DEVELOPING INTEGRATED MACHINE LEARNING MODELS FOR AUTOMATIC COMPUTER-AIDED DIAGNOSIS IN ISCHEMIC ACUTE STROKE MRI

Fast detection and quantification of lesion cores in diffusion weighted images (DWIs) has been highly anticipated in clinical and research communities for planning treatment of acute stroke. The recent emergence of successful machine learning (ML) methods, especially Deep Learning (DL), enables automatic Computer Aided Diagnosis (CAD) of stroke in DWIs. However, the lack of publicly available large-scale data and ML models in clinical acute stroke DWI application are still the bottlenecks. In this work, we established the first large annotated open-source database of 2,888 clinical acute stroke MRIs (Chapter 2) to train and develop ML models for automatic stroke lesion detection and segmentation in clinical acute stroke MRI (Chapter 3). For automatic measurement of infarcted arterial territories, the first digital 3D deformable brain arterial territory atlas was created (Chapter 4). In addition, a fully automatic ML system is created to generate automatic radiological reports (Chapter 5 and 6) for calculation of ASPECTS, prediction and quantification of infarcted arterial and anatomical regions, and estimation of hydrocephalus presented in acute stroke MRI. The complete ML system in this work runs locally in real time with minimal computational requirements. It is publicly available and readily useful for non-expert users

Knowledge-based View in the Franchising Research Literature

Abstract. This study was conducted to understand the state of research on applications of Knowledge-based View in franchise systems. First, we used SALSA (Search, Appraisal, Synthesis, and Analysis), a simple systematic data search method, to obtain 61 sample papers. Second, the citations of authors and publications were analyzed using the bibliometric method to understand the authors and the publications that had the most impact as well as the trend of current studies in the field of knowledge-based theory application in franchise systems. The results showed that the journals that had the most publications on the topic were Entrepreneurship Theory and Practice and Journal of Business Research; the most cited author was S.A. Shane, who had an average rate of 1.016 citations per article, and the most cited study was a paper published by Darr, Argote, & Epple (1995), which was cited by 18 of the 61 sample papers (18/61, 29.51%). Third, we categorized the topic of knowledge-based theory application in franchise systems into six categories, i.e., knowledge transfer, knowledge creation, knowledge sharing, knowledge application, organizational learning, and knowledge exchange, to provide references for future studies.Keywords. Knowledge-based view; Franchising; Bibliometrics.JEL. L10

The impact of revised CLSI cefazolin breakpoints on the clinical outcomes of Escherichia coli bacteremia

AbstractBackground/PurposeThe susceptibility breakpoints of cephalosporins for Enterobacteriaceae were revised by the Clinical and Laboratory Standards Institute (CLSI) in 2010 and 2011. The clinical outcome and susceptibility data were analyzed to evaluate the impact of revised CLSI cefazolin breakpoints on the treatment of Escherichia coli bacteremia.MethodsForty-three bacteremic Escherichia coli isolates from Taichung Veterans General Hospital, Taichung, Taiwan, during the period from January 2013 to December 2013, were selected to analyze the minimum inhibitory concentration (MIC) distributions of cefazolin and the correlated clinical responses to cefazolin therapy.ResultsThe modal cefazolin MIC among the 43 isolates was 1 μg/mL and accounted for 18 (42%) isolates. The cumulative percentage for MICs ≤ 2 μg/mL was 79%. The conventional dosing regimens achieved clinical cure in 33 (97%) of 34 patients with bacteremia due to E. coli with a cefazolin MIC ≤ 2 μg/mL, in all of the six patients with a cefazolin MIC of 4 μg/mL, and all of the three patients with a cefazolin MIC of 8 μg/mL.ConclusionThe microbiological data support the revised CLSI breakpoints of cefazolin. The conventional cefazolin dosing regimens can still achieve satisfactory clinical cure rates for bacteremia of E. coli with a cefazolin MIC ≤ 2 μg/mL in patients without severe septic shock. Before the approval of the efficacy of cefazolin for the treatment of E. coli isolates with a cefazolin MIC of 4 μg/mL, it is prudent to use cefazolin only when a high drug level can be achieved in the infection site, such as the urinary tract

Antimicrobial Susceptibility and Multiplex PCR Screening of AmpC Genes From Isolates of Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens

Background/PurposeThe emergence of multiple drug resistance in Enterobacteriaceae is of particular concern. The aim of this study was to evaluate the antimicrobial susceptibility and screen for the ampC gene in three members of the Enterobacteriaceae family (Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens) found at Taichung Veterans General Hospital during the past 5 years using multiplex polymerase chain reaction (PCR).MethodsThe susceptibility of thirty isolates from each of the three Enterobacteriaceae family members to five antimicrobial agents (ceftazidime, flomoxef, imipenem, moxifloxacin, and colistin) was assessed. The susceptibility was analyzed by disk diffusion, screening and confirmatory tests for extended-spectrum β-lactamases (ESBL) and minimum inhibitory concentration tests according to the recommendations of the Clinical and Laboratory Standards Institute. The detection of ampC genes (3 families, including DHA, EBC and CIT) was performed by multiplex PCR. To detect the coexistence of ESBL genes, PCR was performed using five primer pairs: TEM, SHV, SHV-5, CTX-M-3, and CTX-M-14.ResultsOf the 90 isolates, 53 (58.9%) were positive in the screening test for ESBL. Resistance genes were detected in 12 (22.6%) of these isolates: ampC gene of DHA type in one E. cloacae isolate and EBC type in three E. cloacae isolates; ampC gene of CIT type in four C. freundii isolates; CTX-M-3-like in one C. freundii isolate and one S. marcescens isolate; TEM in three E. cloacae isolates, three C. freundii isolates and two S. marcescens isolates; SHV in one C. freundii isolate.ConclusionAntibiotic phenotypes cannot accurately distinguish the resistance mechanisms caused by ampC or ESBL, and especially in ESBL-ampC combinations. However, PCR is a useful technique for the identification of the different types of resistance genes

Clinical Outcome of Mycobacterium abscessus Infection and Antimicrobial Susceptibility Testing

Background/PurposeMycobacterium abscessus is the most resistant and rapidly growing mycobacterium and causes a wide range of clinical infectious diseases. The relationship between antimicrobial susceptibility and clinical outcome needs to be further evaluated.MethodsForty M. abscessus isolates were obtained from clinical specimens of 40 patients at the Taichung Veterans General Hospital from January 2006 to December 2008. Antimicrobial susceptibility testing was performed using the broth microdilution method according to the recommendations of the National Committee for Clinical Laboratory Standards. The clinical manifestations and outcomes were reviewed from medical records.ResultsTwenty-two patients were diagnosed with M. abscessus infection. Cough (86.3%), hemoptysis (31.8%) and fever (18.1%) were the most common symptoms. The radiographic findings included reticulonodular opacities (50.0%), consolidation (31.8%) and cavitary lesions (18.1%). The 40 isolates were susceptible to amikacin (95.0%), cefoxitin (32.5%), ciprofloxacin (10.0%), clarithromycin (92.5%), doxycycline (7.5%), imipenem (12.5%), moxifloxacin (22.5%), sulfamethoxazole (7.5%) and tigecycline (100%). The rate of treatment failure was 27.3% at the end of the 12th month after the start of treatment, although these patients were treated with a combination of clarithromycin and other antimicrobial agents.ConclusionM. abscessus is naturally susceptible to clarithromycin and amikacin, variably susceptible to cefoxitin and imipenem, and resistant to most other antimicrobial drugs. Combination therapy with clarithromycin, amikacin and other active antimicrobial agents may lead to clinical improvement; however, the rate of treatment failure is still high

The association of molecular typing, vancomycin MIC, and clinical outcome for patients with methicillin-resistant Staphylococcus aureus infections

AbstractBackground/PurposeThere are reports of an increase in vancomycin minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA) over time, a phenomenon referred to as “MIC creep”, but some studies have conflicting results. The aim of this study is to evaluate the association of molecular typing, vancomycin MIC, and clinical outcome for patients with MRSA infections.MethodsThirty-two MRSA isolates from Taichung Veterans General Hospital (TCVGH), Taichung, Taiwan during the period of 2003 to 2008 were analyzed for the association of sequence typing, vancomycin MIC, and the correlated clinical outcome for patients with MRSA infections. The vancomycin MICs of 28 additional isolates from 2014 were used for the detection of MIC creep.ResultsAmong the genotypes of 32 isolates, there were 17 (53.1%) isolates with ST239-SCCmecIII, seven (21.9%) isolates with ST5-SCCmecII, six (18.8%) isolates with ST59-SCCmecIV, and two (6.2%) isolates with ST59-SCCmecVT. Two isolates had an MIC of 2 μg/mL and were identified as ST239-SCCmecIII. No statistically significant change in the distribution of MICs of all isolates was observed between 2003 and 2014 (p = 0.263). There was no significant difference in the mortality rates between two groups of patients with vancomycin MICs < 2 μg/mL and ≥ 2 μg/mL (p = > 0.99).ConclusionThere was no vancomycin MIC creep in the period from 2003 to 2014 in this study. Appropriate prognostic models for assessment of the association among sequence types, vancomycin MICs, and clinical outcome warrant further investigation

Hemolytic Uremic Syndrome Caused by Enteroviral Infection

A 4-year-old boy presented with enteroviral infection complicated with atypical hemolytic uremic syndrome (aHUS). Enterovirus RNA was detected by reverse transcription polymerase chain reaction (RT-PCR) of both blood and kidney biopsy specimens. A survey of the complement system did not reveal a specific complement defect. Supportive therapy with blood components transfusion, plasma therapy, and immunosuppressants was administered, however, renal function did not recover. The results of this report demonstrate that the enterovirus is the cause of aHUS

Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy