Preoperative urine culture with contaminants is not associated with increased risk for urinary tract infection after ureteroscopic stone treatment.

PURPOSE: We aimed to assess whether the presence of contaminants in the pre-operative urine culture (preop-UC) predicts postoperative urinary tract infection (postop-UTI) in patients undergoing elective ureteroscopy with laser lithotripsy. METHODS: A retrospective chart review was performed from 01/2019 to 12/2021 examining patients with unilateral stone burden ≤ 2 cm who underwent ureteroscopy with laser lithotripsy and had a preop-UC within 3 months. Positive, negative, contaminated, and polymicrobial definitions for UCs were established in accordance with current guidelines. Patients with positive and polymicrobial cultures were excluded. Postop-UTI was defined as the presence of urinary symptoms and a positive UC within 30 days of the procedure. Multivariable logistic regression models were utilized to evaluate risk factors for contamination in the preop-UC and the risk of postop-UTI. RESULTS: A total of 201 patients met the inclusion-exclusion criteria. Preop-UC was negative in 153 patients and contaminated in 48 patients. Significant contaminant-related factors included female gender and increased BMI. Postop-UTI was diagnosed in 3.2% of patients with negative preop-UCs and 4.2% of patients with contaminants, with no difference between groups (p = 0.67). The regression model determined that the presence of contaminants in preop-UC failed to predict postop-UTI (OR 0.69, p = 0.64). CONCLUSION: The presence of contaminants in preop-UCs is not associated with an increased risk of postop-UTIs after ureteroscopy. Our study supports that contaminants in the preop-UC can be interpreted as a negative UC in terms of postop-UTI risk stratification. Preoperative antibiotics should not be prescribed for patients undergoing uncomplicated ureteroscopy for stone surgery in the setting of a contaminated preop-UC.

Impact of Renal Access Angle and Speed of Nephroscope Retrieval Movements on the Vortex Effect.

OBJECTIVE: To analyze the influence of different renal access angles (AAs) and nephroscope retrieval speeds on the efficacy of the vortex effect (VE) in mini-percutaneous nephrolithotomy (mini-PCNL). This study aimed to understand the poorly understood physical components of the VE. MATERIALS AND METHODS: A Pexiglas™ (KUS®) model was built based on the dimensions of a 15/16 F mini-PCNL set (Karl Storz). The flow rate was continuous via an automatic pump and calibrated to achieve hydrodynamic equivalence to the real equipment. One experiment consisted of manually retrieving all 30 stone phantoms (3 mm diameter) utilizing only the VE. Cumulative time to retrieve all stones was measured. An accelerometer recorded instant speeds of the nephroscope every 0.08 seconds (s), and 3 experiments were performed at each angle (0°, 45°, and 90°). A logistic regression model was built utilizing maximum speeds and access angles to predict the effectiveness of the VE. RESULTS: Mean cumulative time for complete stone retrieval was 28.1 seconds at 0° vs 116.5 seconds at 45° vs 101.4 seconds at 90° (P < .01). We noted significantly higher speeds at 0° compared to 45° and 90° (P < .01); however, differences in average and maximum speed between 45° and 90° were not statistically significant (P = .21 and P = .25, respectively). The regression model demonstrated a negative association between increasing maximum speed and VE's effectiveness (OR 0.547, CI 95% 0.350-0.855, P < .01). When controlling for maximum speed, the 0° angle had significantly higher chances of achieving at least a partially effective VE. CONCLUSION: Increasing the renal access angle or nephroscope extraction speed negatively impacts the effectiveness of the VE. This significantly increased procedure time in the laboratory model, suggesting that the VE is less effective at higher sheath angles.

Successful Management of Angioinvasive Deep Fungal Infections of the Penis: A Multidisciplinary Approach with Intraoperative Frozen Margins.

BACKGROUND Mucormycosis, a cause of opportunistic infections in immunocompromised patients, is rarely identified in the penis. The literature often describes drastic surgical interventions or rapid patient demise, with scant mention of surgical management specifics. The objective of this report is to detail our experience with this unique infection and highlight the utility of intraoperative frozen margins during surgical management. CASE REPORT Herein, we describe successful treatment of a 55-year-old man with biopsy-proven B-cell acute lymphoblastic leukemia (B-ALL) undergoing Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) therapy who initially presented with an asymptomatic violaceous lesion of the penis. Differential diagnoses ranged from infectious, vasculogenic, and pharmacologic in nature. Ultimately, a punch biopsy tissue culture confirmed angioinvasive fungal infection with Rhizopus and Fusarium species. Initial debridement combined with intravenous antifungal therapy was unsuccessful. However, partial penectomy with use of intraoperative frozen margins, a 5-week course of antifungal therapy, and continued B-ALL treatment allowed effective and lasting resolution of the infection, with partial penile preservation. CONCLUSIONS This case supports a multidisciplinary approach as the primary treatment for penile angioinvasive fungal infections. This includes treatment of the underlying immunocompromising condition, appropriate intravenous antifungal therapy, and urgent operative debridement. This report highlights the importance of utilizing intraoperative frozen sections to ensure negative margins and to optimize overall tissue sparing in this anatomically sensitive area.

