Temporal change of enhancement after gadolinium injection on contrast-enhanced CMR in reperfused acute myocardial infarction.

BACKGROUND: A recent report demonstrated that early enhancement on contrast-enhanced cardiac magnetic resonance (CE-CMR) correlated with myocardial edema detected by T2-weighted CMR in reperfused acute myocardial infarction (AMI). However, the time at which the enhancement in salvaged myocardium disappears is yet to be determined. We aimed to examine the time course of the enhancement with the use of different quantification techniques and to compare the extent of enhancement with the myocardial edema. METHODS AND RESULTS: CE-CMR was performed at 2-20 min after gadolinium administration in 32 AMI patients. The extent of enhancement (% myocardium) was quantified by manual delineation and the threshold methods of 2-5 SDs above remote myocardium. In subendocardial infarct, the enhancement was greatest at 2 min regardless of the quantification techniques and decreased with time, particularly in the first 6 min. In transmural infarct, the change in the size of enhancement was modest although the time course of enhancement varied according to the quantification techniques. The sizes of enhancement were not significantly different between 15 and 20 min regardless of the techniques and infarct transmurality. The best agreement with myocardial edema was found at 2 min with average differences of 0.5% and -1.2% and limits of agreement of ±20.2% and ±21.2% for the manual and 2-SD techniques, respectively. CONCLUSIONS: The optimal timing for delineation of salvaged myocardium on CE-CMR is at 2min when the manual or 2-SD technique was employed. Imaging needs to be completed in a short time (ideally within a minute) because of rapid reduction of enhancement in salvaged myocardium.

Effect of caffeine on intravenous adenosine-induced hyperemia in fractional flow reserve measurement.

BACKGROUND: The interaction between caffeine and adenosine is still a matter of debate. AIMS: We examined whether caffeine attenuated intravenous adenosine-induced hyperemia in the measurement of fractional flow reserve (FFR) and whether an increased dose of adenosine overcame the caffeine antagonism. METHODS: FFR was measured using different adenosine doses (140, 175, and 210 µg/kg/min) and papaverine as a reference standard in patients with intermediate coronary stenoses, who refrained from caffeine for >24 h (no-caffeine group; n = 14) and those who consumed caffeine (caffeine group; n = 28). RESULTS: The median caffeine level in the caffeine group was 2.9 mg/L (interquartile range, 1.8-4.6 mg/L). In the no-caffeine group, FFR with adenosine did not decrease above the dose of 140 µg/kg/min (0.769, 0.771, and 0.770 at 140, 175, and 210 µg/kg/min, respectively) and was not significantly different from that with papaverine (0.765). In the caffeine group, adenosine overestimated FFR (140 µg/kg/min: 0.813, P<.001; 175 µg/kg/min: 0.806, P<.01; 210 µg/kg/min: 0.794, P=.01) compared with papaverine (0.779). The difference in FFR between papaverine and 140 µg/kg/min dose of adenosine was significantly greater in the caffeine group than in the no-caffeine group (0.034 vs 0.004; P<.05). CONCLUSION: Caffeine attenuates intravenous adenosine-induced hyperemia in FFR measurement. Even increased adenosine doses up to 210 µg/kg/min cannot fully surmount the antagonism.

Feasibility of free-breathing late gadolinium-enhanced cardiovascular MRI for assessment of myocardial infarction: navigator-gated versus single-shot imaging.

