Diagnostic value of texture analysis of apparent diffusion coefficient maps for differentiating fat-poor angiomyolipoma from non-clear-cell renal cell carcinoma

Purpose: To investigate the feasibility of texture analysis of apparent diffusion coefficient (ADC) maps for differentiating fat-poor angiomyolipomas (fpAMLs) from non-clear-cell renal cell carcinomas (non-ccRCCs). Methods: In this bi-institutional study, we included two consecutive cohorts from different institutions with pathologically confirmed solid renal masses: 67 patients (fpAML = 46; non-ccRCC = 21) for model development and 39 (fpAML = 24; non-ccRCC = 15) for validation. Patients underwent preoperative magnetic resonance imaging (MRI), including diffusion-weighted imaging. We extracted 45 texture features using a software with volumes of interest on ADC maps. Receiver operating characteristic curve analysis was performed to compare the diagnostic performance between the random forest (RF) model (derived from extracted texture features) and conventional subjective evaluation using computed tomography and MRI by radiologists. Results: RF analysis revealed that grey-level zone length matrix long-zone high grey-level emphasis was the dominant texture feature for diagnosing fpAML. The area under the curve (AUC) of the RF model to distinguish fpAMLs from non-ccRCCs was not significantly different between the validation and development cohorts (p = .19). In the validation cohort, the AUC of the RF model was similar to that of board-certified radiologists (p = .46) and significantly higher than that of radiology residents (p = .03). Conclusions: Texture analysis of ADC maps demonstrated similar diagnostic performance to that of board-certified radiologists for discriminating between fpAMLs and non-ccRCCs. Diagnostic performances in the development and validation cohorts were comparable despite using data from different imaging device manufacturers and institutions

Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation

Increasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also transplanted human ESC-derived retinal sheets into NOG-rd1-2J and confirmed their long-term survival and maturation of the structured graft photoreceptor layer, without rejection or tumorigenesis. We recorded light responses from the host ganglion cells using a multi-electrode array system; this result was consistent with whole-mount immunostaining suggestive of host-graft synapse formation at the responding sites. This study demonstrates an application of our mouse models and provides a proof of concept for the clinical use of human ESC-derived retinal sheets

Human intestinal spirochetosis is significantly associated with sessile serrated adenomas/polyps

It remains unclear whether or not human intestinal spirochetosis (HIS) has any associated symptoms or lesions. In this study, we assessed the prevalence of HIS in sessile serrated adenomas/polyps (SSA/Ps) and their possible association. Following identification of early cecal cancer with SSA/P accompanied by a colonization of HIS, we went on to conduct a retrospective case-control study using endoscopically resected SSA/P specimens to examine the frequency of HIS infection in SSA/Ps. Nineteen SSA/P cases and 172 controls were obtained. The rate of HIS infection was significantly higher at 52.6% (10/19) in the SSA/P cases compared to the controls at 8.1% (14/172). Our SSA/P series were associated with a remarkably higher rate of HIS than controls or than previously reported. This is the first report to provide evidence for potential association between HIS and SSA/Ps. (C) 2014 Elsevier GmbH. All rights reserved

Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study

Abstract Background A prospective, randomised phase II study demonstrated clinical benefit of axitinib dose titration in a subset of treatment-naïve patients treated with axitinib for metastatic renal cell carcinoma. This analysis evaluated patient baseline characteristics that may impact overall survival (OS) with axitinib dose titration. Methods Following a 4-week lead-in period during which all patients received axitinib 5 mg twice-daily (bid); patients meeting the predefined randomisation criteria were randomly assigned to receive axitinib 5 mg bid plus either axitinib or placebo titration. In exploratory analyses, patients were grouped into those who achieved OS ≥24 versus < 24 months, and compared their baseline characteristics with Fisher’s exact test or Cochran-Armitage trend exact test, with a 5% significance level. Potential predictive baseline characteristics associated with effect of axitinib dose titration on OS were investigated using a Cox proportional hazard model. Results Overall, 112 patients were randomised. Three of 56 patients receiving axitinib titration were censored; of the remaining 53, 33 (62%) achieved OS ≥24 months versus 20 (38%) with OS < 24 months. Patients with OS ≥24 vs. < 24 months, respectively, had significantly fewer metastatic sites (≤2 metastases: 52% vs. 10%; ≥3 metastases: 48% vs. 90%), fewer lymph node (45% vs. 75%) or liver (15% vs. 45%) metastases, higher haemoglobin level (i.e., ≥ lower limit of normal: 67% vs. 25%) at baseline, lower neutrophil (≤ upper limit of normal, 97% vs. 75%) and platelet (≤ upper limit of normal, 82% vs. 50%) levels at baseline and ≥ 1 year between histopathological diagnosis and treatment (64% vs. 15%). The primary reason for treatment discontinuation in both OS groups was disease progression. The frequency of toxicity-related discontinuation was comparable between the 2 groups, indicating that it was not a factor for a shorter OS. The multivariate analysis showed that ≥1 year from histopathological diagnosis to treatment and baseline haemoglobin level equal or greater than lower limit of normal were significant covariates associated with favourable OS in patients receiving axitinib titration. Conclusions The current analyses identified potentially predictive factors that could help selecting patients who may benefit from axitinib dose titration. Trial registration ClinicalTrials.gov identifier, NCT00835978. Registered prospectively, February 4, 2009

Impact of Atrial Tachyarrhythmia Recurrence on the Development of Long‐Term Adverse Clinical Events Following Catheter Ablation in Patients With Atrial Fibrillation With Systolic Impairment: A Single‐Center Observational Study

Background Catheter ablation can improve long‐term prognosis of patients with atrial fibrillation with systolic impairment. However, atrial tachyarrhythmia (ATA) recurrence increases during long‐term follow‐up. We aimed to investigate the impact of ATA recurrence on the development of long‐term adverse clinical events following catheter ablation for atrial fibrillation and to identify predictors for the development of adverse clinical events. Methods and Results This single‐center observational study included 75 patients with systolic impairment (left ventricular ejection fraction <50%) who underwent the first catheter ablation procedure for atrial fibrillation at our institution (median follow‐up period: 3.5 [range: 2.4–4.7] years). We compared the cumulative incidence of adverse clinical events (all‐cause death, heart failure hospitalization, stroke, or acute myocardial infarction) between the groups with and without ATA recurrence following the first and last procedures. Multivariable analyses were performed to identify predictors for developing adverse clinical events. Twenty‐one patients (28%) developed adverse clinical events at a median of 2.2 (range: 0.64–2.8) years following the first procedure. The proportion of freedom from adverse clinical events following the first procedure was significantly lower in the ATA recurrence group than in the nonrecurrence group (41% [n=40] versus 95% [n=35], P<0.0005); the proportion following the last procedure also showed a similar tendency (35% [n=26] versus 57% [n=49], P<0.0001). ATA recurrence emerged as an independent predictor for adverse clinical events following both procedures after multivariable adjustment. Conclusions ATA recurrence following catheter ablation procedure could predict adverse clinical events in patients with atrial fibrillation with systolic impairment

Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation

Increasing demand for clinical retinal degeneration therapies featuring human ESC/iPSC-derived retinal tissue and cells warrants proof-of-concept studies. Here, we established two mouse models of end-stage retinal degeneration with immunodeficiency, NOG-rd1-2J and NOG-rd10, and characterized disease progress and immunodeficient status. We also transplanted human ESC-derived retinal sheets into NOG-rd1-2J and confirmed their long-term survival and maturation of the structured graft photoreceptor layer, without rejection or tumorigenesis. We recorded light responses from the host ganglion cells using a multi-electrode array system; this result was consistent with whole-mount immunostaining suggestive of host-graft synapse formation at the responding sites. This study demonstrates an application of our mouse models and provides a proof of concept for the clinical use of human ESC-derived retinal sheets