A symptomatic child with ceftriaxone-associated biliary pseudolithiasis

A 5-year-old boy who had pneumonia was treated in a neighboring hospital. Ceftriaxone was administrated 2 g/day divided into two equal intravenous doses. After 1 week of ceftriaxone therapy, the patient developed abdominal pain. In our hospital, an abdominal sonogram showed a hyperechoic band with postacoustic shadow within the collapsed gallbladder. He was diagnosed with ceftriaxone-associated biliary pseudolithiasis, and ceftriaxone therapy was ceased. On the 8th our hospital day, he again complained of right abdominal pain after supper. A sonogram revealed high-amplitude echoes within the gallbladder neck and common bile duct. Furthermore, bile duct dilatation was observed. He was managed conservatively, after which the symptoms were resolved. On the 11th day, a sonogram showed only sludge within the gallbladder, and on the 13th day, he was discharged from our hospital. It is important for sonographers to recognize the possible occurrence of biliary pseudolithiasis in ceftriaxone-treated patients, especially when a high dose is used in children.     

Analysis of risk factors for multidrug-resistant pathogens and appropriate treatment indications for pneumonia in children with neurologic impairment

IntroductionThe features of pneumonia in children with neurologic impairment (NI) resemble those of healthcare-associated pneumonia is defined as pneumonia occurring in the community associated with healthcare risk factors. There are currently no guidelines for the treatment of pneumonia in children with NI. Here, we assessed whether the guidelines applicable for treating pneumonia in adults could be applied to children with NI.MethodsBetween 2008 and 2019, we enrolled children with NI who developed pneumonia and were treated in the pediatric ward of Kawasaki Medical School Hospital. We evaluated patient characteristics, the frequency of isolation of multidrug-resistant (MDR) pathogens, and clinical outcomes.ResultsMDR pathogens were more frequently isolated from patients receiving tube feeding (TF) and/or with tracheostomy than from patients without these risk factors. Other risk factors, including a history of antibiotic therapy and methicillin-resistant Staphylococcus aureus isolation, recent hospitalization, residence in a nursing home or extended care facility, and low-dose, long-term macrolide therapy, did not significantly affect the frequency of MDR pathogen isolation. In patients receiving TF and/or with tracheostomy, treatment success was achieved in all cases treated with broad-spectrum antibiotics and 72.2% of cases treated with non-broad-spectrum antibiotics (P = 0.007). Conversely, among patients without these risk factors, no such difference was observed.ConclusionsOur findings indicate that the guideline to select antibiotics for treating pneumonia in children with NI should be simpler and more useful than the current guidelines for adult pneumonia, based on risk factor assessment for MDR pathogens.     

Linezolid versus vancomycin for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus in the elderly: A retrospective cohort analysis: Effectiveness of linezolid in the elderly

Objectives

Several reports have compared the efficacy of linezolid (LZD) in Methicillin-resistant Staphylococcus aureus (MRSA) infections with that of vancomycin (VCM); however, these two antibiotics for the treatment of nosocomial MRSA pneumonia in elderly patients has not been well evaluated. The purpose of this study is to evaluate the efficacy and safety of LZD compared with VCM for the treatment of elderly patients with nosocomial MRSA pneumonia in a retrospective chart review of a cohort.

Prognostic value of cardiovascular magnetic resonance derived right ventricular function in patients with interstitial lung disease

Background

Cardiovascular magnetic resonance (CMR) provides non-invasive and more accurate assessment of right ventricular (RV) function in comparison to echocardiography. Recent study demonstrated that assessment of RV function by echocardiography was an independent predictor for mortality in patients with interstitial lung disease (ILD). The purpose of this study was to determine the prognostic significance of CMR derived RV ejection fraction (RVEF) in ILD patients.

Methods

We enrolled 76 patients with ILD and 24 controls in the current study. By using 1.5 T CMR scanner equipped with 32 channel cardiac coils, we performed steady-state free precession cine CMR to assess the RVEF. RV systolic dysfunction (RVSD) was defined as RVEF ≤45.0% calculated by long axis slices. Pulmonary hypertension (PH) was defined as mean pulmonary artery pressure (mPAP) of more than 25 mmHg at rest in the setting of pulmonary capillary wedge pressure ≤15 mmHg.

