Antimicrobial therapy and outcome of methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis. METHODS: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019. RESULTS: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis. CONCLUSION: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2019-2020: General view of the pathogens' antibacterial susceptibility.

The trends and prevalence of antimicrobial susceptibility of pathogens vary by country, region, and time. Long-term regular surveillance is required to investigate trends in the antimicrobial resistance of various isolated bacterial pathogens. We report the results of a nationwide surveillance on the antimicrobial susceptibility of bacterial respiratory pathogens in Japan conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology. The isolates were collected from clinical specimens obtained from adult patients who visited a collaborating medical facility between June 2019 and December 2020 and were diagnosed with respiratory tract infections by a physician. Antimicrobial susceptibility testing was performed in a centralized laboratory according to the methods recommended by the Clinical and Laboratory Standards Institute. Susceptibility testing was performed for 932 strains (201 Staphylococcus aureus, 158 Streptococcus pneumoniae, 6 S. pyogenes, 136 Haemophilus influenzae, 127 Moraxella catarrhalis, 141 Klebsiella pneumoniae, and 163 Pseudomonas aeruginosa) collected from 32 facilities in Japan. The proportions of methicillin-resistant S. aureus and penicillin-resistant S. pneumoniae were 35.3% and 0%, respectively. In H. influenzae, 16.2% and 16.9% were ß-lactamase-producing ampicillin resistant and ß-lactamase-negative ampicillin resistant, respectively. Extended-spectrum ß-lactamase-producing K. pneumoniae accounted for 5.0% of all K. pneumoniae infections. Carbapenemase-producing K. pneumoniae and multi-drug-resistant P. aeruginosa with metallo-ß-lactamase were not detected in this study. This surveillance will be a useful reference for treating respiratory infections in Japan and will provide evidence to enhance the appropriate use of antimicrobial agents.

Adverse events after administration of the first and second doses of messenger RNA-based COVID-19 vaccines in Japanese subjects aged 12-18 years.

OBJECTIVE: Using a prospective observational design, we assessed adverse events (AEs) after COVID-19 vaccination in Japanese patients. METHODS: Two doses of the mRNA-1273 (SPIKEVAX®) or BNT162b2 (COMIRNATY®) vaccine were administered to participants aged 12 to 18 years, and AEs after each dose were recorded for 14 days. Data on the duration and nature (local vs. systemic) of AEs were collected using a questionnaire. Sex-based differences in AE frequency were also analyzed. RESULTS: After the first and second doses, 152 and 135 vaccinees were enrolled, respectively. After the first dose, fever (>37.1°C) occurred in 38.9% of males and 50.0% of females, whereas local pain occurred in 89.8% and 97.7% of males and females, respectively (only SPIKEVAX® was used as the first dose). After the second dose, fever (>37.1°C) occurred in 77.8% and 82.6% of males vaccinated with COMIRNATY® and SPIKEVAX®, respectively, and 82.6% of females (all received SPIKEVAX®). The local pain rates in these groups were 80.6%, 76.3%, and 100%, respectively. After the second dose, local pain, fever (>38.1°C) and headache were significantly more common in female participants, and the median symptom duration was 3 days. CONCLUSIONS: AEs were more frequent after the second dose and in females.

A Prospective Study Regarding the Efficacy and Safety of the BNT162b2 Vaccine in Patients With Solid Malignancies Undergoing Systemic Chemotherapy.

BACKGROUND/AIM: To prospectively evaluate the efficacy and safety of the BNT162b2 vaccine in solid cancer patients undergoing systemic chemotherapy (n=63). PATIENTS AND METHODS: COVID-19 anti-spike protein antibody levels were measured before the first BNT162b2 vaccination, just before the second BNT162b2 vaccination, one month after the second BNT162b2 vaccination, and 3 months after the second BNT162b2 vaccination. Anti-spike protein antibody seropositivity was set at ≥0.8 U/ml. RESULTS: Colorectal cancer was the most commonly observed primary disease (36.5%). ECOG-PS 0 was observed in the majority (52.4%) of patients. The overall response rate and the median (range) anti-spike protein antibody levels in the whole cohort at 3 months after the second BNT162b2 vaccination were 98.4% (62/63) and 206 (0.4-3,813) U/ml. None of the patients required postponement or discontinuation of systemic chemotherapy because of an adverse reaction. CONCLUSION: The BNT162b vaccine in solid cancer patients undergoing systemic chemotherapy is effective and safe.

