Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis

Aim: In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3-positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians. Methods: We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16-79 years). Results: Forty-seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%). Conclusion: In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre-existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without.     

Computational method for estimating progression saturation of analog series

In lead optimization, it is difficult to estimate when an analog series might be saturated and synthesis of additional compounds would be unlikely to yield further progress. Rather than terminating a series, one often continues to generate analogs hoping to reach the final optimization goal, even if obstacles that are faced ultimately prove to be unsurmountable. Clearly, methodologies to better understand series progression and saturation are highly desirable. However, only a few approaches are currently available to monitor series progression and aid in decision making. Herein, we introduce a new computational method to assess progression saturation of an analog series by relating the properties of existing compounds to those of synthetic candidates and comparing their distributions in chemical space. The neighborhoods of analogs are analyzed and the distance relationships between existing and candidate compounds quantified. An intuitive dual scoring scheme makes it possible to characterize analog series and their degree of progression saturation.

Chemical space view of an analog series. Shown are inactive (red) and active (blue) analogs together with virtual candidate compounds (green) available to expand the series. Chemical neighborhoods of analogs are depicted in gray.     

Effective exercise intervention period for improving body function or activity in patients with knee osteoarthritis undergoing total knee arthroplasty: a systematic review and meta-analysis

Background

Various systematic reviews and/or meta-analyses examining the effects of pre- or postoperative exercise on body function or activity in patients undergoing total knee arthroplasty (TKA) have been published. However, the interventional period needed to at least improve outcomes is unknown.

Whole-pelvic volumetric-modulated arc therapy for high-risk prostate cancer: treatment planning and acute toxicity

The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy (VMAT) and daily image guidance in high-risk prostate cancer patients. A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy (WPRT) were enrolled. All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume (PTV), while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions, followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions. Image-guided RT was performed with daily cone-beam computed tomography. Dose–volume parameters for the PTV and the organs at risk (OARs), total number of monitor units (MUs) and treatment time were evaluated. Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. All dosimetric parameters met the present plan acceptance criteria. Mean MU and treatment time were 471 and 146 s for double-arc VMAT, respectively, and were 520 and 76 s for single-arc VMAT, respectively. No Grade 3 or higher acute toxicity was reported. Acute Grade 2 proctitis, diarrhea, and genitourinary toxicity occurred in 12 patients (12%), 6 patients (6%) and 13 patients (13%), respectively. The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity. These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients.     

Cost-utility Analysis of Screening for Diabetic Retinopathy in Japan: A Probabilistic Markov Modeling Study

ABSTRACT

Purpose: To evaluate the cost-effectiveness for a screening interval longer than 1 year detecting diabetic retinopathy (DR) through the estimation of incremental costs per quality-adjusted life year (QALY) based on the best available clinical data in Japan.

Methods: A Markov model with a probabilistic cohort analysis was framed to calculate incremental costs per QALY gained by implementing a screening program detecting DR in Japan. A 1-year cycle length and population size of 50,000 with a 50-year time horizon (age 40–90 years) was used. Best available clinical data from publications and national surveillance data was used, and a model was designed including current diagnosis and management of DR with corresponding visual outcomes. One-way and probabilistic sensitivity analyses were performed considering uncertainties in the parameters.

Results: In the base-case analysis, the strategy with a screening program resulted in an incremental cost of 5,147 Japanese yen (¥; US$64.6) and incremental effectiveness of 0.0054 QALYs per person screened. The incremental cost-effectiveness ratio was ¥944,981 (US$11,857) per QALY. The simulation suggested that screening would result in a significant reduction in blindness in people aged 40 years or over (?16%). Sensitivity analyses suggested that in order to achieve both reductions in blindness and cost-effectiveness in Japan, the screening program should screen those aged 53–84 years, at intervals of 3 years or less.

Conclusions: An eye screening program in Japan would be cost-effective in detecting DR and preventing blindness from DR, even allowing for the uncertainties in estimates of costs, utility, and current management of DR.     

Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys

Contrast‐induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty‐six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m² (CKD and non‐CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = ?0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non‐CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non‐CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media.     

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.     

Complete Resolution of a Case of TAFRO Syndrome Accompanied by Mediastinal Panniculitis,Adrenal Lesion,and Liver Damage with Hyperbilirubinemia

TAFRO syndrome is a systemic inflammatory, lymphoproliferative disorder, but the pathophysiology of the disease is unknown. It is typically characterized by thrombocytopenia, anasarca, a fever, reticulin fibrosis, renal dysfunction, and organomegaly. However, other manifestations have been also reported. We encountered a 43-year-old man with TAFRO syndrome who showed mediastinal panniculitis, liver damage, and adrenal lesions in addition to the core signs. He achieved complete remission with combination therapy of corticosteroids, tocilizumab, and cyclosporin, and remission was maintained even after drug discontinuation at 15 months. Atypical manifestations and complete remission of TAFRO syndrome were remarkable features of our case.     

Ratio of submucosal thickness to total bowel wall thickness as a new sonographic parameter to estimate endoscopic remission of ulcerative colitis

Journal of Gastroenterology - The development of feasible, reliable parameters and criteria for intestinal ultrasound (IUS) to estimate endoscopic remission of ulcerative colitis (UC) is a crucial...