Antifungal susceptibility of Candida species isolated from patients with candidemia in southern Taiwan, 2007–2012: impact of new antifungal breakpoints

The Clinical and Laboratory Standard Institute (CLSI) revised the clinical breakpoints (CBPs) for the azoles and echinocandins against Candida species in 2012. We aimed to report the epidemiology of candidemia and antifungal susceptibility of Candida species and evaluate the impact of new CBPs on antifungal susceptibility in our region. All blood isolates of Candida species were obtained from 2007 to 2012. The minimum inhibitory concentrations of fluconazole, voriconazole, echinocandins and flucytosine against Candida isolates were determined by Sensititre YeastOne system. Differences in susceptibility rates between the CBPs of previous and revised versions of CLSI were examined. Of 709 Candida isolates, the fluconazole‐susceptible rate was 96.5% in Candida albicans, 85.8% in Candida tropicalis and 92.1% in Candida parapsilosis by the revised CBPs. Compared with the susceptibility results by previous CBPs, the marked reductions in susceptibility of C. albicans, C. tropicalis and C. parapsilosis to fluconazole, that of C. tropicalis and C. parapsilosis to voriconazole, that of C. tropicalis and Candida glabrata to anidulafungin and that of C. tropicalis, C. glabrata and Candida krusei to caspofungin by revised CBPs were found. In conclusion, Candida albicans and C. parapsilosis remain highly susceptible to fluconazole. The non‐susceptible rates of Candida species to azoles and echinocandins increase with interpretation by the revised CBPs.     

Antifungal susceptibility profile in vitro of Sporothrix schenckii in two growth phases and by two methods: microdilution and E‐test

The susceptibility profile of 91 Sporothrix schenckii isolates in both growth phases was determined by microdilution test (Antifungal Susceptibility Testing of the European Committee for Antimicrobial Susceptibility Testing; AFST‐EUCAST). Amphotericin B (AMB), itraconazole (ITC), posaconazole, ravuconazole and terbinafine were found active in vitro against both phases but minimum inhibitory concentrations values for mycelial phase were significantly higher. Fluconazole (FLC) and voriconazole (VRC) were inactive in vitro against both phases. The E‐test technique was also performed with 41 representative isolates for AMB, FLC, ITC and VRC. Average agreement rates between yeast phase microdilution results and E‐test results were high for AMB (77.5%) and FLC (87.8%), but low for ITC and VRC with rates of 56.4% and 54.5%, respectively. AFST‐EUCAST is not the most recommended test to perform drug susceptibility testing of S. schenckii in clinical laboratories, and E‐test could be an alternative methodology for this purpose, mainly when the activity in vitro of antifungal agents of AMB and FLC are evaluated.     

Isolation and identification of Malassezia species from Chinese and Korean patients with seborrheic dermatitis and in vitro studies on their bioactivity on sebaceous lipids and IL‐8 production

We investigated the distribution of Malassezia yeast in 120 Chinese (20 patients from each of six cities) and 20 Korean patients with scalp seborrheic dermatitis (SD) and dandruff (SD/D) using ITS1 and ITS2 polymerase chain reaction‐restriction fragment length polymorphism. Bioactivity was studied by quantifying sebum lipid production by human primary sebocytes and inflammatory cytokine, interleukin‐8 (IL‐8) production was studied by exposing HaCaT keratinocytes with extracts of five standard Malassezia strains; M. globosa, M. restricta, M. sympodialis, M. dermatis and M. slooffiae. M. restricta and M. globosa were the most frequently encountered species from both Chinese and Korean patients. These two Malassezia species also promoted neutral lipid synthesis although the result was not statistically significant and induced significant increase in IL‐8 production among the five Malassezia species studied. The study suggests a possible role of these organisms in the pathogenesis of SD/D.     

