Protein remote homology detection and structural alignment using deep learning.

Exploiting sequence-structure-function relationships in biotechnology requires improved methods for aligning proteins that have low sequence similarity to previously annotated proteins. We develop two deep learning methods to address this gap, TM-Vec and DeepBLAST. TM-Vec allows searching for structure-structure similarities in large sequence databases. It is trained to accurately predict TM-scores as a metric of structural similarity directly from sequence pairs without the need for intermediate computation or solution of structures. Once structurally similar proteins have been identified, DeepBLAST can structurally align proteins using only sequence information by identifying structurally homologous regions between proteins. It outperforms traditional sequence alignment methods and performs similarly to structure-based alignment methods. We show the merits of TM-Vec and DeepBLAST on a variety of datasets, including better identification of remotely homologous proteins compared with state-of-the-art sequence alignment and structure prediction methods.

Self-organized intracellular twisters.

Life in complex systems, such as cities and organisms, comes to a standstill when global coordination of mass, energy, and information flows is disrupted. Global coordination is no less important in single cells, especially in large oocytes and newly formed embryos, which commonly use fast fluid flows for dynamic reorganization of their cytoplasm. Here, we combine theory, computing, and imaging to investigate such flows in the Drosophila oocyte, where streaming has been proposed to spontaneously arise from hydrodynamic interactions among cortically anchored microtubules loaded with cargo-carrying molecular motors. We use a fast, accurate, and scalable numerical approach to investigate fluid-structure interactions of 1000s of flexible fibers and demonstrate the robust emergence and evolution of cell-spanning vortices, or twisters. Dominated by a rigid body rotation and secondary toroidal components, these flows are likely involved in rapid mixing and transport of ooplasmic components.

Self-organized intracellular twisters.

Life in complex systems, such as cities and organisms, comes to a standstill when global coordination of mass, energy, and information flows is disrupted. Global coordination is no less important in single cells, especially in large oocytes and newly formed embryos, which commonly use fast fluid flows for dynamic reorganization of their cytoplasm. Here, we combine theory, computing, and imaging to investigate such flows in the Drosophila oocyte, where streaming has been proposed to spontaneously arise from hydrodynamic interactions among cortically anchored microtubules loaded with cargo-carrying molecular motors. We use a fast, accurate, and scalable numerical approach to investigate fluid-structure interactions of 1000s of flexible fibers and demonstrate the robust emergence and evolution of cell-spanning vortices, or twisters. Dominated by a rigid body rotation and secondary toroidal components, these flows are likely involved in rapid mixing and transport of ooplasmic components.

Toward the cellular-scale simulation of motor-driven cytoskeletal assemblies.

The cytoskeleton - a collection of polymeric filaments, molecular motors, and crosslinkers - is a foundational example of active matter, and in the cell assembles into organelles that guide basic biological functions. Simulation of cytoskeletal assemblies is an important tool for modeling cellular processes and understanding their surprising material properties. Here, we present aLENS (a Living Ensemble Simulator), a novel computational framework designed to surmount the limits of conventional simulation methods. We model molecular motors with crosslinking kinetics that adhere to a thermodynamic energy landscape, and integrate the system dynamics while efficiently and stably enforcing hard-body repulsion between filaments. Molecular potentials are entirely avoided in imposing steric constraints. Utilizing parallel computing, we simulate tens to hundreds of thousands of cytoskeletal filaments and crosslinking motors, recapitulating emergent phenomena such as bundle formation and buckling. This simulation framework can help elucidate how motor type, thermal fluctuations, internal stresses, and confinement determine the evolution of cytoskeletal active matter.

On the control of dispersion interactions between biological membranes and protein coated biointerfaces.

