The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Maintenance treatment with poly (ADP-ribose) polymerase (PARP) inhibitor is now the standard of care in patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer following response to chemotherapy. In the SOLO2 trial, adverse event (AE)-associated olaparib interruption, dose reduction, and discontinuation occurred in 50%, 28%, and 17% of patients, respectively. We used data from the SOLO2 trial to evaluate the impact of dose alterations on survival outcomes and identified baseline characteristics associated with dose alteration. PATIENTS AND METHODS: We computed relative dose intensity (RDI) defined as the received dose as a percentage of the standard dose (300 mg twice a day) during the first 12 weeks on treatment. Patients were categorized into RDI >98%, RDI 90%-98%, and RDI <90%. The association between RDI categories with progression-free survival (PFS) and overall survival (OS) were examined using a 12-week landmark Cox regression analysis. Logistic regression analysis was used to correlate baseline factors with RDI at 12 weeks. RESULTS: In patients on olaparib included in the landmark analysis (n = 185), the mean 12-week RDI was 91.4%. There was no significant difference across 12-week RDI >98% (n = 110), 90%-98% (n = 29), and <90% (n = 45) categories for PFS (median, 14.2 versus 19.3 versus 34.4 months; P = 0.37) and OS (median, 49.7 versus 49.5 versus 54.1 months; P = 0.84). Risk of RDI ≤90% increased with baseline performance status 1 [odds ratio (OR): 2.54; 95% confidence interval (CI): 1.11-5.82] any nausea (OR: 3.17; 95% CI: 0.9-11.23), and with body weight ≤70 kg (OR: 1.86; 95% CI: 0.92-3.76). CONCLUSIONS: Dose reduction and interruption for the management of olaparib-associated AEs during the first 12 weeks did not impact on PFS and OS. When counselling patients requiring dose reductions or interruptions due to AEs, the results of this study will help assure patients that their outcomes will not be adversely affected.

Effects of anti-osteoporosis medications on radiological and clinical results after acute osteoporotic spinal fractures: a retrospective analysis of prospectively designed study.

Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). INTRODUCTION: Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. METHODS: A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. RESULTS: IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). CONCLUSIONS: Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.

Staphylococcus aureus-derived membrane vesicles exacerbate skin inflammation in atopic dermatitis.

BACKGROUND: Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD are unknown. OBJECTIVE: We investigated whether and how S. aureus-derived membrane vesicles (MVs) contribute to worsening of AD. METHODS: Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions. HaCaT cells were treated with S. aureus MVs and were analysed for the expression of cytokine genes. Immunopathology and cytokine gene profiles were analysed after topical application of S. aureus MVs to AD-like skin lesions in a mouse model. RESULTS: The MV component SPA was detected in the keratinocytes as well as in the intercellular space of the epidermis of AD lesions colonized with S. aureus. Intact MVs from S. aureus delivered their components to keratinocytes and stimulated pro-inflammatory cytokine gene expression in vitro. A knock-down of Toll-like receptor 2 or nucleotide-binding oligomerization domain 2 using small interfering RNAs suppressed interleukin-8 gene expression. Topical application of intact S. aureus MVs to AD-like skin lesions in the mouse model induced massive infiltration of inflammatory cells and the resulting eczematous dermatitis. This inflammatory reaction was associated with a mixed Th1/Th2 immune response and enhanced expression of chemokine genes in AD-like skin lesions. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed the importance of S. aureus MVs as a potent mediator for worsening of AD among many exogenous worsening factors of AD. Thus, S. aureus MVs may be regarded as one of the therapeutic targets for the management of AD aggravation.

Association between 24-hour combined multichannel intraluminal impedance-pH monitoring and symptoms or quality of life in patients with laryngopharyngeal reflux.