Association between history of HBV vaccine response and anti-SARS-CoV-2 spike antibody response to the BioNTech/Pfizer's BNT162b2 mRNA SARS-CoV-2 vaccine among healthcare workers in Japan: A prospective observational study.

INTRODUCTION: Inadequate vaccine response is a common concern among healthcare workers at the frontlines of the COVID-19 pandemic. We aimed to investigate if healthcare workers with history of weak immune response to HBV vaccination are more likely to have weak responses against the BioNTech/Pfizer's BNT162b2 mRNA SARS-CoV-2 vaccine. METHODS: We prospectively tested 954 healthcare workers for the Anti-SARS-CoV-2 spike (S) protein antibody titers prior to the first and second BNT162b2 vaccination doses and after four weeks after the second dose using Roche's Elecsys® assay. We calculated the percentage of patients who seroconverted after the first and second doses. We estimated the relative risk of non-seroconversion after the first BNT162b2 vaccine (defined as anti-SARS-CoV-2-S titer <15 U/mL) among HBV vaccine non-responders (HBs-Ab titer <10 mIU/mL) and weak responders (≥10 and <100 mIU/mL) compared to normal responders (≥100 mIU/mL). RESULTS: Among 954 healthcare workers recruited between March 9 and March 24, 2021 at Osaka Medical and Pharmaceutical University, weak and normal HBV vaccine responders had comparable S-protein titers after the first BNT162b2 dose (51.4 [95% confidence interval 25.2-137.0] versus 59.7 [29.8-138.0] U/mL, respectively). HBV vaccine non-responders were more likely than normal responders to not seroconvert after a single dose (age and sex-adjusted relative risk 1.85 95% confidence interval [1.10-3.13]) although nearly all participants seroconverted after the second dose. After limiting the analysis to 382 patients with baseline comorbidity data, the comorbidity-adjusted relative risk of non-seroconversion among HBV vaccine non-responders to normal responders was 1.32 (95% confidence interval [0.59-2.98]). DISCUSSION: Long term follow-up studies are needed to understand if protective immunity against SARS-CoV-2 wanes faster among those with history of HBV vaccine non-response and when booster doses are warranted for these healthcare workers.

Probability of target attainment of oral antimicrobials for Escherichia coli and Klebsiella pneumoniae based on Monte Carlo simulations.

Although early transition from intravenous to oral antimicrobials can reduce hospitalization duration, susceptibility breakpoints have not been established for many oral antimicrobials against Escherichia coli and Klebsiella pneumoniae bacteremia. Thus, we used population pharmacokinetic models, pharmacokinetic/pharmacodynamic indices, and Monte Carlo simulations to evaluate the probability of target attainment (PTA) for common oral antimicrobial dosages against E. coli and K. pneumoniae. The oral antimicrobial agents evaluated included cephalexin, cefaclor, cefditoren, amoxicillin/clavulanic acid, faropenem, and levofloxacin. For E. coli, the percentage of isolates with minimum inhibitory concentrations for which a PTA >90% was achieved was 53% and less than 20% for levofloxacin and the ß-lactams, respectively. For K. pneumoniae, the percentages of isolates for which a PTA >90% was achieved were comparatively higher (cephalexin, 73%; amoxicillin/clavulanic acid, 83%; levofloxacin, 96%). Our results suggest clinicians should check if pharmacokinetic/pharmacodynamic indices are achieved in individual patients before transitioning to oral antimicrobial therapy.

Effect of the introduction of a management bundle for blood culture collection.

