[Noise Nonuniformity Dependency on Exposure Settings in Computed Tomography].

PURPOSE: In X-ray computed tomography (CT), noise distribution within images is nonuniform and thought to vary with imaging conditions. This study aimed to evaluate noise nonuniformity by altering specific imaging conditions, such as tube voltage, bow-tie filter (BTF), and phantom size. METHODS: Using four tube voltages (80, 100, 120, and 135 kV), two BTF types (L and M), and circular water phantoms with diameters of 240, 320, and 400 mm, we employed filtered back projection (FBP) for reconstruction. Noise nonuniformity was assessed by defining six regions of interest (ROI) from the image center to the periphery, and the noise nonuniformity index (NNI) was calculated based on the standard deviation (SD) values within these ROIs. RESULTS: Results showed consistently larger noise SD values in the central region compared to the peripheral region under all imaging conditions, with the maximum NNI reaching 32.1%. Variations in NNI were observed, reaching up to 5.5 points for tube voltage, 7.8 points for BTF, and 8.2 points for phantom size. CONCLUSION: In conclusion, our quantitative assessment revealed moderate dependence of noise nonuniformity on imaging conditions in CT images.

Point-of-care molecular diagnosis of Mycoplasma pneumoniae including macrolide sensitivity using quenching probe polymerase chain reaction.

OBJECTIVES: Macrolides are generally considered to be the drugs of choice for treatment of patients with Mycoplasma pneumoniae infection. However, macrolide-resistant M. pneumoniae has been emerging since about 2000. The Smart Gene® system (MIZUHO MEDY Co., Ltd., Tosu, Japan) is a novel fully automated system for detection of pathogens using the method of quantitative polymerase chain reaction (qPCR) with QProbe (QProbe PCR). The entire procedure is completed within 50 min and the size of the instrument is small (15 x 34 x 30 cm). The purpose of this study was to evaluate the usefulness of the Smart Gene® system for detection of M. pneumoniae and detection of a point mutation at domain V of the 23S rRNA gene of M. pneumoniae. MATERIALS: Pharyngeal swab samples were collected from 154 patients who were suspected of having respiratory tract infections associated with M. pneumoniae. RESULTS: Compared with the results of qPCR, the sensitivity and specificity of the Smart Gene® system were 98.7% (78/79) and 100.0% (75/75), respectively. A point mutation at domain V of the 23S rRNA gene was detected from 7 (9.0%) of 78 M. pneumoniae-positive samples by the Smart Gene® system and these results were confirmed by direct sequencing. The minimum inhibitory concentrations of clarithromycin among the 5 isolates of M. pneumoniae with a point mutation at domain V of the 23S rRNA gene were >64 µg/ml and those among the 33 isolates without a mutation in the 23S rRNA gene were <0.0625 µg/ml. CONCLUSION: The Smart Gene® system is a rapid and accurate assay for detection of the existence of M. pneumoniae and a point mutation at domain V of the 23S rRNA gene of M. pneumoniae at the same time. The Smart Gene® system is suitable for point-of-care testing in both hospital and outpatient settings.

P1 gene of Mycoplasma pneumoniae isolated from 2016 to 2019 and relationship between genotyping and macrolide resistance in Hokkaido, Japan.

We characterized 515 Mycoplasma pneumoniae specimens in Hokkaido. In 2013 and 2014, the p1 gene type 1 strain, mostly macrolide-resistant, was dominant and the prevalence of macrolide resistance was over 50 %. After 2017, the p1 gene type 2 lineage, mostly macrolide-sensitive, increased and the prevalence of macrolide resistance became 31.0 % in 2017, 5.3 % in 2018 and 16.3 % in 2019.

Effect of Serum SPARC Levels on Survival in Patients with Digestive Tract Cancer: A Post Hoc Analysis of the AMATERASU Randomized Clinical Trial.

Observational studies suggest that physical activity may improve, whereas sarcopenia may worsen the survival of cancer patients. It has been suggested that secreted protein acidic and rich in cysteine (SPARC), one of the myokines that is secreted into the bloodstream by muscle contraction, has tumor-suppressive effects. Based on the hypothesis that serum SPARC level may be a potential prognostic biomarker, a post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative oral vitamin D supplementation (2000 IU/day) in patients with stage I-III digestive tract cancer from the esophagus to the rectum (UMIN000001977) was conducted with the aim of exploring the association between serum SPARC levels after operation and survival. On multivariate analyses adjusting serum 25-hydroxyvitamin D, vitamin D supplementation, sarcopenia, body mass index, age, sex, cancer loci, stage, and adjuvant chemotherapy, patients with SPARC levels lower than the median level had a significantly higher risk for death than those with higher levels (hazard ratio, 2.25; 95% confidence interval, 1.25-4.05; p = 0.007), whereas there were no significant associations with other outcomes including recurrence. However, on the same multivariate analyses, sarcopenia was not a risk factor for death and/or relapse. These results suggest that serum SPARC levels may be a potential biomarker for death but not cancer relapse.

