Citations

Objective: To characterize agreement in the ascertainment of surgical site infections (SSIs) between the National Surgical Quality Improvement Program (NSQIP), National Healthcare Safety Network (NHSN), and administrative data. Background: The NSQIP, NHSN, and administrative data are the primary systems used to monitor and report SSIs for the purpose of quality control and benchmarking of hospitals and surgeons. These systems have different methods for identifying SSIs. Methods: We queried the NHSN, NSQIP, and administrative data systems for patients who had an operation at 1 of 4 hospitals within a single health system between January 2013 and September 2015. The detection of an SSI during a postoperative hospitalization was the outcome of analysis. Any SSI detected by one (or more) of these systems was analyzed by 2 reviewers to determine the presence of discrete elements of documentation constituting evidence of SSI. Concordance between the 3 systems (NHSN, NSQIP, and administrative data) was analyzed using Cohen's kappa. Results: After application of appropriate exclusion criteria, a cohort of 9447 inpatient operations was analyzed. In total, 130 SSIs were detected by 1 or more of the 3 systems, with reported SSI rates of 0.5% (NHSN), 0.7% (administrative data), and 1.0% (NSQIP). Of these 130 SSIs, only 17 SSIs were reported by all 3 systems. The concordance between these 3 systems was moderate (kappa values NSQIP-NHSN = 0.50 [0.40–0.60], administrative-NHSN = 0.36 [0.24–0.47], and administrative-NSQIP = 0.47 [0.38–0.57]). Chart review found that reasons for discordance were related to issues of different criteria as well as inaccuracies. Conclusion: There is significant discordance in the determination of SSIs reported by the NHSN, NSQIP, and administrative data. The differences and limitations of each of these systems have to be recognized, especially when using these data for quality reports and pay for performance.

Abstract Monocyte maturation to macrophages and transformation into epithelioid granuloma cells in some granulomatous diseases are accompanied by the induction of membrane-bound angiotensin-converting enzyme (ACE). The physiologic and pathophysiologic roles of ACE generated in these processes are not known. The pattern and the mechanism of ACE induction in human monocytes are also not well understood. Dexamethasone is one of the agents reported to induce elevated ACE activity in human monocytes, and therefore a suitable tool for studying the phenomenon. This study shows that dexamethasone augments monocyte ACE in a Diphasic dose-dependent manner with maximum effect at 10-5 M concentration. Although it enhances the level of ACE activity, dexamethasone doss not alter the time course for ACE induction from that found in unstimulated monocytes. The ACE activity of monocytes cultivated in 10 nM dexamethasone and then exposed to 10-3 M diazosulfanilic acid (DASA) is reduced approximately by 80% in comparison with cells not treated with DASA, demonstrating that dexamethasone-induced ACE is an ectoenzyme. Dexamethasone does not increase the activity of other monocyte ectoenzymes: γ-glutamyltransferase, alkaline phosphodiesterase-I, and leucine aminopeptktase, showing that dexamethasone induction of ACE is a specific, rather than generalized, effect on plasma membrane enzymes. It is suggested that the increase in ACE activity is due to the increased rate of enzyme synthesis.

Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study ( ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.