Patient Frailty and Discharge Disposition Following Radical Cystectomy.

BACKGROUND: Patients with bladder cancer who are treated with cystectomy are at high risk for complications and prolonged length of stay. This population tends to be of advanced age with underlying comorbidities, and thus more likely to have decreased physiologic reserve (ie, frailty). Our objective was to evaluate the relationship between frailty and discharge disposition for patients with bladder cancer treated with cystectomy. MATERIALS AND METHODS: Using data from the National Surgical Quality Improvement Program, we identified patients with bladder cancer undergoing cystectomy (2011-2014). Our exposure of interest was frailty, based on the 11-point modified Frailty Index (mFI). Patients were deemed robust (mFI = 0), pre-frail (mFI = 0.09-0.18), or frail (mFI ≥ 0.27). Our outcome of interest was discharge disposition defined as home, skilled nursing facility, and rehabilitation dichotomized as home versus non-home for multivariable logistic regression analysis. We then generated predicted probabilities of non-home discharge based on frailty and in-hospital complications. RESULTS: Among 4330 patients treated with radical cystectomy, 32.8% were robust, 65.1% were pre-frail, and 2.2% were frail. Overall, 86.2% were discharged home, 4.4% to a rehabilitation facility, and 9.4% to a skilled nursing facility. Frail patients were more likely to be discharged to non-home care (vs. robust, odds ratio, 2.33; 95% confidence interval, 1.34-4.03), which was independent of whether they experienced a major complication prior to discharge. CONCLUSION: Frailty is a significant predictor of non-home discharge following radical cystectomy. This finding was independent of inpatient complications. These data will assist providers in setting patient expectations and have important implications for allocating postoperative resources.

Iatrogenic urinary tract injuries: etiology, diagnosis, and management.

Iatrogenic injury to the urinary tract, including the kidneys, ureters, bladder, and urethra, is a potential complication of surgical procedures performed in or around the retroperitoneal abdominal space or pelvis. While both diagnostic and interventional radiologists often play a central and decisive role in the identification and initial management of a variety of iatrogenic injuries, discussions of these injuries are often directed toward specialists such as urologists, obstetricians, gynecologists, and general surgeons whose procedures are most often implicated in iatrogenic urinary tract injuries. Interventional radiologic procedures can also be a source of an iatrogenic urinary tract injury. This review describes the clinical presentation, risk factors, imaging findings, and management of iatrogenic renal vascular and urinary tract injuries, as well as the radiologist's role in the diagnosis, treatment, and cause of these injuries.

Fibroblast Growth Factor 19 Activates the Unfolded Protein Response and Mitogen-Activated Protein Kinase Phosphorylation in H-69 Cholangiocyte Cells.

BACKGROUND: Cholangiocytes are injured in many biliary tract diseases that result in cirrhosis, cholangiocarcinoma and need for liver transplantation. Recent studies demonstrate that the hormone Fibroblast Growth Factor 19 (FGF19) is produced in the ileum and regulates hepatic gene expression via the enterohepatic circulation. However, the role of FGF19 on cholangiocytes remains largely unknown. The purpose of this study was to elucidate the effect of FGF19 on cholangiocyte gene and protein expression. METHODS: Cultured human cholangiocyte-derived H69 cells were treated with FGF19 (0-50ng/ml) and expression of genes and proteins involved in the Unfolded Protein Response (UPR) and mitogen-activated protein kinase (MAPK) pathways were studied using RT-PCR and Western blot analysis. RESULTS: FGF19-induced gene and protein expression of the UPR genes BiP and CHOP increased in a dose-responsive pattern. The UPR protein P-eIF2a displayed a bimodal pattern of protein expression, with 10ng/ml of FGF19 maximally reducing and 50ng/ml maximally increasing expression. MAPK pathway protein expression (P-JNK, P-ERK, P-38) displayed a similar bimodal pattern of expression with 2.5ng/ml of FGF19 decreasing expression and 25ng/ml of FGF19 increasing expression. CONCLUSIONS: FGF19 treatment of H69 cells selectively activates BiP and CHOP in a dose-dependent manner. FGF19 also regulates P-eIF2a and MAPK protein expression with a bimodal response. We speculate that FGF19 has an important role in the pathogenesis of many human cholangiopathies and cholestatic liver disorders.

Admission rates and costs associated with emergency presentation of urolithiasis: analysis of the Nationwide Emergency Department Sample 2006-2009.