Common carotid arteritis and polymyalgia with Mycoplasma pneumoniae infection.

A few pediatric cases with brain vasculitis most frequently affecting the middle cerebral artery have been reported in association with Mycoplasma pneumoniae infection, but involvement of the common carotid artery (CCA) before the bifurcation has not been reported to date. We report herein a case of 10-year-old boy with common carotid arteritis and polymyalgia associated with Mycoplasma pneumoniae infection. His fever and cough began 2 weeks before, and his right upper and lower extremity pains began 2 days before admission. He had initially been treated with clarithromycin followed by tosufloxacin, but his symptoms persisted. His M. pneumonia-specific antibody titer was high on admission (1:10240 by particle agglutination method) and the gene of M. pneumoniae was detected in a throat swab specimen by the loop-mediated isothermal amplification method with initial high levels of serum interleukin-8, tumor necrosis factor-α, and interleukin-18 along with elevated blood levels of complements. On the 5th day of hospitalization, vascular echograms of the extremities and neck showed increasing intima-media thickness of bilateral CCAs without stenosis and/or thrombosis and T2-weighted with lipid suppression magnetic resonance imaging of the neck showed high signal intensity of bilateral CCA walls. Coagulation studies were unremarkable and no autoantibodies were detected as far as tested. He was successfully treated by intravenous administration of prednisolone and was stable without any neurological sequelae 17 months after the onset without medication. His particle agglutination titer decreased to 1:5120, and serum interleukin-8, tumor necrosis factor-α, interleukin-18, and complement levels returned to normal.

Management of maternal anaphylaxis in pregnancy: a case report.

Case: A 26-year-old woman (gravida 2, para 1) at 25 weeks' gestation was brought to the emergency department because of anaphylactic symptoms. She reported eating Japanese soba and developed symptoms of dyspnea, generalized itchy rash, abdominal pain, and severe uterine contractions within 15-30 min of eating. She was immediately treated by normal saline infusion, two injections of epinephrine (intramuscularly), and a nebulized short-acting ß2-receptor agonist, followed by H1-antihistamine and methylprednisolone. Obstetrical management was undertaken by an obstetrician. Outcome: The patient recovered rapidly without a biphasic reaction of anaphylaxis. After 11 weeks, a healthy, neurologically intact baby was born. Conclusion: Management of anaphylaxis in pregnant patients is basically the same of that in non-pregnant ones. Treatment should commence immediately to prevent further development of the anaphylaxis reaction and fetal neurological deficiency.

Classification of Extrapulmonary Manifestations Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis.

The list of extrapulmonary manifestations due to Mycoplasma pneumoniae infection can be classified according to the following three possible mechanisms derived from the established biological activity of M. pneumoniae; (1) a direct type in which the bacterium is present at the site of inflammation and local inflammatory cytokines induced by the bacterium play an important role (2) an indirect type in which the bacterium is not present at the site of inflammation and immune modulations, such as autoimmunity or formation of immune complexes, play an important role, and (3) a vascular occlusion type in which obstruction of blood flow induced either directly or indirectly by the bacterium plays an important role. Recent studies concerning extrapulmonary manifestations have prompted the author to upgrade the list, including cardiac and aortic thrombi as cardiovascular manifestations; erythema nodosum, cutaneous leukocytoclastic vasculitis, and subcorneal pustular dermatosis as dermatological manifestations; acute cerebellar ataxia, opsoclonus-myoclonus syndrome, and thalamic necrosis as neurological manifestations; pulmonary embolism as a respiratory system manifestation; and renal artery embolism as a urogenital tract manifestation. Continuing nosological confusion on M. pneumoniae-induced mucositis (without skin lesions), which may be called M. pneumoniae-associated mucositis or M. pneumoniae-induced rash and mucositis separately from Stevens-Johnson syndrome, is argued in the dermatological manifestations. Serological methods are recommended for diagnosis because pneumonia or respiratory symptoms are often minimal or even absent in extrapulmonary manifestations due to M. pneumoniae infection. Concomitant use of immunomodulators, such as corticosteroids or immunoglobulins with antibiotics effective against M. pneumoniae, can be considered as treatment modalities for most severe cases, such as encephalitis. Further studies would be necessary to construct a comprehensive therapeutic strategy, covering microbiology (antibiotics), immunology (immunomodulators), and hematology (anticoagulants). The possible influence of the emergence of macrolide-resistant M. pneumoniae on extrapulmonary manifestations, which can be considered of limited clinical threat in Japan where the resistant rate has currently decreased, is discussed on the basis of unique biological characteristics of M. pneumoniae, the smallest self-replicating organism.

