Upper Urinary Tract Transitional Cell Carcinoma and Lymph Node Involvement: Pre and Post Operative Outcomes

Background: Upper urinary tract transitional cell carcinomas (UUT-TCC) comprise any malignancy arising from the renal pelvis to distal ureter. These cancers account for approximately 5-10% of all urothelial tumors. Two-thirds of cases are invasive with an estimated 5-year survival rate less than 50%. Pathologic staging, invasion into local structures, and lymph node involvement influence the overall survival rate. Lymph node dissection (LND) is associated with higher overall survival rates in UUT-TCC patients, likely by decreasing regional lymph node metastasis. Current literature suggests that removing eight to ten regional lymph nodes may improve survival. The outcomes of upper urinary tract malignancies (UTM) have significantly improved, however, no standard guidelines exist regarding the role of LND in UUT-TCC. This analysis aims to investigate the impact of LND on outcomes in patients diagnosed with UUT-TCC. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) is a Health Insurance Portability and Accountability Act (HIPAA) compliant data file containing patient cases from 706 participating hospital institutions. A total of 14,186 patients who underwent nephrectomy and nephroureterectomy were initially evaluated. Inclusion criteria included a postoperative diagnosis of UTM (n=923). The cohort was subgrouped to patients with LND. The groups were defined for patients with lymph node positive (LNP) (n=48) and lymph node negative (LNN) (n=255) on pathological staging. Patients without lymph nodes evaluated or unknown status were excluded. The two groups were then compared. Pearson’s Chi-square test was performed for categorical variables, and t-test analysis for continuous variables. A univariate and multivariate analysis was performed with significant variables from the basic statistical analysis to predict independent factors. A Random forest model was also used. Statistical analysis was accepted at p\u3c0.05. Results: The overall rate of lymph node involvement was 5.2% for 923 patients that underwent nephroureterectomy for UTM. Among 303 patients with at least one lymph node evaluated, 48 (15.8%) were LNP. On Chi-square and t-test analysis, the LNN group had higher pT1 staging and planned laparoscopy. The LNP group had higher pT3, pT4, and pM1 staging, and had more planned open procedures compared to the LNN group. Postoperatively, there were no differences between the two groups including rate of lymphoceles or length of hospital stay (Table 1). On multivariate analysis, pT3 (p=0.001) and pT4 (p\u3c0.001) were associated with lymph node involvement. Additionally, the LNP group was less likely to be planned laparoscopic/robotic compared to the LNN group (p=0.03). The previously statistically significant difference in weight, pT1 staging, and pM1 staging were statistically insignificant on multivariable regression analysis. Conclusion: UUT-TCC with lymph node involvement is sparsely discussed in literature. Although rare, upper tract malignancy can present a challenge, partially due to the paucity of treatment guidelines. Our study shows that pT3 and pT4 are independently associated with lymph node involvement. No differences in postoperative outcomes were seen on multivariable analysis including number of nodes evaluated, lymphocele occurrences, or length of hospital stay. Our data suggests that for patients with suspected pT3 or pT4 UUT-TCC, nephroureterectomy should be performed in conjunction with LND

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Infection burden and immunological responses are equivalent for polymeric and metallic implant materials in vitro and in a murine model of fracture-related infection

The development of an infection is a major complication for some patients with implanted biomaterials. Whether the material or surface composition of the used biomaterial influences infection has not been directly compared for key biomaterials currently in use in human patients. We conducted a thorough in vitro and in vivo investigation using titanium (Ti) and polyether–ether–ketone (PEEK) as both commercially available and as modified equivalents (surface polished Ti, and oxygen plasma treated PEEK). Complement activation and cytokine secretion of cell of the immune system was assessed in vitro for all materials in the absence and presence of bacterial stimulants. In a follow‐up in vivo study, we monitored bacterial infection associated with clinically available and standard Ti and PEEK inoculated with Staphylococcus aureus. Complement activation was affected by material choice in the absence of bacterial stimulation, although the material based differences were largely lost upon bacterial stimulation. In the in vivo study, the bacterial burden, histological response and cytokine secretion suggests that there is no significant difference between both PEEK and Ti. In conclusion, the underlying material has a certain impact in the absence of bacterial stimulation, however, in the presence of bacterial stimulation, bacteria seem to dictate the responses in a manner that overshadows the influence of material surface properties. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2018

Infection burden and immunological responses are equivalent for polymeric and metallic implant materials in vitro and in a murine model of fracture-related infection

The development of an infection is a major complication for some patients with implanted biomaterials. Whether the material or surface composition of the used biomaterial influences infection has not been directly compared for key biomaterials currently in use in human patients. We conducted a thorough in vitro and in vivo investigation using titanium (Ti) and polyether-ether-ketone (PEEK) as both commercially available and as modified equivalents (surface polished Ti, and oxygen plasma treated PEEK). Complement activation and cytokine secretion of cell of the immune system was assessed in vitro for all materials in the absence and presence of bacterial stimulants. In a follow-up in vivo study, we monitored bacterial infection associated with clinically available and standard Ti and PEEK inoculated with Staphylococcus aureus. Complement activation was affected by material choice in the absence of bacterial stimulation, although the material based differences were largely lost upon bacterial stimulation. In the in vivo study, the bacterial burden, histological response and cytokine secretion suggests that there is no significant difference between both PEEK and Ti. In conclusion, the underlying material has a certain impact in the absence of bacterial stimulation, however, in the presence of bacterial stimulation, bacteria seem to dictate the responses in a manner that overshadows the influence of material surface properties

The Natural Furanone (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone Disrupts Quorum Sensing-regulated Gene Expression in Vibrio Harveyi by Decreasing the DNA-binding Activity of the Transcriptional Regulator Protein luxR

This study aimed at getting a deeper insight in the molecular mechanism by which the natural furanone (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone disrupts quorum sensing in Vibrio harveyi. Bioluminescence experiments with signal molecule receptor double mutants revealed that the furanone blocks all three channels of the V. harveyi quorum sensing system. In further experiments using mutants with mutations in the quorum sensing signal transduction pathway, the compound was found to block quorum sensing-regulated bioluminescence by interacting with a component located downstream of the Hfq protein. Furthermore, reverse transcriptase real-time polymerase chain reaction with specific primers showed that there was no effect of the furanone on luxRVh mRNA levels in wild-type V. harveyi cells. In contrast, mobility shift assays showed that in the presence of the furanone, significantly lower levels of the LuxRVh response regulator protein were able to bind to its target promoter sequences in wild-type V. harveyi. Finally, tests with purified LuxRVh protein also showed less shifts with furanone-treated LuxRVh, whereas the LuxRVh concentration was found not to be altered by the furanone (as determined by SDS-PAGE). Therefore, our data indicate that the furanone blocks quorum sensing in V. harveyi by rendering the quorum sensing master regulator protein LuxRVh unable to bind to the promoter sequences of quorum sensing-regulated genes