Patients with natural killer T (NK/T) -cell lymphomas have poor survival outcome, and for this condition there is no optimal therapy. The purpose of this study was to design a prognostic model ...specifically for extranodal NK/T-cell lymphoma, which can identify high-risk patients who need more aggressive therapy.
This multicenter retrospective study was comprised of 262 patients who were diagnosed with NK/T-cell lymphoma.
After a median follow-up duration of 51.2 months, 5-year overall survival rate in 262 patients was 49.5%. Prognostic factors for survival were "B" symptoms (P = .0003; relative risk, 2.202; 95% CI, 1.446 to 3.353), stage (P = .0006; relative risk, 2.366; 95% CI, 1.462 to 3.828), lactate dehydrogenase (LDH) level (P = .0005; relative risk, 2.278; 95% CI, 1.442 to 3.598), and regional lymph nodes (P = .0044; relative risk, 1.546; 95% CI, 1.009 to 2.367). Of 262 patients, 219 had complete information on four parameters. We identified four different risk groups: group 1, no adverse factor; group 2, one factor; group 3, two factors; and group 4, three or four factors. The new model showed a superior prognostic discrimination as compared with the International Prognostic Index (IPI). Notably, the distribution of patients was balanced when a new model was adopted (group 1, 27%; group 2, 31%; group 3, 20%; group 4, 22%), whereas 81% of patients were categorized as low or low-intermediate risks using IPI.
The newly proposed model for extranodal NK/T-cell lymphoma demonstrated a more balanced distribution of patients into four groups with better prognostic discrimination as compared with the IPI.
Subependymal enhancement and DWI have been reported to be useful MR imaging markers for identifying true progression. Our aim was to determine whether the subependymal enhancement pattern and ADC can ...differentiate true progression from pseudoprogression in patients with glioblastoma multiforme treated with concurrent chemoradiotherapy by using temozolomide.
Forty-two patients with glioblastoma multiforme with newly developed or enlarged enhancing lesions on the first follow-up MR images obtained within 2 months of concurrent chemoradiotherapy completion were included. Subependymal enhancement was analyzed for the presence, location, and pattern (local or distant relative to enhancing lesions). The mean ADC value and the fifth percentile of the cumulative ADC histogram were determined. A multiple logistic regression analysis was performed to identify independent factors associated with true progression.
Distant subependymal enhancement (ie, extending >1 cm or isolated from the enhancing lesion) was significantly more common in true progression (n = 24) than in pseudoprogression (n = 18) (P = .042). The fifth percentile of the cumulative ADC histogram was significantly lower in true progression than in pseudoprogression (P = .014). Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were independent factors associated with true progression (P = .041 and P = .033, respectively). Sensitivity and specificity for the diagnosis of true progression were 83% and 67%, respectively, by using both factors.
Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were significant independent factors predictive of true progression.
This article reviews important considerations for researchers who are designing adaptive clinical trials. These differ from conventional clinical trials because they allow and even enforce continual ...modifications to key components of trial design while data are being collected. This innovative approach has the potential to reduce resource use, decrease time to trial completion, limit allocation of participants to inferior interventions, and improve the likelihood that trial results will be scientifically or clinically relevant. Adaptive designs have mostly been used in trials evaluating drugs, but their use is spreading. The US Food and Drug Administration recently issued guidance on adaptive trial designs, which highlighted general principles and different types of adaptive clinical trials but did not provide concrete guidance about important considerations in designing such trials. Decisions to adapt a trial are not arbitrary; they are based on decision rules that have been rigorously examined via statistical simulations before the first trial participant is enrolled. The authors review important characteristics of adaptive trials and common types of study modifications and provide a practical guide, illustrated with a case study, to aid investigators who are planning an adaptive clinical trial
Assessment of the collateral status has been emphasized for appropriate treatment decisions in patients with acute ischemic stroke. The purpose of this study was to introduce a multiphase MRA ...collateral imaging method (collateral map) derived from time-resolved dynamic contrast-enhanced MRA and to verify the value of the multiphase MRA collateral map in acute ischemic stroke by comparing it with the multiphase collateral imaging method (MRP collateral map) derived from dynamic susceptibility contrast-enhanced MR perfusion.