BACKGROUND: Inappropriate blood collection subjected to blood culture (BC) causes BC contamination and may complicate the diagnose is of infectious diseases. Therefore, we developed a bundle based on the guideline recommendations for appropriate blood collection and examined the effects of bundle introduction. METHODS: We performed a retrospective analysis of BC samples to determine the contamination rates before and after introducing the BC bundle. We also analyzed the correlation between the compliance rate of the bundle and contamination rate, and between each bundle element and contamination. RESULTS: After the introduction of the bundle, the contamination rate was significantly reduced from 5.4% ± 0.9% to 1.7± 0.7% (P < .01). The compliance rate of the bundle was significantly associated with a lower contamination rate (P < .01). Multivariable logistic regression showed that collection from superficial veins of the cubital fossa (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.13-0.51, P < .01) and disinfection of the skin at the blood collection site with 1% chlorhexidine alcohol swab (OR, 0.41; 95% CI, 0.25-0.68, P < .01) were significantly associated with lower contamination. CONCLUSIONS: This study suggests that the introduction of the BC bundle significantly reduced the contamination rate, and bundle compliance was associated with a lower contamination rate.

Young Healthy Patient With Severe COVID-19 and Fulminant Community-Acquired Pseudomonas aeruginosa Pneumonia: A Case Report.

Community-acquired pneumonia (CAP) caused by Pseudomonas aeruginosa in healthy adults can rapidly lead to severe outcomes. We treated a case of P. aeruginosa-induced CAP and concurrent severe coronavirus disease (COVID-19) in a healthy 39-year-old man without other serious risk factors for severe illness except smoking. Immediately after admission, the patient developed sepsis and received intensive broad-spectrum antibacterial therapy with meropenem and vancomycin, veno-arterial extracorporeal membrane oxygenation (VAECMO), and catecholamine supplementation. Despite receiving multidisciplinary treatment, the patient died within 24 hours. P. aeruginosa with normal antimicrobial susceptibility was identified in blood and sputum cultures of samples taken at admission. Gram staining of the bacteria detected in blood cultures was suspicious for non-glucose-fermenting Gram-negative rods, including P. aeruginosa, and the antimicrobial regimen that was initiated following admission was considered effective. The patient was a plumber and a smoker, which are risk factors for P. aeruginosa-induced CAP, and the clinical course matched those in previous reports of P. aeruginosa-induced CAP, including necrotizing pneumonia with cavities and rapid progression of sepsis. Although COVID-19 can be the sole cause of septic shock, the combination of P. aeruginosa bacteremia and COVID-19 was possibly the cause of septic shock in this case. Even during an infectious disease pandemic, reviewing the patient's occupational history and comorbidities and performing blood and sputum culture tests, including Gram staining, are important for the provision of appropriate treatment.

Multiple Cardiovascular Diseases or Risk Factors Increase the Severity of Coronavirus Disease 2019.

BACKGROUND: This study aimed to determine whether disease severity varied according to whether coronavirus disease 2019 (COVID-19) patients had multiple or single cardiovascular diseases and risk factors (CVDRFs).Methods and Results:COVID-19 patients with single (n=281) or multiple (n=412) CVDRFs were included retrospectively. Multivariable logistic regression showed no significant difference in the risk of in-hospital death between groups, but patients with multiple CVDRFs had a significantly higher risk of acute respiratory distress syndrome (odds ratio: 1.75, 95% confidence interval: 1.09-2.81). CONCLUSIONS: COVID-19 patients with multiple CVDRFs have a higher risk of complications than those with a single CDVRF.

Evaluation of SARS-CoV-2 RNA quantification by RT-LAMP compared to RT-qPCR.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral load of SARS-CoV-2 is associated with mortality in COVID-19 patients. Measurement of viral load requires the use of reverse transcription quantitative PCR (RT-qPCR), which in turn requires advanced equipment and techniques. In this study, we aimed to evaluate the viral load measurement using reverse transcription loop-mediated isothermal amplification (RT-LAMP), which is a simpler procedure compared to RT-qPCR. MATERIALS AND METHODS: RNA was extracted by using the QIAamp Viral RNA Mini Kit. The RT-LAMP assay was performed by using the Loopamp® 2019-SARS-CoV-2 detection reagent kit and 10-fold serial dilutions of known viral load RT-LAMP were used to measure Tt, which is the time until the turbidity exceeds the threshold. Based on the relationship between viral load and Tt, the linearity and detection sensitivity of the calibration curve were evaluated. In addition, 117 clinical specimens were measured, and RT-qPCR and RT-LAMP assay results were compared. RESULTS: The dilution linearity of the calibration curve was maintained at five orders of magnitude 1.0× 106 to 1.0 × 101 copies/µL, and was confirmed to be detectable down to 1.0 × 100 copies/µL. The limit of quantification of RNA extracted from clinical specimens using RT-LAMP correlated well with that obtained using RT-qPCR (r2 = 0.930). CONCLUSION: The findings indicate that RT-LAMP is an effective method to determine the viral load of SARS-CoV-2.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of japanese society of chemotherapy, the japanese association for infectious diseases, and the japanese society for clinical microbiology in 2016: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 41.1% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.5% and 0.6%, respectively.

