Fluoroquinolone therapy for bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae

AbstractBackground/PurposeFor extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, carbapenems are recommended as first line therapy, and clinical data on the therapeutic efficacy of fluoroquinolones (FQs) is limited. This study compares the efficacy of FQs and carbapenems for bloodstream infections caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.MethodsBetween 2008 and 2010, adults with ESBL-producing E. coli or K. pneumoniae bacteremia at two medical centers were reviewed. Adults receiving definitive FQ or carbapenem therapy were compared in a propensity score-matched analysis, and 30-day mortality was the primary endpoint.ResultsA total of 299 patients were eligible. Patients receiving a FQ (n = 24), either ciprofloxacin or levofloxacin, had a lower 30-day mortality rate than those with carbapenem therapy (8.3%, 2/24 vs. 23.3%, 64/275; p = 0.12). Multivariate regression analysis revealed that a critical illness [Pitt bacteremia score ≥ 4 points; odds ratio (OR), 7.09; p < 0.001], rapidly fatal underlying disease (OR, 5.73; p < 0.001), and hospital-associated infection (OR, 2.57; p = 0.01) were independently associated with 30-day mortality. By contrast, FQ definitive therapy was a protective factor compared with carbapenems (OR, 0.18; p = 0.04). There were 72 matched cases with carbapenem therapy in a propensity score-matched analysis, and a difference in the 30-day mortality rate of two groups was noted (8.3% vs. 29.2%; p = 0.05).ConslusionFor ESBL-producing E. coli or K. pneumoniae bacteremia, ciprofloxacin or levofloxacin, if active in vitro, can be considered as a carbapenem-sparing alternative

Bacteremic pneumonia caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: Appropriateness of empirical treatment matters

BackgroundClinical information about bacteremic pneumonia caused by extended-spectrum beta-lactamase (ESBL)-producing organism is limited.MethodsA retrospective study was conducted at two medical centers in Taiwan. From May 2002 to August 2010, clinical information and outcome of adults with bacteremic pneumonia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae were analyzed. The primary outcome is the 30-day mortality.ResultsA total of 111 patients with bacteremic pneumonia caused by E. coli (37 patients, 33.3%) and K. pneumoniae (74, 66.7%) were identified. Their mean age was 69.2 years and 51.4% were male patients. Fifty-seven (51.3%) episodes were classified as hospital-acquired infections, 19 (17.1%) as health-care-associated infections, and four (3.6%) as community-acquired infections. Fifty-one (45.9%) patients received appropriate empiric antimicrobial therapy. The 30-day mortality rate was 40.5% (45 patients). In the multivariate analysis, several independent risk factors, including rapidly fatal underlying disease [odds ratio (OR), 5.75; 95% confidence interval (CI), 1.54–21.48; p = 0.009], severe sepsis (OR, 4.84; 95% CI, 1.55–15.14; p = 0.007), critical illness (OR, 4.28; 95% CI, 1.35–13.57; p = 0.013), and receipt of appropriate empirical therapy (OR, 0.19; 95% CI, 0.07–0.55; p = 0.002), were associated with 30-day mortality. The survival analysis consistently found that individuals with appropriate empiric therapy had a higher survival rate (log-rank test, p < 0.001).ConclusionESBL-producing bacteremic pneumonia, especially health-care-associated infections, often occurred in adults with comorbidities. Appropriate empirical therapy was associated with a favorable outcome

An integrated analysis tool for analyzing hybridization intensities and genotypes using new-generation population-optimized human arrays

The cross-sample plot of the multipoint LOH/LCSH analyses of the three samples used in Fig. 5. The plot comprises four panels: (a) The top-left panel is a cross-sample and cross-chromosome plot. The vertical axis is the index of study samples, and the horizontal axis is the physical position (Mb) on each of the 23 chromosomes. The blue and red bars represent SNPs without and with LOH/LSCH, respectively. (b) The top-right panel is a histogram of cross-chromosome aberration frequency. The vertical axis is the index of study samples, and the horizontal axis is the cross-chromosome aberration frequency of the corresponding samples. The pink (skyblue) background represents that the genetic gender of a sample is female (male). The histogram represents the aberration frequency of LOH/LCSH SNPs across the chromosomes of the corresponding samples. (c) The bottom-left panel is a histogram of the cross-sample aberration frequency. The vertical axis is the cross-sample aberration frequency of a SNP, and the horizontal axis is the physical position (Mb) on each of the 23 chromosomes. The purple line represents the aberration proportion of samples carrying the SNPs with LOH/LCSH. (d) The bottom-right panel is the legend of the genetic gender that is used in panel (b), where the pink (skyblue) background represents that the genetic gender of a sample is female (male). (TIFF 1656 kb

Shear stress regulation of miR-93 and miR-484 maturation through nucleolin.

Pulsatile shear (PS) and oscillatory shear (OS) elicit distinct mechanotransduction signals that maintain endothelial homeostasis or induce endothelial dysfunction, respectively. A subset of microRNAs (miRs) in vascular endothelial cells (ECs) are differentially regulated by PS and OS, but the regulation of the miR processing and its implications in EC biology by shear stress are poorly understood. From a systematic in silico analysis for RNA binding proteins that regulate miR processing, we found that nucleolin (NCL) is a major regulator of miR processing in response to OS and essential for the maturation of miR-93 and miR-484 that target mRNAs encoding Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS). Additionally, anti-miR-93 and anti-miR-484 restore KLF2 and eNOS expression and NO bioavailability in ECs under OS. Analysis of posttranslational modifications of NCL identified that serine 328 (S328) phosphorylation by AMP-activated protein kinase (AMPK) was a major PS-activated event. AMPK phosphorylation of NCL sequesters it in the nucleus, thereby inhibiting miR-93 and miR-484 processing and their subsequent targeting of KLF2 and eNOS mRNA. Elevated levels of miR-93 and miR-484 were found in sera collected from individuals afflicted with coronary artery disease in two cohorts. These findings provide translational relevance of the AMPK-NCL-miR-93/miR-484 axis in miRNA processing in EC health and coronary artery disease

Mobile Edge Computing Platform Deployment in 4G LTE Networks: A Middlebox Approach

This paper has been presented at : USENIX Workshop on Hot Topics in Edge Computing (Hot Edge '18)Low-latency demands for cellular networks have at-tracted much attention. Mobile edge computing (MEC), which deploys a cloud computing platform at the edge closer to mobile users, has been introduced as an enabler of low-latency performance in 4G and 5G networks. In this paper, we propose an MEC platform deployment so-lution in 4G LTE networks using a middlebox approach. It is standard-compliant and transparent to existing cel-lular network components, so they need not be modified. The MEC middlebox sits on the S1 interface, which con-nects an LTE base station to its core network, and does traffic filtering, manipulation and forwarding. It enables the MEC service for mobile users by hosting application servers. Such middlebox approach can save deployment cost and be easy to install. It is different from other stud-ies that require modifications on base stations or/and core networks. We have confirmed its viability through a pro-totype based on the OpenAirInterface cellular platform.We thank our shepherd Weisong Shi for his help, and also thank the anonymous reviewers for their valuable comments on improving this paper. This work was partially supported by the Ministry of Science and Technology, Taiwan, under grant numbers 106-2622-8-009-017 and 106-2218-E-009-018, and by the H2020 collaborative Europe/Taiwan research project 5G-CORAL (grant number 761586)

A large-scale survey of genetic copy number variations among Han Chinese residing in Taiwan

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) have recently been recognized as important structural variations in the human genome. CNVs can affect gene expression and thus may contribute to phenotypic differences. The copy number inferring tool (CNIT) is an effective hidden Markov model-based algorithm for estimating allele-specific copy number and predicting chromosomal alterations from single nucleotide polymorphism microarrays. The CNIT algorithm, which was constructed using data from 270 HapMap multi-ethnic individuals, was applied to identify CNVs from 300 unrelated Han Chinese individuals in Taiwan.</p> <p>Results</p> <p>Using stringent selection criteria, 230 regions with variable copy numbers were identified in the Han Chinese population; 133 (57.83%) had been reported previously, 64 displayed greater than 1% CNV allele frequency. The average size of the CNV regions was 322 kb (ranging from 1.48 kb to 5.68 Mb) and covered a total of 2.47% of the human genome. A total of 196 of the CNV regions were simple deletions and 27 were simple amplifications. There were 449 genes and 5 microRNAs within these CNV regions; some of these genes are known to be associated with diseases.</p> <p>Conclusion</p> <p>The identified CNVs are characteristic of the Han Chinese population and should be considered when genetic studies are conducted. The CNV distribution in the human genome is still poorly characterized, and there is much diversity among different ethnic populations.</p

