, and reverse transcriptase-polymerase chain reaction, respectively. Immunoprecipitation followed by mass spectrometry identified cellular proteins that interact with FAM13A to reveal insights on FAM13A's function. MEASUREMENTS AND MAIN RESULTS: In murine and human lungs, FAM13A is expressed in airway and alveolar type II epithelial cells and macrophages. Fam13a null mice (Fam13a(-/-)) were resistant to chronic cigarette smoke-induced emphysema compared with Fam13a(+/+) mice. In vitro, FAM13A interacts with protein phosphatase 2A and recruits protein phosphatase 2A with glycogen synthase kinase 3ß and ß-catenin, inducing ß-catenin degradation. Fam13a(-/-) mice were also resistant to elastase-induced emphysema, and this resistance was reversed by coadministration of a ß-catenin inhibitor, suggesting that FAM13A could increase the susceptibility of mice to emphysema development by inhibiting ß-catenin signaling. Moreover, human COPD lungs had decreased protein levels of ß-catenin and increased protein levels of FAM13A. CONCLUSIONS: We show that FAM13A may influence COPD susceptibility by promoting ß-catenin degradation.

Haploinsufficiency of Hedgehog interacting protein causes increased emphysema induced by cigarette smoke through network rewiring.

BACKGROUND: The HHIP gene, encoding Hedgehog interacting protein, has been implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS), and our subsequent studies identified a functional upstream genetic variant that decreased HHIP transcription. However, little is known about how HHIP contributes to COPD pathogenesis. METHODS: We exposed Hhip haploinsufficient mice (Hhip (+/-) ) to cigarette smoke (CS) for 6 months to model the biological consequences caused by CS in human COPD risk-allele carriers at the HHIP locus. Gene expression profiling in murine lungs was performed followed by an integrative network inference analysis, PANDA (Passing Attributes between Networks for Data Assimilation) analysis. RESULTS: We detected more severe airspace enlargement in Hhip (+/-) mice vs. wild-type littermates (Hhip (+/+) ) exposed to CS. Gene expression profiling in murine lungs suggested enhanced lymphocyte activation pathways in CS-exposed Hhip (+/-) vs. Hhip (+/+) mice, which was supported by increased numbers of lymphoid aggregates and enhanced activation of CD8+ T cells after CS-exposure in the lungs of Hhip (+/-) mice compared to Hhip (+/+) mice. Mechanistically, results from PANDA network analysis suggested a rewired and dampened Klf4 signaling network in Hhip (+/-) mice after CS exposure. CONCLUSIONS: In summary, HHIP haploinsufficiency exaggerated CS-induced airspace enlargement, which models CS-induced emphysema in human smokers carrying COPD risk alleles at the HHIP locus. Network modeling suggested rewired lymphocyte activation signaling circuits in the HHIP haploinsufficiency state.

Canadian Cardiovascular Society position statement on familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is the most common genetic disorder causing premature cardiovascular disease and death. Heterozygous FH conservatively affects approximately 1:500 Canadians, and the more serious homozygous form affects approximately 1:1,000,000 Canadians, although these numbers might be underestimated. Of approximately 83,500 Canadians estimated to have FH, most are undiagnosed, which represents a simultaneous public health deficit and opportunity, because early treatment of heterozygous FH can normalize life expectancy. Diagnostic algorithms for FH incorporate increased plasma low-density lipoprotein cholesterol, pathognomonic clinical features, and family history of early cardiovascular disease and hyperlipidemia. DNA-based detection of causative mutations in FH-related genes can help with diagnosis. Maximizing diagnosis and treatment of FH in Canada will involve a multipronged approach, including: (1) increasing awareness of FH among health care providers and patients; (2) creating a national registry for FH individuals; (3) setting standards for screening, including cascade screening in affected families; (4) ensuring availability of standard-of-care therapies, in particular optimization of plasma low-density lipoprotein cholesterol levels and timely access to future validated therapies; (5) promoting patient-based support and advocacy groups; and (6) forming alliances with international colleagues, resources, and initiatives that focus on FH. This document aims to raise awareness of FH nationally, and to mobilize knowledge translation, patient support, and availability of treatment and health care resources for this underrecognized, but important medical condition.

Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

Gene expression analysis uncovers novel hedgehog interacting protein (HHIP) effects in human bronchial epithelial cells.

Hedgehog interacting protein (HHIP) was implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS). However, it remains unclear how HHIP contributes to COPD pathogenesis. To identify genes regulated by HHIP, we performed gene expression microarray analysis in a human bronchial epithelial cell line (Beas-2B) stably infected with HHIP shRNAs. HHIP silencing led to differential expression of 296 genes; enrichment for variants nominally associated with COPD was found. Eighteen of the differentially expressed genes were validated by real-time PCR in Beas-2B cells. Seven of 11 validated genes tested in human COPD and control lung tissues demonstrated significant gene expression differences. Functional annotation indicated enrichment for extracellular matrix and cell growth genes. Network modeling demonstrated that the extracellular matrix and cell proliferation genes influenced by HHIP tended to be interconnected. Thus, we identified potential HHIP targets in human bronchial epithelial cells that may contribute to COPD pathogenesis.