HYPOTHESIS: Interaction of cellular membranes with biointerfaces is of vital importance for a number of medical devices and implants. Adhesiveness of these surfaces and cells is often regulated by depositing a layer of bovine serum albumin (BSA) or other protein coatings. However, anomalously large separations between phospholipid membranes and the biointerfaces in various conditions and buffers have been observed, which could not be understood using available theoretical arguments. METHODS: Using the Lifshitz theory, we here evaluate the distance-dependent Hamaker coefficient describing the dispersion interaction between a biointerface and a membrane to understand the relative positioning of two surfaces. Our theoretical modeling is supported by experiments where the biointerface is represented by a glass substrate with deposited BSA and protein layers. These biointerfaces are allowed to interact with giant unilamellar vesicles decorated with polyethylene glycol (PEG) using PEG lipids to mimic cellular membranes and their pericellular coat. RESULTS: We demonstrate that careful treatment of the van der Waals interactions is critical for explaining the lack of adhesiveness of the membranes with protein-decorated biointerfaces. We show that BSA alone indeed passivates the glass, but depositing an additional protein layer on the surface BSA, or producing multiple layers of proteins and BSA results in repulsive dispersion forces responsible for 100 nm large equilibrium separations between the two surfaces.

Development of atrial fibrillation following trauma increases short term risk of cardiovascular events.

CONTEXT: New onset atrial fibrillation (AF) is associated with poor outcomes in several different patient populations. OBJECTIVES: To assess the effect of developing AF on cardiovascular events such as myocardial infarction (MI) and cerebrovascular accident (CVA) during the acute index hospitalization for trauma patients. METHODS: The Healthcare Cost and Utilization Project State Inpatient Databases for California and Florida were used to identify adult trauma patients (18 years of age or older) who were admitted between 2007 and 2010. After excluding patients with a history of AF and prior history of cardiovascular events, patients were evaluated for MI, CVA, and death during the index hospitalization. A secondary analysis was performed using matched propensity scoring based on age, race, and preexisting comorbidities. RESULTS: During the study period, 1,224,828 trauma patients were admitted. A total of 195,715 patients were excluded for a prior history of AF, MI, or CVA. Of the remaining patients, 15,424 (1.5%) met inclusion criteria and had new onset AF after trauma. There was an associated increase in incidence of MI (2.9 vs. 0.7%; p<0.001), CVA (2.6 vs. 0.4%; p<0.001), and inpatient mortality (8.5 vs. 2.1%; p<0.001) during the index hospitalization in patients who developed new onset AF compared with those who did not. Cox proportional hazards regression demonstrated an increased risk of MI (odds ratio [OR], 2.35 [2.13-2.60]), CVA (OR, 3.90 [3.49-4.35]), and inpatient mortality (OR, 2.83 [2.66-3.00]) for patients with new onset AF after controlling for all other potential risk factors. CONCLUSIONS: New onset AF in trauma patients was associated with increased incidence of myocardial infarction (MI), cerebral vascular accident (CVA), and mortality during index hospitalization in this study.

Association of Impaired Renal Function With Changes in Urinary Mineral Excretion and Stone Composition.

OBJECTIVE: To investigate the effect of kidney function on stone composition and urinary mineral excretion in patients undergoing surgical intervention for nephrolithiasis. METHODS: Using our institutional kidney stone database, we performed a retrospective review of stone patients who underwent surgical intervention between 2004 and 2015. Patients' demographic information, 24-hour urinary mineral excretion, and stone characteristics were reported. The patients' estimated glomerular filtration rates (eGFR) were compared with their stone compositions and 24-hour urine mineral excretions. RESULTS: A statistically significant difference was noted between the groups, with uric acid stones being associated with lower eGFR and calcium phosphate stones associated with higher eGFR. No relationship could be demonstrated between eGFR and calcium oxalate or struvite stones. Patients with lower eGFR also demonstrated a statistically significant association with lower urinary pH as well as lower urinary excretion of calcium and citrate. CONCLUSION: While various factors have been found to play significant roles in kidney stone formation and composition, our findings demonstrate a definite relationship between these and renal function. This paper highlights the fact that renal function evaluation should be considered an important component in the evaluation, counseling, and management of patients with nephrolithiasis.

Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling.

The essential functions required for mitotic spindle assembly and chromosome biorientation and segregation are not fully understood, despite extensive study. To illuminate the combinations of ingredients most important to align and segregate chromosomes and simultaneously assemble a bipolar spindle, we developed a computational model of fission-yeast mitosis. Robust chromosome biorientation requires progressive restriction of attachment geometry, destabilization of misaligned attachments, and attachment force dependence. Large spindle length fluctuations can occur when the kinetochore-microtubule attachment lifetime is long. The primary spindle force generators are kinesin-5 motors and crosslinkers in early mitosis, while interkinetochore stretch becomes important after biorientation. The same mechanisms that contribute to persistent biorientation lead to segregation of chromosomes to the poles after anaphase onset. This model therefore provides a framework to interrogate key requirements for robust chromosome biorientation, spindle length regulation, and force generation in the spindle.

Before a cell divides, it must make a copy of its genetic material and then promptly split in two. This process, called mitosis, is coordinated by many different molecular machines. The DNA is copied, then the duplicated chromosomes line up at the middle of the cell. Next, an apparatus called the mitotic spindle latches onto the chromosomes before pulling them apart. The mitotic spindle is a bundle of long, thin filaments called microtubules. It attaches to chromosomes at the kinetochore, the point where two copied chromosomes are cinched together in their middle. Proper cell division is vital for the healthy growth of all organisms, big and small, and yet some parts of the process remain poorly understood despite extensive study. Specifically, there is more to learn about how the mitotic spindle self-assembles, and how microtubules and kinetochores work together to correctly orient and segregate chromosomes into two sister cells. These nanoscale processes are happening a hundred times a minute, so computer simulations are a good way to test what we know. Edelmaier et al. developed a computer model to simulate cell division in fission yeast, a species of yeast often used to study fundamental processes in the cell. The model simulates how the mitotic spindle assembles, how its microtubules attach to the kinetochore and the force required to pull two sister chromosomes apart. Building the simulation involved modelling interactions between the mitotic spindle and kinetochore, their movement and forces applied. To test its accuracy, model simulations were compared to recordings of the mitotic spindle ­ including its length, structure and position ­ imaged from dividing yeast cells. Running the simulation, Edelmaier et al. found that several key effects are essential for the proper movement of chromosomes in mitosis. This includes holding chromosomes in the correct orientation as the mitotic spindle assembles and controlling the relative position of microtubules as they attach to the kinetochore. Misaligned attachments must also be readily deconstructed and corrected to prevent any errors. The simulations also showed that kinetochores must begin to exert more force (to separate the chromosomes) once the mitotic spindle is attached correctly. Altogether, these findings improve the current understanding of how the mitotic spindle and its counterparts control cell division. Errors in chromosome segregation are associated with birth defects and cancer in humans, and this new simulation could potentially now be used to help make predictions about how to correct mistakes in the process.

