Laterality Classification of Fundus Images Using Interpretable Deep Neural Network

In this paper, we aimed to understand and analyze the outputs of a convolutional neural network model that classifies the laterality of fundus images. Our model not only automatizes the classification process, which results in reducing the labors of clinicians, but also highlights the key regions in the image and evaluates the uncertainty for the decision with proper analytic tools. Our model was trained and tested with 25,911 fundus images (43.4% of macula-centered images and 28.3% each of superior and nasal retinal fundus images). Also, activation maps were generated to mark important regions in the image for the classification. Then, uncertainties were quantified to support explanations as to why certain images were incorrectly classified under the proposed model. Our model achieved a mean training accuracy of 99%, which is comparable to the performance of clinicians. Strong activations were detected at the location of optic disc and retinal blood vessels around the disc, which matches to the regions that clinicians attend when deciding the laterality. Uncertainty analysis discovered that misclassified images tend to accompany with high prediction uncertainties and are likely ungradable. We believe that visualization of informative regions and the estimation of uncertainty, along with presentation of the prediction result, would enhance the interpretability of neural network models in a way that clinicians can be benefitted from using the automatic classification system.     

Rituximab-ESHAP as a mobilization regimen for relapsed or refractory B-cell lymphomas: a comparison with ESHAP

BACKGROUND: It has previously been shown that ESHAP was an effective mobilization regimen for patients with pretreated lymphoma. To extend these observations, the efficacy and feasibility of rituximab plus ESHAP regimen in CD20+ B-cell NHL were assessed. STUDY DESIGN AND METHODS: The mobilization efficacy and engraftment characteristics were compared in the 22 patients who received the rituximab plus ESHAP (R-ESHAP) with 33 historical controls who received ESHAP. RESULTS: The two treatment groups were well matched in patient characteristics. In the R-ESHAP group, 62 pheresis procedures were performed. Apheresis procedures were started on median Day 16 (range, Days 13-18). The median number of collected CD34+ cells was 10.6 x 10(6) per kg (range, 4.9 x 10(6)-52.6 x 10(6)/kg). Nineteen (95%) patients achieved optimal peripheral blood hematopoietic progenitor cell (PBPC) collection, defined as at least 5 x 10(6) CD34+ cells per kg. There were no significant differences between the two groups with respect to mobilization efficacy. Sixteen patients in the R-ESHAP group (73%) underwent autologous peripheral blood progenitor cell transplantation (APBPCT). The median time to absolute neutrophil count at least 0.5 x 10(9) per L was 10 days (range, 8-17 days), and the median time to a platelet count of at least 20 x 10(9) per L was 12 days (range, 7-27 days). Lymphocyte recovery was slower in the R-ESHAP group, but the rate of infectious complications was similar in the two groups. In the R-ESHAP group, the 2-year overall survival and progression-free survival after APBPCT were 63.2 and 57.4 percent, respectively. CONCLUSION: Addition of rituximab to ESHAP chemotherapy did not have any adverse effects on PBPC mobilization. Further studies are needed, however, to determine whether addition of rituximab improves outcomes.     

Manual reduction of torsion of an intrascrotal appendage under ultrasonographic monitoring.

OBJECTIVE: The purpose of this study was to evaluate the feasibility and safety of manual reduction of torsion of an intrascrotal appendage under ultrasonographic monitoring. METHODS: Fifteen boys with torsion of an intrascrotal appendage, confirmed by scrotal ultrasonography and clinical status, were included in the study. The boys were 6 to 13 years old (mean age, 9 years). They all had painful, unilateral swelling of the scrotum and a palpable, tender nodule on physical examination. Scrotal ultrasonography indicated a single, variably echoic mass corresponding to the intrascrotal appendage. The mass was avascular according to Doppler ultrasonography. Thirteen boys underwent manual reduction under ultrasonographic monitoring. We tried to pull and release the swollen appendage in 8 patients and gently squeezed the appendage in 5. The procedure was considered successful when ultrasonography showed reperfusion in the appendage and the patients stated complete relief of scrotal pain. In 14 boys, follow-up scrotal ultrasonography was performed after the manual reduction. RESULTS: Successful reduction was obtained in 12 (80.0%) of 15 boys. Only 1 boy was regarded as having reduction failure; this patient had intractable pain after the trial reduction, and ultrasonography showed transient vascular flow that promptly disappeared in the appendage. On follow-up ultrasonography, the maximal diameter +/- SD of the intrascrotal appendages significantly decreased from 6.1 +/- 1.2 to 4.0 +/- 1.3 (P=.005) in 11 patients with successful reduction. CONCLUSIONS: Manual reduction under ultrasonographic monitoring seems to be a feasible and effective method for the treatment of torsion of an intrascrotal appendage to immediately relieve pain.     

A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties

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Are Metastases Really Hypovascular in the Arterial Phase?