Comparison of a Chinese Herbal Medicine (CCH1) and Lactulose as First-Line Treatment of Constipation in Long-Term Care: A Randomized, Double-Blind, Double-Dummy, and Placebo-Controlled Trial

Many institutionalized patients and their healthcare providers are dissatisfied with current laxative therapy. This study compared therapeutic efficacy, safety, and laxative cost of an herbal formula (CCH1) and lactulose for long stay patients with constipation. In this double-blind, double-dummy, and placebo-controlled trial, we randomized 93 residents with chronic constipation from two long-term care facilities in Taiwan to receive either CCH1 with lactulose placebo or CCH1 placebo with lactulose for 8 weeks, then followed up for 4 weeks without study medication. Both treatments were effective and well tolerated for patients, but CCH1 produced more spontaneous bowel movements, less rectal treatments, less amount of rescue laxative, and lower laxative cost than lactulose during treatment. No significant differences were found in stool consistency, stool amount, global assessment, and safety concerns. In conclusion, our results suggest that CCH1 may have better efficacy and could be used as an alternative option to lactulose in the treatment of constipation in long-term care

Dedifferentiated liposarcoma can induce a leukemoid reaction

SummaryLiposarcoma is one of the most common malignant soft tissue neoplasms in adults; however, few reports of liposarcoma had been described the expression of leukocytosis and granulocyte-colony stimulating factor (G-CSF). In this report, we present the rare case of a patient who had de-differentiated liposarcoma and elevated G-CSF levels that resulted in a leukemoid reaction. The patient was a 65-year-old man who had been lame for one month due to right thigh swelling. His body temperature was slightly elevated at 38°C and leukocytosis with an elevated white blood cell (WBC) count (41500/μL) was noted. The findings of computed tomography of the lower extremities indicated the presence of a malignancy. Therefore, an incision biopsy was performed. Based on the finding of magnetic resonance imaging (MRI) and the biopsy pathology report, we diagnosed the patient with liposarcoma. Moreover, the preoperative serum G-CSF level was elevated (261.8 pg/mL). An en bloc excision including the entire biopsy pathway was performed 5 days after admission. After en bloc excision of the tumor, WBC count, C-reactive protein (CRP) level, and G-CSF expression decreased. The final pathologic report confirmed the diagnosis of de-differentiated liposarcoma. No local recurrence or distant metastasis was detected in the follow-up image study, and the patient has remained asymptomatic 2 years after surgery. The case described here is a rare type of liposarcoma that produces G-CSF, which in turn, induces leukocytosis. Liposarcoma with elevated G-CSF levels resulting in a leukemoid reaction may indicate a poorly differentiated cell type and may be associated with a poor prognosis; however, en bloc excision of the tumor remains the primary treatment for this type of tumor. Moreover, the WBC count and G-CSF serum level can be as the tools monitoring the tumor recurrence

Be Stars in the Open Cluster NGC 6830

We report the discovery of 2 new Be stars, and re-identify one known Be star in the open cluster NGC 6830. Eleven H-alpha emitters were discovered using the H-alpha imaging photometry of the Palomar Transient Factory Survey. Stellar membership of the candidates was verified with photometric and kinematic information using 2MASS data and proper motions. The spectroscopic confirmation was carried out by using the Shane 3-m telescope at Lick observatory. Based on their spectral types, three H-alpha emitters were confirmed as Be stars with H-alpha equivalent widths > -10 Angstrom. Two objects were also observed by the new spectrograph SED-Machine on the Palomar 60 inch Telescope. The SED-Machine results show strong H-alpha emission lines, which are consistent with the results of the Lick observations. The high efficiency of the SED-Machine can provide rapid observations for Be stars in a comprehensive survey in the future.Comment: 11 pages, 8 figures, AJ in pres