Carbonic anhydrase IX expression predicts outcome of interleukin 2 therapy for renal cancer.

PURPOSE: Renal cancer response to interleukin 2 (IL-2) therapy and patient survival has been correlated with tumor histology and carbonic anhydrase IX (CAIX) expression. In an effort to confirm and expand these observations, we examined CAIX expression in pathology specimens from renal cancer patients who had previously received IL-2 therapy. EXPERIMENTAL DESIGN: Paraffin-embedded tissue sections of renal cancer were immunostained with the MN-75 monoclonal antibody to CAIX and expression levels were correlated with histologic findings and clinical outcome. RESULTS: Tissue specimens were obtained from 66 patients; 27 of whom (41%) had responded to IL-2-based therapy. Fifty-eight specimens were assessed as clear cell, with 56, 33, and 4 having alveolar, granular, and papillary features, respectively. Twenty-four (36%), 31 (47%), and 11 (17%) were classified into good, intermediate, and poor prognosis groups according to the Upton pathology model. Forty-one specimens (62%) had high CAIX expression. Twenty-one of 27 (78%) responding patients had high CAIX expressing tumors compared with 20 of 39 (51%) nonresponders (odds ratio, 3.3; P = 0.04). Median survival was prolonged (P = 0.04) and survival >5 years was only seen in high CAIX expressers. In patients with intermediate pathologic prognosis, all nine responders had high CAIX expression versus 11 of 22 nonresponders. A resultant group with good pathologic prognosis alone or with intermediate pathologic prognosis and high CAIX contained 26 of 27 (96%) responders compared with 18 of 39 (46%) nonresponders (odds ratio, 30; P < 0.01) and exhibited longer median survival (P < 0.01). CONCLUSIONS: CAIX expression seems to be an important predictor of outcome in renal cell carcinoma patients receiving IL-2-based therapy and may enhance prognostic information obtained from pathology specimens.     

Deletion of the β-Acetoacetyl Synthase FabY in Pseudomonas aeruginosa Induces Hypoacylation of Lipopolysaccharide and Increases Antimicrobial Susceptibility

The β-acetoacetyl-acyl carrier protein synthase FabY is a key enzyme in the initiation of fatty acid biosynthesis in Pseudomonas aeruginosa. Deletion of fabY results in an increased susceptibility of P. aeruginosa in vitro to a number of antibiotics, including vancomycin and cephalosporins. Because antibiotic susceptibility can be influenced by changes in membrane lipid composition, we determined the total fatty acid profile of the ΔfabY mutant, which suggested alterations in the lipid A region of the lipopolysaccharide. The majority of lipid A species in the ΔfabY mutant lacked a single secondary lauroyl group, resulting in hypoacylated lipid A. Adding exogenous fatty acids to the growth media restored the wild-type antibiotic susceptibility profile and the wild-type lipid A fatty acid profile. We suggest that incorporation of hypoacylated lipid A species into the outer membrane contributes to the shift in the antibiotic susceptibility profile of the ΔfabY mutant.     

An exploration of nurse-physician perceptions of collaborative behaviour

Interprofessional collaboration is a key element in providing safe, holistic patient care in the acute care setting. Trended data at a community hospital indicated opportunities for improvement in collaboration on micro, meso, and macro levels. The aim of this survey study was to assess the current state of collaboration between frontline nurses and physicians at a non-academic acute care hospital. A convenience sample of participants was recruited with a final respondent sample of 355 nurses and 82 physicians. The results indicated that physicians generally perceived greater collaboration than nurses. Physician ratings did not vary by primary practice area, whereas nurse ratings varied by clinical practice area. Nurse ratings were the lowest in the operating room and the highest in the emergency department. Text-based responses to an open-ended question were analysed by role and coded by two independent research teams. Emergent themes emphasised the importance of rounding, roles, respect, and communication. Despite recognition of the need for improved collaboration and relational behaviours, strategies to improve collaborative practice must be fostered at the meso level by organisational leaders and customised to address micro-level values. At the study site, findings have been used to address and improve collaboration towards the goal of becoming a high reliability organisation.