Major Adverse Cardiovascular Events Associated With Postoperative Atrial Fibrillation After Noncardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent occurrence after noncardiac surgery. It remains unclear whether POAF is associated with an increased risk of major adverse events. We aimed to elucidate the risk of stroke, myocardial infarction, and death associated with POAF following noncardiac surgery by a meta-analysis of randomized controlled studies and observational studies. METHODS: We searched electronic databases from inception up to August 1, 2019 for all studies that reported stroke or myocardial infarction in adult patients who developed POAF following noncardiac surgery. We used random-effects models to summarize the studies. RESULTS: The final analyses included 28 studies enrolling 2 612 816 patients. At 1-month (10 studies), POAF was associated with an ≈3-fold increase in the risk of stroke (weighted mean 2.1% versus 0.7%; odds ratio [OR], 2.82 [95% CI, 2.15-3.70]; P<0.001). POAF was associated with ≈4-fold increase in the long-term risk of stroke with (weighted mean, 2.0% versus 0.6%; OR, 4.12 [95% CI, 3.32-5.11]; P≤0.001) in 8 studies with ≥12-month follow-up. There was a significant overall increase in the risk of stroke and myocardial infarction associated with POAF (weighted mean, 2.5% versus 0.9%; OR, 3.44 [95% CI, 2.38-4.98]; P<0.001) and (weighted mean, 12.6% versus 2.7%; OR, 4.02 [95% CI, 3.08-5.24]; P<0.001), respectively. Furthermore, POAF was associated with a 3-fold increase in all-cause mortality at 30 days (weighted mean, 15.0% versus 5.4%; OR, 3.36 [95% CI, 2.13-5.31]; P<0.001). CONCLUSIONS: POAF was associated with markedly higher risk of stroke, myocardial infarction, and all-cause mortality following noncardiac surgery. Future studies are needed to evaluate the impact of optimal cardiovascular pharmacotherapies to prevent POAF and to decrease the risk of major adverse events in these high-risk patients.

Thirty-day hospital revisits after prostate brachytherapy: who is at risk?

BACKGROUND: Transperineal prostate brachytherapy is a common outpatient procedure for the treatment of prostate cancer. Whereas long-term morbidity and toxicities are widely published, rates of short-term complications leading to hospital revisits have not been well described. MATERIALS AND METHODS: Patients who underwent brachytherapy for prostate cancer in an ambulatory setting were identified in the Healthcare Cost and Utilization Project State Ambulatory Surgery Database for California between 2007 and 2011. Emergency department (ED) visits and inpatient admissions within 30 days of treatment were determined from the California Healthcare Cost and Utilization Project State Emergency Department Database and State Inpatient Database, respectively. RESULTS: Between 2007 and 2011, 9,042 patients underwent brachytherapy for prostate cancer. Within 30 days postoperatively, 543 (6.0%) patients experienced 674 hospital encounters. ED visits comprised most encounters (68.7%) at a median of 7 days (interquartile range 2-16) after surgery. Inpatient hospitalizations occurred on 155 of 674 visits (23.0%) at a median of 12 days (interquartile range 5-20). Common presenting diagnoses included urinary retention, malfunctioning catheter, hematuria, and urinary tract infection. Logistic regression demonstrated advanced age {65-75 years: odds ratio [OR], 1.3 [95% confidence interval (CI) 1.06-1.60, P = 0.01]; >75 years: OR 1.5 [95% CI 1.18-1.97, P = 0.001]}, inpatient admission within 90 days before surgery [OR 2.68 (95% CI 1.8-4.0, P < 0.001)], and ED visit within 180 days before surgery [OR 1.63 (95% CI 1.4-1.89, P < 0.001)] as factors that increased the risk of hospital-based evaluation after outpatient brachytherapy. Charlson comorbidity score did not influence risk. CONCLUSIONS: ED visits and inpatient admissions are not uncommon after prostate brachytherapy. Risk of revisit is higher in elderly patients and those who have had recent inpatient or ED encounters.

Statistical Mechanics of an Elastically Pinned Membrane: Equilibrium Dynamics and Power Spectrum.

In biological settings, membranes typically interact locally with other membranes: the extracellular matrix in the exterior or internal cellular structures such as the cytoskeleton, locally pinning the membrane. Characterizing the dynamical properties of such interactions presents a difficult task. Significant progress has been achieved through simulations and experiments, yet analytical progress in modeling pinned membranes has been impeded by the complexity of governing equations. Here, we circumvent these difficulties by calculating analytically the time-dependent Green's function of the operator governing the dynamics of an elastically pinned membrane in a hydrodynamic surrounding and subject to external forces. This enables us to calculate the equilibrium power spectral density for an overdamped membrane pinned by an elastic, permanently attached spring subject to thermal excitations. By considering the effects of the finite experimental resolution on the measured spectra, we show that the elasticity of the pinning can be extracted from the experimentally measured spectrum. Membrane fluctuations can thus be used as a tool to probe mechanical properties of the underlying structures. Such a tool may be particularly relevant in the context of cell mechanics, in which the elasticity of the membrane's attachment to the cytoskeleton could be measured.