From a prospectively maintained registry of acute ischemic stroke, MR imaging data of patients with acute ischemic stroke caused by steno-occlusive lesions of the unilateral ICA and/or the M1 segment of the MCA were analyzed. We generated collateral maps using dynamic signals from dynamic contrast-enhanced MRA and DSC-MRP using a Matlab-based in-house program and graded the collateral scores of the multiphase MRA collateral map and the MRP collateral map independently. Interobserver reliabilities and intermethod agreement between both collateral maps for collateral grading were tested.
Seventy-one paired multiphase MRA and MRP collateral maps from 67 patients were analyzed. The interobserver reliabilities for collateral grading using multiphase MRA or MRP collateral maps were excellent (weighted κ = 0.964 and 0.956, respectively). The agreement between both collateral maps was also excellent (weighted κ = 0.884; 95% confidence interval, 0.819-0.949).
We demonstrated that the dynamic signals of dynamic contrast-enhanced MRA could be used to generate multiphase collateral images and showed the possibility of the multiphase MRA collateral map as a useful collateral imaging method in acute ischemic stroke.
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since ...then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
Summary
Introduction
The aim of this study was to characterize clinicopathological features of acute panmyelosis with myelofibrosis (APMF), acute megakaryoblastic leukemia with myelofibrosis ...(AMKL‐MF), primary myelofibrosis (PMF) and myelodysplastic syndrome with myelofibrosis (MDS‐MF) in order to provide the keys to the differential diagnosis of bone marrow (BM) fibrosis.
Methods
We compared age, gender, splenomegaly, serum lactate dehydrogenase level, blood cell counts, blast counts in peripheral blood (PB) and BM, megakaryocyte counts, BM cellularity, dysplasia, and the karyotypes of patients with APMF (n = 6), AMKL‐MF (n = 7), PMF (n = 44), and MDS‐MF (n = 44).
Results
APMF showed hyperplasia of all three lineages, increase in megakaryocyte count with dysplasia and frequent abnormal karyotypes. AMKL‐MF was associated with elevated BM blast counts, decreased BM megakaryocyte count with rare megakaryocytic dysplasia and chromosome 21 abnormality. PMF patients displayed splenomegaly, rare blasts in PB/BM, and JAK2 V617F mutation. MDS‐MF patients showed pancytopenia, dysplasia in all three lineages and recurrent chromosomal abnormalities involving chromosome 5,7,12, and 17.
Conclusions
Although differential diagnosis among APMF, AMKL‐MF, PMF, and MDS‐MF is very challenging due to the overlapping clinical and morphological features, meticulous investigation of the patient with respect to splenomegaly, blood cell count, PB and BM findings, and karyotype will serve as a guide to correct diagnosis.
Background and purpose
Cerebral microbleeds (CMBs) have been extensively studied in healthy controls and patients with cerebrovascular disease and Alzheimer's disease. Our aim was to characterize the ...clinical and radiological features of CMBs in idiopathic Parkinson's disease (IPD).
Methods
This cross‐sectional study included consecutive parkinsonian patients who attended the authors' movement disorders clinic from March 2010 to February 2012 and underwent a standard magnetic resonance imaging (MRI) protocol with gradient recalled echo taken with a 3 T MRI machine.
Results
Amongst parkinsonian disorders, CMBs were most common in vascular parkinsonism (VP) (56%) and least common in IPD (17.7%). In IPD, CMBs were significantly associated with white matter hyperintensities and concurrent lacunar infarctions. The presence of CMBs had no effect on various cognitive domains in IPD. IPD with CMBs was discriminated from VP by clinical and neuroimaging findings: frequencies of motor subtypes were similar between IPD with and without CMBs, whereas all VP patients were the postural‐instability gait difficulty type. In 90.9% of the IPD cases with CMBs, the numbers of CMBs were three or less, whereas the numbers of CMBs exceeded three in 50% of the cases of VP and exceeded 10 in 31.3% of the cases (P < 0.001). The topography of the CMBs in IPD was also different from that in VP (P < 0.01).
Conclusions
Cerebral microbleeds are not rare in IPD, and IPD with CMBs does not appear to be a form of VP. Further studies in larger populations are needed to elucidate the clinical implications of CMBs in terms of prognoses and cognitive changes in IPD.
