Immediate and Long-Term Outcomes of Reperfusion Therapy in Patients With Cancer.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528­6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

Effects of human recombinant granulocyte-colony stimulating factor treatment during in vitro culture on porcine pre-implantation embryos.

Granulocyte-colony stimulating factor (G-CSF), a pleiotropic cytokine, belongs to the hematopoietic growth factor family. Recent studies have reported that G-CSF is a predictive biomarker of oocyte and embryo developmental competence in humans. The aim of our study was to determine whether CSF3 and its receptor (CSF3R) were expressed in porcine maternal reproductive tissues (oviduct and uterus), cumulus cells, and embryos and to investigate the effects of human recombinant G-CSF (hrG-CSF) supplementation during in vitro culture (IVC) on the developmental competence of pre-implantation embryos. To do this, we first performed reverse-transcription polymerase chain reaction (RT-PCR). Second, we performed parthenogenetic activation (PA), in vitro fertilization (IVF), and somatic cell nuclear transfer (SCNT) to evaluate the embryonic developmental potential after hrG-CSF supplementation based on various concentrations (0 ng/mL, 10 ng/mL, 50 ng/mL, and 100 ng/mL) and durations (Un-treated, Days 0-3, Days 4-7, and Days 0-7) of IVC. Finally, we examined transcriptional levels of several marker genes in blastocysts. The results of our study showed that CSF3 transcript was present in all samples we assessed. CSF3-R was also detected, except in cumulus cells and blastocysts from PA. Furthermore, 10 ng/mL and Days 0-7 were the optimal concentration and duration for the viability of in vitro embryonic development, especially for SCNT-derived embryos. The rate of blastocyst formation and the total cell number of blastocysts were significantly enhanced, while the number and index of apoptotic nuclei were significantly decreased in optimal condition groups compared to others. Moreover, the transcriptional levels of anti-apoptotis- (BCL2), proliferation- (PCNA), and pluripotency- (POU5F1) related genes were dramatically upregulated. In conclusion, for the first time, we demonstrated that CSF3 and CSF3R were expressed in porcine reproductive organs, cells, and embryos. Additionally, we determined that hrG-CSF treatment improved porcine embryonic development capacity in vitro.

Reconstruction error based deep neural networks for coronary heart disease risk prediction.

Coronary heart disease (CHD) is one of the leading causes of death worldwide; if suffering from CHD and being in its end-stage, the most advanced treatments are required, such as heart surgery and heart transplant. Moreover, it is not easy to diagnose CHD at the earlier stage; hospitals diagnose it based on various types of medical tests. Thus, by predicting high-risk people who are to suffer from CHD, it is significant to reduce the risks of developing CHD. In recent years, some research works have been done using data mining to predict the risk of developing diseases based on medical tests. In this study, we have proposed a reconstruction error (RE) based deep neural networks (DNNs); this approach uses a deep autoencoder (AE) model for estimating RE. Initially, a training dataset is divided into two groups by their RE divergence on the deep AE model that learned from the whole training dataset. Next, two DNN classifiers are trained on each group of datasets separately by combining a RE based new feature with other risk factors to predict the risk of developing CHD. For creating the new feature, we use deep AE model that trained on the only high-risk dataset. We have performed an experiment to prove how the components of our proposed method work together more efficiently. As a result of our experiment, the performance measurements include accuracy, precision, recall, F-measure, and AUC score reached 86.3371%, 91.3716%, 82.9024%, 86.9148%, and 86.6568%, respectively. These results show that the proposed AE-DNNs outperformed regular machine learning-based classifiers for CHD risk prediction.

Arthroscopic-assisted plate fixation for displaced large-sized comminuted greater tuberosity fractures of proximal humerus: a novel surgical technique.