OBJECTIVE: To evaluate the association between the parameters of 24-hour multichannel intraluminal impedance (MII)-pH monitoring and the symptoms or quality of life (QoL) in laryngopharyngeal reflux (LPR) patients. DESIGN: Prospective cohort study without controls. SETTING: University teaching hospital. METHODS: Forty-five LPR patients were selected from subjects who underwent 24-hour MII-pH monitoring and were diagnosed with LPR from September 2014 to May 2015. Reflux Symptom Index (RSI), Health-related Quality of Life (HRQoL), Short Form 12 (SF-12) Survey questionnaires were surveyed. Spearman's correlation was used to analyse the association between the symptoms or QoL and 24-hour MII-pH monitoring. RESULTS: Most parameters in 24-hour MII-pH monitoring showed weak or no correlation with RSI, HRQoL and SF-12. Only number of non-acid reflux events that reached the larynx and pharynx (LPR-non-acid) and number of total reflux events that reached the larynx and pharynx (LPR-total) parameters showed strong correlation with heartburn in RSI (R = 0.520, P < 0.001, R = 0.478, P = 0.001, respectively). Multiple regression analysis showed that there was only one significant regression coefficient between LPR-non-acid and voice/hoarseness portion of HRQoL (b = 1.719, P = 0.022). CONCLUSION: Most parameters of 24-hour MII-pH monitoring did not reflect subjective symptoms or QoL in patients with LPR.

Does bisphosphonate-based anti-osteoporosis medication affect osteoporotic spinal fracture healing?

UNLABELLED: Effects of bisphosphonate on fracture healing were prospectively investigated for osteoporotic spinal fracture. Although there were no significant differences in clinical outcomes, the presence of intravertebral cleft was related to the medication use. These results suggest that suspension of bisphosphonate use should be considered during the fracture healing period. INTRODUCTION: The purpose of this prospective study is to investigate whether bisphosphonate-based anti-osteoporosis medication affects fracture healing and clinical outcomes of conservatively treated osteoporotic spinal fractures (OSFs). METHODS: A total of 105 patients who were diagnosed with acute OSFs were prospectively enrolled. According to their previous medication history, the patients were allocated into group I (n = 39, no history of bisphosphonate use) or group II (n = 66, history of bisphosphonate use). Clinical outcomes were assessed using visual analogue scale (VAS), and Oswestry disability index (ODI). Radiographic parameters including changes in height loss and kyphotic angle at the index vertebra were measured, and radiographic findings suggesting impaired fracture healing such as the intravertebral cleft (IVC) sign and fracture instability were evaluated. Univariate and multivariate regression analyses were used to identify related factors. RESULTS: There were no significant differences in the last VAS and ODI between groups. There were also no significant differences in the radiographic parameters. Although the IVC sign was seen more commonly in group II (30.3 %) than in group I (20.5 %), fracture instability combined with IVC was noted in the same number of cases. On multiple regression analysis, medication history showed no significant relationship with the clinical parameters. However, the presence of the IVC sign was related to medication history (odds ratio 4.8; 95 % confidence interval [CI] 1.02-22.69). CONCLUSIONS: Bisphosphonate use does not significantly affect the clinical results during conservative treatment for OSFs. However, the occurrence of the IVC sign was related to medication history. Although further studies are needed to verify our findings, these results suggest that suspension of bisphosphonate use should be considered during the fracture healing period for acute OSFs.

Effect of postoperative proton pump inhibitor therapy on voice outcomes following phonomicrosurgery for vocal fold polyp: a randomized controlled study.

OBJECTIVE: To determine the effect of a postoperative proton pump inhibitor (PPI) on voice outcomes after phonomicrosurgery in patients with vocal fold polyp. STUDY DESIGN: This is a prospective, randomized controlled study. SETTINGS: This study was carried out in a tertiary care referral medical centre. PARTICIPANTS: A total of 48 patients underwent phonomicrosurgery for vocal fold polyps. After surgery, patients were randomized to the PPI group (lansoprazole 15 mg twice daily for 2 months) and the non-PPI group. MAIN OUTCOME MEASURES: Voice handicap index (VHI) and perceptual and acoustic voice analysis were evaluated at baseline and 2 months after surgery. RESULTS: Among 48 enrolled patients, a total of 42 patients [non-PPI group (n = 23), PPI group (n = 19)] completed the study. The VHI, perceptual and most acoustic parameters significantly improved in both groups after surgery. However, there was no significant difference in the per cent of change in those parameters. CONCLUSION: Postoperative PPI treatment did not significantly influence voice outcomes after phonomicrosurgery in patients with vocal fold polyp.

