The value of aspiration cytologic examination of the breast. A statistical review of the medical literature.

The decision to perform surgery in patients with a breast mass usually is made on the basis of combined diagnostic information, with fine-needle aspiration cytologic examination (FNAC) playing a central role. To determine and compare the quality of FNAC of the breast, a search was performed of the English literature for articles with quantitative information about their results. Twenty-nine such articles, containing 31,340 aspirations, were identified and summarized. Required data were extracted from these articles. These numbers were analyzed with the use of a two-by-four contingency table to relate the FNAC result (definitely malignant, suspect, benign, or unsatisfactory cytologic material) with the final diagnosis (malignant or benign breast disease). Test characteristics such as sensitivity, specificity, and the likelihood ratios for the four different FNAC results were derived for each study and compared. There was a striking difference between studies with regard to the probability of a particular FNAC upshot (e.g., in patients with breast cancer, the chance of obtaining definitely malignant cytologic material ranged from 0.35 to 0.92), the sensitivity (range, 0.65 to 0.98), the specificity (range, 0.34 to 1.0), and likelihood ratios. In the opinion of the authors, it is virtually impossible to infer general test characteristics of FNAC of the breast from the medical literature because of differences in methods and different biases. At best, the maximum attainable performance of this test can be described. For the development of a policy for breast mass management, the local test characteristics of this highly operator-dependent test should be established.     

Is the auditory sensory memory sensitive to visual information?

The mismatch negativity (MMN) component of auditory event-related brain potentials can be used as a probe to study the representation of sounds in auditory sensory memory (ASM). Yet it has been shown that an auditory MMN can also be elicited by an illusory auditory deviance induced by visual changes. This suggests that some visual information may be encoded in ASM and is accessible to the auditory MMN process. It is not known, however, whether visual information affects ASM representation for any audiovisual event or whether this phenomenon is limited to specific domains in which strong audiovisual illusions occur. To highlight this issue, we have compared the topographies of MMNs elicited by non-speech audiovisual stimuli deviating from audiovisual standards on the visual, the auditory, or both dimensions. Contrary to what occurs with audiovisual illusions, each unimodal deviant elicited sensory-specific MMNs, and the MMN to audiovisual deviants included both sensory components. The visual MMN was, however, different from a genuine visual MMN obtained in a visual-only control oddball paradigm, suggesting that auditory and visual information interacts before the MMN process occurs. Furthermore, the MMN to audiovisual deviants was significantly different from the sum of the two sensory-specific MMNs, showing that the processes of visual and auditory change detection are not completely independent.     

A 2-year, randomized, comparative, placebo-controlled study on the effects of raloxifene on lipoprotein(a) and homocysteine

OBJECTIVES: Lipoprotein(a) (Lp(a)) and homocysteine (Hcy) are independent cardiovascular risk factors, which have been shown to be lowered by hormone replacement therapy (HRT). In this 2-year study, the long-term effects of raloxifene (Rlx) in two doses, on Lp(a) and Hcy, were studied and compared with the effects of continuously combined hormone replacement therapy (ccHRT). METHODS: In a prospective, randomized, double-blind, placebo-controlled 2-year study, 95 healthy, non-hysterectomized, early postmenopausal women, received daily either oral Rlx 60 mg (N=24) or 150 mg (N=23), ccHRT (conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg; N=24) or placebo (N=24). Fasting serum Lp(a) and plasma Hcy concentrations were measured at baseline and at 6, 12 and 24 months. RESULTS: The mean individual changes compared to baseline after 24 months were for Lp(a): Rlx 60: - 5%, Rlx 150: -7%, ccHRT: -34%, placebo: +1% and for Hcy: Rlx 60: -3%, Rlx 150: -4%, ccHRT: -4%, placebo: +6%. ANCOVA was significant for Lp(a) under ccHRT versus placebo (P=0.001) and for Lp(a) under ccHRT versus each of the two Rlx groups (P<0.05). CONCLUSIONS: Long-term treatment with Rlx was not as effective as ccHRT in lowering Lp(a). Although not significant and without an obvious dose-related response, the Hcy values showed the same trend for each treatment arm, which is in line with data reported earlier.     

Large-scale suspension culture with limited facilities

Methods in Cell Science -     

Genomic Analysis of Reduced Susceptibility to Tigecycline in Enterococcus faecium

Tigecycline (TIG) is approved for use for the treatment of complicated intra-abdominal infections, skin and skin structure infections, as well as pneumonia. Acquired resistance or reduced susceptibility to TIG has been observed in Gram-negative rods, has seldom been reported in Gram-positive organisms, and has not yet been reported in Enterococcus faecium. Using the serial passage method, in vitro mutant AusTig and in vitro mutants HMtig1 and HMtig2 with decreased TIG susceptibility (MICs, 0.25 μg/ml) were obtained from strains E. faecium Aus0004 and HM1070 (MICs, 0.03 μg/ml), respectively. In addition, two vancomycin-resistant E. faecium clinical isolates (EF16 and EF22) with reduced susceptibility to TIG (MICs, 0.5 and 0.25 μg/ml, respectively) were studied. Compared to the wild-type strains, the in vitro mutants also showed an increase in the MICs of other tetracyclines. An efflux mechanism did not seem to be involved in the reduced TIG susceptibility, since the presence of efflux pump inhibitors (reserpine or pantoprazole) did not affect the MICs of TIG. Whole-genome sequencing of AusTig was carried out, and genomic comparison with the Aus0004 genome was performed. Four modifications leading to an amino acid substitution were found. These mutations affected the rpsJ gene (efau004_00094, coding for the S10 protein of the 30S ribosomal subunit), efau004_01228 (encoding a cation transporter), efau004_01636 (coding for a hypothetical protein), and efau004_02455 (encoding the l-lactate oxidase). The four other strains exhibiting reduced TIG susceptibility were screened for the candidate mutations. This analysis revealed that three of them showed an amino acid substitution in the same region of the RpsJ protein. In this study, we characterized for the first time genetic determinants linked to reduced TIG susceptibility in enterococci.     

A Risk Scoring System to Determine Recurrence in Early-Stage Type 1 Endometrial Cancer: A French Multicentre Study

Background

To develop a risk scoring system (RSS) to determine recurrence in women with early-stage type 1 endometrial cancer (EC).

Methods

Data of 396 women with early-stage type 1 EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from multicentre database (training set). A risk model for predicting recurrence was developed and internally validated with the bootstrap technique. The RSS was externally validated using data from an independent population.

Results

Overall, the recurrence rate was 12.1 %. The median follow-up and initial time to recurrence were 34 (range 1–152) and 26 (range 1–151) months, respectively. Recurrence was associated with five variables: age ≥60 years, histological grade III, primary tumor diameter >2 cm, depth of myometrial invasion ≥50 %, and the positive lymphovascular space involvement status. These variables were included in the RSS and assigned scores. A total score of 6.5 points corresponded to the optimal threshold of the RSS. For women with a score <6.5 or ≥6.5, the recurrence rates were 8.4 % (30/357) and 48.7 % (19/39) in the training set, respectively. At this threshold, the diagnostic accuracy of the RSS was 87 %. Areas under the curve of the receiver-operating characteristics for predicting recurrence at internal and external validation were 0.74 [95 % confidence interval (CI) 0.71–0.77] and 0.82 (95 % CI 79–85), respectively.

Conclusions

This RSS identified two subsets of women with low and high risk of recurrence among women with early-stage type 1 EC. It could be helpful to better define indications for nodal staging and adjuvant therapy.