OBJECTIVES: The aim of this study was to evaluate the feasibility of two free-breathing late gadolinium-enhanced cardiovascular magnetic resonance (LGE-CMR) techniques (two-dimensional segmented navigator-gated [NAV-LGE] and single-shot [SS-LGE]) by comparing with breath-hold LGE-CMR (BH-LGE) as reference. METHODS: A total of 200 consecutive patients underwent the three LGE-CMR imaging techniques. BH patterns were assessed with dynamic navigator MR imaging. Image quality was graded on a 5-point scale (4=optimal; 0=not assessable). In patients with sufficient BH capability (diaphragmatic movement with a deviation of <3mm), hyperenhancement was scored with a 5-point scale, and global infarct size (%left ventricle) was quantified. RESULTS: Compared to free-breathing LGE-CMR, BH-LGE had higher image quality grade in patients with sufficient BH capability (P<0.01 [vs. NAV-LGE]; P<0.001 [vs. SS-LGE]) but poorer image quality in patients with insufficient BH capability (P<0.001 [vs. NAV-LGE]; P<0.01 [vs. SS-LGE]). NAV-LGE had higher sensitivity for infarct detection than SS-LGE (97.1% vs. 88.4%, P<0.05), but specificity was not significantly different (97.3% vs. 94.7%, P=0.37). By Bland-Altman analysis, the average differences in global infarct size were 0.4% and 1.2%, and the limits of agreement were ± 4.0% and ± 5.9% for NAV- and SS-LGE, respectively. CONCLUSIONS: Although both NAV- and SS-LGE improve the image quality in patients with insufficient BH capability, NAV-LGE is superior to SS-LGE in infarct detection and infarct size measurement. NAV-LGE can be a possible first-line technique for patients with inability to perform sufficient BH.

The efficacy of cefmetazole against pyelonephritis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae.

OBJECTIVES: Urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are on the increase. Although cefmetazole is stable in vitro against the hydrolyzing activity of ESBLs, no clinical study has ever evaluated its role in infections caused by these organisms. We therefore evaluated the efficacy of cefmetazole compared to carbapenems against pyelonephritis caused by ESBL-producing Enterobacteriaceae. METHODS: A retrospective chart review was conducted at a tertiary care hospital from August 2008 to July 2010. Chart reviews were done for patients with ESBL-producing organisms in urine identified in the microbiology database. Patients who were treated with cefmetazole were compared to those treated with carbapenems. The clinical and bacteriological cure rates at 4 weeks after completion of therapy were evaluated. RESULTS: Two hundred and fifty-six urine cultures growing ESBL-producing organisms were identified during the study period. Ten patients treated with cefmetazole and 12 patients treated with carbapenems were evaluated. There was no difference in clinical (9/10 vs. 12/12, p = 0.46) or bacteriological cure rate (5/7 vs. 6/7, p = 1.00) at 4 weeks after the completion of therapy. There was no difference in the incidence of adverse effects (2/10 vs. 2/12, p = 1.00). CONCLUSIONS: Cefmetazole may be a useful option for the treatment of UTIs caused by ESBL-producing organisms. Prospective and larger sized studies are needed to confirm our findings.

Hospital-acquired pneumonia in Japan may have a better mortality profile than HAP in the United States: a retrospective study.

The characteristics of hospital-acquired pneumonia (HAP) are not well documented. In the present study we investigated the severity and mortality, microbiological profile, and the value of Gram staining in culture-confirmed HAP in a Japanese hospital by retrospective review conducted at a Japanese university hospital. Only culture-confirmed cases with good specimen quality were included in the analysis. The clinical characteristics of HAP, as well as the causative organisms, were investigated. Furthermore, the prognostic ability of existing prediction rules were evaluated for prediction of overall mortality. Forty-two cases were enrolled in this analysis. The majority of patients were admitted to the ICU (61.9 %), and 40.5 % had ventilator-associated pneumonia (VAP). The 30-day mortality was 23.8 %, which is less than that reported in the United States. Factors commonly known to be associated with worse outcome in the USA did not appear to influence the mortality from HAP in Japan. The most frequent causative organisms were methicillin-resistant Staphylococcus aureus (MRSA), followed by Pseudomonas spp. Sensitivity and negative predictive value of Gram staining were 89.4 and 85.7 %, respectively. SMART-COP predicted 30-day mortality with an area under the ROC curve (AUC) >0.7. The characteristics of HAP in Japan differ from HAP reported in the USA. In addition to lower mortality, we found both fewer ICU cases and VAP. Gram staining of good-quality specimens demonstrated promising sensitivity to predict the causative organisms. SMART-COP predicted mortality with appropriate ROC curve (AUC).

Impact of hyponatremia and the syndrome of inappropriate antidiuresis on mortality in elderly patients with aspiration pneumonia.

