MRI-Targeted, Systematic, and Combined Biopsy for Prostate Cancer Diagnosis.

BACKGROUND: The use of 12-core systematic prostate biopsy is associated with diagnostic inaccuracy that contributes to both overdiagnosis and underdiagnosis of prostate cancer. Biopsies performed with magnetic resonance imaging (MRI) targeting may reduce the misclassification of prostate cancer in men with MRI-visible lesions. METHODS: Men with MRI-visible prostate lesions underwent both MRI-targeted and systematic biopsy. The primary outcome was cancer detection according to grade group (i.e., a clustering of Gleason grades). Grade group 1 refers to clinically insignificant disease; grade group 2 or higher, cancer with favorable intermediate risk or worse; and grade group 3 or higher, cancer with unfavorable intermediate risk or worse. Among the men who underwent subsequent radical prostatectomy, upgrading and downgrading of grade group from biopsy to whole-mount histopathological analysis of surgical specimens were recorded. Secondary outcomes were the detection of cancers of grade group 2 or higher and grade group 3 or higher, cancer detection stratified by previous biopsy status, and grade reclassification between biopsy and radical prostatectomy. RESULTS: A total of 2103 men underwent both biopsy methods; cancer was diagnosed in 1312 (62.4%) by a combination of the two methods (combined biopsy), and 404 (19.2%) underwent radical prostatectomy. Cancer detection rates on MRI-targeted biopsy were significantly lower than on systematic biopsy for grade group 1 cancers and significantly higher for grade groups 3 through 5 (P<0.01 for all comparisons). Combined biopsy led to cancer diagnoses in 208 more men (9.9%) than with either method alone and to upgrading to a higher grade group in 458 men (21.8%). However, if only MRI-target biopsies had been performed, 8.8% of clinically significant cancers (grade group ≥3) would have been misclassified. Among the 404 men who underwent subsequent radical prostatectomy, combined biopsy was associated with the fewest upgrades to grade group 3 or higher on histopathological analysis of surgical specimens (3.5%), as compared with MRI-targeted biopsy (8.7%) and systematic biopsy (16.8%). CONCLUSIONS: Among patients with MRI-visible lesions, combined biopsy led to more detection of all prostate cancers. However, MRI-targeted biopsy alone underestimated the histologic grade of some tumors. After radical prostatectomy, upgrades to grade group 3 or higher on histopathological analysis were substantially lower after combined biopsy. (Funded by the National Institutes of Health and others; Trio Study ClinicalTrials.gov number, NCT00102544.).

Utilizing head-mounted eye trackers to analyze patterns and decision-making strategies of 3D virtual modelling platform (IRIS™) during preoperative planning for renal cancer surgeries.

PURPOSE: IRIS™ provides interactive, 3D anatomical visualizations of renal anatomy for pre-operative planning that can be manipulated by altering transparency, rotating, zooming, panning, and overlaying the CT scan. Our objective was to analyze how eye tracking metrics and utilization patterns differ between preoperative surgical planning of renal masses using IRIS and CT scans. METHODS: Seven surgeons randomly reviewed IRIS and CT images of 9 patients with renal masses [5 high complexity (RENAL score ≥ 8), 4 low complexity (≤ 7)]. Surgeons answered a series of questions regarding patient anatomy, perceived difficulty (/100), confidence (/100), and surgical plan. Eye tracking metrics (mean pupil diameter, number of fixations, and gaze duration) were collected. RESULTS: Surgeons spent significantly less time interpreting data from IRIS than CT scans (- 67.1 s, p < 0.01) and had higher inter-rater agreement of surgical approach after viewing IRIS (α = 0.16-0.34). After viewing IRIS, surgical plans although not statistically significant demonstrated a greater tendency towards a more selective ischemia approaches which positively correlated with improved identification of vascular anatomy. Planned surgical approach changed in 22/59 of the cases. Compared to viewing the CT scan, left and right mean pupil diameter and number/duration of fixations were significantly lower when using IRIS (p < 0.01, p < 0.01, p = 0.42, p < 0.01, respectively), indicating interpreting information from IRIS required less mental effort despite under-utilizing its interactive features. CONCLUSIONS: Surgeons extrapolated more detailed information in less time with less mental effort using IRIS than CT scans and proposed surgical approaches with potential to enhanced surgical outcomes.