PURPOSE: The purpose of the present study was to describe the use of a novel hybrid surgical technique-arthroscopic-assisted plate fixation-and evaluate its clinical and anatomical outcomes in the management of large, displaced greater tuberosity (GT) fractures with comminution. METHODS: From 2009 to 2011, this novel technique was performed in 11 patients [2 men and 9 women; median age, 64 years (range 41-83 years)] with large, comminuted GT fractures, with fragment displacements of >5 mm. The preoperative mean posterior and superior migration of the fractured fragment, as measured on computed tomography (CT), was 19.5 and 5.5 mm, respectively. Two patients had shoulder fracture-dislocation, and three had associated undisplaced surgical neck fracture. The mean duration between injury and surgery was 4 days. The mean follow-up duration was 26 months. RESULTS: At the final follow-up, the mean postoperative ASES, UCLA and SST scores were 84, 29, and 8, respectively. The mean range of motion was as follows: forward flexion, 138°; abduction, 135°; external rotation at the side, 19°; and internal rotation, up to the L2 level. The mean posterior and superior displacements of fracture fragments on postoperative CT scan [0.7 ± 0.8 mm (range 0-2.1 mm) and 2.8 ± 0.5 mm (range 3.4-5.3 mm), respectively] were significantly improved (p < 0.05). On arthroscopy, a partial articular-side supraspinatus tendon avulsion lesion was identified in 10 of 11 patients (91 %), and 1 of these patients had a partial tear of the biceps and 1 had a partial subscapularis tear, respectively (9 %). Intraoperatively, 1 anchor pullout and 1 anchor protrusion through the humeral head were noted and corrected. Postoperatively, the loss of reduction in the fracture fragment was noted in 1 patient at 4 weeks, after corrective reduction and fixation surgery. CONCLUSIONS: The novel arthroscopic-assisted anatomical plate fixation technique was found to be effective in reducing large-sized, displaced, comminuted GT fractures and in allowing concurrent management of intra-articular pathologies and early functional rehabilitation. Compared with the conventional plate fixation or arthroscopic suture anchor fixation technique, arthroscopic-assisted plate fixation enabled accurate restoration of the medial footprint of the GT fracture and provided an effective buttress to the large-sized GT fracture fragments. LEVEL OF EVIDENCE: Retrospective clinical study, Level IV.

Factors associated with ischemic stroke on therapeutic anticoagulation in patients with nonvalvular atrial fibrillation.

PURPOSE: In this study, we investigated the stroke mechanism and the factors associated with ischemic stroke in patients with nonvalvular atrial fibrillation (NVAF) who were on optimal oral anticoagulation with warfarin. MATERIALS AND METHODS: This was a multicenter case-control study. The cases were consecutive patients with NVAF who developed cerebral infarction or transient ischemic attack (TIA) while on warfarin therapy with an international normalized ratio (INR) ≥2 between January 2007 and December 2011. The controls were patients with NVAF without ischemic stroke who were on warfarin therapy for more than 1 year with a mean INR ≥2 during the same time period. We also determined etiologic mechanisms of stroke in cases. RESULTS: Among 3569 consecutive patients with cerebral infarction or TIA who had NVAF, 55 (1.5%) patients had INR ≥2 at admission. The most common stroke mechanism was cardioembolism (76.0%). Multivariate analysis demonstrated that smoking and history of previous ischemic stroke were independently associated with cases. High CHADS2 score (≥3) or CHA2DS2-VASc score (≥5), in particular, with previous ischemic stroke along with ≥1 point of other components of CHADS2 score or ≥3 points of other components of CHA2DS2-VASc score was a significant predictor for development of ischemic stroke. CONCLUSION: NVAF patients with high CHADS2/CHA2DS2-VASc scores and a previous ischemic stroke or smoking history are at high risk of stroke despite optimal warfarin treatment. Some other measures to reduce the risk of stroke would be necessary in those specific groups of patients.

Establishment of transgenic fibroblasts for producing recombinant human interferon-α and erythropoietin in bovine milk.

Human interferon α (IFN-α) and erythropoietin (EPO) have been used for a variety of purposes in clinical medicine. Human IFN-α has been used to treat several types of viral infection and cancer, as well as renal anemia, via stimulation of erythrocyte formation in the bone marrow. Transgenic cattle are excellent candidates for pharmaceutical production for humans due to their ability to produce recombinant proteins in milk. The purpose of the present study was to generate bovine transgenic fibroblasts capable of producing recombinant human IFN-α and EPO proteins in transgenic cattle milk. First, we analyzed the promoter activities of various bovine milk protein genes in HC11 mouse mammary epithelial cells. The bovine milk protein gene promoters were cloned into the Luc gene in a promoter-less pGL3-Basic vector. Presence of the αS1-casein promoter (-175 to +796 nt) resulted in an up to 16-fold increase in luciferase activity compared with that of the promoter-less construct. In addition, the human IFN-α and EPO genes were identified as significantly overexpressed in HC11 cells compared with the promoter-less construct. Together, the present results demonstrate that the construct with the αS1-casein promoter may induce secretion of recombinant human IFN-α and EPO into bovine milk. Furthermore, we generated transgenic fibroblasts expressing human IFN-α and EPO cDNA controlled by the αS1-casein promoter and two screening markers, enhanced green fluorescent protein and neomycin resistance. These transgenic fibroblasts may be a source of somatic cells for generating transgenic cattle that produce recombinant human IFN-α and EPO proteins during lactation.

Effects of repetitive ionomycin treatment on in vitro development of bovine somatic cell nuclear transfer embryos.