The Vortex Effect in Minimally Invasive Percutaneous Nephrolithotomy.

OBJECTIVE: To describe the physical principles of the vortex effect to better understand its applicability in minimally invasive percutaneous nephrolithotomy (MIP) procedures. METHODS: Two acrylic phantom models were built based on the cross-sectional area (CSA) ratio of a MIP nephroscope and access sheaths (15/16F and 21/22F MIP-M, Karl Storz). The nephroscope phantom was 10 mm in diameter. The access sheaths had diameters of 14 mm (CSA ratio: 0.69) and 20 mm (CSA ratio: 0.30). The models were adapted to generate hydrolysis, and hydrogen bubbles enhanced flow visualization on a green laser background. After calibration, the experimental flow rate was set to 12.0 mL/s. Three 30-second trials assessing the flow were performed with each model. Computational fluid dynamic simulations were completed to determine the speed and pressure profiles. RESULTS: In both models, as the incoming fluid from the nephroscope phantom attempted to move toward the collecting system, a stagnation point was demonstrated. No fluid entered the collecting system phantom. Utilizing the 14 mm sheath, we observed a random generation of several vortices and a pressure gradient (PG) of 114.4 N/m2 between the nephroscope's tip and stagnation point. In contrast, examining the 20 mm sheath revealed a significantly smaller PG (19.4 N/m2) and no noticeable vortices were noted. CONCLUSION: The speed of the fluid and equipment geometry regulate the PG and the vortices field, which are responsible for the production of the vortex effect. Considering the same flow rate, a higher ratio between the CSA of the nephroscope and access sheath results in improved efficacy of the vortex effect.

Caution! AI Bot Has Entered the Patient Chat: ChatGPT Has Limitations in Providing Accurate Urologic Healthcare Advice.

OBJECTIVE: To conduct the first study examining the accuracy of ChatGPT, an artificial intelligence (AI) chatbot, derived patient counseling responses based on clinical care guidelines in urology using a validated questionnaire. METHODS: We asked ChatGPT a set of 13 urological guideline-based questions three times. Answers were evaluated for appropriateness and using Brief DISCERN (BD), a validated healthcare information assessment questionnaire. Data analysis included descriptive statistics and Student's t test (SAS Studio). RESULTS: 60% (115/195) of ChatGPT responses were deemed appropriate. Variability existed between responses to the same prompt, with 25% of the 13 question sets having discordant appropriateness designations. The average BD score was 16.8 ± 3.59. Only 7 (54%) of 13 topics and 21 (54%) of 39 responses met the BD cut-off score of ≥16 to denote good-quality content. Appropriateness was associated with higher overall and Relevance domain scores (both P < .01). The lowest BD domain scores were for Source categories, since ChatGPT does not provide references by default. With prompting, 92.3% had ≥1 incorrect, misinterpreted, or nonfunctional citations. CONCLUSION: While ChatGPT provides appropriate responses to urological questions more than half of the time, it misinterprets clinical care guidelines, dismisses important contextual information, conceals its sources, and provides inappropriate references. Chatbot models hold great promise, but users should be cautious when interpreting healthcare-related advice from existing AI models. Additional training and modifications are needed before these AI models will be ready for reliable use by patients and providers.

Optimizing stone harvesting in miniaturized-PCNL: a critical examination of renal access angles, technology, and the role they play in operative efficiency.