Correction: Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population.

[This corrects the article DOI: 10.1371/journal.pgen.1007329.].

A synthetic-diploid benchmark for accurate variant-calling evaluation.

Existing benchmark datasets for use in evaluating variant-calling accuracy are constructed from a consensus of known short-variant callers, and they are thus biased toward easy regions that are accessible by these algorithms. We derived a new benchmark dataset from the de novo PacBio assemblies of two fully homozygous human cell lines, which provides a relatively more accurate and less biased estimate of small-variant-calling error rates in a realistic context.

Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population.

As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10-100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel contributing alleles, show evidence of association to CD. Independently, we find that genomewide common variant risk defined by GWAS shows a strong difference between AJ and non-AJ European control population samples (0.97 s.d. higher, p<10-16). Taken together, the results suggest coordinated selection in AJ population for higher CD risk alleles in general. The results and approach illustrate the value of exome sequencing data in case-control studies along with reference data sets like ExAC (sites VCF available via FTP at ftp.broadinstitute.org/pub/ExAC_release/release0.3/) to pinpoint genetic variation that contributes to variable disease predisposition across populations.

Internal validation and decision curve analysis of a preoperative nomogram predicting a postoperative complication in pheochromocytoma surgery: An international study.

OBJECTIVES: To develop a preoperative nomogram that would predict the risk of a postoperative complication for pheochromocytoma patients undergoing adrenalectomy using an international database. METHODS: We retrospectively analyzed preoperative variables and postoperative outcomes in patients who underwent adrenalectomy for pheochromocytoma in three institutions from 2000 to 2017. Internal validation of a generated nomogram was carried out with receiver operating characteristics, calibration plots, and decision curve analyses. RESULTS: A total of 153 patients who had undergone 166 adrenalectomies were included in the study. Overall, post-adrenalectomy complications were seen in 30% of patients, whereas 9.6% of patients sustained a Clavien ≥3a complication. Independent predictors of a complication were a history of hypertension, body mass index, tumor size, and Charlson Comorbidity Index score. On internal validation, the multivariable model generated a nomogram that predicted a postoperative complication or clinically hemodynamic event with an area under the curve of 0.86, showed good calibration and had an overall net benefit. CONCLUSIONS: An internally validated nomogram combining body mass index, Charlson Comorbidity Index score and tumor size can predict the probability of a post-adrenalectomy complication in those with and without hypertension. The model, the first of its kind in pheochromocytoma surgery, identifies patients at risk of a postoperative complication at the time of their presentation with pheochromocytoma.

A Grading System for the Assessment of Risk of Extraprostatic Extension of Prostate Cancer at Multiparametric MRI.