To artificially activate embryos in somatic cell nuclear transfer (SCNT), chemical treatment with ionomycin has been used to induce transient levels of Ca(2+) and initiate reprogramming of embryos. Ca(2+) oscillation occurs naturally several times after fertilization (several times with 15- to 30-min intervals). This indicates how essential additional Ca(2+) influx is for successful reprogramming of embryos. Hence, in this report, the experimental design was aimed at improving the developmental efficiency of cloned embryos by repetitive Ca(2+) transients rather than the commonly used ionomycin treatment (4 min). To determine optimal Ca(2+) inflow conditions, we performed three different repetitive ionomycin (10 µM) treatments in reconstructed embryos: Group 1 (4-min ionomycin treatment, once), Group 2 (30-sec treatment, 4 times, 15-min intervals) and Group 3 (1-min treatment, 4 times, 15-min intervals). Pronuclear formation rates were checked to assess the effects of repetitive ionomycin treatment on reprogramming of cloned embryos. Cleavage rates were investigated on day 2, and the formation rates of blastocysts (BLs) were examined on day 7 to demonstrate the positive effect of repeated ionomycin treatment. In Group 3, a significant increase in BL formation was observed [47/200 (23.50%), 44/197 (22.33%) and 69/195 (35.38%) in Groups 1, 2 and 3, respectively]. Culturing embryos with different ionomycin treatments caused no significant difference among the groups in terms of the total cell number of BLs (164.3, 158.5 and 145.1, respectively). Additionally, expression of the anti-apoptotic Bcl-2 gene and MnSOD increased significantly in Group 3, whereas the expression of the pro-apoptotic Bax decreased statistically. In conclusion, the present study demonstrated that repeated ionomycin treatment is an improved activation method that can increase the developmental competence of SCNT embryos by decreasing the incidence of apoptosis.

Prediction of long-term outcome by percent improvement after the first day of thrombolytic treatment in stroke patients.

BACKGROUND: We investigated a method for assessing early improvement and predictive factors of early and late outcomes in patients receiving thrombolytic therapy. METHODS: A total of 160 consecutive patients who received thrombolytic therapy were included in the study. Using National Institutes of Health Stroke Scale (NIHSS) scores, percent improvement [(baseline NIHSS score-24-hour NIHSS score)/baseline NIHSS score x 100] was calculated and compared with delta (baseline NIHSS score-24-hour NIHSS score) and with major neurological improvement (MNI, NIHSS score of 0-1 or >or=8 point improvement at 24 h) by receiver operating characteristic (ROC) curve analysis. Finally, we investigated the independent predictors of improvement at 24 h after the thrombolytic therapy and of favorable 3-month outcome (modified Rankin scale score 0-2). RESULTS: By pairwise comparison of ROC curves, percent improvement was stronger than delta (p=0.004) and MNI (p<0.001) in predicting long-term outcome. First day improvement (FDI), defined as greater than 20% improvement, was a strong predictor of favorable 3-month outcome (OR 12.55, 95% CI 5.41-29.10). Recanalization (OR 3.30, 95% CI 1.28-8.45), absence of carotid T occlusion (OR 0.09, 95% CI 0.02-0.42) and hemorrhagic transformation (OR 0.25, 95% CI 0.09-0.73) were independent predictors of FDI. Independent predictors of favorable 3-month outcome were FDI, current smoking, absence of carotid T occlusion and hemorrhagic transformation. CONCLUSIONS: Percent improvement at 24 h after thrombolytic therapy is a useful surrogate marker for predicting the long-term outcome. Our findings highlight the importance of early stroke management.

Effects of insulin-transferrin-selenium in defined and porcine follicular fluid supplemented IVM media on porcine IVF and SCNT embryo production.

Insulin-transferrin-selenium (ITS) together has been used in different in vitro maturation system to support in vitro maturation of oocytes. The present study was designed to evaluate the effects of ITS in defined (0.1% PVA) and porcine follicular fluid (10% pFF) supplemented IVM media on the developmental competence of porcine oocytes. Three combinations of ITS, 10 mg/L insulin (Ins), 5.5mg/L transferrin (Tf) and 5 microg/L selenium (Se), 20mg/L Ins, 11 mg/L Tf and 10 microg/L Se, and 30 mg/L Ins, 16.5 mg/L TF and 15 microg/L Se, were used. The data were analyzed by one-way ANOVA and Tukey was used as the post hoc test. Both in the defined and pFF supplemented media, higher concentration of intracellular glutathione was observed in presence of ITS (4.6-4.8, and 6.9-7.1 picomole/oocyte for defined and pFF groups, respectively) compared to the respective control (2.1 and 4.3 picomole/oocyte for defined and pFF group, respectively). ITS decreased polyspermy and increased male pronucleus formation in both the defined and pFF supplemented medium. There was no difference in different treatment groups. The highest frequency of blastocyst formation rate and number of cells in blastocyst following IVF and SCNT was observed in pFF+ITS group (p<0.05). In conclusion, ITS addition during IVM improved the developmental competence of porcine oocytes in both the defined and pFF supplemented groups. Thus, we recommended to supplement porcine IVM medium with 10 microg/mL insulin, 5.5 microg/mL transferrin and 5 microg/mL selenium.