Results

The median RVEF was 59.2% in controls (n = 24), 53.8% in ILD patients without PH (n = 42) and 43.1% in ILD patients with PH (n = 13) (p < 0.001 by one-way ANOVA). During a mean follow-up of 386 days, 18 patients with RVSD had 11 severe events (3 deaths, 3 right heart failure, 3 exacerbation of dyspnea requiring oxygen, 2 pneumonia requiring hospitalization). In contrast, only 2 exacerbation of dyspnea requiring oxygen were observed in 58 patients without RVSD. Multivariate Cox regression analysis showed that RVEF independently predicted future events, after adjusting for age, sex and RVFAC by echocardiography (hazard ratio: 0.889, 95% confidence interval: 0.809 – 0.976, p = 0.014).

Conclusions

The current study demonstrated that RVSD in ILD patients can be clearly detected by cine CMR. Importantly, low prevalence of PH (17%) indicated that population included many mild ILD patients. CMR derived RVEF might be useful for the risk stratification and clinical management of ILD patients.     

A retrospective study of the epidemiology of Clostridium difficile infection at a University Hospital in Japan: genotypic features of the isolates and clinical characteristics of the patients

Clostridium difficile is a major cause of antibiotic-associated diarrhea and frequently results in healthcare-associated infections. The epidemiology of C. difficile infection (CDI), including the prevalent polymerase chain reaction (PCR) ribotypes and the clinical characteristics of the patients, is not well known in Japan, compared to the situation in the United States and Europe. We performed PCR ribotyping of C. difficile isolates from 71 consecutive patients with CDI at a University Hospital over a 3-year period and investigated the clinical features of those patients. CDI was diagnosed when a patient with diarrhea or colitis was found to have toxin B-positive C. difficile with no other enteropathogenic microorganisms. Toxin A-positive, toxin B-positive, binary toxin-positive (A⁺B⁺CDT⁺) strains; toxin A-positive, toxin B-positive, binary toxin-negative (A⁺B⁺CDT^?) strains; and toxin A-negative, toxin B-positive, binary toxin-negative (A^?B⁺CDT^?) strains were isolated from 4, 58, and 9 patients, respectively, indicating that infections with binary toxin-positive strains were uncommon (5.6%). PCR ribotyping of the isolates demonstrated that among the 71 strains, 20 different PCR ribotypes were identified and that types smz, yok, and hr were predominant (19, 14, and 13 isolates, respectively), all of which were A⁺B⁺CDT^?. No specific time periods or wards were found to be associated with the three types; PCR ribotyping analysis clearly showed that the three types spread almost evenly in all wards for the 3 years studied. Comparative analysis of the clinical characteristics of patients harboring the three C. difficile types indicated that the duration of CDI was longer in the yok group than in the hr group. PCR ribotyping, which is easy to perform, appears to give us useful information to trace CDI cases in clinical settings. Further, the analysis of a large number of CDI cases may allow evaluation of the possible relationship between specific C. difficile types and the clinical features of patients.     

Evaluation of four commercial severe acute respiratory coronavirus 2 antibody tests

IntroductionNumerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital.MethodsThis study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses.ResultsThe varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11–15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed.ConclusionsOur results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis.     

Clustered components of the metabolic syndrome and platelet counts in Japanese females.

BACKGROUND: Blood platelet counts (PCs) play a role in the development of cardiovascular disease (CVD). The metabolic syndrome (MS) is also associated with high CVD risk. However, the connection between PCs and MS has not yet been thoroughly investigated in relation to various biosocial factors that can affect both PCs and the pathophysiology of MS. METHODS: A total of 152 asymptomatic female subjects (mean age 50 years) with almost normal levels of hemoglobin and white blood cell counts were recruited. MS was diagnosed according to the NCEP-ATP III criteria with a minor modification. The relationships between PCs and MS were analyzed according to the number of MS components (0, 1-2, > or =3). Biosocial factors including age and some lifestyle factors (smoking, alcohol intake and physical activity) were included in the analyses. RESULTS: PCs in subjects with > or =3 MS components (233+/-43 [SD]x10(9) /L) were strikingly and significantly higher than in subjects with 0 (194+/-34 x 10(9)/L) or 1-2 MS components (207+/-38 x 10(9)/L). General linear model analysis for PCs, adjusted for all biosocial factors and number of MS components, revealed a significant and positive correlation between PCs and number of MS components (p<0.0001). CONCLUSIONS: The results suggest that PCs may be a potential marker associated with clustered MS components, independent of some biosocial factors, in Japanese females.     

Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice

HDLs protect against the development of atherosclerosis, but the underlying mechanisms are poorly understood. HDL and its apolipoproteins can promote cholesterol efflux from macrophage foam cells via the ATP-binding cassette transporters ABCA1 and ABCG1. Experiments addressing the individual roles of ABCA1 and ABCG1 in the development of atherosclerosis have produced mixed results, perhaps because of compensatory upregulation in the individual KO models. To clarify the role of transporter-mediated sterol efflux in this disease process, we transplanted BM from Abca1(-/-)Abcg1(-/-) mice into LDL receptor-deficient mice and administered a high-cholesterol diet. Compared with control and single-KO BM recipients, Abca1(-/-)Abcg1(-/-) BM recipients showed accelerated atherosclerosis and extensive infiltration of the myocardium and spleen with macrophage foam cells. In experiments with isolated macrophages, combined ABCA1 and ABCG1 deficiency resulted in impaired cholesterol efflux to HDL or apoA-1, profoundly decreased apoE secretion, and increased secretion of inflammatory cytokines and chemokines. In addition, these cells showed increased apoptosis when challenged with free cholesterol or oxidized LDL loading. These results suggest that the combined effects of ABCA1 and ABCG1 in mediating macrophage sterol efflux are central to the antiatherogenic properties of HDL.     

Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation

OBJECTIVE: Acute lung injury is a detrimental complication for victims of burn accidents. Airway obstruction plays an important role in pulmonary dysfunction in these patients. In this study, we tested the hypothesis that aerosolized anticoagulants will reduce the degree of airway obstruction and improve pulmonary function in sheep with severe combined burn and smoke inhalation injury by preventing the formation of airway fibrin clots. DESIGN: Prospective, randomized, controlled, experimental animal study. SETTING: Investigational intensive care unit at a university hospital. SUBJECTS: Adult female sheep. INTERVENTIONS: After 7 days of surgical recovery, sheep were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, <40 degrees C) under halothane anesthesia. After injury, sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Sheep were randomly divided into five groups: sham, noninjured and nontreated (n = 6); control, injured and aerosolized with saline (n = 6); recombinant human antithrombin (rhAT) + heparin, injured and aerosolized with rhAT (290 units for each) and heparin (10,000 units for each) (n = 6); rhAT, injured and aerosolized with rhAT alone (290 units for each; n = 5); and heparin, injured and aerosolized with heparin alone (10,000 units for each; n = 5). rhAT and heparin were aerosolized every 4 hrs, starting at 2 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary hemodynamics were monitored during a 48-hr experimental time period. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and extensive airway obstruction. These variables were stable in sham animals. The aerosolization of rhAT or heparin alone did not significantly improve deteriorated pulmonary gas exchange. However, aerosolization of these anticoagulants in combination significantly attenuated all the observed pulmonary pathophysiology. CONCLUSIONS: The results provide definitive evidence that aerosolized rhAT and heparin in combination may be a novel treatment strategy for pulmonary pathology in burn victims with smoke inhalation injury.     

A 18F-Labeled BF-227 Derivative as a Potential Radioligand for Imaging Dense Amyloid Plaques by Positron Emission Tomography

Purpose

The aims of this study were to evaluate the binding and pharmacokinetics of novel ¹⁸F-labeled ethenyl-benzoxazole derivatives (i.e., [¹⁸F] fluorinated amyloid imaging compound of Tohoku university ([¹⁸F]FACT)) as amyloid positron emission tomography (PET) tracers and to assess [¹⁸F]FACT efficacy in imaging of Alzheimer’s disease (AD).

Procedures

Binding assay was conducted using synthetic amyloid-β (Aβ) fibrils, fluorescence microscopy, and autoradiogram in three postmortem AD brains. Pharmacokinetics of [¹⁸F]FACT was assessed using 12 Crj:CD-1 (ICR) mice. In vivo binding ability with brain amyloid was investigated using amyloid precursor protein (APP) transgenic mouse. Clinical PET scanning using [¹⁸F]FACT was performed in ten healthy controls and ten mild cognitive impairment and ten AD patients.

Results

[¹⁸F]FACT showed high binding affinity for synthetic Aβ fibrils, preferential binding to dense cored plaques in brain sections, and excellent brain uptake and rapid clearance in mice. Injection in APP mice resulted in specific in vivo labeling of amyloid deposits in the brain. PET scans of AD patients showed significantly higher [¹⁸F]FACT uptake in the neocortex compared to controls (P?<?0.05, Kruskal–Wallis test).

Conclusion

[¹⁸F]FACT is a promising agent for imaging dense Aβ plaques in AD.