Purpose To evaluate MRI features associated with pathologically defined extraprostatic extension (EPE) of prostate cancer and to propose an MRI grading system for pathologic EPE. Materials and Methods In this prospective study, consecutive male study participants underwent preoperative 3.0-T MRI from June 2007 to March 2017 followed by robotic-assisted laparoscopic radical prostatectomy. An MRI-based EPE grading system was defined as follows: curvilinear contact length of 1.5 cm or capsular bulge and irregularity were grade 1, both features were grade 2, and frank capsular breach were grade 3. Multivariable logistic regression and decision curve analyses were performed to compare the MRI grade model and clinical parameters (prostate-specific antigen, Gleason score) for pathologic EPE prediction by using the area under the receiver operating characteristic curve (AUC) value. Results Among 553 study participants, the mean age was 60 years ± 8 (standard deviation); the median prostate-specific antigen value was 6.3 ng/mL. A total of 125 of 553 (22%) participants had pathologic EPE at radical prostatectomy. Detection of pathologic EPE, defined as number of pathologic EPEs divided by number of participants with individual MRI features, was as follows: curvilinear contact length, 88 of 208 (42%); capsular bulge and irregularity, 78 of 175 (45%); and EPE visible at MRI, 37 of 56 (66%). For MRI, grades 1, 2, and 3 for detection of pathologic EPE were 18 of 74 (24%), 39 of 102 (38%), and 37 of 56 (66%), respectively. Clinical features plus the MRI-based EPE grading system (prostate-specific antigen, International Society of Urological Pathology stage, MRI grade) predicted pathologic EPE better than did MRI grade alone (AUC, 0.81 vs 0.77, respectively; P < .001). Conclusion Higher MRI-based extraprostatic extension (EPE) grading categories were associated with a greater risk of pathologic EPE. Clinical features plus MRI grading had the highest diagnostic performance for prediction of pathologic EPE. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Eberhardt in this issue.

When to Biopsy the Seminal Vesicles: A Validated Multiparametric Magnetic Resonance Imaging and Target Driven Model to Detect Seminal Vesicle Invasion of Prostate Cancer.

PURPOSE: Current imaging and biopsy practices offer limited insight into preoperative detection of seminal vesicle invasion despite the implications for treatment decisions and patient prognoses. We identified magnetic resonance imaging features to assess the risk of seminal vesicle invasion and inform the inclusion of seminal vesicle sampling during biopsy. MATERIALS AND METHODS: Patients underwent multiparametric magnetic resonance imaging and fusion targeted biopsy with or without seminal vesicle biopsy. Magnetic resonance imaging suspicion of seminal vesicle invasion, multiparametric magnetic resonance imaging of prostate base lesions of moderate or greater suspicion, extraprostatic extension, anatomical zone and biopsy data were used to generate multivariable logistic regression models. One model without and one with biopsy data were externally validated in a multi-institutional cohort. Decision curve analyses were done to determine net benefit of the 2 models. RESULTS: The training and validation cohorts comprised 564 and 250 patients, respectively. In the training cohort 55 patients (9.8%) had pathologically confirmed seminal vesicle invasion. In the prebiopsy model magnetic resonance imaging suspicion of seminal vesicle invasion (OR 9.5, 95% CI 4.0-22.4, p <0.001), multiparametric magnetic resonance imaging base lesions of moderate or greater suspicion with extraprostatic extension (OR 13.6, 95% CI 4.0-46.5, p <0.001), and a transition and/or central zone location (OR 11.6, 95% CI 3.5-38.3, p <0.001) showed strong correlations. In the post-biopsy model the risk of pathologically confirmed seminal vesicle invasion increased with the base Gleason Group (Gleason Group 5 OR 85.3, 95% CI 11.8-619.1, p <0.001). In the validation cohort the AUC of the prebiopsy and post-biopsy models was 0.84 and 0.93, respectively (p = 0.030). CONCLUSIONS: Magnetic resonance imaging evidence of seminal vesicle invasion or extraprostatic extension at the prostate base transition and/or central zone and high grade prostate cancer from the prostate base are significant features associated with an increased risk of pathologically confirmed seminal vesicle invasion. Our models successfully incorporated these features to predict seminal vesicle invasion and inform when to biopsy the seminal vesicles.

Predicting Gleason Group Progression for Men on Prostate Cancer Active Surveillance: Role of a Negative Confirmatory Magnetic Resonance Imaging-Ultrasound Fusion Biopsy.

PURPOSE: Active surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging. MATERIALS AND METHODS: All patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time. RESULTS: Of the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01). CONCLUSIONS: A negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.

Use of multiparametric magnetic resonance imaging and fusion-guided biopsies to properly select and follow African-American men on active surveillance.

OBJECTIVES: To determine the rate of Gleason Grade Group (GGG) upgrading in African-American (AA) men with a prior diagnosis of low-grade prostate cancer (GGG 1 or GGG 2) on 12-core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non-AA) population. PATIENTS AND METHODS: A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan-Meier curves were generated for AA men and non-AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log-rank test. RESULTS: AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non-AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non-AA men then continued AS, with a median (interquartile range) follow-up of 39.19 (24.24-56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80). CONCLUSIONS: AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non-AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

INTRODUCTION: Multiparametric magnetic resonance imaging (mpMRI) has improved clinicians' ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx. METHODS: A literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed "PCa mimics," that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement. RESULTS: Despite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from "PCa mimics" or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy. CONCLUSIONS: A better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Comparison of Elastic and Rigid Registration during Magnetic Resonance Imaging/Ultrasound Fusion-Guided Prostate Biopsy: A Multi-Operator Phantom Study.

PURPOSE: The relative value of rigid or elastic registration during magnetic resonance imaging/ultrasound fusion guided prostate biopsy has been poorly studied. We compared registration errors (the distance between a region of interest and fiducial markers) between rigid and elastic registration during fusion guided prostate biopsy using a prostate phantom model. MATERIALS AND METHODS: Four gold fiducial markers visible on magnetic resonance imaging and ultrasound were placed throughout 1 phantom prostate model. The phantom underwent magnetic resonance imaging and the fiducial markers were labeled as regions of interest. An experienced user and a novice user of fusion guided prostate biopsy targeted regions of interest and then the corresponding fiducial markers on ultrasound after rigid and then elastic registration. Registration errors were compared. RESULTS: A total of 224 registration error measurements were recorded. Overall elastic registration did not provide significantly improved registration error over rigid registration (mean ± SD 4.87 ± 3.50 vs 4.11 ± 2.09 mm, p = 0.05). However, lesions near the edge of the phantom showed increased registration errors when using elastic registration (5.70 ± 3.43 vs 3.23 ± 1.68 mm, p = 0.03). Compared to the novice user the experienced user reported decreased registration error with rigid registration (3.25 ± 1.49 vs 4.98 ± 2.10 mm, p <0.01) and elastic registration (3.94 ± 2.61 vs 6.07 ± 4.16 mm, p <0.01). CONCLUSIONS: We found no difference in registration errors between rigid and elastic registration overall but rigid registration decreased the registration error of targets near the prostate edge. Additionally, operator experience reduced registration errors regardless of the registration method. Therefore, elastic registration algorithms cannot serve as a replacement for attention to detail during the registration process and anatomical landmarks indicating accurate registration when beginning the procedure and before targeting each region of interest.

Added Value of Multiparametric Magnetic Resonance Imaging to Clinical Nomograms for Predicting Adverse Pathology in Prostate Cancer.

PURPOSE: We examined the additional value of preoperative prostate multiparametric magnetic resonance imaging and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy when performed in combination with clinical nomograms to predict adverse pathology at radical prostatectomy. MATERIALS AND METHODS: We identified all patients who underwent 3 Tesla multiparametric magnetic resonance imaging prior to fusion biopsy and radical prostatectomy. The Partin and the MSKCC (Memorial Sloan Kettering Cancer Center) preradical prostatectomy nomograms were applied to estimate the probability of organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement using transrectal ultrasound guided systematic biopsy and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy Gleason scores. With radical prostatectomy pathology as the gold standard we developed multivariable logistic regression models based on these nomograms before and after adding multiparametric magnetic resonance imaging to assess any additional predictive ability. RESULTS: A total of 532 patients were included in study. When multiparametric magnetic resonance imaging findings were added to the systematic biopsy based MSKCC nomogram, the AUC increased by 0.10 for organ confined disease (p <0.001), 0.10 for extraprostatic extension (p = 0.003), 0.09 for seminal vesicle invasion (p = 0.011) and 0.06 for lymph node involvement (p = 0.120). Using Gleason scores derived from targeted biopsy compared to systematic biopsy provided an additional predictive value of organ confined disease (Δ AUC 0.07, p = 0.003) and extraprostatic extension (Δ AUC 0.07, p = 0.048) at radical prostatectomy with the MSKCC nomogram. Similar results were obtained using the Partin nomogram. CONCLUSIONS: Magnetic resonance imaging alone or in addition to standard clinical nomograms provides significant additional predictive ability of adverse pathology at the time of radical prostatectomy. This information can be greatly beneficial to urologists for preoperative planning and for counseling patients regarding the risks of future therapy.