Comparison of anterior chamber depth measurement between Orbscan IIz and ultrasound biomicroscopy.

PURPOSE: To compare the measurement of anterior chamber depth exclusive of corneal thickness using Orbscan IIz and ultrasound biomicroscopy (UBM) and evaluate the repeatability of each method. METHODS: Three consecutive measurements of anterior chamber depth were prospectively performed using Orbscan IIz and Paradigm 50-MHz UBM in 40 eyes in 20 individuals. Mean values were compared using the paired t test. For 12 eyes in 6 individuals, anterior chamber depth measurements were performed 5 times to estimate the repeatability of each method by a coefficient of variation. Refractive errors were measured to correlate with anterior chamber depth. RESULTS: The mean anterior chamber depth was 2.82 +/- 0.46 mm with the Orbscan IIz and 2.91 +/- 0.43 mm in UBM. This difference was statistically significant (P < .001), but not clinically meaningful. The coefficient of variation was 1.15% and 1.10% in Orbscan IIz and UBM, respectively. A negative correlation between anterior chamber depth and spherical equivalent refraction was noted within the range of -5.50 to +3.00 diopters. CONCLUSIONS: The mean anterior chamber depth of Orbscan IIz was 0.087 mm less than that of UBM. Both methods were precise. Orbscan IIz seems to be a useful and more convenient method to measure anterior chamber depth for phakic intraocular lens implantation.

Application of high throughput cell array technology to FISH: investigation of the role of deletion of p16 gene in leukemias.

Bio-cell chip is a chip that has hundreds of types of cells arrayed and immobilized on a small slide. To elucidate the role of deletion of the p16 gene in hematologic malignancies, the bio-cell chip technique was applied to fluorescent in situ hybridization (FISH) study. We made a bio-cell chip with bone marrow specimen from 109 patients with acute lymphoblastic leukemia (ALL), 102 patients with acute myelogenous leukemia (AML), 47 patients with chronic myelogenous leukemia (CML), and 25 patients with multiple myeloma (MM). A glass slide with 96 separated areas was fabricated, onto which was added methanol/acetic acid fixed cell suspensions for high-throughput FISH for p16. With the successful application of bio-cell chip technique, we found that the deletion of p16 contributed to the oncogenesis in acute leukemia, but not in chronic leukemia. In conclusion, the bio-cell chip, a cell version of ultrahigh-throughput technology, was successfully applied to the FISH study, which can be utilized efficiently in the molecular cytogenetic investigation of hematologic malignancies.

Distribution and characteristics of peripheral anterior synechiae in primary angle-closure glaucoma.

PURPOSE: To evaluate the characteristics of peripheral anterior synechiae (PAS) in primary angle-closure glaucoma (PACG). METHODS: We reviewed the charts of 155 patients (244 eyes) with PACG. We divided these patients into one of four clinical subtypes: acute angle-closure glaucoma (ACG), chronic ACG, angle-closure hypertension, and ACG suspect. The prevalence, extent, and location of PAS were evaluated according to PACG subtypes. Correlation analysis was used to evaluate relationships between the highest IOP level without treatment and the extent of PAS. RESULT: The average degree of angle-closure with PAS was 14.6 +/- 9.1 in eyes that were classified as ACG suspect, 83.8 +/- 48.3 in angle-closure hypertension, 140.5 +/- 31.3 in acute ACG, and 180.3 +/- 31.9 in chronic ACG (ANOVA test, P < 0.05). PAS was most frequently found in the superior part of the eye, especially from 12 to 1 o' clock. The incidence of broad PAS (PAS over 30 degrees in width) was highest in superior part, but the medium and narrow PAS (PAS limited to within 30 degrees in width) was distributed throughout all 12 sectors relatively equally. Prior to a laser iridotomy (LI) and other medical treatments, a positive correlation was found between the highest IOP (intraocular pressure) levels and the extent of PAS in chronic ACG (r = 0.423, P < 0.0001). However, statistically significant relationships were not found between the highest IOP levels before treatment and the extent of PAS in any of the other clinical subtypes. CONCLUSIONS: Our results suggest that acute and chronic ACG patients are most likely to have a greater extent of PAS than patients in the angle-closure hypertension or ACG suspect subtypes. PAS may be narrower in earlier stages and broader in later stages. PAS was also found most frequently in the superior part of the eye. The extent of synechial closure of the angle may play a role in raising IOP levels in later stages of the disease rather than early on.