Observational study to determine the optimal dose of daptomycin based on pharmacokinetic/pharmacodynamic analysis.

High doses of daptomycin (DAP) (>6 mg/kg/day) have been preliminarily recommended in recent practical guidelines for methicillin-resistant Staphylococcus aureus infection, to achieve better clinical effects. While such doses can elevate the plasma trough concentration (Cmin) of DAP, there is an associated risk of creatine phosphokinase (CPK) elevation warranting further investigation. In the current study relationships between DAP Cmin and CPK elevation were investigated, and optimal DAP doses were determined. Plasma DAP concentrations were measured in 20 patients. Logistic regression analysis was performed to assess relationships between DAP Cmin and CPK elevation, then a population pharmacokinetic model of DAP was developed. To determine an optimal DAP dose a Monte Carlo simulation (MCS) was performed to minimize the risk of CPK elevation and maximize the probability of successful treatment. In logistic regression analysis DAP Cmin was significantly associated with CPK elevation (odds ratio 1.21, p = 0.048). With respect to dose-dependent increases in the probability of CPK elevation and exposure to DAP, MCS estimated an optimal DAP dose of 4-6 mg/kg/day, corresponding to a minimum inhibitory concentration (MIC) of ≤0.5 µg/mL. For an MIC of 1 µg/mL, MCS estimated an optimal DAP dose of 10 mg/kg/day. However, the probability of CPK elevation associated with high doses of DAP was higher than that associated with the approved doses. In cases where high doses of DAP are administered, close CPK monitoring is required and therapeutic drug monitoring of DAP may be desirable.

Transient depression of myocardial function after influenza virus infection: A study of echocardiographic tissue imaging.

BACKGROUND: Influenza virus infection (IVI) was reported to be associated with minor cardiac changes, mostly those detected on electrocardiogram with and without elevated blood markers of myocardial injury; however, the characteristics of myocardial involvement in association with IVI are poorly understood. This study used echocardiographic tissue imaging (tissue Doppler, strain, and strain rate) to evaluate changes in left atrial (LA) and left ventricular (LV) myocardial function after IVI. METHODS AND RESULTS: We examined 20 adult individuals (mean age, 43 years) at 2 and 4 weeks after diagnosis of IVI. For myocardial functional variables, we obtained LV global longitudinal strain (GLS), LV early diastolic strain rate (e'sr), LA strain, and LA stiffness (E/e'/LA strain), in addition to data on tissue Doppler (s', e', and a') and myocardial performance index. Blood markers of myocardial injury were also examined. During follow-up, there were no significant changes in global chamber function such as LV ejection fraction, E/e', and LA volume. However, significant changes in myocardial function were observed, namely, in s' (8.0 ± 1.6 cm/s to 9.3 ± 1.5 cm/s; p = 0.01), e' (10.2 ± 2.8 cm/s to 11.4 ± 3.0 cm/s; p < 0.001), e'sr (1.43 ± 0.44 1/s to 1.59 ± 0.43 1/s; p = 0.005), and LA strain (35 ± 8% to 40 ± 12%; p = 0.025), and the myocardial performance index (0.52 ± 0.20 to 0.38 ± 0.09; p = 0.009), but not in a', LA stiffness, or GLS. Cardiac troponin T and creatinine kinase isoenzyme MB were not elevated significantly at any examination. CONCLUSIONS: Myocardial dysfunction during IVI recovery appeared to be transient particularly in the absence of myocardial injury. Echocardiographic tissue imaging may be useful to detect subclinical cardiac changes in association with IVI.

The incidence of endophthalmitis or macular involvement and the necessity of a routine ophthalmic examination in patients with candidemia.