Targeted biopsy: benefits and limitations.

PURPOSE OF REVIEW: To review the current literature regarding the role of multiparametric MRI and fusion-guided biopsies in urologic practice. RECENT FINDINGS: Fusion biopsies consistently show an increase in the detection of clinically significant cancers and decrease in low-risk disease that may be more suitable for active surveillance. Although, when to incorporate multiparametric MRI into workup is not clearly agreed upon, studies have shown a clear benefit in both biopsy naïve and those with prior negative biopsies in determining the appropriate treatment strategy. More recently, cost-analysis models have been published that show that upfront MRIs are more cost-effective when considering missed cancers and treatment courses. SUMMARY: With improved accuracy over systematic biopsies, fusion biopsies are a superior method for detection of the true grade of cancer for both biopsy naïve and patients with prior negative biopsies, choosing appropriate candidates for active surveillance, and monitoring progression on active surveillance.

Pyramidal cell-selective GluN1 knockout causes impairments in salience attribution and related EEG activity.

Schizophrenia is a disabling psychiatric disease characterized by symptoms including hallucinations, delusions, social withdrawal, loss of pleasure, and inappropriate affect. Although schizophrenia is marked by dysfunction in dopaminergic and glutamatergic signaling, it is not presently clear how these dysfunctions give rise to symptoms. The aberrant salience hypothesis of schizophrenia argues that abnormal attribution of motivational salience to stimuli is one of the main contributors to both positive and negative symptoms of schizophrenia. The proposed mechanisms for this hypothesis are overactive striatal dopaminergic and hypoactive glutamatergic signaling. The current study assessed salience attribution in mice (n = 72) using an oddball paradigm in which an infrequent stimulus either co-occurred with shock (conditioned group) or was presented alone (non-conditioned group). Behavioral response (freezing) and electroencephalogram (whole brain and amygdala) were used to assess salience attribution. Mice with pyramidal cell-selective knockout of ionotropic glutamate receptors (GluN1) were used to reproduce a prominent physiological change involved in schizophrenia. Non-conditioned knockout mice froze significantly more in response to the unpaired stimulus than non-conditioned wild-type mice, suggesting that this irrelevant cue acquired motivational salience for the knockouts. In accordance with this finding, low-frequency event-related spectral perturbation was significantly increased in non-conditioned knockout mice relative to both conditioned knockout and non-conditioned wild-type mice. These results suggest that pyramidal cell-selective GluN1 knockout leads to inappropriate attribution of salience for irrelevant stimuli as characterized by abnormalities in both behavior and brain circuitry functions.

Sepsis after elective ureteroscopy.

