Application of Deep Learning Techniques for Detection of Pneumothorax in Chest Radiographs.

With the advent of Artificial Intelligence (AI) and even more so recently in the field of Machine Learning (ML), there has been rapid progress across the field. One of the prominent examples is image recognition in the medical category, such as X-ray imaging, Computed Tomography (CT), and Magnetic Resonance Imaging (MRI). It has the potential to alleviate a doctor's heavy workload of sifting through large quantities of images. Due to the rising attention to lung-related diseases, such as pneumothorax and nodules, ML is being incorporated into the field in the hope of alleviating the already strained medical resources. In this study, we proposed a system that can detect pneumothorax diseases reliably. By comparing multiple models and hyperparameter configurations, we recommend a model for hospitals, as its focus on minimizing false positives aligns with the precision required by medical professionals. Through our cooperation with Poh-Ai Hospital, we acquired a total of over 8000 X-ray images, with more than 1000 of them from pneumothorax patients. We hope that by integrating AI systems into the automated process of scanning chest X-ray images with various diseases, more resources will be available in the already strained medical systems. Our proposed system showed that the best model that is used for transfer learning from our dataset performed with an AP of 51.57 and an AP75 of 61.40, with accuracy at 93.89%, a false positive of 1.12%, and a false negative of 4.99%. Based on the feedback from practicing doctors, they are more wary of false positives. For their use case, we recommend another model due to the lower false positive rate and higher accuracy compared with other models, which in our test shows a rate of only 0.88% and 95.68%, demonstrating the feasibility of the research. This promising result showed that it could be utilized in other types of diseases and expand to more hospitals and medical organizations, potentially benefitting more people.

Insulin-like growth factor (IGF) and hepatocyte growth factor (HGF) in follicular fluid cooperatively promote the oncogenesis of high-grade serous carcinoma from fallopian tube epithelial cells: Dissection of the molecular effects.

Incessant ovulation is believed to be a potential cause of epithelial ovarian cancer (EOC). Our previous investigations have shown that insulin-like growth factor (IGF2) and hepatocyte growth factor (HGF) in the ovulatory follicular fluid (FF) contributed to the malignant transformation initiated by p53 mutations. Here we examined the individual and synergistic impacts of IGF2 and HGF on enhancing the malignant properties of high-grade serous carcinoma (HGSC), the most aggressive type of EOC, and its precursor lesion, serous tubal intraepithelial carcinoma (STIC). In a mouse xenograft co-injection model, we observed that FF co-injection induced tumorigenesis of STIC-mimicking cells, FE25. Co-injection with IGF2 or HGF partially recapitulated the tumorigenic effects of FF, but co-injection with both resulted in a higher tumorigenic rate than FF. We analyzed the different transformation phenotypes influenced by these FF growth signals through receptor inhibition. The IGF signal was necessary for clonogenicity, while the HGF signal played a crucial role in the migration and invasion of STIC and HGSC cells. Both signals were necessary for the malignant phenotype of anchoring-independent growth but had little impact on cell proliferation. The downstream signals responsible for these HGF activities were identified as the tyrosine-protein kinase Met (cMET)/mitogen-activated protein kinase and cMET/AKT pathways. Together with the previous finding that the FF-IGF2 could mediate clonogenicity and stemness activities via the IGF-1R/AKT/mammalian target of rapamycin and IGF-1R/AKT/NANOG pathways, respectively, this study demonstrated the cooperation of the FF-sourced IGF and HGF growth signals in the malignant transformation and progression of HGSC through both common and distinct signaling pathways. These findings help develop targeted prevention of HGSC.

Exploiting the Nanostructural Anisotropy of ß-Ga2O3 to Demonstrate Giant Improvement in Titanium/Gold Ohmic Contacts.

Here we demonstrate a dramatic improvement in Ti/Au ohmic contact performance by utilizing the anisotropic nature of ß-Ga2O3. Under a similar doping concentration, Ti/Au metallization on (100) Ga2O3 shows a specific contact resistivity 5.11 × 10-5 Ω·cm2, while that on (010) Ga2O3 is as high as 3.29 × 10-3 Ω·cm2. Temperature-dependent contact performance and analyses suggest that field emission or thermionic field emission is the dominant charge transport mechanism across the Ti/Au-(100) Ga2O3 junction, depending on whether reactive ion etching was used prior to metallization. Cross-sectional high-resolution microscopy and elemental mapping analysis show that the in situ-formed Ti-TiOx layer on (100) Ga2O3 is relatively thin (2-2.5 nm) and homogeneous, whereas that on (010) substrates is much thicker (3-5 nm) and shows nanoscale facet-like features at the interface. The anisotropic nature of monoclinic Ga2O3, including anisotropic surface energy and mass diffusivity, is likely to be the main cause of the differences observed under microscopy and in electrical properties. The findings here provide direct evidence and insights into the dependence of device performance on the atomic-scale structural anisotropy of ß-Ga2O3. Moreover, the investigative strategy here─combining comprehensive electrical and materials characterization of interfaces on different semiconductor orientations─can be applied to assess a variety of other anisotropic oxide junctions.

Effect of ovulation IGF and HGF signaling on the oncogenesis of murine epithelial ovarian cancer cell ID8.

The incidence and mortality of epithelial ovarian cancer (EOC) are increasing in Taiwan and worldwide. The prognosis of this disease has improved little in the last few decades due to insufficient knowledge of the etiology. Previous studies on the role of ovulation in the development of EOC have unveiled IGF2, HGF, and other carcinogens in ovulatory follicular fluid (FF) that exert transformation activities on the exposed fallopian tube fimbria epithelium. However, an orthotopic proof in an animal model is lacking. By using the murine ID8 EOC cells and the syngenic transplantation model, this study explored the effect of FF on the oncogenesis of mouse ovarian cancer. We found FF promoted clonogenicity and anchorage-independent growth of ID8 cells, largely through the IGF-1R and cMET signaling. In contrast, FF modestly promoted cell proliferation independent of the two signals and did not affect cell migration and invasion. Transplantation of ID8 cells into the ovarian bursa of C57BL6/J mice orthotopically grew ovarian tumors and metastasized to the peritoneum with ascites formation. The tumorigenic rate and severity of the disease were positively correlated with the level of IGF-1R and cMET receptors on the cell surface. Our data demonstrated that ovulation, through the signaling of IGF/IGF-1R and HGF/cMET, promotes oncogenic phenotypes in a murine EOC model. The results provide further proof of the carcinogenic effect of ovulation in the development of EOC.

Acute encephalitis after COVID-19 vaccination: A case report and literature review.

Vaccine-related immune responses are one of the causes of encephalitis. Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) have been administered worldwide due to the ongoing global pandemic; cases of SARS-CoV-2 vaccination-related encephalitis were scarcely reported. An 82-year-old female was diagnosed with acute encephalitis following her first dose of vaccination with mRNA-1273 against SARS-CoV-2. The patient presented with fever and headache five days after vaccination, followed by behavior change 17 days after vaccination. Electroencephalographic recordings revealed focal slow waves in the right frontoparietal regions. Brain MRI revealed the signal change in the right middle and posterior temporal lobe. Cerebrospinal fluid analysis showed mildly elevated protein. She responded well to steroid pulse therapy and made a full recovery. The severity of the immune response following COVID-19 vaccination may be alleviated if adequate treatment is achieved. Physicians must be alert for encephalitis after vaccination to help ensure a favorable outcome.

Disseminated Mycobacterium peregrinum and Mycobacterium avium infection in a patient with AIDS: A case report and review of literature.

Disseminated nontuberculous mycobacterial infections are frequently recognized in patients living with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS) and Mycobacterium avium-intracellulare complex (MAIC) is the most common species. Mycobacterium peregrinum is a rapidly growing mycobacterium that accounts for 1-2% of community-acquired and healthcare-associated infections. It mainly causes skin and soft tissue infection. Disseminated infection by M. peregrinum has never been reported in patients with AIDS. We describe a case of disseminated co-infection of M. peregrinum and M. avium in a 33-year-old male with newly diagnosed AIDS, and review the literature regarding M. peregrinum infection. The patient's bone marrow culture grew M. peregrinum and his blood culture grew M. avium. The diagnosis of disseminated co-infection of M. peregrinum and M. avium was confirmed. Disseminated infection due to M. peregrinum is rare and diagnosis can be challenging. Due to limited case numbers, there is no treatment guideline for M. peregrinum nowadays. Further study is warranted for better understanding M. peregrinum related infections.

Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation.

The fallopian tube fimbrial epithelium, which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma. Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of fallopian tube epithelium. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor-thrombin-HGF activator (HGFA)-HGF cleavage cascade confers a sustained transformation activity to fallopian tube epithelium, high-grade serous carcinoma. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation.

Insuline-Like Growth Factor-2 (IGF2) and Hepatocyte Growth Factor (HGF) Promote Lymphomagenesis in p53-null Mice in Tissue-specific and Estrogen-signaling Dependent Manners.

Background: Trp53-/- mice are prone to develop lymphomas at old ages. Factors promoting this tumorigenesis are unknown. Here, we showed human ovulatory follicular fluid (FF) largely promotes lymphomagenesis in Trp53-/- mice at earlier ages. Meanwhile, we clarified that IGF2 and HGF are important cell transforming factors within FF. Methods: To induce tumor formation, 5% FFs, 100 ng/ml IGF2, 20 ng/ml HGF, or both IGF2 and HGF in a volume of 200 µl PBS, was injected into 8-wk-old female Trp53 -/- mice at the mammary fat pad. The injection was repeated weekly for up to 7 weeks or extending to 13 weeks to observe the accumulative incidence of lymphomagenesis. Immunohistochemistry staining and gene rearrangement analysis were used to identify the tumor type. Results: By injecting FF into the mammary fat pad weekly, lymphomas developed in 8/16 (50%) of mice by seven weeks. We identified IGF2 and HGF in FF is largely responsible for this activity. The same weekly injection of IGF2, HGF, and their combination induced lymphomas in 4/11 (36%), 3/8 (38%), and 6/9 (67%) mice, respectively. Interestingly, tumorigenesis was induced only when those were injected into the adipose tissues in the mammary gland, but not when injected into non-adipose sites. We also found this tumor-promoting activity is estradiol (E2)-dependent and relies on estrogen receptor (ER) α expression in the adipose stroma. No tumor or only tiny tumor was yielded when the ovaries were resected or when ER is antagonized. Finally, an extension of the weekly FF-injection to 13 weeks did not further increase the lymphomagenesis rate, suggesting an effect on pre-initiated cancer cells. Conclusions: Taken together, the study disclosed a robust tumor-promoting effect of IGF2 and HGF in the p53 loss-initiated lymphomagenesis depending on an adipose microenvironment in the presence of E2. In light of the clarity of this spontaneous tumor promotion model, we provide a new tool for studying p53-mediated lymphomagenesis and suggest that, as a chemoprevention test, this is a practical model to perform.

Acute Transverse Myelitis Following COVID-19 Vaccination.

An increasing number of people are undergoing vaccination for COVID-19 because of the ongoing pandemic. The newly developed, genetically engineered mRNA vaccines are critical for controlling the epidemic disease. However, major adverse effects, including neuroimmunological disorders, are being attributed to this vaccine. For instance, several cases of acute transverse myelitis (ATM) after COVID-19 vaccination have been reported in clinical trials. Here, we report an exceedingly rare case of longitudinally extensive transverse myelitis (LETM), a rare subtype of ATM involving three or more vertebral segments, that occurred shortly after vaccination with the Moderna COVID-19 (mRNA-1273) vaccine, with a comorbidity of vitamin B12 deficiency. The findings of subsequent investigations suggest the possibility that autoimmune responses are triggered by the reactions between anti-SARS-CoV-2 spike protein antibodies and tissue proteins, as well as the interaction between spike proteins and angiotensin-converting enzyme 2 receptors.

Accelerated Aging Stability of ß-Ga2O3-Titanium/Gold Ohmic Interfaces.

Stable ohmic contacts are critical to enable efficient operation of high-voltage electronic devices using ultrawide bandgap semiconductors. Here we perform, for the first time, thermally accelerated aging of Ti/Au ohmic interfaces to (010) ß-Ga2O3. We find that a heavily doped semiconductor, doped n-type by Si-ion implantation, treated with reactive ion etch (RIE), results in a low specific contact resistance of ∼10-5 Ω cm2 that is stable upon accelerated thermal aging at 300 °C for 108 h. The low resistance interface is due to thermionic field emission of electrons over an inhomogeneous barrier. Scanning/transmission electron microscopy indicates that the multi-layered structure and elemental distribution across the contact interface, formed during a 1 min 470 °C post-metallization anneal, do not change noticeably over the aging period. A ∼1 nm interfacial layer is observed by high-resolution microscopy at the Ti-TiOx/Ga2O3 interface on all samples exposed to RIE, which may contribute to their excellent stability. In addition, longer-range facet-like interfacial features are observed, which may contribute to the inhomogeneous barrier. In contrast, Ti/Au junctions to moderately doped (010) Ga2O3 made with no RIE treatment exhibit a high contact resistance that increases upon accelerated aging, along with a partially lattice-matched interface. The methods used here to understand the process, structure, and electrical property relationships for Ti/Au contact interfaces to ß-Ga2O3 can be applied to assess and tune the stability of a variety of other oxide-semiconductor interfaces.

Methicillin-resistant Staphylococcus aureus nasal colonization among HIV-infected patients in Taiwan: prevalence, molecular characteristics and associated factors with nasal carriage.

BACKGROUND: To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan. METHODS: From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized. RESULTS: Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within 1 year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909-31.731]) and antibiotic use within 1 year (aOR 3.89, [95% CI, 1.219-12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or VT, endemic community strains in Taiwan, four isolates as ST 8/SCCmec IV (USA 300) and one isolate as ST 239/SCCmec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). CONCLUSIONS: Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.

The clinical impact of patients with bloodstream infection with different groups of Viridans group streptococci by using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

The accuracy of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for identifying viridans group streptococcus (VGS) was improving. However, the clinical impact of identifying VGS had not been well recognized. Our study had comprehensively studied the clinical manifestations and outcome of VGS blood stream infection by using MALDI-TOF MS for identification.This retrospective study enrolled 312 adult patients with a monomicrobial blood culture positive for VGS. Blood culture was examined through MALDI-TOF MS.The most common VGS species were the Streptococcus anginosus group (38.8%) and Streptococcus mitis group (22.8%). Most species showed resistance to erythromycin (35.6%), followed by clindamycin (25.3%) and penicillin (12.5%). Skin and soft tissue infection and biliary tract infection were significantly related to S. anginosus group bacteremia (P = .001 and P = .005, respectively). S. mitis group bacteremia was related to infective endocarditis and bacteremia with febrile neutropenia (P = .005 and P < .001, respectively). Infective endocarditis was also more likely associated with S. sanguinis group bacteremia (P = .009). S. anginosus group had less resistance rate to ampicillin, erythromycin, clindamycin, and ceftriaxone (P = .019, <.001, .001, and .046, respectively). A more staying in intensive care unit, underlying solid organ malignancy, and a shorter treatment duration were independent risk factors for 30-day mortality. This study comprehensively evaluated different VGS group and their clinical manifestations, infection sources, concomitant diseases, treatments, and outcomes. Categorizing VGS into different groups by MALDI-TOF MS could help clinical physicians well understand their clinical presentations.

C-reactive protein levels can predict positive 18F-FDG PET/CT findings that lead to management changes in patients with bacteremia.

BACKGROUND/PURPOSE: Bacteremia portends high rates of morbidity and mortality. Although 18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET/CT) imaging has clinical value in assessing fever of unknown origin, its usefulness in bacteremia has not been entirely elucidated. We therefore designed the current single-center retrospective study to investigate 1) the clinical value of 18F-FDG PET/CT imaging in assessing bacteremia and 2) the association between laboratory data and imaging findings. METHODS: We examined 102 patients with bacteremia who had undergone 18F-FDG PET/CT imaging. The patients' clinical and laboratory data were reviewed and analyzed in relation to 18F-FDG PET/CT findings. Patients showing positive results underwent quantitative measurements of 18F-FDG uptake. RESULTS: Positive 18F-FDG PET/CT findings were identified in 74 (72.5%) patients, and 40 (54.1%) underwent modified treatment or management because of the imaging results (p = 0.003). Positive 18F-FDG PET/CT findings were significantly associated with higher white blood cell (WBC) counts and C-reactive protein (CRP) levels (p = 0.012 and < 0.001, respectively). Notably, CRP levels accurately predicted (area under curve = 0.752; p < 0.001) positive 18F-FDG PET/CT findings (optimal cut-off point: 54.025 mg/L). CONCLUSION: A majority (54.1%, n = 40) of the patients with positive 18F-FDG PET/CT results underwent treatment modifications; they accounted for most cases (87%) of management changes in our cohort. Leukocytosis and increased CRP levels are significantly associated with positive 18F-FDG PET/CT findings in patients with bacteremia. CRP levels >54.025 mg/L were accurate predictors of positive 18F-FDG PET/CT results.

Vancomycin-resistant Enterococcus faecium at a university hospital in Taiwan, 2002-2015: Fluctuation of genetic populations and emergence of a new structure type of the Tn1546-like element.

BACKGROUND/PURPOSES: Vancomycin resistance increased significantly to 31.3% among Enterococcus faecium in 2006 and remained high thereafter at a university hospital in Taiwan. A longitudinal study was retrospectively conducted to characterize these vancomycin-resistant E. faecium (VRE-fm). METHODS: A total of 378 non-repetitive VRE-fm blood isolates collected during 2002-2015 were studied. Multilocus sequence typing, pulsed-field gel electrophoresis, analysis of van genes and the Tn1546 structure, and conjugation experiments were performed. RESULTS: The majority (78.0%) of the isolates were associated with hospital-acquired infections. Molecular typing revealed nine major pulsotypes and five predominant sequence types (STs): ST17 (33.9%), ST78 (18.3%), ST414 (14.6%), ST18 (10.6%), and ST203 (7.4%). Fluctuation of these prevailing STs among the study years in association with some major pulsotypes was noted. All isolates carried vanA genes, except that in four isolates vanB genes were found. Among the vanA-carrying Tn1546-like elements, one predominant structure type (Type I, 55.9%) was noted throughout the study years. Since 2009, another predominant structure type (Type II, 40.1%) has emerged firstly in ST414 and gradually spread to other 11 STs in subsequent years. Isolates carrying these Type II Tn1546-like elements have become the most predominant population since 2014, majorly found in ST78 and ST17. Preliminary experiments indicated that plasmids carrying the Type II Tn1546-like elements demonstrated ten-fold higher efficiency than those carrying the Type I Tn1546-like elements. CONCLUSION: Dissemination of some major STs and horizontal transfer of plasmids carrying two major structure types of Tn1546-like elements may have together contributed to the increase of VRE-fm infection.

Use of prokinetic agents or antibiotics is associated with the occurrence of spontaneous bacterial peritonitis in cirrhotic patients.

BACKGROUND: Prokinetics have been shown to improve intestinal bacterial overgrowth and dysmotility in cirrhotic patients. Antibiotics are suggested for high risk patients for prophylaxis of spontaneous bacterial peritonitis (SBP). However, limited studies have investigated the association of SBP and these medications. We examined the association of prokinetics or antibiotics use and the first episode of SBP development in patients with cirrhosis. METHODS: We conducted a case-crossover study using the Taiwanese National Health Insurance Research Database from 2001 to 2010. A total of 129 cirrhotic patients with SBP were identified (defined as International Classification of Disease-Ninth Revision-CM codes: 571.xx for cirrhosis; 567.2, 567.8, and 567.9 for ascites; 789.5 for SBP). We investigated the short term (defined as 14-day period) effect of prokinetic agents or antibiotics use on SBP development using conditional logistic regressions with the adjustment of potential confounders. RESULTS: The results suggested that prokinetic agents or antibiotics use during the 14 days before SBP were associated with an increased risk of SBP [adjusted odds ratio (OR) = 3.2, 95% confidence interval (CI): 1.02-10.04 for prokinetic agents; and adjusted OR = 2.95, 95% CI: 1.05-5.23 for antibiotics]. In dose analysis, the use of prokinetic agents more than 0.5 defined daily dose was more commonly found in the case period without a statistical difference (adjusted OR = 3.637; 95% CI: 0.69-19.13). CONCLUSION: The results demonstrated an increased risk of primary SBP development among cirrhotic patients with prokinetic agents or antibiotics use. It is important to closely monitor those patients for the occurrence of SBP.

Clinical utility of FDG PET/CT in acute complicated pyelonephritis-results from an observational study.