Socioeconomic and patient-related factors for the management of male urethral stricture disease.

PURPOSE: We sought to determine the socioeconomic and patient factors that influence the utilization of urethroplasty and location of management in the treatment of male urethral stricture disease. METHODS: A retrospective review using the Healthcare Cost and Utilization Project State Inpatient and Ambulatory Surgery and Services Databases for California and Florida was performed. Adult men with a diagnosis of urethral stricture who underwent treatment with urethroplasty or endoscopic dilation/urethrotomy between 2007 and 2011 in California and 2009 and 2014 in Florida were identified by ICD-9 or CPT codes. Patients were categorized based on whether they had a urethroplasty or serial dilations/urethrotomies. Patients were assessed for age, insurance provider, median household income by zip code, Charlson Comorbidity Index, race, prior stricture management, and location of the index procedure. A multivariable logistic regression model was fit to assess factors influencing treatment modality (urethroplasty vs endoscopic management) and location (teaching hospital vs non-teaching hospital). RESULTS: Twenty seven thousand, five hundred and sixty-eight patients were identified that underwent treatment for USD. 25,864 (93.8%) treated via endoscopic approaches and 1704 (6.2%) treated with urethroplasty. Factors favoring utilization of urethroplasty include younger age, lower Charlson Comorbidity score, higher zip code median income quartile, private insurance, prior endoscopic treatment, and management at a teaching hospital. CONCLUSION: Socioeconomic predictors of urethroplasty utilization include higher income status and private insurance. Patient-specific factors influencing urethroplasty were younger age and fewer medical comorbidities. A primary driver of urethroplasty utilization was treatment at a teaching hospital. Older and Hispanic patients were less likely to seek care at these facilities.

Socioeconomic Disparities in the Acute Management of Stone Disease in the United States.

INTRODUCTION: Patients admitted to the hospital with an acute, noninfected episode of urolithiasis are candidates for medical expulsive therapy, ureteral stent placement, or upfront ureteroscopy (URS). We sought to assess socioeconomic factors influencing treatment decisions in managing urolithiasis and to determine differences in outcomes based on treatment modality. MATERIALS AND METHODS: The Healthcare Cost and Utilization Project State Inpatient Database, State Ambulatory Surgery and Services Database, and State Emergency Department Database for California from 2007 to 2011 and for Florida from 2009 to 2014 were utilized. Patients who were admitted to the hospital with a primary diagnosis of kidney or ureteral stone were identified. The initial treatment modality utilized was assessed and factors that influenced that decision were analyzed. Multivariate logistic regression model was fit to determine factors independently associated with upfront URS. Lastly, outcomes of noninfected patients who underwent stent alone vs URS were compared. RESULTS: We identified 146,199 patients who had an inpatient admission with urolithiasis. Overall, 45% of patients had no intervention at the time of their evaluation. Of the 55% of patients who underwent surgical intervention, 42% underwent stent alone, 44% underwent upfront URS, 1% had a PCN tube placement, 8% underwent extracorporeal shockwave lithotripsy, while 5% underwent PCNL. On multivariate logistic regression model, minorities, younger patients, publicly uninsured patients, more comorbid patients, those admitted on the weekends, and those admitted to an academic institution had significantly lower odds of undergoing upfront URS. Secondary analysis demonstrated clinical and economic advantages of upfront URS vs stent alone in eligible patients. CONCLUSION: Upfront URS is an overlooked procedure that has clinical and cost-saving implications. Unfortunately, minorities, publicly insured patients, and those admitted on the weekend are less likely to undergo upfront URS, a disparity that should be addressed by urologist.

The July Effect in Urological Surgery-Myth or Reality?