Symptomatic bilateral delayed partial ureteral obstruction after bilateral endoscopic correction of vesicoureteral reflux with dextranomer/hyaluronic acid polymer.

Endoscopic correction of vesicoureteral reflux using dextranomer/hyaluronic acid copolymer (Deflux) is a widely used technique. Complications are uncommon, and ureteral obstruction occurs particularly infrequently. We present a case of delayed symptomatic partial bilateral ureteral obstruction after bilateral high-volume (>1.0 mL) Deflux injections that required surgical repair 16 months after injection (Clavien classification IIIb.) Bilateral delayed obstruction after endoscopic correction of vesicoureteral reflux has not been previously reported. Previous reports of immediate and delayed ureteral obstruction after Deflux injection are reviewed.

Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP.

Multiple intergenic single-nucleotide polymorphisms (SNPs) near hedgehog interacting protein (HHIP) on chromosome 4q31 have been strongly associated with pulmonary function levels and moderate-to-severe chronic obstructive pulmonary disease (COPD). However, whether the effects of variants in this region are related to HHIP or another gene has not been proven. We confirmed genetic association of SNPs in the 4q31 COPD genome-wide association study (GWAS) region in a Polish cohort containing severe COPD cases and healthy smoking controls (P = 0.001 to 0.002). We found that HHIP expression at both mRNA and protein levels is reduced in COPD lung tissues. We identified a genomic region located ∼85 kb upstream of HHIP which contains a subset of associated SNPs, interacts with the HHIP promoter through a chromatin loop and functions as an HHIP enhancer. The COPD risk haplotype of two SNPs within this enhancer region (rs6537296A and rs1542725C) was associated with statistically significant reductions in HHIP promoter activity. Moreover, rs1542725 demonstrates differential binding to the transcription factor Sp3; the COPD-associated allele exhibits increased Sp3 binding, which is consistent with Sp3's usual function as a transcriptional repressor. Thus, increased Sp3 binding at a functional SNP within the chromosome 4q31 COPD GWAS locus leads to reduced HHIP expression and increased susceptibility to COPD through distal transcriptional regulation. Together, our findings reveal one mechanism through which SNPs upstream of the HHIP gene modulate the expression of HHIP and functionally implicate reduced HHIP gene expression in the pathogenesis of COPD.

Organ-specific radiation dose rates and effective dose rates during percutaneous nephrolithotomy.

BACKGROUND AND PURPOSE: Radiation exposure during medical procedures continues to be an increasing concern for physicians and patients. We determined organ-specific dose rates and calculated effective dose rates during right and left percutaneous nephrolithotomy (PCNL) using a validated phantom model. MATERIALS AND METHODS: A validated anthropomorphic adult male phantom was placed prone on an operating room table. Metal oxide semiconductor field effect transistor dosimeters were placed at 20 organ locations in the model and were used to measure the organ dosages. A portable C-arm was used to provide continuous fluoroscopy for three 10 minute runs each to simulate a left and right PCNL. Organ dose rate (mGy/s) was determined by dividing organ dose by fluoroscopy time. The organ dose rates were multiplied by their tissue weighting factor and summed to determine effective dose rate (EDR) (mSv/s). Two-dimensional radiation distribution in the abdomen during a left-sided PCNL was visually determined using radiochromic film. RESULTS: The EDR for a left PCNL was 0.021 mSv/s ± 0.0008. The EDR for a right PCNL was 0.014 mSv/s ± 0.0004. The skin entrance was exposed to the greatest amount of radiation during left and right PCNL, 0.24 mGy/s and 0.26 mGy/s, respectively. Radiochromic film demonstrates visually the nonuniform dose distribution as the x-ray beam enters through the skin from the radiation source. CONCLUSIONS: The effective dose rate is higher for a left-sided PCNL compared with a right-sided PCNL. The distribution of radiation exposure during PCNL is not uniform. Further studies are needed to determine the long-term implications of these radiation doses during percutaneous stone removal.

The digital flexible ureteroscope: in vitro assessment of optical characteristics.