OBJECTIVE: The purpose of this study was to describe enhancement and vascularity characteristics of liver metastases on real-time low-mechanical index contrast-enhanced ultrasonography. METHODS: This retrospective study was approved for chart review by our Research Ethics Board. Informed consent was waived. Fifty metastases (colorectal [n = 28], neuroendocrine [n = 6], pancreatic [n = 6], melanoma [n = 3], and other [n = 7]) in 50 patients (38-84 years, 24 male and 26 female) were analyzed. Contrast-enhanced ultrasonography was performed after intravenous injection of a microbubble contrast agent. Two radiologists independently reviewed digital cine clips and static images for the arterial phase intensity and pattern of enhancement and the presence of dysmorphic vessels. Observations on wash-out included its presence and completeness. Disagreement was resolved by consensus. The interval to peak arterial enhancement and beginning of wash-out were determined. Reader agreement was estimated with the kappa statistic. RESULTS: All but 6 metastases (44/50 [88%]) showed arterial hypervascularity, with dysmorphic vessels in 21 (42%) of 50. The pattern of enhancement was rim in 21 (42%) of 50 and diffuse in 29 (58%) of 50. The time to peak arterial enhancement ranged from 8 to 27 seconds (mean, 15.1 seconds), and the beginning of wash-out ranged from 13 to 50 seconds (mean, 25.2 seconds). Although a thin margin of residual enhancement was seen in 27 (54%) of 50 lesions in the early wash-out phase, all lesions (50/50) showed uniform complete wash-out in the portal phase. CONCLUSIONS: Contrary to popular belief based on computed tomography and magnetic resonance imaging studies, most hepatic metastases, including those thought to be hypovascular, show transient arterial hypervascularity on contrast-enhanced ultrasonography, followed by rapid and complete wash-out initiated within the conventional arterial phase.     

Combination Therapy of Rosuvastatin and Ezetimibe in Patients with High Cardiovascular Risk

Purpose

The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk.

A variant 2677A allele of the MDR1 gene affects fexofenadine disposition

BACKGROUND AND OBJECTIVES: There have been considerable disagreements regarding the influence of MDR1 (ABCB1) polymorphisms on the disposition of P-glycoprotein (P-gp) substrates. We speculated that the unknown function of the A allele of exon 21 G2677T/A (Ala893Ser/Thr) provides one of the reasons for the contradictory results. This study was performed to clarify the effects of major MDR1 gene polymorphisms, including a variant A allele in exon 21, on fexofenadine pharmacokinetics. METHODS: We investigated the occurrence of 3 high-frequency single-nucleotide polymorphisms (SNPs) in exons 12 (C1236T), 21 (G2677T/A), and 26 (C3435T) of the MDR1 gene in 232 healthy Koreans, using a polymerase chain reaction-restriction fragment length polymorphism method, and performed haplotype analysis on these 3 SNPs. A single oral dose of 180 mg fexofenadine hydrochloride was administered to 33 healthy Korean male volunteers, who were divided into 6 groups based on the MDR1 genotype for the G2677T/A polymorphism in exon 21 and the C3435T polymorphism in exon 26. RESULTS: A strong linkage disequilibrium was observed among the 3 SNPs. The frequencies of the 4 major haplotypes, 1236C-2677A-3435C, C-G-C, T-G-C, and T-T-T, were 16.4%, 18.6%, 21.6%, and 32.2%, respectively. Fexofenadine disposition varied considerably among the groups. In the 2677AA/3435CC genotype group (n=3), the values of area under the concentration-time curve from time 0 to 24 hours [AUC(0-24)] were significantly lower (P=.014) than those of the other 5 genotype groups (GG/CC, GT/CT, TT/TT, GA/CC, and TA/CT). As compared with the 2677GG/3435CC subjects, the AUC(0-24) values were 17% lower in the 2677AA/3435CC subjects and 47% higher in the 2677TT/3435TT subjects (GG/CC versus AA/CC versus TT/TT, 4017 +/- 1137 ng . h/mL versus 3315 +/- 958 ng . h/mL versus 5934 +/- 2,064 ng . h/mL; P=.018). By stratification for genotypes at position 3435, homozygous 3435TT subjects were found to have significantly higher AUC(0-24) (P=.024) and maximum plasma concentration (P=.040) values than CC subjects [AUC(0-24), 5934 +/- 2064 ng . h/mL versus 3998 +/- 1241 ng . h/mL; maximum plasma concentration, 958 +/- 408 ng/mL versus 673 +/- 242 ng/mL]. CONCLUSIONS: The plasma concentrations of fexofenadine after a single oral administration were lower in 2677AA/3435CC subjects than in subjects with the other 5 genotype combinations of the SNPs of G2677T/A and C3435T. These findings confirm the importance of analyzing MDR1 haplotypes and provide a plausible explanation for the conflicting results regarding the effect of MDR1 polymorphisms on the disposition of P-gp substrates.