Early electrocardiographic indices for predicting chronic doxorubicin-induced cardiotoxicity

BackgroundDealing with chemotherapy-related cardiac dysfunction (CTRCD) remains a significant problem complicated by the difficulty in early detection of cardiotoxicity. Electrocardiogram (ECG) is expected to be the most realistic methodology due to lower cost-performance and non-invasiveness. We investigated the long-term visual fluctuations in the ECG waveforms in patients with chronic doxorubicin (DOX)-induced cardiotoxicity to identify ECG indices for the early detection of cardiotoxicity.MethodsWe conducted a retrospective case series study by reviewing the medical records of 470 consecutive patients with malignant lymphoma who were treated with DOX at our institute between January 2010 and December 2017. Of them, 23 (4.9%) patients developed left ventricular dysfunction and were diagnosed with CTRCD using echocardiography. We assessed the ECG indices on 12-lead ECG recordings before and after treatment in 15 patients; eight patients were excluded due to conduction disturbances or atrial fibrillation.ResultsCTRCD was detected at a median of 475 (interquartile range, IQR: 341–1333) days after initiating chemotherapy. The evaluation of ECG indices preceding CTRCD development was performed 93 (IQR: 52–232) days before the detection of CTRCD. In the stage of CTRCD, the most significant ECG change was T-wave flattening in leads V3–V6 (12 patients, 80%). Additionally, QTa prolongation was observed in leads I and aVL (n = 10, 66%), leads II, III, and aVF (n = 9, 60%), and leads V3–V6 (n = 10, 73%). These ECG changes were not observed before the treatment but were detected mildly in the pre-CTRCD stage, which subsequently worsened in the CTRCD stage.ConclusionsThis study indicated that T-wave changes and QTa prolongation may be useful as an early indicator before the onset of CTRCD in patients with DOX-induced cardiotoxicity.     

Aplastic Anemia in a Patient with Cronkhite-Canada Syndrome

Cronkhite-Canada syndrome (CCS) is a rare polyposis disorder accompanied by alopecia and onychodystrophy. A 63-year-old man with a history of CCS and repeated embolism developed progressive thrombocytopenia and mild anemia. Laboratory testing, a bone marrow examination, and magnetic resonance imaging of the spine resulted in a diagnosis of concurrent aplastic anemia (AA). Paroxysmal nocturnal hemoglobinuria (PNH)-type cells were detected in a peripheral blood specimen. In addition, human leukocyte antigen (HLA) included DRB1*15:01 and DRB1*15:02. Mesalazine was discontinued in consideration of possible drug-induced pancytopenia. Immunosuppressive therapy ameliorated both the gastrointestinal symptoms of CCS and pancytopenia. A common autoimmune abnormality might underlie both CCS and AA.     

Role of radial strain and displacement imaging to quantify wall motion dyssynchrony in patients with left ventricular mechanical dyssynchrony and chronic right ventricular pressure overload

Left ventricular (LV) deformation with ventricular septal shift is one of the most distinctive echocardiographic observations in patients with chronic right ventricular (RV) pressure overload (PO). However, little is known about the effects of RVPO on LV performance and regional synchrony. Accordingly, our objective was to test the hypothesis that chronic RVPO affects regional wall motion, synchronicity, and global LV function using a novel speckle-tracking approach to quantify and characterize regional LV wall motion dyssynchrony. Displacement and strain imaging echocardiographic studies were performed in 20 patients with RVPO from pulmonary arterial hypertension or pulmonic stenosis (mean age 53 +/- 16 years, New York Heart Association class 2.6 +/- 0.7, and peak RV systolic pressure 73 +/- 28 mm Hg) and 20 age-matched normal subjects (mean age 47 +/- 16 years). Segmental signals from 6 segments around the mid-LV short axis were defined as dyssynchronous if their changes were opposite to that of the global LV signal at each time frame, and overall LV dyssynchrony was calculated as the percentage of dyssynchrony in all 6 segments within the specified time interval from onset of QRS to the end of isovolumic relaxation. RVPO was associated with a large degree of regional dyssynchrony with paradoxical ventricular septal motion observed by displacement imaging (21 +/- 6%, p <0.05 vs control group), which was closely associated with LV eccentricity index (r = 0.79, p <0.05) and LV myocardial performance index with linear regression (r = 0.76, p <0.05). In contrast, strain imaging showed uniform segmental radial thickening in the RVPO group, which was similar to the control group, and suggests that there was no intrinsic LV contractile dyssynchrony. In conclusion, LV wall motion dyssynchrony assessed by displacement imaging, not intrinsic contractile dyssynchrony by strain imaging, coexists with LV chamber deformation with ventricular septal shift and is closely associated with impairment of LV performance.     