BACKGROUND: The incidence of ocular candidiasis (OC) in patients with candidemia varies across different reports, and the issue of whether routine ophthalmoscopy improves outcomes has been raised. This study investigated the incidence of OC and evaluate whether the extent of OC impacts the clinical outcomes. METHODS: This retrospective study included non-neutropenic patients with candidemia who underwent treatment at one of 15 medical centers between 2010 and 2016. Chorioretinitis without other possible causes for the ocular lesions and endophthalmitis was classified as a probable OC. If signs of chorioretinitis were observed in patients with a systemic disease that causes similar ocular lesions, they were classified as a possible OC. RESULTS: In total, 781 of 1089 patients with candidemia underwent an ophthalmic examination. The prevalence of OC was 19.5%. The time from the collection of a positive blood culture to the initial ophthalmic examination was 5.0 ± 3.9 days in patients with OC. The leading isolate was Candida albicans (77.9%). Possible OC was associated with unsuccessful treatments (resolution of ocular findings) (odds ratio: 0.354, 95% confidence interval: 0.141-0.887), indicating an overdiagnosis in patients with a possible OC. If these patients were excluded, the incidence fell to 12.8%. Endophthalmitis and/or macular involvement, both of which require aggressive therapy, were detected in 43.1% of patients; a significantly higher incidence of visual symptoms was observed in these patients. CONCLUSION: Even when early routine ophthalmic examinations were performed, a high incidence of advanced ocular lesions was observed. These results suggest that routine ophthalmic examinations are still warranted in patients with candidemia.

The Prevalence and Findings of Subclinical Influenza-associated Cardiac Abnormalities among Japanese Patients.

Objective Although life-threatening cardiac complications in influenza infection are rare, subclinical influenza-associated cardiac abnormalities may occur more frequently. We investigated the prevalence of subclinical cardiac findings. Methods After obtaining their written informed consent, 102 subjects were enrolled in the present study. The study subjects underwent a first set of examinations, which included electrocardiography (ECG), echocardiography, and the measurement of their cardiac enzyme levels. Those with one or more abnormal findings among these examinations were encouraged to undergo a repeat examination 2 weeks later. Results Among the 102 subjects enrolled, 22 (21.6%) were judged to have cardiac findings, including ST-T abnormalities, pericardial effusion, diastolic dysfunction, and cardiac enzyme elevation. Eighteen of these 20 subjects underwent a second screening at a median of 14 days later, and it was found that 11 of the 18 subjects were free from cardiac findings on this second examination. This suggested that the abnormalities were only transient and they therefore might have been associated with influenza. Approximately 20% of the influenza patients enrolled had cardiac findings, including ST-T segment abnormalities, pericardial effusion, and cardiac enzyme elevation. Conclusion Among the 102 patients who were studied, the cardiac findings were only mild and transient; however, physicians should be aware of influenza infection-associated cardiac abnormalities because such abnormalities may not be rare.

False Prolongation of Prothrombin Time in the Presence of a High Blood Concentration of Daptomycin.

Prothrombin time (PT) can reportedly be falsely prolonged by the antimicrobial drug daptomycin (DAP), and concomitant use of phosphatidylglycerol (PG). Although high doses of DAP (>6 mg/kg/day) are recommended for severe infection and result in a high blood concentration, the extent to which high blood concentrations of DAP interfere with PT, in the presence or absence of PG, has yet to be determined when using the HemosIL RecombiPlasTin 2G (Werfen Japan, Tokyo, Japan). We examined the effects of high doses of DAP on PT using this reagent. DAP (0-500 mg/L) was added to normal plasma and plasma with an already prolonged PT in the presence or absence of liposomal amphotericin B (L-AMB, 5-50 mg/L) or COATSOME EL-01 empty cationic liposomes (CS, 25-250 mg/L). Furthermore, we undertook a Monte Carlo simulation to calculate the probability of achieving DAP concentrations >100, >200 and >500 mg/L 0-48 hr after administering 6-12 mg/kg of DAP. Apparent PT increased with increasing DAP concentration, but neither L-AMB nor CS appeared to further elevate PT when co-administered with DAP. The probability of achieving DAP concentrations >100 and >200 mg/L increased with DAP dose. Higher doses of DAP than the approved dose caused false prolongation of PT. PT should be monitored carefully in patients taking high doses of DAP; ideally, PT should be measured at the trough blood concentration of DAP. Concomitant use of L-AMB and CS did not generally further elevate PT when co-administered with DAP.