BACKGROUND: Acute complicated pyelonephritis (ACP) is an upper urinary tract infection associated with coexisting urinary tract abnormalities or medical conditions that could predispose to serious outcomes or treatment failures. Although CT and magnetic resonance imaging (MRI) are frequently used in patients with ACP, the clinical value of 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) has not been systematically investigated. This single-center retrospective study was designed to evaluate the potential usefulness of FDG PET/CT in patients with ACP. METHODS: Thirty-one adult patients with ACP who underwent FDG PET/CT were examined. FDG PET/CT imaging characteristics, including tracer uptake patterns, kidney volumes, and extrarenal imaging findings, were reviewed in combination with clinical data and conventional imaging results. RESULTS: Of the 31 patients, 19 (61%) showed focal FDG uptake. The remaining 12 study participants showed a diffuse FDG uptake pattern. After volumetric approximation, the affected kidneys were found to be significantly enlarged. Patients who showed a focal uptake pattern had a higher frequency of abscess formation requiring drainage. ACP patients showing diffuse tracer uptake patterns had a more benign clinical course. Seven patients had suspected extrarenal coinfections, and FDG PET/CT successfully confirmed the clinical suspicion in five cases. FDG PET/CT was as sensitive as CT in identifying the six patients (19%) who developed abscesses. Notably, FDG PET/CT findings caused a modification to the initial antibiotic regimen in nine patients (29%). CONCLUSIONS: FDG PET/CT may be clinically useful in the assessment of patients with ACP who have a progressive disease course.

Clinical characteristics and treatment outcomes of vancomycin-resistant Enterococcus faecium bacteremia.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE-fm) bacteremia causes significant mortality in hospitalized patients. We sought to investigate clinical characteristics, treatment outcomes, and microbiological eradication associated with VRE-fm bacteremia. METHODS: A retrospective cohort study was conducted and included 210 adult patients admitted between January 1, 2011 and December 31, 2015. RESULTS: The mean Pitt bacteremia score was 4.7. ICU stay (48.6%) and mechanical ventilation (46.2%) were common. Diabetes mellitus was the most common concomitant disease (43.3%), followed by malignancies, including hematologic malignancies (14.3%) and solid cancers (28.1%). The 14-day and 28-day mortality rates were 37.1% and 50.5%, respectively. Linezolid or daptomycin treatment for at least 10 days and higher Pitt bacteremia scores were independently associated with 14-day and 28-day mortality. Longer treatment duration of linezolid or daptomycin predicted microbiological eradication independently. Daptomycin-treated patients tended to have higher 14-day and 28-day mortality, and lower microbial eradication rates (20.8% versus 8.7%; 40.6% versus 26.1%; 14.1% versus 26.1%; respectively) than linezolid-treated patients, and cumulative survival rates at 14 and 28 days tended to be lower in patients who received low-dose daptomycin (<10 mg/kg/day) than that in those who received linezolid and high-dose daptomycin (≥10 mg/kg/day); however, the differences were not statistically significant. CONCLUSION: Higher disease severity and inappropriate treatment were associated with increased mortality and longer treatment duration of linezolid or daptomycin was associated with microbial eradication for the patient with VRE-fm bacteremia.

Characterization of two novel variants of staphylococcal cassette chromosome mec elements in oxacillin-resistant Staphylococcus lugdunensis.

OBJECTIVES: Staphylococcus lugdunensis, a species of CoNS, has become an important hospital pathogen because of increasing resistance to ß-lactam antibiotics such as methicillin and oxacillin. Methicillin resistance is mainly due to the acquisition of the staphylococcal cassette chromosome (SCC) mec (SCCmec). Little is known about the structure of SCCmec in methicillin- or oxacillin-resistant CoNS. METHODS: WGS was performed to determine the structure of SCCmec elements of two clinical S. lugdunensis isolates: CMUH-22 and CMUH-25. RESULTS: These elements were found to be flanked by DRs and IRs with unique mosaic structures and a common integration site in the 3' end of the rlmH gene. The sequences of the regions located between rlmH and the ISSau4-like transposase genes of both elements were similar to those of SCCmec Vt of Staphylococcus aureus PM1. The SCCmec (type V, 5C2&4) of CMUH-25 harboured a novel ccrC complex and a C2-like mec complex in opposite orientations, similar to the type V SCCmec of S. aureus WIS. The sequences of the ccrA4B4 genes and J1 and J2 regions of CMUH-25 were similar to those of the SCC element of Staphylococcus haemolyticus NCTC 11042. In contrast, portions of the sequence of the J1 region of type Vt (5C2) SCCmec in strain CMUH-22 were highly similar to portions of those of Staphylococcus epidermidis RP62A and the composite SCCmec type V of S. aureus WAMRSA40. CONCLUSIONS: These observations suggest that the SCCmec elements of CMUH-25 and CMUH-22 evolved separately and assembled through different recombination events.