Immuno-based detection of extracellular vesicles in urine as diagnostic marker for prostate cancer.

Extracellular vesicles (including the subclass exosomes) secreted by cells contain specific proteins and RNA that could be of interest in determining new markers. Isolation/characterization of PCa-derived exosomes from bodily fluids enables us to discover new markers for this disease. Unfortunately, isolation with current techniques (ultracentrifugation) is labor intensive and other techniques are still under development. The goal of our study was to develop a highly sensitive time-resolved fluorescence immunoassay (TR-FIA) for capture/detection of PCa-derived exosomes. In our assay, biotinylated capture antibodies against human CD9 or CD63 were incubated on streptavidin-coated wells. After application of exosomes, Europium-labeled detection antibodies (CD9 or CD63) were added. Cell medium from 37 cell lines was taken to validate this TR-FIA. Urine was collected (after digital rectal exam) from patients with PCa (n = 67), men without PCa (n = 76). As a control, urine was collected from men after radical prostatectomy (n = 13), women (n = 16) and patients with prostate cancer without digital rectal exam (n = 16). Signal intensities were corrected for urinary PSA and creatinine. This TR-FIA can measure purified exosomes with high sensitivity and minimal background signals. Exosomes can be measured in medium from 37 cell lines and in urine. DRE resulted in a pronounced increase in CD63 signals. After DRE and correction for urinary PSA, CD9 and CD63 were significantly higher in men with PCa. This TR-FIA enabled us to measure exosomes with high sensitivity directly from urine and cell medium. This TR-FIA forms the basis for testing different antibodies directed against exosome membrane markers to generate disease-specific detection assays.

Efficacy of palonosetron for the prevention of postoperative nausea and vomiting: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: The aim of this study was to evaluate the efficacy of palonosetron, the latest 5-HT3 receptor antagonist, for the prevention of postoperative nausea and vomiting (PONV) during the first 72 h after operation. METHODS: In this randomized, double-blinded, placebo-controlled study, 204 healthy inpatients who were undergoing elective surgery with general anaesthesia were enrolled. Patients were divided into two groups: the palonosetron group (palonosetron 0.075 mg i.v.; n=102) and the placebo group (normal saline i.v.; n=102). The treatments were given after the induction of anaesthesia. The incidence of nausea, vomiting, severity of nausea, and the use of rescue anti-emetics during the first 72 h after surgery were evaluated. RESULTS: The incidence of PONV was lower in the palonosetron group compared with the placebo group during the 0-24 h (33% vs 47%) and 0-72 h period (33% vs 52%) (P<0.05), but not during the 24-72 h postoperative period (6% vs 11%). The incidence of nausea was also significantly lower in the palonosetron group than in the placebo group during the 0-24 and 0-72 h period (P<0.05), but not during the 24-72 h postoperative period. However, there were no significant differences in the incidence of vomiting, and the use of rescue anti-emetics between the groups. CONCLUSIONS: Palonosetron 0.075 mg i.v. effectively reduced the incidence of PONV during the first 72 h after operation, with most of the reduction occurring in the first 24 h.

Clinical relevance of lymph node ratio in breast cancer patients with one to three positive lymph nodes.

BACKGROUND: To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT). METHODS: Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR). RESULTS: Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17-0.89; P=0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT. CONCLUSION: This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.

Elevated levels of preoperative CA 15-3 and CEA serum levels have independently poor prognostic significance in breast cancer.