Presence of Postsystolic Shortening Increases the Likelihood of Coronary Artery Disease: A Rest Electrocardiography-Gated Myocardial Perfusion SPECT Study.

UNLABELLED: Postsystolic shortening (PSS), which is a delayed myocardial contraction that occurs after end-systole, has been considered an important diagnostic index of myocardial ischemia. Recent technological advancements in quantitative gated SPECT (QGS) software enables the left ventricular (LV) regional analysis and may be useful for PSS measurement. The purpose of this study was to evaluate whether PSS at the resting condition determined by QGS is useful to identify patients with coronary artery disease. METHODS: The study comprised 146 patients (mean age ± SD, 71 ± 8 y; 98 men) with normal LV wall motion (mean LV ejection fraction ± SD, 72% ± 9%) who underwent both coronary angiography and resting (99m)Tc-tetrofosmin myocardial perfusion SPECT. The sum of the difference between post-end-systolic maximal LV thickening and end-systolic LV thickening, designated PSS index, was calculated from 17 LV myocardial segments using QGS. RESULTS: The PSS index was significantly higher in patients with significant stenosis of the coronary artery than in the other patients (9.8 ± 10.2 vs. 5.6 ± 5.1; P < 0.01). A cutoff point of 6.0 of the PSS index had sensitivity, specificity, positive predictive value, and negative predictive values of 55%, 70%, 76%, and 47%, respectively, for the diagnosis of coronary artery disease. Multivariate logistic regression analysis demonstrated that a PSS index greater than 6.0 was an independent predictor for the presence of coronary artery disease (odds ratio, 2.46; 95% confidence interval, 1.1-5.4; P < 0.05). CONCLUSION: Among subjects with normal LV function, PSS index even in the resting condition determined using QGS may help to identify patients with coronary artery disease.

Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study.

OBJECTIVE: Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers. METHODS: A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted. PATIENTS: This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011. RESULTS: The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/µL than for a WBC count of 4,000-8,000/µL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease. CONCLUSION: The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

Cardiovascular protection by ezetimibe and influence on oxidative stress in mice exposed to intermittent hypoxia.

Ezetimibe is as an inhibitor of NPC1L1 protein, which has a key role in cholesterol absorption. The aim of this study was to evaluate the influence of ezetimibe on the plasma lipid profile, atherosclerotic lesions, and cardiomyocyte ultrastructure in an animal model of atherosclerosis with intermittent hypoxia. Apolipoprotein E-knockout mice received a high-fat diet for 30 days. Then animals were exposed to intermittent hypoxia for 10 days or were maintained under normoxic conditions. In the ezetimibe group, ezetimibe (5 mg/kg/day) was added to the diet. Under normoxic conditions, the total cholesterol level was significantly lower in the ezetimibe group (63.6±6.6 mg/dl) than in the control group (116.3±16.9 mg/dl, P<0.001). Intermittent hypoxia accelerated atherosclerosis associated with increased superoxide production, which also caused degeneration of cardiomyocytes, mitochondrial abnormalities, and interstitial fibrosis. Compared with the control group, the ezetimibe group showed significantly less advanced atherosclerotic lesions and lower superoxide production in the thoracic aorta, as well as reduced oxidative stress, preservation of cardiomyocyte ultrastructure, and reduced interstitial fibrosis in the left ventricular myocardium. In conclusion, ezetimibe not only reduces total cholesterol, but also prevents the development of atherosclerosis and cardiovascular events due to intermittent hypoxia at least partly through suppression of oxidative stress.

Lung Nocardia elegans infection diagnosed on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

A 73-year-old man with adultonset Still's disease developed a high fever, coughing, dyspnea and bloody sputum and was therefore admitted to our hospital. Thoracic X-ray and CT scans revealed oval lesions in the bilateral lungs. A bacterial isolate from the sputum was identified to be Nocardia elegans (N. elegans) on comparative 16S rRNA gene sequencing and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). The patient recovered following treatment with imipenem/cilastatin and amikacin. To the best of our knowledge, this is the first case of nocardiosis caused by N. elegans identified on MALDI-TOF MS.