BACKGROUND: Hyponatremia is associated with pneumonia, and aspiration pneumonia is common in the elderly, however, there has been no study of hyponatremia in this population. OBJECTIVE: To determine the impact of hyponatremia on mortality in elderly patients with aspiration pneumonia, while focusing on the comparison between those with and without the syndrome of inappropriate antidiuresis (SIAD). DESIGN: Retrospective review of existing database and medical records. SETTING: A community teaching hospital in Japan. PATIENTS: Two hundred and twenty-one elderly patients hospitalized with aspiration pneumonia. MEASUREMENTS: Multivariate logistical regression models were used to compare 30-day and in-hospital mortality, in patients with hyponatremia of various severities and etiologies, with that in patients with normal serum sodium concentrations. RESULTS: Sixty-five (29%) of 221 patients had hyponatremia. Of these 62 (95%) had hypotonic hyponatremia, which were further assessed as having hypovolemic (39 [63%]), hypervolemic (3 [5%]), and euvolemic (20 [32%]) hyponatremia. Of the 20 euvolemic patients, 14 (70%) had SIAD. Both moderate and severe hypotonic hyponatremia were significantly associated with increased in-hospital mortality (odds ratio [OR] 6.05, 95% confidence interval [CI] 1.46-25.0, and OR 5.65, 95% CI 1.14-28.1, respectively). Hyponatremia due to SIAD was significantly associated with both increased 30-day mortality (OR 7.40, 95% CI 1.73-31.7) and increased in-hospital mortality (OR 22.3, 95% CI 4.26-117). In contrast, hypovolemic hyponatremia was not significantly associated with increased mortality. CONCLUSIONS: Hyponatremia due to SIAD was strongly associated with increased mortality in elderly patients with aspiration pneumonia, whereas hypovolemic hyponatremia was not associated with increased mortality.

Peri-infarct zone on early contrast-enhanced CMR imaging in patients with acute myocardial infarction.

OBJECTIVES: The aims of this study were to evaluate hyperenhanced regions on contrast-enhanced cardiovascular magnetic resonance (CE-CMR) imaging in patients with acute myocardial infarction (AMI) between early contrast-enhanced cardiovascular magnetic resonance (ECE) (2 min) and late contrast-enhanced cardiovascular magnetic resonance (LCE) (10 to 15 min) after gadolinium administration, and to compare the CE-CMR images with area at risk (AAR) derived from T2-weighted (T2W) CMR. BACKGROUND: Although CE-CMR imaging can demarcate the infarcted myocardium, the value of hyperenhancement in AMI is still in dispute. The size of hyperenhanced regions may vary with time, and overestimation can be often observed with early acquisition. METHODS: Thirty-four patients with successfully reperfused AMI underwent CMR within 4 days after the event. Myocardial regions as percentage of left ventricular (LV) myocardium were quantified on CE and T2W images. Relative peri-infarct zone was calculated as the difference in hyperenhanced regions between ECE and LCE, normalized to the individual infarct size. RESULTS: Both ECE and LCE images revealed hyperenhancement in the territory of the infarct-related artery in all patients. The hyperenhanced region on ECE extended transmurally and was consistently larger than that on LCE (39 ± 12% vs. 27 ± 12% of LV myocardium, p<0.001). The relative peri-infarct zone was inversely correlated with the transmurality of infarction (r=-0.59, p<0.001) and the time from symptom to reperfusion (r=-0.46, p<0.01). The hyperenhanced region on ECE was correlated with the T2W CMR-derived AAR (r=0.86, p<0.001) with the average difference of -0.8% and the limits of agreement of ±11.9%. CONCLUSIONS: ECE depicts ischemically injured but salvaged myocardium, as well as infarcted myocardium in patients with AMI. The myocardium at risk and infarcted myocardium after reperfusion can be retrospectively assessed by the combination of ECE and LCE.

Highly cooperative double metalation of a bis(N2O2) ligand based on bipyridine-phenol framework driven by intramolecular π-stacking of square planar nickel(II) complex moieties.