Posaconazole susceptibility testing against Candida species: comparison of broth microdilution and E-test methods

Posaconazole (POS) is a newer triazole with activity against yeasts and moulds. POS and fluconazole were tested in vitro against 32 Candida albicans, 30 C. glabrata, 21 C. tropicalis, 29 C. krusei, 28 C. parapsilosis, 50 C. inconspicua, 13 C. kefyr and 5 C. famata isolates using CLSI broth microdilution method (BMD). We compared E-test and a modified BMD using polyethylene-glycol (PEG) as solvent to the CLSI method. BMDs and E-test were performed according to CLSI and the manufacturer's instructions respectively. Geometric means of POS MICs using BMD were 0.71, 0.22 and 0.21 microg ml(-1) against C. glabrata, C. krusei and C. inconspicua, respectively, and remained below 0.1 microg ml(-1) against all other species tested. One of two C. albicans and two of three C. glabrata isolates resistant to fluconazole showed MICs above 8 microg ml(-1) to POS. The impact of using PEG instead of DMSO had only a minor effect (agreements above 95% with the exception of C. parapsilosis). E-tests read after 24 h showed good agreement with the BMD. POS exhibited excellent in vitro activity against Hungarian Candida strains. E-test showed good correlation with the CLSI method, but to facilitate the comparability of results we believe that DMSO should be used as solvent in the BMD.     

In vitro testing of Aspergillus fumigatus clinical isolates for susceptibility to voriconazole, amphotericin B and itraconazole: comparison of sensititre versus NCCLS M38-A using two different inocula

Voriconazole, amphotericin B and itraconazole were tested in vitro against 18 strains of Aspergillus fumigatus isolated from cystic fibrosis patients. Susceptibility was tested with the broth microdilution method (M38-A protocol-NCCLS). Results of this reference method were compared with those of an experimental commercial microdilution broth method (Sensititre). Two different inocula, prepared from 2- and 7-day cultures, were used. Minimum inhibitory concentrations (MICs) of the reference method ranged from 0.25 to 2 microg/ml for voriconazole, 0.06 to 1 microg/ml for amphotericin B, 0.016 to >16 microg/ml for itraconazole. There were no significant differences in the MIC ranges or MIC90 values obtained with the two testing methods or with the two types of inocula. These findings confirm the good in vitro activity of voriconazole, itraconazole and amphotericin B against A. fumigatus. They also indicate that reliable susceptibility data can be generated more rapidly by commercial systems and use of 2-day cultures for inoculum preparation.     

Attitude towards genetic testing for breast cancer susceptibility: a comparison of affected and unaffected women

BRUNO M., DIGENNARO M., TOMMASI S., STEA B., DANESE T., SCHITTULLI F. & PARADISO A. (2010) European Journal of Cancer Care 19 , 360–368
Attitude towards genetic testing for breast cancer susceptibility: a comparison of affected and unaffected women The objective of this study is to evaluate women's awareness and interest in genetic testing for breast cancer risk, to identify socio‐demographic factors, to analyse the reasons for wanting or not wanting to be tested and finally to determine whether breast cancer patients and healthy women have different attitudes towards genetic testing. Consecutive series of 879 women without and with breast cancer participated in a 20‐item self‐completing questionnaire. Among breast cancer patients, 57% answered that they would definitely or probably accept being tested, compared with 84% of women without breast cancer. At the multiple logistic regression analysis only to have a diagnosis of breast cancer conditioned significantly the interest to have genetic testing. Surprisingly, a family history of breast cancer was found to have no significant impact. The most frequently cited reason for being interested in genetic testing was ‘to learn about your children's risk’. Although women's awareness about breast cancer genes is inadequate, the interest in genetic testing is substantial and higher both in healthy women and in women with breast cancer. These results provide important indications for the development of educational strategies.     

Psychological impact of genetic testing for cancer susceptibility: an update of the literature

This article presents an overview of the rapidly evolving body of literature on the psychological impact of genetic testing for hereditary breast/ovarian cancer susceptibility, hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP). Uptake of genetic testing for BRCA1/2 and HNPCC-related mutations is more consistently related to psychological factors, rather than sociodemographic variables. Most studies on the psychological impact of genetic testing amongst individuals who have never been affected by cancer demonstrate that non-carriers derive significant psychological benefits from genetic testing, while no adverse effects have been observed amongst carriers. These benefits are more clear-cut for HNPCC, compared to hereditary breast/ovarian cancer, reflecting differences in risk management options. The few studies available on individuals affected with cancer indicate that the impact of genetic testing is mediated and amplified by their former experience of cancer. Future directions and challenges of research in this area are reviewed. In particular, more empirical data are needed on the broader impact of genetic testing on those with inconclusive results or results of uncertain significance. As genetic testing is becoming available for other types of familial cancer, additional investigations will be needed as there is evidence to suggest that the impact of genetic testing may be unique to each type of familial cancer.     