Changes in serum levels of metalloproteinases and their inhibitors by treatment of chronic hepatitis C with interferon

We treated 18 patients with chronic hepatitis C by recombinant interferon-α (6 MIU for 24 weeks). In seven patients, serum aminotransferase levels declined to normal (responders). To evaluate the effect of interferon on matrix metalloproteinases (MMPs) and their inhibitors, namely tissue inhibitors of metalloproteinases (TIMPs), the serum levels of these enzymes were determined by enzyme immunoassay (EIA) using a specific monoclonal antibody. In responders, there was a tendency, but not a significant one, towards either an increase in serum MMP 1 levels or a decrease in serum TIMP 1 levels. In contrast, in nonresponders, both a significant decrease in MMP 1 and MMP 3 and a significant increase in TIMP 1 were observed. The number of cases of either increase in serum MMP levels or decrease in serum TIMP levels was significantly larger in responders than in nonresponders. Furthermore, the ratio of MMP 1 to TIMP 1 significantly increased in responders, suggesting that the balance between matrix formation and degradation in hepatic fibrosis tended to move toward degradation. These data indicate that interferon may exert a beneficial effect on hepatic fibrosis in parallel with improvement of aminotransferase activity.     

Imaging of pulmonary emphysema: A pictorial review

The term ‘emphysema’ is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease. In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules. Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema. In this pictorial review, we discuss the radiological – pathological correlation in each type of pulmonary emphysema. HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders. With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung. Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema. In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung. Paraseptal emphysema is characterized by subpleural well-defined cystic spaces. Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease.     

Enhanced wound healing by topical administration of mesenchymal stem cells transfected with stromal cell-derived factor-1

The objective of this study was to investigate the ability of mesenchymal stem cells (MSC) genetically engineered with stromal cell-derived factor-1 (SDF-1) to heal skin wounds. When transfected with SDF-1 plasmid DNA, MSC which were isolated from the bone marrow of rats, secreted SDF-1 for 7 days. In vitro cell migration assay revealed that the SDF-1-engineered MSC (SDF-MSC) enhanced the migration of MSC and dermal fibroblasts to a significantly greater extent than MSC. The SDF-MSC secreted vascular endothelial growth factor, hepatocyte growth factor, and interleukin 6 at a significantly high level. A skin defect model of rats was prepared and MSC and SDF-MSC were applied to the wound to evaluate wound healing in terms of wound size and histological examinations. The wound size decreased significantly faster with SDF-MSC treatment than with MSC and PBS treatments. The length of the neoepithelium and the number of blood vessels newly formed were significantly larger. A cell-tracing experiment with fluorescently labeled cells demonstrated that the percent survival of SDF-MSC in the tissue treated was significantly high compared with that of MSC. It was concluded that SDF-1 genetic engineering is a promising way to promote the wound healing activity of MSC for a skin defect.     

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

Purpose:To evaluate the feasibility for the detection of slight contrast effects after intravenous administration of single dose gadolinium-based contrast agent (IV-SD-GBCA), the time course of the GBCA distribution up to 24 h was examined in various fluid spaces and brain parenchyma using 3D-real IR imaging and MR fingerprinting (MRF).Methods:Twenty-four patients with a suspicion of endolymphatic hydrops were scanned at pre-administration and at 10 min, 4 and 24 h post-IV-SD-GBCA. 3D-real IR images and MRF at the level of the internal auditory canal were obtained. The signal intensity on the 3D-real IR image of the cerebrospinal fluid (CSF) in the cerebellopontine angle cistern (CPA), Sylvian fissure (Syl), lateral ventricle (LV), and cochlear perilymph (CPL) was measured. The T₁ and T₂ values of cerebellar gray (GM) and white matter (WM) were measured using MRF. Each averaged value at the various time points was compared using an analysis of variance.Results:The signal intensity on the 3D-real IR image in each CSF region peaked at 4 h, and was decreased significantly by 24 h (P < 0.05). All patients had a maximum signal intensity at 4 h in the CPA, and Syl. The mean CPL signal intensity peaked at 4 h and decreased significantly by 24 h (P < 0.05). All patients but two had a maximum signal intensity at 4 h. Regarding the T₁ value in the cerebellar WM and GM, the T₁ value at 10 min post-IV-GBCA was significantly decreased compared to the pre-contrast scan, but no significant difference was observed at the other time points. There was no significant change in T₂ in the gray or white matter at any of the time points.Conclusion:Time course of GBCA after IV-SD-GBCA could be evaluated by 3D-real IR imaging in CSF spaces and in the brain by MRF.     

Transient hypoglycorrhachia with paroxysmal abnormal eye movement in early infancy

Paroxysmal abnormal eye movement in early infancy is one of the initial symptoms of glucose transporter 1 deficiency syndrome (GLUT1DS). We describe four early infants with transient hypoglycorrhachia presenting with abnormal eye movements. Their symptoms disappeared after the introduction of a ketogenic diet (KD), and their development was normal. Since no variants in SLC2A1 were detected, the CSF-to-blood glucose ratios (C/B) were re-examined, and within normal range. None of the four patients displayed recurrent symptoms after withdrawal from the KD. Because long-term KD has potential adverse effects and could affect the quality of life of patients and their families, re-examination of CSF glucose during late infancy should be considered in the case of absence of the SLC2A1 pathogenic variant.