PURPOSE: Stone retrieval can be a laborious aspect of percutaneous nephrolithotomy (PCNL). A unique phenomenon of mini-PCNL is the vortex-effect (VE), a hydrodynamic form of stone retrieval. Additionally, the vacuum-assisted sheath (VAS) was recently developed as a new tool for stone extraction. The purpose of our study is to investigate the impact of renal access angle (as a surrogate for patient positioning) on stone retrieval efficiency and compare the efficiency among methods of stone retrieval. METHODS: A kidney model was filled with 3 mm artificial stones. Access to the mid-calyx was obtained using a 15Fr sheath. Stones were retrieved over three minutes at angles of 0°, 25°, and 75° utilizing the VE, VAS, and basket. Stones were weighed for comparison of stones/retraction and stones/minute. Trials were repeated three times at each angle. RESULTS: Renal access angle of 0° was associated with increased stone retrieval for both the VE and VAS (p < 0.05). The VE was the most effective method for stones retrieved per individual retraction at an angle of 0° (p < 0.005), although when analyzed as stones retrieved per minute, the VE and VAS were no longer statistically different (p = 0.08). At 75°, none of the methods were statistically different, regardless if analyzed as stones per retraction or per minute (p = 0.20-0.40). CONCLUSIONS: Renal access angle of 0° is more efficient for stone retrieval than a steep upward angle. There is no difference in stone retrieval efficiency between the VE and VAS methods, although both are superior to the basket at lower sheath angles.

On the rocks: can urologists identify stone composition based on endoscopic images alone? A worldwide survey of urologists.

PURPOSE: As part of the management of nephrolithiasis, determination of chemical composition of stones is important. Our objective in this study is to assess urologists' accuracy in making visual, intraoperative determinations of stone composition. MATERIALS AND METHODS: We conducted a REDCap survey asking urologists to predict stone composition based on intraoperative images of 10 different pure-composition kidney stones of 7 different types: calcium oxalate monohydrate (COM), calcium oxalate dihydrate (COD), calcium phosphate (CP) apatite, CP brushite, uric acid (UA), struvite (ST) and cystine (CY). To evaluate experience, we examined specific endourologic training, years of experience, and number of ureteroscopy (URS) cases/week. A self-assessment of ability to identify stone composition was also required. RESULTS: With a response rate of 26% (366 completed surveys out of 1,370 deliveries), the overall accuracy of our cohort was 44%. COM, ST, and COD obtained the most successful identification rates (65.9%, 55.7%, and 52.0%, respectively). The most frequent misidentified stones were CP apatite (10.7%) and CY (14.2%). Predictors of increased overall accuracy included self-perceived ability to determine composition and number of ureteroscopies per week, while years of experience did not show a positive correlation. CONCLUSIONS: Although endoscopic stone recognition can be an important tool for surgeons, it is not reliable enough to be utilized as a single method for stone identification, suggesting that urologists need to refine their ability to successfully recognize specific stone compositions intraoperatively.

Breakage Costs in Flexible Ureteroscopy: Digital vs. Fiberoptic Modalities.

OBJECTIVE: To compare the maintenance costs of digital flexible ureteroscopes (DFU) versus fiberoptic flexible ureteroscopes (FFU) to understand the long-term financial impact associated with breakage in a flexible ureteroscopy (f-URS) program. METHODS: Data for breakage of FFU and DFU at an academic institution from 2019 to 2021 were obtained from our vendor (Karl Storz) and analyzed by month. Correlation test was used to evaluate significant differences in number of procedures, number of breakage events, breakage rates, and repair cost per month. Cumulative analyses were utilized to examine the number of procedures before failure (time to failure - TTF) and repair costs per procedure (RCpP). RESULTS: We performed a total of 2,154 f-URS, including 1,355 with FFU and 799 with DFU (P<.001). Although we found a higher number of breakage events in FFU (n=124) than DFU (n=73) (P<.001), the overall breakage rate was similar, 9.9% vs. 8.8%, respectively (P=0.86). On cumulative analysis, both modalities reached the same TTF plateau (11 cases) after 18 months. After 400 cases, the RCpP for DFU was 1.25 times higher than for FFU (P=0.04). CONCLUSION: Overall, we found no difference in overall scope breakage rates between DFU and FFU. Although there was no difference in TTF over time, at the beginning DFU displayed considerable higher durability, leading to lower RCpP. Furthermore, DFU's endurance leveled off to FFU over time, resulting in higher RCpP after 400 cases. This finding may be explained by the presence of renewed scopes after repair.

Image Distortion During Flexible Ureteroscopy: A Laboratory Model Comparing Super Pulsed Thulium Fiber Laser vs High-Power Ho:YAG Laser.