INTRODUCTION: The July effect is the widely held belief that medical care is compromised at the beginning of the academic year due to transitioning medical trainees. We determined its impact on surgical outcomes in urological surgery. METHODS: The Healthcare Cost and Utilization Project State Inpatient Database, State Ambulatory Surgery and Services Database and State Emergency Department Database for California were used for the years 2007 to 2011. Patients were identified who underwent surgery in July, August, April and May, and separated into early (July and August) and late (April and May) cohorts. Surgical outcomes for early vs late surgery were compared for academic centers. Adjusted multivariate models were fit to determine the effect of early surgery as a predictor of adverse outcomes. RESULTS: For major urological surgery July/August timing had no impact on length of stay, 30-day readmission, 30-day emergency room visits, never events, perioperative complications or mortality (all values p >0.05). Similarly, for stone, groin, bladder outlet and cystoscopic bladder procedures, July/August surgery had no impact on rates of urinary retention, emergency room visits within 30 days, clot evacuations within 30 days, perioperative complications or 30-day readmissions (all values p >0.05). At the end of the year cystectomies had increased odds of intraoperative complications (OR 0.63, 95% CI 0.4-0.97) while nephrectomies had higher odds of major complications (OR 0.69, 95% CI 0.53-0.89). CONCLUSIONS: Surgical outcomes are not compromised by having surgery at the beginning of the academic year, despite resident turnover, representing appropriate oversight during this potentially vulnerable time.

Role of Multiparametric Magnetic Resonance Imaging Prostate Specific Antigen Density and PI-RADS™ Score in Predicting Up Staging in Men on Active Surveillance.

INTRODUCTION: Using a combination of magnetic resonance imaging of the prostate and prostate specific antigen density, we determined which men on active surveillance are at risk for up staging and which men could avoid repeat biopsy while remaining on surveillance. METHODS: We reviewed the records of 110 men on active surveillance with Gleason 6 disease who underwent magnetic resonance imaging followed by UroNav fusion biopsy (Invivo, Gainesville, Florida). Using univariable and multivariable logistic regression analyses we examined the effect of age, race, prostate specific antigen, prostate specific antigen density, prostate volume, PI-RADS (Prostate Imaging Reporting and Data System) score, number and size of target lesions, and time on surveillance to determine the likelihood of up staging to Gleason 7 or greater disease. RESULTS: A total of 33 cases (30%) were up staged. On multivariable analysis prostate specific antigen density and PI-RADS score were significant predictors of up staging with adjusted odds ratios of 3.97 for prostate specific antigen density of 0.16 or more (CI 1.31-12.00, p <0.05), 13.8 for a PI-RADS 4 lesion (CI 2.3-81.3, p <0.01) and 25 for a PI-RADS 5 lesion (CI 3.8-163.5, p <0.01). When cross-tabulating these factors, men with a PI-RADS score of 3 or greater with a prostate specific antigen density of 0.16 ng/ml/cc or more had a 61.2% chance of up staging. Conversely, in men with PI-RADS score 3 or less and prostate specific antigen density less than 0.15, no up staging was seen. CONCLUSIONS: A combination of PI-RADS score and prostate specific antigen density predicts patients at risk for up staging at surveillance biopsy. Conversely, this combination may help determine which men may safely forgo biopsy.

Antepartum nephrolithiasis and the risk of preterm delivery.