INTRODUCTION: Recent advances in endoscope design have placed the charged coupled device chip on the tip of the endoscope. The image is instantly digitalized and converted into an electrical signal for transmission. Digital technology was first introduced into flexible cystoscopes/nephroscopes and subsequently into rigid and flexible ureteroscopes. Herein, we assess the image characteristics and advantages of a new generation of digital flexible ureteroscopes. METHODS: The Olympus URF-V flexible digital ureteroscope and the Olympus URF-P3 fiberoptic ureteroscope were assessed in vitro for image resolution, distortion, color representation, grayscale imaging, field of view, and depth of field. RESULTS: The digital ureteroscope had a higher resolution at 3, 5, 10, and 20 mm (25.2 lines/mm vs. 8.0, 14.1 vs. 5.0, 6.3 vs. 2.8, and 3.2 vs. 1.3), respectively. Distortion with the digital flexible ureteroscope was lower, though not statistically significant. Color representation was better with the digital ureteroscope, whereas contrast evaluation was comparable between both scopes. The digital flexlible ureteroscope produced a 5.3 times larger image size compared with the standard fiberoptic flexible uretersocpe with a narrower field of view. The depth of field was limited by light and not the optic or the camera for both ureteroscopes. CONCLUSIONS: The development of digital flexible ureteroscopes represents a significant technological advance in urology. These devices offer significantly improved resolution and color reproduction as compared with traditional fiberoptic flexible ureteroscopes. Future clinical trials are warranted to ultimately determine the advantages of these innovative endoscopes.

Reduced radiation exposure with the use of an air retrograde pyelogram during fluoroscopic access for percutaneous nephrolithotomy.

INTRODUCTION: Fluoroscopy with retrograde pyelogram is commonly used to obtain access for percutaneous nephrolithotomy (PNL). Our practice uses room air for retrograde identification of calyceal anatomy. Herein we explore whether an air pyelogram was associated with a decrease in radiation exposure compared with standard retrograde pyelogram. METHODS: We retrospectively reviewed all PNL procedures performed at our institution over the past 2 years. Of the 260 PNL procedures performed during the study period, 96 had information on radiation dosage required for analysis. The effective dose (ED) was calculated using accepted conversion tables. Multivariable linear regression was used to determine the association between ED and the use of air pyelogram controlling for factors thought to affect radiation exposure. RESULTS: Of the 96 PNL procedures included in the study, 60 (63%) were performed with an air retrograde pyelogram (AP) and 36 (37%) used contrast retrograde pyelogram (CP). Both groups were matched in terms of age, body mass index, stone burden, and number of access tracts. Multivariable linear regression showed significantly lower radiation exposure in the AP group than in the CP group (p = 0.001). There was no difference in fluoroscopy time between the two groups. Using an AP lowered the mean adjusted ED nearly twofold, from 7.67 (CI = 5.99-9.81) to 4.45 (CI = 3.68-5.38) mSv. CONCLUSIONS: An air retrograde pyelogram is associated with decreased radiation exposure during PNL when compared with a contrast retrograde pyelogram.

Third prize: the role of endoscopic nephron-sparing surgery in the management of upper tract urothelial carcinoma.

INTRODUCTION: Upper tract urothelial carcinoma (UT-UC) is an uncommon disease with pronounced difference in 5-year survival for noninvasive (96%) versus invasive (17%) disease. High survival rate of early disease questioned the accepted norm of using radical nephroureterectomy (RNU) for all stages. This review assesses effectiveness of endoscopic management for UT-UC. METHODS: A review of 131 UT-UC patients seen between January 1999 and October 2009 was performed. Demographic, clinicopathologic, and outcomes data were collected and compared between patients initially managed with RNU versus those initially managed with nephron-sparing surgery (NSS). The chi-square or Fisher's exact tests for categorical variables and the Wilcoxon-Mann-Whitney test for continuous variables were used. Clinical and pathologic stages of RNU patients were evaluated with chi-square testing, whereas difference in length of stay was detected using linear regression. Recurrence rates were compared using multivariate Cox regression. RESULTS: The two arms had similar distributions of age, sex, frequency of medical comorbidities, American Society of Anesthesiologists (ASA), and Charlson scores. Mean-adjusted length of stay was 2.1 (95% confidence interval [1.6, 2.5]) and 5.5 days (95% confidence interval [5.3, 6.4]) for the NSS and RNU groups, respectively (p < 0.001). Comparison of clinical and pathologic stages of RNU patients showed a difference (p < 0.001), with under-staging noted in 32%. Men (Hazards Ratio = 2.9 [1.5-5.5], p = 0.001) and NSS patients (hazards ratio [HR] = 3.5 [1.7-7.3], p < 0.001) had threefold increased recurrence risk. CONCLUSION: NSS offered shorter hospital stay but had increased risk of recurrence. Therefore, extreme care should be made to rule out occult invasive tumors preoperatively. Patients being managed endoscopically must be informed of the necessity for close follow-up.

Factors affecting patient radiation exposure during percutaneous nephrolithotomy.