INTRODUCTION: We sought to determine our rate of postoperative sepsis after ureteroscopy as well as identifying associative factors, common antibiotic practices along with culture data. MATERIALS AND METHODS: Records of all patients who underwent elective ureteroscopy from 2010 to 2015 at an urban tertiary care facility were retrospectively reviewed. Factors thought to be associated with infection were collected, along with comorbidities depicted as Charlson Age-Adjusted Comorbidity Index (CAACI) and American Society of Anesthesia (ASA) score. Each patient's course was reviewed to determine if they were treated for postoperative sepsis as defined by standardized criteria. RESULTS: A total of 345 patients underwent elective ureteroscopy with 15 (4.3%) being treated for sepsis postoperatively. This resulted in an additional 5.33 ± 3.84 days of hospitalization per patient. The sepsis group grew three gram positive organisms and five multi-drug resistant (MDR) gram negatives while 7/15 (46.7%) had negative cultures. The most common preoperative antibiotics used in the sepsis group were cefazolin (60.0%), gentamicin (48.5%) and ciprofloxacin (20.0%). Univariate analysis showed prior endoscopic procedures, recent treatment for urinary tract infections (UTI), multiple comorbidities and longer operative times associated with sepsis. However, significant variables after multivariate analysis were treatment for UTI within the last month, (OR) 7.19 (2.25-22.99), p = 0.001. CONCLUSIONS: Patients with multiple comorbidities, prior endoscopic procedures, longer operative times and especially those recently treated for a urinary infection should be carefully monitored after ureteroscopy for signs of sepsis. Perioperative antibiotics in these patients should be selected to cover both MDR organisms and gram positives.

A simple and accurate craniofacial midsagittal plane definition.

INTRODUCTION: In this article, we aimed to establish an ideal definition for the craniofacial midsagittal plane (MSP) by first finding an optimal "plane of best fit" and then deriving a simple approximation for clinical use that is highly accurate. METHODS: For 60 adolescent patients, 3-dimensional coordinates of 8 central landmarks and 6 pairs of lateral landmarks were collected. Across all patients, the coplanarity of the central landmarks was compared with that of the midpoints of the lateral landmarks. The MSP of best fit was then found by minimizing the mean square distance of the 8 central landmarks to a plane. Across all patients, each possible 3-point plane was compared with the MSP of best fit with respect to both orientation and proximity. RESULTS: The central landmarks were more coplanar and thus more accurate than the midpoints of the lateral pairs. The plane defined by nasion, basion, and incisive foramen was the closest to the MSP of best fit in both orientation and proximity. CONCLUSIONS: The nasion-basion-incisive foramen plane should be used for skull orientation and 3-dimensional cephalometric analyses because it approximates the MSP of best fit with high accuracy, avoids the use of horizontal reference planes, avoids influence from upper and midface asymmetry, uses easily identifiable relevant landmarks, and is simple to define.

Factors Influencing Readmission after Elective Ureteroscopy.

PURPOSE: Ureteroscopy is increasingly used to manage nephrolithiasis, upper urinary tract urothelial carcinoma and other urological conditions. In this study we determine the rate of readmission and emergency department visits after ureteroscopy in an underserved population, as well as factors associated with these unplanned visits. MATERIALS AND METHODS: A retrospective chart review from 2010 to 2014 of all elective ureteroscopies was conducted at a single tertiary hospital serving an underserved population in a major metropolis. Demographic, operative and discharge characteristics were collected and analyzed. RESULTS: A total of 276 ureteroscopies were performed with 15.6% presenting to the emergency department within 30 days. Overall 5.8% were readmitted. Readmitted patients were more likely to have hypertension (OR 3.64, p=0.02), asthma or chronic obstructive pulmonary disease (OR 5.54, p=0.001), 2 or more comorbidities (OR 3.65, p=0.12), or a complication associated with ureteroscopy (OR 7.27, p=0.007). The patients who sought care in the emergency department after ureteroscopy were less likely to have had a ureteral stent in place before ureteroscopy (OR 0.35, p=0.017) or an endoscopic urological procedure within the last 30 days (OR 0.35, p=0.045). About two-thirds of patients who presented to the emergency department complained of pain alone, while the most common complaints for readmitted patients were fever and pain (43.8%). CONCLUSIONS: The majority of emergency department visits after ureteroscopy were due to pain. These patients were less likely to have a preoperative ureteral stent placed or a history of recent urological procedures. Readmission rates were associated with overall comorbidities and complications.