Antepartum nephrolithiasis presents a complex clinical scenario which often requires an intervention such as ureteral stent or percutaneous nephrostomy tube (PCNT) placement, especially in the setting of urinary tract infection (UTI). We assess the risk of UTI and preterm labor in the setting of antepartum nephrolithiasis. A retrospective review of an administrative dataset for California and Florida was performed, which included pregnant women admitted for a delivery between 2008 and 2011. Antepartum nephrolithiasis admissions were identified, as were urological intervention (ureteral stent/ureteroscopy) or PCNT placement. Descriptive statistics were performed, as was multivariable logistic regression to identify predictors of UTI and preterm delivery. Of the 2,750,776 deliveries included in this dataset, 3904 (0.14%) were complicated by antepartum nephrolithiasis. 71.4% of these patients were managed conservatively, while 20.6% (n = 803) underwent urological intervention and 8.0% (n = 312) underwent PCNT placement. Preterm delivery rates increased from a baseline of 7.0% for patients without a stone to 9.1% for patients with stones managed conservatively, 11.2% for those undergoing a urologic intervention, and 19.6% for patients who had PCNT placement. On multivariable analysis, conservative management (adjusted odds ratio, aOR 1.3), urologic intervention (aOR 1.5), and PCNT (aOR 2.3) placement each independently increased the risk of preterm delivery (all p < 0.001). Antepartum nephrolithiasis is a condition that affects 1 in 714 women and has been correlated with increased risk of UTI and preterm labor. Intervention with ureteral stent or PCNT placement independently increase these risks, however, receipt of a nephrostomy tube confers the greatest risk of UTI and preterm delivery to the antepartum nephrolithiasis patient.

The LACE Score as a Tool to Identify Radical Cystectomy Patients at Increased Risk of 90-Day Readmission and Mortality.

INTRODUCTION: Radical cystectomy for bladder cancer is associated with high rates of readmission. We investigated the LACE score, a validated prediction tool for readmission and mortality, in the radical cystectomy population. MATERIALS & METHODS: Patients who underwent radical cystectomy for bladder cancer were identified by ICD-9 codes from the Healthcare Cost and Utilization Project State Inpatient Database for California years 2007-2010. The LACE score was calculated as previously described, with components of L: length of stay, A: acuity of admission, C: comorbidity, and E: number of emergency department visits within 6 months preceding surgery. RESULTS: Of 3,470 radical cystectomy patients, 638 (18.4%) experienced 90-day readmission, and 160 (4.6%) 90-day mortality. At a previously validated "high-risk" LACE score ≥ 10, patients experienced an increased risk of 90-day readmission (22.8 vs. 17.7%, p = 0.002) and mortality (9.1 vs. 3.5%, p < 0.001). On adjusted multivariable analysis, "high risk" patients by LACE score had increased 90-day odds of readmission (adjusted OR = 1.24, 95% CI: 0.99-1.54, p = 0.050) and mortality (adjusted OR = 2.09, 95% CI: 1.47-2.99, p < 0.001). CONCLUSION: The LACE score reasonably identifies patients at risk for 90-day mortality following radical cystectomy, but only poorly predicts readmission. Providers may use the LACE score to target high-risk patients for closer follow-up or intervention.

Metabolic Syndrome Increases Risk of Postoperative Myocardial Infarction Following Percutaneous Nephrolithotomy.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the gold standard treatment for upper tract stone burdens greater than 2 cm. Metabolic syndrome (MetS) is a constellation of conditions (diabetes mellitus, hypertension, dyslipidemia, and obesity) and is a risk factor for nephrolithiasis. Our objective was to investigate adverse cardiovascular outcomes of PCNL in patients with comorbid MetS diagnoses. MATERIALS AND METHODS: Data from the Healthcare Cost and Utilization Project State Inpatient Database for Florida and California were used to identify PCNL patients (ICD9: 55.03, 55.04) between 2007 and 2011. Patients were categorized having 0, 1-2, or 3-4 components of MetS. Postoperative myocardial infarction (MI) and inhospital mortality rate outcomes were identified. Multivariate logistic regression was used to control for patient characteristics (age, race, and primary insurance provider) and medical comorbidities. RESULTS: PCNL was performed on 39,868 patients, of whom 17,932 (45.0%) had no MetS conditions, 19,268 (48.3%) had 1-2 MetS conditions, and 2668 (6.7%) had 3-4 MetS conditions. With increasing MetS conditions, patients had increased incidence of postoperative MI (0: 0.6%; 1-2: 1.0%; 3-4: 1.8%, p < 0.001). On multivariate analysis, the presence of 3-4 MetS comorbidities increased the odds of a postoperative MI (1-2: odds ratio [OR] 1.2, 95% confidence interval [CI] 0.94-1.53, p = 0.147; 3-4: OR 2.2, 95% CI 1.54-3.15, p < 0.001). CONCLUSIONS: MetS patients have an increased risk of MI following PCNL given their pre-existing comorbidities. Routine preoperative cardiac testing may benefit this population before PCNL.

