The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Inter-Alpha-Inhibitor Proteins Are Endogenous Furin Inhibitors and Provide Protection against Experimental Anthrax Intoxication

Inter-alpha-inhibitor protein (IαIp) functions as an endogenous serine protease inhibitor in human plasma, and IαIp levels diminish rapidly during acute inflammatory states. One potential target for IαIp is furin, a cell-associated serine endopeptidase essential for the activation of protective antigen and the formation of anthrax lethal toxin (LT). IαIp blocks furin activity in vitro and provides significant protection against cytotoxicity for murine peritoneal macrophages exposed to up to 500 ng/ml LT. A monoclonal antibody (MAb), 69.31, that specifically blocks the enzymatic activity of IαIp eliminates its protective effect against LT-induced cytotoxicity. IαIp (30 mg/kg of body weight) administered to BALB/c mice 1 hour prior to an intravenous LT challenge resulted in 71% survival after 7 days compared with no survivors among the control animals (P < 0.001). We conclude that human IαIp may be an effective preventative or therapeutic agent against anthrax intoxication

Receptor for advanced glycation end products (RAGE) protein expression in lung tissue from individual RAGE(lanes 1 to 3), RAGE(lanes 4 to 6), and RAGE(lanes 7 to 9) animals

<p><b>Copyright information:</b></p><p>Taken from "Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection"</p><p>http://ccforum.com/content/11/6/R122</p><p>Critical Care 2007;11(6):R122-R122.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2246216.</p><p></p> Actin was used to demonstrate equal loading

Delayed administration of the anti-RAGE antibody is protective in cecal ligation and puncture (CLP)

<p><b>Copyright information:</b></p><p>Taken from "Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection"</p><p>http://ccforum.com/content/11/6/R122</p><p>Critical Care 2007;11(6):R122-R122.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2246216.</p><p></p> The Kaplan-Meier survival analysis following CLP in BALB/c mice compares delayed anti-RAGE monoclonal antibody (mAb) treatment given at various time intervals after CLP with serum control. Each group had a significantly greater survival than the control group (< 0.01), except for the 36-hour delayed treatment group (= 0.12). RAGE, receptor for advanced glycation end products

Modulation of receptor for advanced glycation end products (RAGE) protects mice from the effects of cecal ligation and puncture (CLP)

<p><b>Copyright information:</b></p><p>Taken from "Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection"</p><p>http://ccforum.com/content/11/6/R122</p><p>Critical Care 2007;11(6):R122-R122.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2246216.</p><p></p> Kaplan-Meier survival analysis following CLP comparing wild-type RAGE129SvEvBrd mice (= 15), RAGEmice (= 15), RAGEmice (= 23), and anti-RAGE monoclonal antibody-treated (15 mg/kg intravenously 30 to 60 minutes before CLP) wild-type mice (= 15). < 0.001 for each group in comparison with the wild-type CLP control group. Sham surgery-treated wild-type 129SvEvBrd mice (= 5) were used as an additional control group. WT, wild-type

Lethality from cecal ligation and puncture (CLP) is decreased in BALB/c mice administered an anti-RAGE monoclonal antibody (mAb)

<p><b>Copyright information:</b></p><p>Taken from "Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection"</p><p>http://ccforum.com/content/11/6/R122</p><p>Critical Care 2007;11(6):R122-R122.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2246216.</p><p></p> The Kaplan-Meier survival analysis following CLP compares anti-RAGE mAb-treated animals given 7.5 mg/kg (= 15) or 15 mg/kg (= 15) intravenously 30 to 60 minutes before CLP with serum control animals (= 15). The group given 15 mg/kg had a significantly greater survival than the group given 7.5 mg/kg (< 0.05) or serum control (< 0.001). RAGE, receptor for advanced glycation end products

Inhibition or deletion of receptor for advanced glycation end products (RAGE) does not disrupt the host mechanism for clearance of

<p><b>Copyright information:</b></p><p>Taken from "Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection"</p><p>http://ccforum.com/content/11/6/R122</p><p>Critical Care 2007;11(6):R122-R122.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2246216.</p><p></p> Quantitative levels of in organ samples (liver and spleen, = 10 per group) 48 hours after an intraperitoneal injection of 10colony-forming units (CFU) per animal (< 0.001 anti-tumor necrosis factor [TNF] monoclonal antibody [mAb] group versus all other groups)