Butyrylcholinesterase level as an independent prognostic factor for overall survival in patients on maintenance hemodialysis: a single-center retrospective study

Clinical and Experimental Nephrology - We investigated whether butyrylcholinesterase (BChE) was independently related to the overall survival (OS) of patients on maintenance hemodialysis (MHD)....     

Homogeneously enhancing breast lesions on contrast enhanced US: differential diagnosis by conventional and contrast enhanced US findings

Objective

To clarify the details of homogeneously enhancing lesions on contrast-enhanced ultrasonography (CEUS) and also to elucidate whether their differential diagnosis is possible.

Methods

Seventy-three homogeneously enhancing lesions on CEUS were retrospectively selected. Two radiologists first assessed conventional US findings alone in consensus to differentiate malignant vs. benign lesions. Then, qualitative and quantitative CEUS findings were analyzed to determine the useful findings for the differential diagnosis. Determined CEUS findings were applied to the indeterminate lesions based on conventional US findings to see whether CEUS can improve the diagnostic performance.

Results

There were 42 cancers (58 %) out of 73. Sensitivity and specificity using conventional US findings alone were 91 and 55 %, respectively. Among the CEUS findings tested, multivariate analysis revealed only the type 3 enhancement pattern, which indicates a larger enhancing area than the precontrast hypoechoic lesion, was related to malignancy (p < 0.05). By adding this information, however, no improvement was achieved in the diagnostic performance as determined by conventional US findings.

Conclusions

Approximately half of the homogeneously enhancing lesions on CEUS are malignant, and differentiation of malignant from benign lesions may be possible, at least to some extent, by meticulous assessment of the conventional US rather than CEUS findings.

     

The essence of the Japan Radiological Society/Japanese College of Radiology Imaging Guideline

Diagnostic imaging is undoubtedly important in modern medicine, and final clinical decisions are often made based on it. Fortunately, Japan has the highest numbers of diagnostic imaging instruments, such as CT and MRI devices, and boasts easy access to them as well as a high level of diagnostic accuracy. In consequence, a very large number of imaging examinations are performed, but diagnostic instruments are installed in so many medical facilities that expert management of these examinations tends to be insufficient. Particularly, in order to avoid risks, clinicians have recently become indifferent to indications of imaging modalities and tend to rely on CT or MRI resulting in increasing the number of imaging examinations in Japan. This is a serious problem from the viewpoints of avoidance of unnecessary exposure and medical economy. Under these circumstances, the Japan Radiological Society and Japanese College of Radiology jointly initiated the preparation of new guidelines for diagnostic imaging. However, the field of diagnostic imaging is extremely wide, and it is impossible to cover all diseases. Therefore, in drafting the guidelines, we selected important diseases and focused on “showing evidence and suggestions in the form of clinical questions (CQs)” concerning clinically encountered questions and “describing routine imaging techniques presently considered to be standards to guarantee the quality of imaging examinations”. In so doing, we adhered to the basic principles of assuming the readers to be “radiologists specializing in diagnostic imaging”, “simultaneously respecting the global standards and attending to the situation in Japan”, and “making the guidelines consistent with those of other scientific societies related to imaging”. As a result, the guidelines became the largest ever, consisting of 152 CQs, nine areas of imaging techniques, and seven reviews, but no other guidelines in the world summarize problems concerning diagnostic imaging in the form of CQs. In this sense, the guidelines are considered to reflect the abilities of diagnostic radiologists in Japan. The contents of the guidelines are essential knowledge for radiologists, but we believe that they are also of use to general clinicians and clinical radiological technicians. While the number and contents of CQs are still insufficient, and while chapters such as those on imaging in children and emergency imaging need to be supplemented, the guidelines will be serially improved through future revisions. Lastly, we would like to extend our sincere thanks to the 153 members of the drafting committee who authored the guidelines, 12 committee chairpersons who coordinated their efforts, six members of the secretariat, and affiliates of related scientific societies who performed external evaluation.     

Risk factors associated with relapse or infectious complications in Japanese patients with microscopic polyangiitis

Background

The prevention of relapse and infection complications during remission maintenance therapy is required to improve the prognosis of patients with microscopic polyangiitis (MPA) showing rapidly progressive glomerulonephritis (RPGN). The clinicopathological characteristics of patients with ANCA-positive MPA were examined to determine the risk factors for relapse or infectious complications after remission induction therapy.