Purpose: Digital ureteroscopes employ "chip-on-the-tip" technology that allows for significant improvement in image resolution. However, image distortion often occurs during laser lithotripsy owing to acoustic wave production. We sought to compare image distortion using different laser power settings and distances from the laser fiber tip to the scope for the Super Pulsed Thulium Fiber (SPTF) laser and high-power Holmium:YAG (Ho:YAG) laser. Materials and Methods: Ureteroscopy was simulated using a silicon kidney-ureter-bladder model fitted with a 12F/14F access sheath and the Lithovue™ (Boston Scientific), disposable digital flexible ureteroscope. At defined laser parameters (10, 20, 30 and 40 W, short pulse), a 200-µm laser fiber was slowly retracted toward the tip of the ureteroscope during laser activation. Image distortion was identified, and distance from the laser tip to the scope tip was determined. Data from the two lasers were compared utilizing t-tests. Results: After controlling for frequency, power, and laser mode, utilizing 1.0 J of energy was significantly associated with less feedback than 0.5 J (-0.091 mm, p ≤ 0.05). Increased power was associated with larger feedback distance (0.016 mm, p ≤ 0.05); however, increase in frequency did not have a significant effect (-0.001 mm, p = 0.39). The SPFT laser had significantly less feedback when compared with all Holmium laser modes. Conclusions: Increased total power results in image distortion occurring at greater distances from the tip of the ureteroscope during laser activation. Image distortion occurs further from the ureteroscope with Ho:YAG laser than with SPTF fibers at the same laser settings. In clinical practice, the tip of the laser fiber should be kept further away from the tip of the scope during ureteroscopy as the power increases as well as when utilizing the Ho:YAG system compared with the SPTF laser platform. The SPTF laser may have a better safety profile in terms of potential scope damage.

When virtual becomes reality: short term impressions of a two-week virtual urology sub-internship program.

INTRODUCTION: The COVID-19 pandemic disrupted medical student education and posed a unique challenge for educators, especially for surgical clerkships. In response to COVID-19 rotation restrictions, we implemented a virtual urologic surgery sub-internship program and evaluated medical student impressions of the experience. MATERIALS AND METHODS: A two-week urology curriculum was created with content delivered by interactive videoconferencing. The curriculum included synchronous and individual learning with live patient clinical experiences in the outpatient clinic and operating room, lectures, departmental conferences, a suture lab, self-reflective writing exercises, and an oral presentation. Student impressions were assessed with an exit survey. Descriptive statistics were utilized to evaluate the 5-point Likert scale responses. RESULTS: A total of 40 students applied, and 18 were selected for 1 of 5 two-week rotation blocks. All students successfully passed the rotation. Of the 18 students who participated, 16 (88.9%) completed the exit survey. The overall experience was rated as "strongly positive" by 14 of 16 (87.5%) students. The learning experience was rated as 4.75 (0.45) (average (SD)). The rotation positively impacted our virtual students' plan to apply to this residency program (mean 4.81 (0.54)). All students reported they would recommend this rotation to a fellow student, and feedback regarding the self-reflection activities was positive. CONCLUSIONS: We successfully implemented a two-week virtual urology sub-internship rotation with a wide variety of clinical and educational experiences. The rotation was well received by our medical students. This is a unique experience in urology that can easily be implemented by other surgical sub-specialty programs in the future.

Exceeding the maximum recommended dose of onabotulinumtoxinA in urologic patients.

INTRODUCTION: Although onabotulinumtoxinA (BTX) is commonly utilized by multiple specialists, it is unclear how often or reasons why patients receive more than the recommended maximum dose. The goal of this study was to determine if excess BTX use occurs in urologic practice. MATERIALS AND METHODS: This retrospective cohort identified patients who underwent intravesical BTX between 01/2013-12/2017 at an academic hospital. All BTX administrations for any indication were identified. Excess BTX was defined as receiving greater than the current recommended maximum dosage of 400 units within 3 months. RESULTS: A total of 361 patient received intravesical BTX. These patients underwent 755 procedures using BTX, 673(89.1%) intravesical and 82(10.9%) non-urologic. Other site injections occurred in 14 patients, and 7 (50.0%) of these patients had at least one instance of excess. In these 7 patients, there were a total of 15 instances of excess use from either a single injection (3 instances) or a subsequent injection within 3 months (12 instances). No excess use occurred in patients who received only intravesical BTX. Discordance was noted between the administered dose, pharmacy dispensing information (46.9%), and nursing medication administration record (MAR) (54.3%). All dosages matched in only 39.2% procedures. CONCLUSIONS: Although excess BTX use is overall infrequent in urologic practice, it is common in our patients prescribed the drug by non-urologic providers (50%). Pharmacy dispensing and nursing MAR information are unreliable in determining the actual administered dose. This highlights the need for providers to further discuss BTX use with patients and the need for improved tracking of BTX administration and communication across specialties.