BACKGROUND: To evaluate the prognostic value of preoperative tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA), in breast cancers. PATIENTS AND METHODS: Preoperative CA 15-3 and CEA levels of 1681 patients were measured. The association of both tumor markers levels with clinicopathological parameters and outcomes was investigated by univariate and multivariate analyses. RESULTS: Among 1681 patients, elevated preoperative CA15-3 and CEA levels were identified in 176 and 131 patients, respectively. Higher preoperative CA 15-3 and CEA levels were significantly associated with a larger tumor size, axillary node metastases, and advanced stage. Patients with elevated CA 15-3 and CEA levels showed worse survival, even in stage-matched analysis. Patients with normal levels of both CA15-3 and CEA showed better survival than those with one or both markers levels elevated. In multivariate analysis, elevated preoperative CA 15-3 and CEA levels were independent prognostic factors. The statistical significance of elevated preoperative tumor markers levels on survival was solidified with longer follow-up and larger study population. CONCLUSIONS: Elevated preoperative CA 15-3 and CEA levels are associated with tumor burden and showed independent prognostic significance. Therefore, new treatment strategies are necessary for patients with elevated preoperative CA 15-3 and CEA levels in clinical practice.

Multicentre phase II trial of bevacizumab combined with docetaxel-carboplatin for the neoadjuvant treatment of triple-negative breast cancer (KCSG BR-0905).

BACKGROUND: This phase II neoadjuvant trial evaluated bevacizumab-docetaxel and carboplatin in triple-negative breast cancer. PATIENTS AND METHODS: Women with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-negative, stage II/III breast cancer received six cycles of 75 mg/m(2) docetaxel, carboplatin (AUC = 5) and 15 mg/kg bevacizumab every 21 days. The primary end point was pathological complete response (pCR) in breasts and axillary lymph nodes (ALN). RESULTS: Forty-five patients were recruited from the Korean Cancer Study Group. The median age was 45 (range 30-72) years. ALNs were positive in 80% of patients (n = 36) at diagnosis. Overall, 98% of patients (n = 44) completed therapy and underwent surgery. The pCR rate was 42% (n = 19); clinical response rate 96% (n = 43); complete 13% (n = 6); partial 82% (n = 37); stable disease 2% (n = 1). Breast-conserving surgery was undertaken in 78% of patients (n = 35). Most frequent grade 3/4 adverse events were neutropenia (84%, n = 38) and febrile neutropenia (9%, n = 4). One patient experienced delayed wound healing after surgery. CONCLUSIONS: Neoadjuvant bevacizumab, docetaxel and carboplatin resulted in an encouraging pCR rate and negligible wound healing problems after surgery.

Cardiac troponin I in congenital heart defects with pressure or volume overload.

OBJECTIVE: To evaluate the prevalence of cardiac troponin I (cTnI) and autoantibodies to cTn in children with congenital heart defects with volume or pressure overload fulfilling the criteria for treatment, and in healthy children. DESIGN: The study groups comprised 78 children with volume overload caused by an atrial septal defect or a patent ductus arteriosus, and 60 children with pressure overload caused by coarctation of the aorta or stenosis of the aortic or the pulmonary valve, and 74 healthy controls. Serum levels of natriuretic peptides, cTnI, and autoantibodies to cTn were analyzed at baseline, prior to treatment and in 64 patients 6 months after treatment. RESULTS: At baseline, one child with volume overload, 12 children with pressure overload, and one healthy control had positive cTnI. Further analysis of the pressure overload subgroup revealed that the children with positive cTnI were younger than those with negative cTnI, and had higher levels of natriuretic peptides. The pressure gradient at the coarctation site or stenotic valve was higher in those with positive TnI. Six months after treatment, 63 of 64 children examined were cTnI negative. CONCLUSIONS: The cTnI release is more frequently associated with pressure than volume overload which resolves after treatment in most children.

The efficacy of i-SCAN for detecting reflux esophagitis: a prospective randomized controlled trial.