PURPOSE: We identified patient and stone characteristics that may contribute to increased radiation exposure during percutaneous nephrolithotomy and offer technique modifications to limit the radiation dose. MATERIAL AND METHODS: We reviewed the records of 96 patients who underwent percutaneous nephrolithotomy in the last 2 years. The effective radiation dose was calculated using accepted conversion tables. We performed multivariate linear regression to determine the association of the effective radiation dose with specific patient, stone and procedural characteristics. RESULTS: Mean±SD patient age was 51.5±13.4 years and 62.5% of the patients were female. Median body mass index was 32.0±9.7 kg/m2 (range 16.2 to 59.6) and the median stone burden was 4 cm2. Increased body mass index (p<0.001), higher stone burden (p=0.013), stone nonbranched configuration (p=0.002) and a greater number of percutaneous access tracts (p=0.040) were significantly associated with an increased effective radiation dose. Specifically obese patients with a body mass index of 30 to 39.9 kg/m2 had a more than 2-fold increase in the mean adjusted effective radiation dose and morbidly obese patients with a body mass index of 40 kg/m2 or greater had a greater than 3-fold increase vs that in normal weight patients with a body mass index of less than 25 kg/m2 (6.49 and 9.13 mSv, respectively, vs 2.66, p<0.001). Other stone specific parameters, including site and composition, percutaneous access site and estimated blood loss were not associated with the effective radiation dose. CONCLUSIONS: Patients with higher body mass index, greater stone burden, nonbranched stones and multiple nephrostomy access tracts are at risk for increased radiation exposure during percutaneous nephrolithotomy. Urologists must seek alternative strategies to minimize radiation exposure, such as tighter collimation to the region of interest, judicious use of magnification and the acquisition of as few images as possible during stone removal.

The impact of new methods of imaging on radiation dosage delivered to patients.

PURPOSE OF REVIEW: Ionizing radiation is produced by many of the imaging studies used in the diagnosis, management, and follow-up of patients with urolithiasis. Knowing the small, but significant, risks of solid and hematological malignancies associated with increased radiation exposure, our purpose is to discuss new imaging modalities that limit radiation exposure without compromising the valuable information needed by clinicians for appropriate management. RECENT FINDINGS: Recent studies suggest that many patients with urolithiasis may be subjected to relatively high doses of ionizing radiation during acute stone episodes and throughout the management of their disease, due, in large part, to the rapidly increasing usage of computed tomography (CT). Certain imaging modalities, most notably low-dose CT, have shown promise in reducing radiation dose to patients while maintaining comparable sensitivity and specificity to standard CT, under most conditions. SUMMARY: Urologists who use radiographic imaging in the care of their patients, must be aware of the risks of ionizing radiation. Accordingly, every effort must be made to limit radiation exposure, especially in the most susceptible populations. In our view, low-dose CT is currently the best imaging modality for patients with urolithiasis, as it offers adequate image quality with much reduced radiation exposure.

Predictive factors of invasion in eyes with retinoblastoma enucleated after eye salvage treatments.

BACKGROUND: The impact of chemotherapy, focal therapies, radiation and co-existing ocular morbidities on histology of eyes with retinoblastoma enucleated following chemoreduction is not well known. PROCEDURE: Twenty-five eyes (23 patients) with retinoblastoma enucleated after failing eye-salvage therapy were evaluated. Reasons for enucleation (tumor progression, subretinal or vitreous seeds) and co-morbid conditions (neovascular glaucoma, cataract, vitreous hemorrhage and retinal detachment) were documented. All specimens were reviewed for evidence of ciliary body, choroidal, optic nerve, and scleral invasion. RESULTS: The median age at diagnosis was 14 months (range, 1-37 months). Twenty eyes were classified as Reese-Ellsworth Group IV-V at diagnosis. Twenty-four eyes had recurrent disease at enucleation; one eye was enucleated for neovascular glaucoma and vitreous hemorrhage. Co-existing ocular morbidities at enucleation included vitreous hemorrhage (n = 6), retinal detachment (n = 9), neovascular glaucoma (n = 9) and cataracts (n = 3). Histologic findings included choroidal invasion (n = 7), ciliary body invasion (n = 4), optic nerve invasion (n = 6) and scleral invasion (n = 3). The median time from diagnosis to enucleation was 11 months. Co-existing retinal detachment and vitreous hemorrhage significantly increased the likelihood of optic nerve invasion (P = 0.014 and P = 0.011, respectively). Prolonged time to enucleation was significantly associated with the likelihood of choroidal (P = 0.010) and ciliary body (P = 0.021) invasion as well as invasion of multiple sites. CONCLUSION: In eyes with retinoblastoma enucleated after chemoreduction, co-existing ocular morbidities and time to enucleation are predictive of extra-retinal extension.