The presence of leukaemia‐associated phenotypes is an independent predictor of induction failure in acute myeloid leukaemia

Immunophenotyping of acute myeloid leukaemia (AML) has controversial implications with regards to prognosis. The aims of the present study were to determine the frequency of leukaemia‐associated phenotypes (LAP) in AML and to correlate their presence with response to induction chemotherapy. We analysed bone marrow samples at diagnosis from 84 AML patients using triple staining flow cytometry with routine standard panel of monoclonal antibodies. The association of LAP and response to induction chemotherapy was evaluated retrospectively. LAP were observed in 54 (64%) patients: lineage infidelity in 19 (35%), asynchronous antigen expression in 28 (52%), and lack of expected lineage specific antigens in 19 (35%). Significant correlation was found between LAP and responses to induction chemotherapy. Response to induction chemotherapy was more frequent in the absence of LAP (P < 0.05, estimated risk ratio of 1.6, 95%CI, 1.0–2.6) in a multivariate analysis. In conclusion, our data show the presence of LAP in AML is an independent predictor for response to induction chemotherapy and risk of relapse and should be considered for counselling patients and planning therapy.     

Proactive infection control measures to prevent nosocomial transmission of carbapenem-resistant Enterobacteriaceae in a non-endemic area

Background Identification of hospitalized carbapenem-resistant Enterobacteriaceae （CRE）-positive patient is important in preventing nosocomial transmission.The objective of this study was to illustrate the implementation of proactive infection control measures in preventing nosocomial transmission of CRE in a healthcare region of over 3200 beds in Hong Kong between October 1,2010 and December 31,2011.Methods The program included active surveillance culture in patients with history of medical tourism with hospitalization and surgical operation outside Hong Kong within 12 months before admission,and ＂added test＂ as an opportunistic CRE screening in all fecal specimens submitted to the laboratory.Outbreak investigation and contact tracing were conducted for CRE-positive patients.Serial quantitative culture was performed on CRE-positive patients and the duration of fecal carriage of CRE was analyzed.Results During the study period,a total of 6533 patients were screened for CRE,of which 76 patients were positive （10 from active surveillance culture,65 from ＂added test＂,and 1 secondary case from contact tracing of 223 patients with no nosocomial outbreak）,resulting in an overall rate of CRE fecal carriage of 1.2％.The median time of fecal carriage of CRE was 43 days （range,13-119 days）.Beta-lactam-beta-lactamase-inhibitors,cephalosporins,and fluoroquinolones were associated significantly with high fecal bacterial load when used 90 days before CRE detection,while use of cephalosporins,carbapenems,and fiuoroquinolones after CRE detection are significantly associated with longer duration of carriage.The duration of fecal carriage of CRE also correlates significantly with the initial fecal bacterial load （Pearson correlation：0.53; P=0.02）.Conclusion Proactive infection control measures by enhanced surveillance program identify CRE-positive patients and data obtained are useful for the planning of and resource allocation for CRE control.     

IGF2R genetic variants, circulating IGF2 concentrations and colon cancer risk in African Americans and Whites

The Mannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R) encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations between IGF2R non-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of IGF2R genetic variants and CC risk. Women homozygous for the IGF2R c.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for the IGF2R c.901 C>G variant. Whites homozygous for the IGF2R c.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9-5.4)], whereas carrying the IGF2R c.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for the IGF2R c.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying the IGF2R c.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2.     

Disposable versus reusable biopsy forceps for colorectal epithelial cell proliferation in humans.

The performance of various measures of rectal mucosal proliferation has been evaluated in the literature, but the performance of the forceps used to obtain the tissue has received little attention. We used data from two large studies of proliferation at a single institution to compare reusable and disposable endoscopic forceps. Endoscopic pinch biopsies were taken 10 cm from the anal verge using either reusable or disposable, oval-cupped, sheathed forceps. The specimens were fixed, embedded, and sectioned, taking care to orient the specimens longitudinally. Five sections were placed on each slide. We determined how many slides did not contain eight scorable crypts (inadequate) and how many sections were necessary to identify eight complete crypts. There were 395 subjects who had biopsies taken with reusable forceps and 185 subjects who had biopsies taken with disposable forceps. The specimens were inadequate in 27.6% of the reusable forceps specimens versus 2.7% of the disposable forceps (P < 0.0001). The mean number of tissue sections necessary to identify eight scorable crypts for the reusable forceps was 3.82 (SD, 0.87) compared with 3.17 (SD, 0.83) for disposable forceps (P = 0.0001). The specimens taken with the disposable forceps were better, probably because the forceps were sharper. We believe that the better quality of the specimens and the sterility justify the higher cost of disposable forceps. We would urge investigators in proliferation studies to evaluate the biopsy equipment as carefully as they evaluate other aspects of their methods.