New imaging technologies have been applied in endoscopy to improve the detection and differentiation of subtle mucosal changes using a digital contrast method. Among them, i-SCAN technology is the most recently developed image-enhancing technology. We investigated whether i-SCAN could improve the detection rate of reflux esophagitis. Interobserver agreement between endoscopists was compared with conventional white light (WL) endoscopic examination. We performed a prospective randomized controlled trial. A consecutive series of 514 subjects that underwent an esophagogastroduodenoscopy for health inspection were enrolled and randomized into the i-SCAN group (n = 246) and WL group (n = 268). An esophagogastroduodenoscopy with video recording was used for detecting reflux esophagitis, and reflux esophagitis were categorized by the modified Los Angeles (LA) classification. The total number of reflux esophagitis identified by WL and i-SCAN was 58 (21.7%) and 74 (30.1%), respectively. The diagnostic yield of reflux esophagitis was significantly higher (P = 0.034) in the i-SCAN group (30.1%) as compared to the WL group (21.6%). Using the modified LA classification, the detection rate of minimal changes was significantly higher (P = 0.017) in the i-SCAN group (11.8%) as compared to the WL group (5.6%), but the detection rates of LA-A and LA-B were not significantly different between the two groups (P = 0.897 and P = 0.311, respectively). After comparison of the interobserver agreement using randomly selected video clips, the i-SCAN group showed better agreement than the WL group (Kappa value, 0.793 vs. 0.473). Compared to WL endoscopy, applying i-SCAN in daily practice can improve the diagnostic yield of reflux esophagitis by detecting more minimal changes in the squamo-columnar junction of the esophagus and can improve the interobserver agreement of the modified Los Angeles classification.

False negative results in axillary lymph nodes by ultrasonography and ultrasonography-guided fine-needle aspiration in patients with invasive ductal carcinoma.

PURPOSE: For preoperative evaluation of ALN status using various methods, axillary US and subsequent US-FNA targeting the LNs suspicious for metastasis are the most widely used methods. The purpose of our study was to assess the rate of false-negative results at preoperative ultrasonography (US) and ultrasonography guided fine needle aspiration (US-FNA) of axillary lymph nodes (ALNs) in breast cancer patients and the number of false-negative lymph nodes, and to evaluate factors related to ALN false negative results in US and/or US-FNA in patients diagnosed with invasive ductal carcinoma. MATERIALS AND METHODS: Among 317 patients who underwent surgery for invasive ductal carcinoma during 2009 in Severance hospital, 237 patients had no reported ALN metastasis on preoperative US-FNA and US. We retrospectively reviewed the subsequent surgical pathology and clinicopathologic findings and assessed the rate of false-negative results from US and US-FNA of ALN and the number of false-negative lymph node. We performed univariate analysis and multivariate logistic regression analysis to evaluate the relationships between variable clinicopathologic factors (T-stage, position of ALN, hormone receptors, histologic grade, lymphovascular invasion (LVI) and performance of FNA) and cytologic results (false-negative result; FNALN and true negative result; TNALN) from US and/or US-FNA of ALN. RESULTS: The rate of false-negative results was 42.4 % (59/139) in both US and US-FNA of ALN but among them, 57.6 % (34/59) showed only one metastatic ALN. Breast cancer with FNALN on US and US-FNA was significantly related to positive estrogen receptor (p = 0.003), positive progesterone receptor (p = 0.001), and the presence of LVI (p = 0.004) in univariate analysis. In multivariate analysis, high T stages (≥ T2, odds ratio (OR) 4.007, p = 0.004) and LVI (OR 7.951, p = 0.001) showed significant correlation with FNALN on US and US-FNA. CONCLUSION: More than half of patients with FNALN showed only one metastatic ALN. LVI and high T-stages were the most important factors attributed to FNALN on US and US-FNA in patients with invasive ductal carcinoma.

Evaluation of sequence-specific priming and real-time polymerase chain reaction assays for detecting HLA-B*51 alleles confirmed by sequence-based typing.

The human leukocyte antigen (HLA)-B*51 genotype is one of the well-known genetic factors associated with the development of Behcet's disease. We evaluated three sequence-specific priming (SSP) assays and one real-time PCR assay for detecting HLA-B*51 alleles using 93 whole blood samples, which were genotyped by high-resolution sequence-based typing (SBT). All HLA-B*51 alleles determined by SBT were detected by the four evaluated assays, and the results for all HLA-B alleles other than HLA-B*51 were negative on all assays. Thus, all HLA-B51 tests showed 100% sensitivity and 100% specificity for detecting HLA-B*51 alleles. The three SSP assays and the real-time PCR test for HLA-B*51 genotyping are simple, but reliable for detecting HLA-B*51 alleles in clinical laboratories.

CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA.

Spark erosion: a high production rate method for producing Bi(0.5)Sb(1.5)Te3 nanoparticles with enhanced thermoelectric performance.

We report a new 'spark erosion' technique for producing high-quality thermoelectric nanoparticles at a remarkably high rate and with enhanced thermoelectric properties. The technique was utilized to synthesize p-type Bi(0.5)Sb(1.5)Te(3) nanoparticles with a production rate as high as 135 g h(-1), using a relatively small laboratory apparatus and low energy consumption. The compacted nanocomposite samples made from these nanoparticles exhibit a well-defined, 20-50 nm size nanograin microstructure, and show an enhanced figure of merit, ZT, of 1.36 at 360 K. Such a technique is essential for providing inexpensive, oxidation-free nanoparticles which are required for the fabrication of high performance thermoelectric devices for power generation from waste heat, and for refrigeration.

Carbapenem-resistant Acinetobacter baumannii: diversity of resistant mechanisms and risk factors for infection.

Carbapenem-resistant Acinetobacter baumannii (CRAB) are an increasing infectious threat in hospitals. We investigated the clinical epidemiology of CRAB infections vs. colonization in patients, and examined the mechanisms of resistance associated with elevated minimum inhibitory concentrations (MICs) for carbapenems. From January to June 2009, 75 CRAB strains were collected. CRAB infection was significantly associated with malignancy and a high APACHE II score. The most dominant resistance mechanism was ISAba1 preceding OXA-51, producing strains with overexpression of efflux pump. Strains carrying blaOXA-23-like enzymes had higher carbapenem MICs than those carrying blaOXA-51-like enzymes; however, the presence of multiple mechanisms did not result in increased resistance to carbapenems. There was no difference in the resistance mechanisms in strains from infected and colonized patients. The majority of strains were genetically diverse by DNA macrorestriction although there was evidence of clonal spread of four clusters of strains in patients.

Diagnostic value of 18F-FDG PET/CT in patients with fever of unknown origin.

This study investigates the diagnostic value of (18) F-fluorodeoxyglucose positron emission tomography/computed tomography ((18) F-FDG PET/CT) in patients with 109 classical fever of unknown origin (FUO). Of the 48 (18) F-FDG PET/CT scans, 41 (85.4%) were interpreted as abnormal, and 25 (52.1% of all scans) were considered clinically helpful. The final cause of fever was determined in 41 patients (85.4%); infection (25%), malignancy (12.5%), non-infectious inflammatory disease (16.7%) and miscellaneous causes (31.3%). (18) F-FDG PET/CT contributed to the final diagnosis of FUO in 65.8%.

Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers.

BACKGROUND: The objective of the study was to evaluate the implications of androgen receptor (AR) in breast cancers. PATIENTS AND METHODS: We investigated immunohistochemical AR expression from the tissue microarrays of 931 patients between 1999 and 2005, and analyzed demographics and outcomes using uni-/multivariate analyses. Tumors with ≥10% nuclear-stained cells were considered positive for AR. RESULTS: AR was expressed in 58.1% of patients. AR was significantly related to older age at diagnosis, smaller size, well-differentiated tumors, higher positivity of hormone receptors, non-triple-negative breast cancers (non-TNBCs), and lower proliferative index. In estrogen receptor (ER)-negative tumors, AR was distinctively associated with human epidermal growth factor receptor type 2 (HER2) overexpression. With a mean follow-up of 72.7 months, AR was positively related to survival in ER-positive but not in ER-negative tumors. In Cox's models, AR was an independent prognostic factor for disease-free survival in ER-positive cancers. Interestingly, molecular apocrine tumors (ER negative and AR positive) with HER2 positive status showed trends of poorer outcome, but AR had no impact on survival in patients with TNBC. CONCLUSIONS: AR is significantly associated with favorable features in breast cancers and related to better outcomes in ER-positive not in ER-negative tumors. These results suggest that AR could be an additional marker for endocrine responsiveness in ER-positive cancers and a candidate for therapeutic targeting of ER-negative tumors.