Utilization of MOSES Modulated Pulse Mode Results in Improved Efficiency in Holmium:YAG Laser Ablation of the Prostate.

OBJECTIVE: To determine if MOSES technology improves efficiency and short-term outcomes in holmium laser ablation of the prostate (HoLAP). METHODS: A retrospective review of patients who underwent HoLAP between August 2016 and November 2019 was conducted. All procedures before and after the implementation of MOSES technology at our institution were evaluated. Preoperative patient characteristics and intraoperative data were collected. Postoperative International Prostate Symptom Score, quality of life, and postvoid residual measurements at 6 weeks and 3 months postoperatively were analyzed. RESULTS: This cohort included 65 males who underwent HoLAP, 32 without and 33 with MOSES. Patients in the MOSES group were slightly older, but no other differences in baseline characteristics were observed between the two groups. Ablation time was similar at 49.6 ± 26.1 minutes without and 40.7 ± 41.2 minutes with MOSES (P = .38). However, HoLAP with MOSES had significantly higher ablation efficiency (0.59 ± 0.24 g/min without vs 0.86 0.5 g/min with MOSES, P = .01). On multivariable regression modeling, HoLAP without MOSES added 12 minutes to operating time (estimate 12.3, standard error 3.44, P < .01) after controlling for prostate size and laser energy usage. Duration of catheterization, urinary incontinence and need for reoperation within 3 months were similar. There were no differences between groups in International Prostate Symptom Score, quality of life, or postvoid residual at 3 months postoperatively. CONCLUSION: Utilization of MOSES technology resulted in improved efficiency in HoLAP, translating into time savings in the operating room. Postoperative outcomes out to 3 months were similar among patients who underwent the procedure utilizing either laser pulse mode. Further studies are needed to investigate long-term outcomes as the use of MOSES is likely to become more commonly utilized.

Periureteral Marginal Zone Lymphoma Resulting in Hydronephrosis and Flank Pain in the Absence of Disseminated Disease: Case Report of Two Patients Presenting with Rare But Important Differential.

Background: Extrinsic compression of the ureter can result from multiple different malignancies, typically in the presence of known or disseminated disease. Rarely, hydroureteronephrosis and flank pain can occur as the presenting sign and symptom of lymphoma. In this study, we present two cases of primary ureteral obstruction in patients without a prior diagnosis of lymphoma and without bulky retroperitoneal lymphadenopathy. Case Presentation: Case #1 was a healthy 58-year-old man who presented with acute left flank pain. He was found to have left hydroureteronephrosis secondary to a proximal periureteral mass. Diagnostic ureteroscopy demonstrated this to be an extrinsic compression on the ureter and preoperative imaging was negative aside from one enlarged periaortic node. Laparoscopic ureterolysis and biopsy were remarkable for periureteral dystrophic tissue concerning for lymphoma. Case #2 was a 47-year-old woman with a solitary kidney secondary to prior left nephrectomy who presented with hydronephrosis of her solitary kidney and acute kidney injury. Retrograde pyelogram showed high-grade obstruction at the junction of the mid- and distal ureter. Periureteral thickening was noted, but no definitive masses were seen on cross-sectional imaging. Robotic ureterolysis showed dense fibrosis around the ureter. Pathology report from Cases #1 and #2 were both remarkable for marginal zone lymphoma and both patients received bendamustine and rixuximab with resolution of ureteral obstruction and their lymphoma. Conclusion: Ureteral compression as the primary presentation of periureteral lymphoma is a rare but important etiology of extrinsic malignant ureteral obstruction. These cases emphasize that malignant obstruction can occur even in the absence of disseminated disease.

Perception, knowledge, and interest of urologic surgery: a medical student survey.