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

Immunochemical faecal occult blood testing (FIT) provides quantitative test results, which allows optimisation of the cut-off value for follow-up colonoscopy. We conducted a randomised population-based trial to determine test characteristics of FIT (OC-Sensor micro, Eiken, Japan) screening at different cut-off levels and compare these with guaiac-based faecal occult blood test (gFOBT) screening in an average risk population. A representative sample of the Dutch population (n=10 011), aged 50–74 years, was 1 : 1 randomised before invitation to gFOBT and FIT screening. Colonoscopy was offered to screenees with a positive gFOBT or FIT (cut-off 50 ng haemoglobin/ml). When varying the cut-off level between 50 and 200 ng ml⁻¹, the positivity rate of FIT ranged between 8.1% (95% CI: 7.2–9.1%) and 3.5% (95% CI: 2.9–4.2%), the detection rate of advanced neoplasia ranged between 3.2% (95% CI: 2.6–3.9%) and 2.1% (95% CI: 1.6–2.6%), and the specificity ranged between 95.5% (95% CI: 94.5–96.3%) and 98.8% (95% CI: 98.4–99.0%). At a cut-off value of 75 ng ml⁻¹, the detection rate was two times higher than with gFOBT screening (gFOBT: 1.2%; FIT: 2.5%; P<0.001), whereas the number needed to scope (NNscope) to find one screenee with advanced neoplasia was similar (2.2 vs 1.9; P=0.69). Immunochemical faecal occult blood testing is considerably more effective than gFOBT screening within the range of tested cut-off values. From our experience, a cut-off value of 75 ng ml⁻¹ provided an adequate positivity rate and an acceptable trade-off between detection rate and NNscope.     

Diffusion-weighted MR-imaging for the detection of pulmonary nodules at 1.5 Tesla: intraindividual comparison with multidetector computed tomography

Introduction: To investigate the feasibility of diffusion‐weighted imaging (DWI) MRI for detecting pulmonary nodules at 1.5 Tesla in comparison with standard multidetector computed tomography (MDCT). Methods: Twenty patients with disseminated cancer disease in which MDCT had assured the presence of at least one pulmonary nodule were examined using a respiratory‐gated DWI MR‐sequence. Grey scale inverted source images and coronal maximum intensity projection (MIP) images were consensually analysed by two experienced radiologists. Size and location of any nodule detected were assessed. Additionally, the readers evaluated each hemithorax for the presence of at least one nodule and applied a four‐point conspicuity scale (1‐hemithorax definitely affected; 4‐hemithorax definitely not affected). MDCT data served as reference. Results: At MDCT, a total of 71 pulmonary noduIes was found (size 3–5 mm, n = 16; 6–9 mm, n = 22; ≥10 mm, n = 33). For the DWI MR‐sequence, a sensitivity of 86.4% was calculated for nodules ranging 6–9 mm and 97% for nodules ≥10 mm. In contrast, only 43.8% of lesions ≤5 mm was detected. The separate analysis of each hemithorax for the presence of at least one pulmonary nodule revealed a specificity rate, PPV and NPV of DWI‐MR of 92.3%, 96% and 80%, respectively. Conclusions: The presented study is the first to confirm the diagnostic potential of DWI‐MR in the detection of solid lung nodules. This technique allows for the detection of nodules ≥6 mm with reasonably high sensitivity rates (>86%). The observation of false positive findings decreases the accuracy of this approach compared with MDCT.     