Highly cooperative double metalation took place when a novel ligand based on a bipyridine-phenol framework was allowed to react with nickel(II) acetate. The π-stacking of the square planar metal complex moieties is responsible for the highly cooperative double metalation judging from the X-ray crystal structure in which two complex moieties stack on top of each other in a parallel fashion.

Clinical findings in parvovirus B19 infection in 30 adult patients in Kyoto.

To relate the clinical findings of parvovirus B19 infection to the phase of the disease, we performed a retrospective chart review of 30 adult patients who tested positive for IgM antibody against parvovirus B19 at our hospital from March 2003 to November 2008. Median patient age was 38 years, with 86.7% aged between 26 and 45 years. The male-to-female ratio was 4:26 (86.7% female). Symptoms in the first phase were mainly flu-like, including fever, headache, or myalgia. Symptoms in the second phase were arthralgia in 24 (85.7%) and rash in 23 (82.1%). Fever was observed in 21 (70.0%), and 22 (75.9%) were found to be lymphopenic. The onsets in 73.3% of cases were concentrated within 10.1% of the study period, an observation nearly consistent with an outbreak of erythema infectiosum. Three patients had symmetrical swelling of joints, all of whom also had rash. Most patients visited the hospital within a week of onset and prognosis was favorable. In the parvovirus B19 infection, flu-like symptoms were frequent in the first phase, while rash and arthralgia were common in the second. Female sex, age between 26 and 45, and presence of rash, arthralgia, fever, and lymphopenia were clinical findings with a high frequency (≥70%), and these factors may contribute to diagnosis. In an era when early diagnosis and therapy is required in rheumatoid arthritis, it is important to recognize the parvovirus B19 infection with a presentation of acute arthritis and a favorable prognosis.

Effect of neutrophil elastase inhibitor (sivelestat sodium) in the treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis.

INTRODUCTION: Sivelestat is neutrophil elastase inhibitor, which is widely used in Japan for the treatment of acute lung injury. However, the clinical efficacy of the medication has not been convincingly demonstrated. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials on sivelestat for the treatment of acute lung injury and acute respiratory distress syndrome. Studies were identified using MEDLINE, EMBASE, Cochrane library, conference proceedings, and references of included studies. Authors were contacted if necessary. ICHUSHI, the Japanese database for medical literature and conference proceedings was also used for the search, since many studies on sivelestat were published in Japanese language and not registered in major databases such as MEDLINE. The primary outcome was mortality within 28-30 days after randomization. Relative risks were pooled with the random effect model. RESULTS: 8 trials were included in the analysis. There was no difference in mortality within 28-30 days after randomization (relative risk 0.95, 95% confidence interval 0.72 to 1.26). Subgroup analysis conducted only on studies conducted in Japan showed the same result (0.59, 0.28 to 1.28). There was no difference in mechanical ventilation days (standardized mean difference -0.43, -1.12 to 0.27), but sivelestat was associated with a better short term PaO(2)/FiO(2) ratio (0.30, 0.05 to 0.56). Heterogeneity was not significant for the main analysis and funnel plot did not suggest publication bias. CONCLUSION: Sivelestat was not associated with decreased mortality, even when including studies published in Japanese language.

Late gadolinium-enhanced cardiovascular MRI at end-systole: feasibility study.