Gene and cytokine profile analysis of macrolide-resistant Mycoplasma pneumoniae infection in Fukuoka, Japan.

BACKGROUND: Recent epidemiologic data suggest that the prevalence of macrolide resistant Mycoplasma pneumoniae (MR-M. pneumoniae) is increasing rapidly worldwide. This study assessed the present status of M. pneumoniae infection in Japan and clinical end-points to distinguish children with MR-M. pneumoniae. METHODS: During an outbreak of M. pneumoniae infections in Fukuoka, Japan in 2010-11, a total of 105 children with clinically suspected M. pneumoniae infection were enrolled. M. pneumoniae was analyzed for macrolide resistance in domain V of the 23S rRNA gene. Sixty -five patients with PCR positive for M. pneumoniae were analyzed with regard to clinical symptoms, efficacy of several antimicrobial agents and several laboratory data. RESULTS: Causative pathogens were detected in 81.0% (85 of 105) and M. pneumoniae was identified 61.9% (65 of 105). The resistance rate of M. pneumoniae was 89.2% (58 of 65) in this general pediatric outpatient setting. Patients infected with MR-M. pneumoniae showed longer times to resolution of fever and required frequent changes of the initially prescribed macrolide to another antimicrobial agent. We observed three different genotypes of M. pneumoniae including the rarely reported A2063T mutation (A2063G: 31 strains, A2063T: 27 strains, no mutation: 7 strains). Drug susceptibility testing showed different antimicrobial susceptibility profiles for each genotype. Serum IFN-gamma, IL-6 and IP-10 levels were higher in patients with MR-genotypes than in those infected with no-mutation strains (p < 0.001). CONCLUSIONS: Macrolide resistance is more common than previously thought and a small epidemic of rarely reported A2063T mutation was observed in Fukuoka, Japan. Furthermore our results reveal the possibility that levels of certain inflammatory cytokines may be a candidate to predict MR-M.pneumoniae infection.

Late increase of interleukin-18 levels in blood during Mycoplasma pneumoniae pneumonia.

To the Editor, we read with great interest the article by Chung et al. which appeared recently in the journal. In that paper the authors reported that the decreased IL-18 response in severe pneumonia group vs. non-severe group was observed regardless of asthma status of the patients, whose findings were somewhat different from ours on non-asthmatic patients which showed higher serum levels of IL-18 in severe cases of pneumonia than in mild cases in terms of both in children and in adults. In this point, the timing of venous sampling must be an important factor in explaining the discrepant results. Our previous results suggest that the level of IL-18 in blood as a marker of disease severity should cautiously be interpreted considering a timing of sampling; a value of IL-18 in a blood sample which is obtained at the first visit to the hospital does not always represent the highest level of IL-18 because of the fact that the time which elapsed from the onset of illness to the blood sampling may vary among patients. Analyses on sequential samples, therefore, must be necessary to fully understand the perplexing nature of cytokine activation during Mycoplasma pneumoniae infection.

Rhabdomyolysis associated with antimicrobial drug-resistant Mycoplasma pneumoniae.

We describe a case of rhabdomyolysis in a patient infected with antimicrobial drug-resistant Mycoplasma pneumoniae The patient's acute-phase serum levels of interleukin-18 and tumor necrosis factor-α were high, which suggests a pathogenic role for M. pneumoniae. In an era of increasing antimicrobial drug resistance, a system for rapidly identifying resistant M. pneumoniae would be beneficial.

Complete genome sequence of Mycoplasma pneumoniae type 2a strain 309, isolated in Japan.

Mycoplasma pneumoniae strain 309, a type 2a (subtype 2 variant) strain of this bacterium, has variations in the P1 protein, which is responsible for attachment of the bacterium to host cells. Here, we report the complete genome sequence of M. pneumoniae strain 309 isolated from a pneumonia patient in Japan.

Clinical implications of interleukin-18 levels in pediatric patients with Mycoplasma pneumoniae pneumonia.