Heterotopic ossification after total hip arthroplasty (THA) in congenital hip disease: comparison of two different prophylactic protocols

Introduction  We aimed to evaluate retrospectively the efficacy of combined postoperative radiotherapy and indomethacin compared to indomethacin alone for the prevention of heterotopic ossification (HO) in high-risk patients with congenital disease of hip (CDH) undergoing total hip arthroplasty (THA). Materials and methods  Fifty-five patients received indomethacin alone (Group A), while 44 patients received the combined protocol (Group B). Patients ≥55 years were enrolled in Group B and those younger than 55 years in Gro up A. Patients were evaluated radiologically for the pre sence of HO 6 months after the operation. Results  The incidence of HO in Group A was 34.5% (95% confidence interval 22.2–48.6%), while the respective incidence in Group B patients was 27.3% (95% CI 15.0–42.8%). The difference was not statistically significant (p=0.5). No significant treatment-related side effects were reported. Conclusions  This is the first study evaluating the impact of HO prophylaxis in an immiscible population of patients with secondary arthritis due to CDH undergoing THA. Further future randomised evidence is required in order to ascertain the observed trend towards improved efficacy of the combined protocol for HO development.     

Histological grade of differentiation of hepatocellular carcinoma: comparison of the efficacy of diffusion-weighted MRI with T2-weighted imaging and angiography-assisted CT

Introduction: The purpose of this study is to determine the usefulness of diffusion‐weighted imaging (DWI) for evaluating the histological grade of differentiation of hepatocellular carcinoma (HCC) compared with T2‐weighted imaging (T2WI) and tumour haemodynamics. Methods: We retrospectively evaluated 32 patients with 42 pathologically confirmed HCC nodules. These patients underwent MRI, CT during arterial portography and CT hepatic arteriography. We evaluated the relationship between the histological grade of differentiation and the apparent diffusion coefficient (ADC) values, conspicuity of tumour on DWI, DWI and T2WI contrast‐to‐noise (C/N) ratios and tumour haemodynamics. Results: There was no correlation between the histological grade of differentiation and the ADC values. The DWI C/N ratio was significantly different among all histological grades, but the T2WI C/N ratio was not. Tumour conspicuity on DWI correlated well with the histological grade of differentiation, but tumour haemodynamics only partially correlated with the histological grade of differentiation. Conclusion: DWI was useful for evaluating the histological grade of differentiation of HCC.     

Primary nasal lymphoma,NK/T‐cell type: Report of two cases with similar presentation but different outcome

Two cases of natural killer (NK)/T‐cell primary nasal lymphoma with similar clinical presentations are reported, for comparison and contrast, to highlight the clinical issues and challenges posed by this unusual disease, its aggressiveness being matched only by its rarity. Presenting as a lesion in the nasal cavity with histological features of malignant lymphoma, primary nasal lymphoma is an uncommon extranodal lymphoma, which poses problems in both diagnosis and management. In people of oriental descent, the common cell subtype is NK/T‐cell. Although it is generally thought that combination treatment with chemotherapy and radiation is the best management for early stage non‐Hodgkin's lymphoma (NHL), there is still debate as to whether combined therapy is optimal treatment for this particular subtype of NHL, given that it responds less well to conventional chemotherapy. Herein we report two patients to illustrate these controversies.     

Results of radiation therapy combined with neoadjuvant hormonal therapy for stage III prostate cancer: comparison of two different definitions of PSA failure

Background We herein report the clinical outcome of radical radiation therapy combined with neoadjuvant hormonal therapy (NHT) for stage III (International Union Against Cancer [UICC] 1997: UICC 97) prostate cancer. Prostate-specific antigen (PSA) failure-free survival was assessed according to two different definitions, and the appropriateness of each definition is discussed. Methods Between October 1997 and December 2000, 27 patients with stage III prostate cancer were enrolled in this study. The median pretreatment PSA level was 29 ng/ml (range, 7.4–430 ng/ml). The Gleason score (GS) was 7 or more in 22 patients (81%). All patients received 3 months of NHT with a luteinizing hormone-releasing hormone (LH-RH) analogue, in combination with an antiandrogen (flutamide), given during the first 2 weeks, followed by 70-Gy external-beam radiation therapy (EBRT) in 35 fractions. The initial 46 Gy was given with a four-field technique, while the remainder was given with a dynamic conformal technique. No adjuvant hormonal therapy (AHT) was given. Results The median follow-up time was 63 months. PSA levels decreased to the normal range (<4 ng/ml) after irradiation in all but one patient. The 5-year PSA failure-free survival was 34.8% according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition and it was 43.0% according to the “nadir plus 2” definition. Discordance of the results between the two definitions was seen in two patients. The 5-year overall and cause-specific survivals were 83.0% and 93.3%, respectively. No severe acute or late adverse effects were observed. Conclusion Seventy Gy of EBRT following 3 months of NHT produced therapeutic results comparable to those reported in other studies which used long-term AHT. The value of long-term AHT for Japanese men should be tested in a clinical trial.     