OBJECTIVE: The purpose of this article is to evaluate the image quality and infarct size of segmented late gadolinium-enhanced cardiovascular MRI at end-systole, compared with middiastole, in patients with sinus rhythm (SR) and to compare the image quality of end-systole images in patients with atrial fibrillation (AFib) to that of end-systole and middiastole images in patients with SR. SUBJECTS AND METHODS: Study patients (n = 121) were distributed according to heart rate and rhythm: SR with low heart rate (≤ 65 beats/minute), SR with intermediate heart rate (66-75 beats/minute), SR with high heart rate (≥ 76 beats/minute), and AFib. Image quality was graded on a 5-point scale, where 4 equals optimal and 0 equals not assessable. Global infarct size (percentage of left ventricle [LV] myocardium) in patients with SR with myocardial infarction was quantified using a visual quantitative approach with a 5-point scale and a semiautomatic method. RESULTS: End-systole imaging had higher image quality than did middiastole imaging for patients with SR with high heart rate, whereas middiastole imaging had higher image quality than did end-systole imaging for patients with SR with low heart rate (p < 0.05 for patients with SR with low heart rate, p = 0.60 for patients with SR with intermediate heart rate, and p = 0.001 for patients with SR with high heart rate). The quality of end-systole imaging in patients with AFib was not significantly different from that in patients with SR (p = 0.40 vs SR middiastole imaging and p = 0.38 vs SR end-systole imaging). The average difference of global infarct size was -0.3% and 0.2% of LV myocardium, and the limits of agreement were ± 2.4% and ± 3.3% of LV myocardium, for visual assessment and semiautomatic assessment, respectively. CONCLUSION: End-systole imaging can provide accurate diagnosis of myocardial infarction, comparable to middiastole imaging. The image quality of end-systole imaging is less susceptible to heart rate and rhythm compared with middiastole imaging.

Systematic review and metaanalysis: urinary antigen tests for Legionellosis.

BACKGROUND: Urinary antigen assays offer simplicity and rapidity in diagnosing Legionnaires' disease, though studies report a range of sensitivities. We conducted a systematic review to assess the test characteristics of Legionella urinary antigen. METHODS: We searched Medline, Excerpta Medica Database, and bibliographies of retrieved articles. English-language studies were used and included if the absolute number of true-positive, false-negative, true-negative, and false-positive observations were available, and the "gold standards" were described clearly. Two investigators independently reviewed articles and extracted data. Quality was assessed with the Quality Assessment for Diagnostic Accuracy Studies (QUADAS). Sensitivities and specificities were pooled using a random-effects model weighted with the inverse of the SE calculated through the Wald method. RESULTS: Fifty articles were retrieved for detailed evaluation, and 30 met the inclusion criteria. All but two studies focused on serotype 1 Legionella. Forty assays were reported using six different methodologies, whereas 26 assays used commercial tests, and 14 assays used in-house tests. Study quality was generally low, with average QUADAS scores of 4.4 of a total of 14 points (range, 1 to 9 points). The pooled sensitivity was 0.74 (95% CI, 0.68 to 0.81), and the specificity was 0.991 (95% CI, 0.984 to 0.997). Higher quality studies had lower sensitivity, and there was evidence of publication bias. CONCLUSIONS: Legionella urinary antigen for serotype 1 appears to have excellent specificity, though modest sensitivity. However, the poor quality of the included studies and the presence of publication bias suggest an overestimation of test performance. High-quality studies are needed.

ECG-edited middiastolic phase reconstruction improves image quality at 64-MDCT coronary angiography of patients with atrial fibrillation.

OBJECTIVE: The aims of this study were to evaluate image quality at the absolute middiastolic and absolute end-systolic phases of 64-MDCT coronary angiography of patients with atrial fibrillation and to compare the findings with those among patients in sinus rhythm. SUBJECTS AND METHODS: Nineteen consecutively registered patients with atrial fibrillation and 19 patients in sinus rhythm taking heart-rate-lowering agents as needed underwent MDCT. Images were reconstructed with a half-scan reconstruction algorithm after ECG editing (deletion of short R-R intervals, insertion of additional temporal windows into the middiastolic phase of long R-R intervals, and shift of R points). We used a 5-point scale (4, no motion artifacts; 0, unevaluable) to evaluate motion artifacts and coronary artery image discontinuities greater than 1 mm on the curved multiplanar reconstruction images. Each coronary artery image with a motion score of 2 or greater for all segments and with 2 or fewer discontinuities was considered acceptable for diagnosis. RESULTS: Middiastolic images of patients with atrial fibrillation showed fewer motion artifacts and image discontinuities than did end-systolic images of patients with atrial fibrillation. Despite greater heart rate variability under the condition of similar mean heart rates in patients with atrial fibrillation, motion artifacts and image discontinuities on middiastolic images were not significantly different from those on sinus rhythm images. Acceptable quality was achieved on 91% of middiastolic atrial fibrillation images and 93% of sinus rhythm images. CONCLUSION: ECG-edited middiastolic atrial fibrillation images with aggressive heart rate control were of better quality than end-systolic images in patients with atrial fibrillation. The diagnostic image quality of the middiastolic images was comparable with that of sinus rhythm images.