Patients and methods

The study population consisted of 52 patients diagnosed as ANCA-positive MPA showing RPGN from 2002 to 2012, after publication of the Japanese guideline for RPGN. The clinicopathological findings were examined between the presence and absence of relapse or infectious complications.

Results

The value of vasculitis damage index (VDI) was high for the relapse group and VDI value was identified as the leading factor associated with relapse [hazard ratio (HR) 3.36, 95 % confidence interval (CI) 1.58–7.12, P < 0.01]. On the other hand, the values of Birmingham Vasculitis Activity Score, clinical grade category of RPGN at diagnosis, and VDI at remission were high in the infectious group. Furthermore, clinical grade category of RPGN was the leading factor associated with infectious complications (HR 5.30, 95 % CI 1.41–19.9, P = 0.01).

Conclusion

The disease activity at diagnosis and severity of organ damage at remission were associated with relapse and infectious complications during remission maintenance therapy and infectious complication affected kidney survival and all-cause mortality in patients with ANCA-positive MPA exhibiting RPGN.

     

Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Background

The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.

Methods

A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC_∞) and maximal concentration (C _max) were calculated by Bayesian analysis.

Results

In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC_∞. There were significant differences of AUC_∞ and C _max by age group. No relationship was observed between the administration method of MZR and serum concentration.

Conclusion

The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.

     

p63 - Key molecule in the early phase of epithelial abnormality in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the most common lung disease predisposing lung cancer. To clarify the early phase of epithelial abnormalities in IPF, we used an in vitro squamous metaplasia model, transforming growth factor beta1 (TGF beta1)-treated airway epithelial cells (BEAS-2B). The model repeated the expression of squamous epithelial character, such as involucrin, and keratin 6 and 14. DNA microarray analysis disclosed a unique expression signature in TGF beta1-treated airway epithelial cells, 20 specifically up-regulated genes including p63, jagged 1 (jag1) and the genes of structure proteins. Western blotting and RT-PCR analysis revealed that DeltaNp63alpha was the dominant isoform of p63 in our experimental model. Immunohistochemical analysis demonstrated the expression of p63 and jag1 in lung tissues of IPF. Inhibition of p63 with siRNA caused the down-regulation of jag1 expression, but not of involucrin, or keratin 6 and 14. Interestingly, the up-regulation of p63 was totally suppressed by N-acetyl-l-cysteine (NAC), but not by dexamethasone or pirfenidone. Thus, the p63-jag1 pathway may be up-regulated at an early phase of epithelial abnormalities in IPF, which can be overcome by NAC even in the TGF beta1-rich milieu.     

Bartlett‐type corrections and bootstrap adjustments of likelihood‐based inference methods for network meta‐analysis

In network meta‐analyses that synthesize direct and indirect comparison evidence concerning multiple treatments, multivariate random effects models have been routinely used for addressing between‐studies heterogeneities. Although their standard inference methods depend on large sample approximations (eg, restricted maximum likelihood estimation) for the number of trials synthesized, the numbers of trials are often moderate or small. In these situations, standard estimators cannot be expected to behave in accordance with asymptotic theory; in particular, confidence intervals cannot be assumed to exhibit their nominal coverage probabilities (also, the type I error probabilities of the corresponding tests cannot be retained). The invalidity issue may seriously influence the overall conclusions of network meta‐analyses. In this article, we develop several improved inference methods for network meta‐analyses to resolve these problems. We first introduce 2 efficient likelihood‐based inference methods, the likelihood ratio test–based and efficient score test–based methods, in a general framework of network meta‐analysis. Then, to improve the small‐sample inferences, we developed improved higher‐order asymptotic methods using Bartlett‐type corrections and bootstrap adjustment methods. The proposed methods adopt Monte Carlo approaches using parametric bootstraps to effectively circumvent complicated analytical calculations of case‐by‐case analyses and to permit flexible application to various statistical models network meta‐analyses. These methods can also be straightforwardly applied to multivariate meta‐regression analyses and to tests for the evaluation of inconsistency. In numerical evaluations via simulations, the proposed methods generally performed well compared with the ordinary restricted maximum likelihood–based inference method. Applications to 2 network meta‐analysis datasets are provided.