Targeted oncolytic viruses and immunostimulatory therapeutics are being developed as novel cancer treatment platforms. These approaches can be combined through the expression of immunostimulatory ...cytokines from targeted viruses, including adenoviruses and herpesviruses. Although intratumoral injection of such viruses has been associated with tumor growth inhibition, eradication of distant metastases was not reported. The major limitations for this approach to date have been (1) inefficient intravenous virus delivery to tumors and (2) the lack of predictive, immunocompetent preclinical models. To overcome these hurdles, we developed JX-594, a targeted, thymidine kinase(-) vaccinia virus expressing human GM-CSF (hGM-CSF), for intravenous (i.v.) delivery. We evaluated two immunocompetent liver tumor models: a rabbit model with reproducible, time-dependent metastases to the lungs and a carcinogen-induced rat liver cancer model. Intravenous JX-594 was well tolerated and had highly significant efficacy, including complete responses, against intrahepatic primary tumors in both models. In addition, whereas lung metastases developed in all control rabbits, none of the i.v. JX-594-treated rabbits developed detectable metastases. Tumor-specific virus replication and gene expression, systemically detectable levels of hGM-CSF, and tumor-infiltrating CTLs were also demonstrated. JX-594 holds promise as an i.v.-delivered, targeted virotherapeutic. These two tumor models hold promise for the optimization of this approach.
This report discusses the structural and spectroscopic analysis of yttria-stabilized-zirconia (YSZ) thin films grown on Al2O3(0001) substrates. It is found that the changes of oxygen partial pressure ...during the growth are closely related to the surface chemical compositions and the surface crystal orientations of the thin films. The presence of oxygen partial pressure produces a polycrystalline structure on the thin film while a preferred orientation of crystal structures is formed under no oxygen partial pressure. Difficulty arises in identifying the structure of the thin films due to the broad characteristics of the x-ray diffraction (XRD) peaks; however, the XRD rocking scan suggests the existence of two lateral domain sizes. The chemical analysis of the thin films from x-ray photoelectron spectroscopy measurements indicates the enrichment of surface yttrium-oxide as the oxygen partial pressure increases. The detailed analysis of valence band spectra also suggests that the thin films undergo a surface structural phase transition, i.e., transforming from a single tetragonal structure to a mixed (cubic+monoclinic) structure. Furthermore, the optical data display the small increments of the band gap as the oxygen partial pressure increases, which reflects the presence of the structural phase transition of the thin films.
► The rocking scan suggests the existence of two lateral domain sizes. ► The XPS indicates the enrichment of surface yttrium-oxide. ► The valence band spectra suggest that the thin films exhibit structure transforms. ► The optical data display the small increments of the band gap. ► This reflects the presence of the structural phase transition of the thin films.
The in situ primary production rates and various environmental variables were investigated in the Chukchi Sea during the RUSALCA expedition, which was conducted in 2012, to identify the current ...status of primary production. A 13C–15N dual-tracer technique was used to measure the daily primary production rates, which ranged from 0.02 to 1.61 g C m−2 d−1 (mean ±SD = 0.42 ± 0.52 g C m−2 d−1). The primary production rates showed large regional differences, with the southern region (0.66 ± 0.62 g C m−2 d−1) producing approximately 5 times as much as the northern region (0.14 ± 0.10 g C m−2 d−1), which was primarily due to the differences in phytoplankton biomasses induced by regional nutrient conditions. The primary production rates in the Chukchi Sea were averaged using data acquired during the three different RUSALCA expeditions (2004, 2009, and 2012) as 0.33 g C m−2 d−1 (SD = 0.40 g C m−2 d−1), which was significantly lower than previously reported rates. In addition to strong seasonal and interannual variations in primary production, recent decreases in the concentrations of major inorganic nutrients and chlorophyll a could be among the reasons for the recent low primary production in the Chukchi Sea because the primary production is mainly affected by nutrient concentration and phytoplankton biomass. The nutrient inventory and primary production appear to be largely influenced by the freshwater content (FWC) variability in the region due to the significant relationships between FWC, nitrate inventory (r = 0.54, p < 0.05), and primary production rates (r = 0.56, p < 0.05). Moreover, we found highly significant relationships between the nutrient inventory and the primary production rates (r = 0.75, p < 0.001). In conclusion, the primary production in the Chukchi Sea is primarily controlled by nutrient availability, which is strongly related to the FWC variability. Our results imply that the predicted increase in freshwater accumulation might cause a decrease in primary production by lowering the nutrient inventory in the euphotic zone of the Chukchi Sea.
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