Single- versus two- layer intestinal anastomosis: a meta-analysis of randomized controlled trials.

BACKGROUND: To compare single- with two- layer intestinal anastomosis after intestinal resection: a meta-analysis of randomized controlled trials. METHODS: Randomized controlled trials comparing single- with two-layer intestinal anastomosis were identified using a systematic search of Medline, Embase and the Cochrane Library Databases covering articles published from 1966 to 2004. Outcome of primary interest was postoperative leak. A risk ratio for trial outcomes and weighted pooled estimates for data were calculated. A fixed-effect model weighted using Mantel-Haenszel methods and a random-effect model using DerSimonian-Laird methods were employed. RESULTS: Six trials were analyzed, comprising 670 participants (single-layer group, n = 299; two-layer group, n = 371). Data on leaks were available from all included studies. Combined risk ratio using DerSimonian-Laird methods was 0.91 (95% CI = 0.49 to 1.69), and indicated no significant difference. Inter-study heterogeneity was significant (chi2 = 10.5, d.f. = 5, p = 0.06). CONCLUSION: No evidence was found that two-layer intestinal anastomosis leads to fewer post-operative leaks than single layer. Considering duration of the anastomosis procedure and medical expenses, single-layer intestinal anastomosis appears to represent the optimal choice for most surgical situations.

Treatment of acute pancreatitis with protease inhibitors: a meta-analysis.

OBJECTIVES: Protease inhibitors are used to treat acute pancreatitis, but their effectiveness remains unclear. We performed a meta-analysis to determine whether treatment with protease inhibitors reduces overall mortality or morbidity from acute pancreatitis. METHODS: Articles of randomized controlled trials evaluating effects of protease inhibitors for acute pancreatitis were retrieved by systematically searching Medline, the Cochrane Library and Journal@ovid databases published from January 1966 through December 2003. References of review articles were also searched manually. The main outcome in interest was the overall mortality rate from acute pancreatitis. RESULTS: Ten studies met the inclusion criteria. Treatment with protease inhibitors did not significantly reduce the mortality rate from acute pancreatitis (pooled risk difference, -0.03; 95% confidence interval, -0.07 to 0.01). Subgroup analyses showed that treatment with protease inhibitors significantly reduced the mortality rate in patients with moderate to severe pancreatitis (pooled risk difference, -0.07; 95% confidence interval, -0.13 to -0.01) as defined by mortality rate in the control group (control mortality rate > 0.10). The decrease in mortality rate was not significant in mild pancreatitis (pooled risk difference, 0.00; 95% confidence interval, -0.04 to 0.05). CONCLUSIONS: Treatment with protease inhibitors does not significantly reduce the mortality in patients with acute or mild pancreatitis, but may reduce the mortality in patients with moderate to severe pancreatitis.

Late-onset X-linked sideroblastic anemia following hemodialysis.

X-linked sideroblastic anemia (XLSA) is due to deficient activity of erythroid-specific 5-aminolevulinate synthase (ALAS2). We report here a patient who developed sideroblastic anemia at the age of 81 years while undergoing hemodialysis. The diagnosis of sideroblastic anemia was established by the presence of ringed sideroblasts in the bone marrow, and treatment with oral pyridoxine completely eliminated the ringed sideroblasts. We identified a novel point mutation in the fifth exon of this patient's ALAS2 gene, which resulted in an amino acid change at residue 159 from aspartic acid to asparagine (Asp159Asn). In vitro analyses of recombinant Asp159Asn ALAS2 revealed that this mutation accounted for the pyridoxine-responsiveness of this disease. The very late onset in this case of XLSA emphasizes that nutritional deficiencies caused either by dietary irregularities in the elderly or, as in this case, by maintenance hemodialysis therapy, may uncover occult inherited enzymatic deficiencies in the heme biosynthetic pathway.