The immunological pathogenesis of Mycoplasma pneumoniae pneumonia is known to involve several cytokines. The serum levels of interleukin-18 (IL-18) were examined using enzyme-linked immunosorbent assay in 23 pediatric patients (median age 6 years; range 4-13 years; 14 girls and 9 boys) with M. pneumoniae pneumonia admitted to our hospital. Serum levels of IL-18 ranged from 22 to 1808 pg/ml with a mean of 543 pg/ml. We started steroid therapy in two cases with IL-18 values greater than 1000 pg/ml without being aware of IL-18 levels. Examination of associations between IL-18 levels determined by enzyme-linked immunosorbent assay and a routine laboratory test showed that levels of lactate dehydrogenase (LDH) and IL-18 were significantly correlated. To determine the appropriateness of steroid administration in M. pneumoniae pneumonia patients, serum LDH should be examined. Patients with elevated levels of LDH are likely to have significantly elevated IL-18 values (≥1000 pg/ml) and thus can be candidates for steroid therapy.

Pathogenesis of extrapulmonary manifestations of Mycoplasma pneumoniae infection with special reference to pneumonia.

Although pneumonia has been a hallmark of Mycoplasma pneumoniae infection, it has been revealed that this infection can cause a number of extrapulmonary manifestations in the absence of pneumonia. While the host immune response has been implicated in the pathomechanism of pneumonia, the pathomechanisms of extrapulmonary manifestations remain largely unknown. It is proposed in this review that extrapulmonary manifestations due to M. pneumoniae infection can be classified into three categories; the first is a direct type in which inflammatory cytokines locally induced by lipoproteins contained in the bacterial cell membrane must play a role, the second is an indirect type in which immune modulation such as autoimmunity through cross-reaction between the bacterial cell components and human cells must play a role, and the third is a vascular occlusion type in which vasculitis and/or thrombosis with or without systemic hypercoagulable state induced by the bacterium must play a role. Based on this classification, a literature review was carried out for extrapulmonary manifestations due to M. pneumoniae infection with special reference to pneumonia, including cardiovascular, dermatological, digestive organ, hematological/hematopoietic system, musculoskeletal, sensory organ, and urogenital tract manifestations. Consequently, most extrapulmonary manifestations due to M. pneumoniae infection can be reasonably classified into and explained by one of the three types of pathomechanisms mentioned above. Noticeably in this review, Kawasaki disease and infectious mononucleosis in association with M. pneumoniae infection, which are not unusual in Japan but have seldom been reported from Western countries, are included in the panel of extrapulmonary manifestations due to M. pneumoniae infection.

Three familial cases of drug-resistant Mycoplasma pneumoniae infection.

UNLABELLED: Mycoplasma pneumoniae infection is believed to result from defective host immune response rather than from direct cell injury by the organism itself. In this context, emergence of drug-resistant M. pneumoniae may provide us with special opportunities to study the pathogenesis from a clinical point of view. In this report, three patients with intrafamilial M. pneumoniae infection are presented. M. pneumoniae was isolated with a Hayflick pleuropneumonia-like organism diphasic medium. Minimal inhibitory concentrations of antibiotics were determined by a broth microdilution method. Polymerase chain reaction and restriction fragment length polymorphism analysis were done to determine point mutation in domain V of the 23S rRNA gene. As a result, all three strains from the three intrafamilial cases had the same drug-resistant point mutation, specifically A-to-G transition at position 2063. However, their clinical courses were quite different; a 6-year-old girl suffered severe pneumonia, a 5-year-old girl had mild pneumonia, and a 3-year-old boy had only a fever of 1-day duration without pneumonia. CONCLUSIONS: Our clinical and laboratory observations strongly support the idea that the host immune maturity, rather than a virulence factor of the organism, is a major determinant factor of disease severity of M. pneumoniae infection and that drug resistance does not necessarily lead to a serious clinical outcome.

Pathogenesis of neurologic manifestations of Mycoplasma pneumoniae infection.

Mycoplasma pneumoniae has been associated with various neurologic manifestations, but exactly how the organism can cause such a wide variety of diseases is a long-standing mystery. In this respect, although pneumonia has been considered the hallmark of Mycoplasma pneumoniae infection, emerging accumulations of data have revealed that the infection can cause a number of extrapulmonary manifestations even in the absence of pneumonia. The importance of host immune response in the pathomechanism of pneumonia has been established, but the pathomechanisms of extrapulmonary manifestations remain largely unknown. For this review, extrapulmonary manifestations due to M. pneumoniae infection were classified into three categories: a direct type, in which locally induced cytokines must play a role; an indirect type, in which immune modulation such as autoimmunity must play a role; and a vascular occlusion type, in which vasculitis or thrombosis (either or both, and with or without systemic hypercoagulable state) must play a role. This classification was then applied within a literature review for neurologic manifestations. Most neurologic manifestations due to M. pneumoniae infection could be reasonably classified into and explained by one of the three types of pathomechanisms.