Adhesive Bowel Obstruction Following Urologic Surgery: Improved Outcomes with Early Intervention.

Objective: To describe the long-term incidence of adhesive bowel obstruction following major urologic surgery, and the effect of early surgery on perioperative outcomes. Methods: The Healthcare Cost and Utilization Project State Inpatient Databases for California and Florida (2006-2011) were used to identify major urologic oncologic surgery patients. Subsequent adhesive bowel obstruction admissions were identified and Kaplan-Meier time-to-event analysis was performed. Early surgery for bowel obstruction was defined as occurring on-or-before hospital-day four. The effects of early surgery on postoperative minor/moderate complications (wound infection, urinary tract infection, deep vein thrombosis, and pneumonia), major complications (myocardial infarction, pulmonary embolism, and sepsis), death, and postoperative length-of-stay were assessed. Results: Major urologic surgery was performed on 104,400 patients, with subsequent 5-year cumulative incidence of adhesive bowel obstruction admission of 12.4% following radical cystectomy, 3.3% following kidney surgery, and 0.9% following prostatectomy. During adhesive bowel obstruction admission, 71.6% of patients were managed conservatively and 28.4% surgically. Early surgery was performed in 65.4%, with decreased rates of minor/moderate complications (18 vs. 30%, p = 0.001), major complications (10 vs. 19%, p = 0.002), and median postoperative length of stay (8 vs. 11 days, p < 0.001) compared with delayed surgery. On multivariate analysis early surgery decreased the odds of minor/ moderate complications by 43% (p = 0.01), major complications by 45% (p = 0.03), and postoperative length of stay by 3.1 days (p = 0.01). Conclusion: Adhesive bowel obstruction is a significant long-term sequela of urologic surgery, for which early surgical management may be associated with improved perioperative outcomes.

Impact and treatment success of new-onset atrial fibrillation with rapid ventricular rate development in the surgical intensive care unit.

BACKGROUND: Atrial fibrillation (AF) with rapid ventricular rate (RVR; heart rate >100) in noncardiac postoperative surgical patients is associated with poor outcomes. The objective of this study was to evaluate the practice patterns of AF management in a surgical intensive care unit to determine practices associated with rate and rhythm control and additional outcomes. MATERIALS AND METHODS: Adult patients (≥18 y) admitted to the surgical intensive care unit (SICU) from June 2014 to June 2015 were retrospectively screened for the development of new-onset AF with RVR. Demographics, hospital course, evaluation and treatment of AF with RVR, and outcome were evaluated and analyzed. RESULTS: Thousand seventy patients were admitted to the SICU during the study period; 33 met inclusion criteria (3.1%). Twenty-six patients (79%) had rate and rhythm control within 48 h of AF with RVR onset. ß-Blockers were the most commonly used initial medication (67%) but were successful at rate and rhythm control in only 27% of patients (6/22). Amiodarone had the highest rate of success if used initially (5/6, 83%) and secondarily (11/13, 85%). Failure to control rate and rhythm was associated with a greater likelihood of comorbidities (100% versus 57%; P = 0.06). CONCLUSIONS: New-onset AF with RVR in the noncardiac postoperative patient is associated with a high mortality (21%). Amiodarone is the most effective treatment for rate and rhythm control. Failure to establish rate and rhythm control was associated with cardiac comorbidities. These results will help to form future algorithms for the treatment of AF with RVR in the SICU.