Influence of borderline cefepime MIC on the outcome of cefepime-susceptible Pseudomonas aeruginosa bacteremia treated with a maximal cefepime dose: a hospital-based retrospective study.

BACKGROUND: We assessed the influence of current cefepime minimal inhibitory concentration (MIC) breakpoints and the maximal cefepime dose on treatment outcomes in patients with bacteremia caused by cefepime-susceptible Pseudomonas aeruginosa. METHODS: Adult patients hospitalized between July 2010 and June 2014 with a positive blood culture for cefepime-susceptible P. aeruginosa and receipt of cefepime as the primary therapy throughout the course were reviewed. Cefepime Etest® MICs and clinical outcomes for P. aeruginosa bacteremia were reviewed to identify the MIC breakpoint influencing treatment outcomes. RESULTS: Of the 90 patients enrolled, 49 (54.4%) were male (mean age = 66.8 years). The mean Acute Physiology and Chronic Health Evaluation II score was 22.01. Sixty patients (66.7%) received a maximal cefepime dose, and the 30-day crude mortality rate was 36.7%. MIC90 of cefepime for P. aeruginosa was 8 mg/L. The cumulative survival rate at 30 days revealed that a lower cefepime MIC (<4 mg/L) for P. aeruginosa was associated with a higher survival rate than a higher MIC (≥4 mg/L) (72.6% vs. 23.5%, p < 0.0001). A cefepime MIC of ≥4 mg/L and age were independent risk factors for mortality, whereas the maximal cefepime dose was the independent protective factor. The use of a maximal cefepime dose did not improve the outcomes of patients with P. aeruginosa bacteremia at a MIC of ≥4 mg/L. CONCLUSIONS: A cefepime MIC of 4 mg/L may predict an unfavorable outcome among patients with serious infections caused by P. aeruginosa, even the MICs still within the CLSI susceptibility breakpoint.

Development of carbapenem resistance in Pseudomonas aeruginosa is associated with OprD polymorphisms, particularly the amino acid substitution at codon 170.

Objectives: Pan-susceptible Pseudomonas aeruginosa (PSPA) clinical isolates carrying an OprD with loop 7 shortening (the group-1A allele) were found to rapidly develop carbapenem resistance under continuous selection pressure. We further studied whether OprD polymorphisms are associated with the potential to develop carbapenem resistance. Methods: OprD amino acid sequences of 126 PSPA clinical isolates were analysed to determine their STs using P. aeruginosa strain PAO1 as the control strain. Site-directed mutagenesis was performed in PAO1 to generate polymorphisms of interest. A disc diffusion method was used to select carbapenem-resistant variants from the mutant strains. Expression levels of oprD were determined by quantitative RT-PCR. MICs of carbapenems were determined by Etest. Results: Forty-eight (38.1%) of the tested isolates carried the group-1A allele. Another two major STs, C1 and C2, both of which harboured an F170L polymorphism, were found in 21 (16.7%) and 39 (31.0%) isolates, respectively. The PAO1 type was also found in 14 (11.1%) isolates. Under continuous selective pressure, isolates of most STs developed carbapenem resistance at different numbers of passaging events; only those belonging to the PAO1 type remained susceptible. However, PAO1 mutants carrying either the oprD group-1A allele or the OprD-F170L polymorphism were able to develop carbapenem resistance. Reduced oprD expression triggered by continuous imipenem challenge was found in PAO1 mutants, but not in the PAO1 WT strain. Conclusions: OprD polymorphisms, particularly the F170L substitution and the specific shortening in loop 7, appear to determine the potential for P. aeruginosa to develop carbapenem resistance.