BACKGROUND: Although only a limited number of medical schools require a formal educational rotation in urologic surgery, urology as a medical specialty continues to attract a large number of students into the match each year. The purpose of this study was to describe medical student awareness, perception, and knowledge of urology, to determine factors influencing students' consideration of urology as a career, and to determine if prior urology clerkship experience is associated with differences in these variables. METHODS: In this cross-sectional study, medical students were electronically surveyed in 07/2016. Self-reported and question-based knowledge of urology were determined. A total of 25 factors were assessed with a five-point Likert scale to determine their influence on students' consideration of urology as a career. Data analysis was performed using R. RESULTS: The survey was completed by 114 students (13.5% of all medical students). A total of 11(9.65%)students had previously participated in a urology clerkship. All students reported awareness of urology; however, only 74 students (64.9%) correctly identified the training pathway and job duties of urologists. Self-perceived knowledge of urology was poor but improved with increased medical school training. Question-based assessment also demonstrated increased knowledge with advanced medical school training (27% per year; p < 0.01). Prior urology clerkship experience appeared to be associated with increased urologic knowledge; however, this was confounded by year in medical school training. When assessing factors impacting students' consideration of a career in urology, 'combination of medicine and surgery' was the most positively influential and 'competitiveness of the specialty' was the most negatively influential. CONCLUSIONS: Although medical students are aware of urology as a specialty, they perceive their knowledge of urology as poor. However, knowledge of urology increases throughout medical school training. Multiple factors influence students' consideration of urology as a career choice. Additional studies are needed to further explore how participation in a formal urology experience alters students' perceptions and influences their consideration of urology as a career choice. TRIAL REGISTRATION: Retrospectively registered.

Three-Hour Bundle Compliance and Outcomes in Patients With Undiagnosed Severe Sepsis.

BACKGROUND: The aim of this study was to compare completion of the Surviving Sepsis Campaign 3-hour treatment recommendations and patient-centered outcomes between patients with severe sepsis who received a sepsis-specific diagnosis code with those who did not. METHODS: This was a retrospective cohort analysis of adult patients admitted through an academic medical center ED who received an antibiotic and met criteria for severe sepsis. We measured and compared the Surviving Sepsis Campaign 3-hour treatment recommendations along with patient-centered outcomes in patients who were diagnosed with severe sepsis and those who were not. RESULTS: A total of 5,631 patients were identified (60.6 ± 17.2 years of age; 48.9% women). Less than half (32.8%) received an International Classification of Diseases, ninth revision, diagnosis code of 995.92. Completion of all four bundle components in < 3 hours was low for all patients (8.72%). Therapeutic components (a broad-spectrum antibiotic and IV fluids) were completed more often (31.3%). Those with a diagnosis code received all four bundle components (10.2% vs 7.9%; P < .005), as well as therapeutic components at a higher frequency (36.0% vs 29.0%; P < .001). Patients with a diagnosis code had higher mortality (6.3% vs 2.3%), more frequent ICU admissions (44.7% vs 22.5%), and longer hospitalizations (9.2 ± 6.9 days vs 6.9 ± 6.7 days) than did patients with severe sepsis with no diagnosis code (all P < .001). CONCLUSIONS: Severe sepsis continues to be an underdiagnosed and undertreated condition. Patients who were diagnosed had higher treatment rates yet experienced worse outcomes. Continued investigation is needed to identify factors contributing to diagnosis, treatment, and outcomes in patients with severe sepsis.

Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients.

OBJECTIVES: To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock. DESIGN: Retrospective cohort. SETTING: Six hundred fifty-six bed urban academic medical center. PATIENTS: Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded. INTERVENTIONS: Not available. MEASUREMENTS AND MAIN RESULTS: We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96-6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60-4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01-1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11-1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02-1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06-1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05-1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03-1.07). CONCLUSIONS: This study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.

WITHDRAWN: Impact of Initial Antibiotic Selection on Adverse Outcomes Among Patients With Severe Sepsis and Septic Shock.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Crit Care Med, 43 (2015) 263, http://dx.doi.org/10.1097/01.ccm.0000474875.35054.b3. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Dormant Intestinal Stem Cells Are Regulated by PTEN and Nutritional Status.

The cellular and molecular mechanisms underlying adaptive changes to physiological stress within the intestinal epithelium remain poorly understood. Here, we show that PTEN, a negative regulator of the PI3K→AKT→mTORC1-signaling pathway, is an important regulator of dormant intestinal stem cells (d-ISCs). Acute nutrient deprivation leads to transient PTEN phosphorylation within d-ISCs and a corresponding increase in their number. This release of PTEN inhibition renders d-ISCs functionally poised to contribute to the regenerative response during re-feeding via cell-autonomous activation of the PI3K→AKT→mTORC1 pathway. Consistent with its role in mediating cell survival, PTEN is required for d-ISC maintenance at baseline, and intestines lacking PTEN have diminished regenerative capacity after irradiation. Our results highlight a PTEN-dependent mechanism for d-ISC maintenance and further demonstrate the role of d-ISCs in the intestinal response to stress.