BACKGROUND AND PURPOSE: We sought to examine a large nationwide (United States) sample of emergency department (ED) visits to determine data related to utilization and costs of care for urolithiasis in this setting. METHODS: Nationwide Emergency Department Sample was analyzed from 2006 to 2009. All patients presenting to the ED with a diagnosis of upper tract urolithiasis were analyzed. Admission rates and total cost were compared by region, hospital type, and payer type. Numbers are weighted estimates that are designed to approximate the total national rate. RESULTS: An average of 1.2 million patients per year were identified with the diagnosis of urolithiasis out of 120 million visits to the ED annually. Overall average rate of admission was 19.21%. Admission rates were highest in the Northeast (24.88%), among teaching hospitals (22.27%), and among Medicare patients (42.04%). The lowest admission rates were noted for self-pay patients (9.76%) and nonmetropolitan hospitals (13.49%). The smallest increases in costs over time were noted in the Northeast. Total costs were least in nonmetropolitan hospitals; however, more patients were transferred to other hospitals. When assessing hospital ownership status, private for-profit hospitals had similar admission rates compared with private not-for-profit hospitals (16.6% vs 15.9%); however, costs were 64% and 48% higher for ED and inpatient admission costs, respectively. CONCLUSIONS: Presentation of urolithiasis to the ED is common, and is associated with significant costs to the medical system, which are increasing over time. Costs and rates of admission differ by region, payer type, and hospital type, which may allow us to identify the causes for cost discrepancies and areas to improve efficiency of care delivery.

Testosterone supplementation does not worsen lower urinary tract symptoms.

PURPOSE: Testosterone replacement therapy is commonly used to treat men with hypogonadism. However, there has been caution in using testosterone replacement therapy in men with moderate to severe lower urinary tract symptoms for fear of worsening the symptoms. In this study we examine the effect of testosterone replacement therapy on lower urinary tract symptoms in hypogonadal men. MATERIALS AND METHODS: We retrospectively reviewed our outpatient database and identified patients with a diagnosis of hypogonadism who received testosterone replacement therapy from 2002 to 2012. Lower urinary tract symptoms were assessed using the AUASI (American Urological Association symptom index) before and after testosterone replacement therapy. Testosterone and prostate specific antigen were also continuously measured, and all patients were closely monitored for side effects of testosterone replacement therapy. Patients who had progression of lower urinary tract symptoms to the point of requiring surgery were included in the study. RESULTS: We identified 120 hypogonadal men who received testosterone replacement therapy, the majority of whom had topical therapy or a combination of topical and pellet based therapy (57.5% and 20.8%, respectively). Mean baseline AUASI (±SD) was 10.8 (±7.8) and mean duration of testosterone replacement therapy was 692 days (±773). Mean change in AUASI was -1.07 (±6.06). Mean baseline prostate specific antigen was 1.6 ng/dl (±1.9) and mean change in prostate specific antigen was 0.44 (±2.2). Of the patients 8.1% had a baseline prostate specific antigen greater than 4.0 ng/dl, and these patients had greater improvement in AUASI than those with a baseline prostate specific antigen less than 4.0 ng/dl (-1.9 vs -1.0, p not significant). Overall 45.8% of patients had a less than 3-point change in AUASI in either direction. Of the 120 patients 38 (31.7%) had improvement in AUASI 3 or more points while 27 (22.5%) had worsening of AUASI 3 or more points. Patients with an improved AUASI had a mean prostate specific antigen change of 0.3 (±3.4), while those who had worsening of AUASI had a mean prostate specific antigen change of 0.7 (±2.2) (p not significant). Approximately 9 of 120 (7.5%) of these men initiated new medications for lower urinary tract symptoms during the course of the study. There was no significant change in AUASI compared to patients without any use of lower urinary tract symptoms medications. In addition, 4 (3.3%) patients had progression of lower urinary tract symptoms and required transurethral resection of the prostate. CONCLUSIONS: We demonstrate that initiating testosterone replacement therapy in hypogonadal men involves a low risk of worsening lower urinary tract symptoms. In fact, many men experience symptom improvement while changes in prostate specific antigen appear minor. Future research should focus on larger patient population studies to further examine this relationship.

Role of FimW, FimY, and FimZ in regulating the expression of type i fimbriae in Salmonella enterica serovar Typhimurium.

Type I fimbriae in Salmonella enterica serovar Typhimurium are surface appendages that facilitate binding to eukaryotic cells. Expression of the fim gene cluster is known to be regulated by three proteins--FimW, FimY, and FimZ--and a tRNA encoded by fimU. In this work, we investigated how these proteins and tRNA coordinately regulate fim gene expression. Our results indicate that FimY and FimZ independently activate the P(fimA) promoter which controls the expression of the fim structural genes. FimY and FimZ were also found to strongly activate each other's expression and weakly activate their own expression. FimW was found to negatively regulate fim gene expression by repressing transcription from the P(fimY) promoter, independent of FimY or FimZ. Moreover, FimW and FimY interact within a negative feedback loop, as FimY was found to activate the P(fimW) promoter. In the case of fimU, the expression of this gene was not found to be regulated by FimW, FimY, or FimZ. We also explored the effect of fim gene expression on Salmonella pathogenicity island 1 (SPI1). Our results indicate that FimZ alone is able to enhance the expression of hilE, a known repressor of SPI1 gene expression. Based on our results, we were able to propose an integrated model for the fim gene circuit. As this model involves a combination of positive and negative feedback, we hypothesized that the response of this circuit may be bistable and thus a possible mechanism for phase variation. However, we found that the response was continuous and not bistable.