Comparison of fks gene mutations and minimum inhibitory concentrations for the detection of Candida glabrata resistance to micafungin: A systematic review and meta‐analysis

Candida resistance to antifungals impaired invasive candidiasis outcome. In a context of echinocandin resistance development, we aimed to evaluate the association between phenotypic resistance to micafungin and fks mutations of Candida glabrata. For this systematic review and meta‐analysis, we searched MEDLINE, Scopus and Web of Science for reports published up to December 2017. Studies of C glabrata candidiasis with minimum inhibitory concentrations (MIC) determination of micafungin and fks genotyping were included. Reviews, studies not using reference methods, non‐glabrata Candida, experimental isolates and undetailed mutations were excluded. Two authors independently assessed the eligibility of articles and extracted data. The main outcome was the diagnostic accuracy of fks mutations compared to micafungin MIC for C glabrata, measured as fixed‐effect odd ratio. Heterogeneity was calculated with the I² statistic. This study is registered with PROSPERO (CRD42018082023). Twenty‐four studies were included in the meta‐analysis. Pooled analysis found that S663P (OR 7.25, 95% CI 3.50‐15.00; P < 0.00001), S629P (OR 3.70, 1.64‐8.33; P = 0.002) and F659del (OR 5.66, 1.22‐26.18; P = 0.03) were associated with increased risk of having a resistant isolate according to authors' interpretation of MICs. In sensitivity analysis based on new CLSI clinical breakpoints, the ORs for S663P and S629P remained significant. Genotyping of isolates of C glabrata for S663P and S629P mutations is an effective alternative to micafungin susceptibility tests. Relevant molecular markers of drug resistance will significantly improve the management of C glabrata infections.     

Repositioning accuracy of two different mask systems-3D revisited: comparison using true 3D/3D matching with cone-beam CT

PURPOSE: The repositioning accuracy of mask-based fixation systems has been assessed with two-dimensional/two-dimensional or two-dimensional/three-dimensional (3D) matching. We analyzed the accuracy of commercially available head mask systems, using true 3D/3D matching, with X-ray volume imaging and cone-beam CT. METHODS AND MATERIALS: Twenty-one patients receiving radiotherapy (intracranial/head-and-neck tumors) were evaluated (14 patients with rigid and 7 with thermoplastic masks). X-ray volume imaging was analyzed online and offline separately for the skull and neck regions. Translation/rotation errors of the target isocenter were analyzed. Four patients were treated to neck sites. For these patients, repositioning was aided by additional body tattoos. A separate analysis of the setup error on the basis of the registration of the cervical vertebra was performed. The residual error after correction and intrafractional motility were calculated. RESULTS: The mean length of the displacement vector for rigid masks was 0.312 +/- 0.152 cm (intracranial) and 0.586 +/- 0.294 cm (neck). For the thermoplastic masks, the value was 0.472 +/- 0.174 cm (intracranial) and 0.726 +/- 0.445 cm (neck). Rigid masks with body tattoos had a displacement vector length in the neck region of 0.35 +/- 0.197 cm. The intracranial residual error and intrafractional motility after X-ray volume imaging correction for rigid masks was 0.188 +/- 0.074 cm, and was 0.134 +/- 0.14 cm for thermoplastic masks. CONCLUSIONS: The results of our study have demonstrated that rigid masks have a high intracranial repositioning accuracy per se. Given the small residual error and intrafractional movement, thermoplastic masks may also be used for high-precision treatments when combined with cone-beam CT. The neck region repositioning accuracy was worse than the intracranial accuracy in both cases. However, body tattoos and image guidance improved the accuracy. Finally, the combination of both mask systems with 3D image guidance has the potential to replace therapy simulation and intracranial stereotaxy.