Consolidation treatment of durvalumab after chemoradiation in real-world patients with stage III unresectable non-small cell lung cancer.

BACKGROUND: Treatment for stage III non-small cell lung cancer (NSCLC) of unresectable disease mainly involves concurrent chemoradiation (CRT). Post-CRT consolidation treatment with durvalumab is a major therapeutic advance that provides survival benefit in this group of patients. However, the performance of this treatment strategy remains to be studied in a real-world setting. METHODS: A total of 31 patients who had disease control post-CRT were included in the durvalumab early access program (EAP) as an intent-to-treat cohort and retrospectively reviewed for post-CRT progression-free survival (PFS) and time to metastatic disease or death (TMDD). The neutrophil-to-lymphocyte ratio (NLR) at the initiation of durvalumab was analyzed in 29 patients. RESULTS: The median time from the completion of concurrent CRT to the initiation of durvalumb was 2.8 months. The objective response was 25.8% and the 12 month PFS and TMDD-free rate were 56.4% and 66.9%, respectively. The low NLR patients showed a significantly longer post-CRT PFS (not reach vs. 12.0 months [95% CI: 5.5-not estimable]; P = 0.040; the hazard ratio for disease progression or death, 0.23 [95% CI: 0.05-1.00]; P = 0.048) and the 12 month post-CRT PFS rate (82.5 vs. 42.6%). The post-CRT TMDD (not reach vs. 12.6 months, [95% CI: 10.8-not estimable]; P = 0.010; the hazard ratio for distant metastasis or death, 0.11 [95% CI: 0.01-0.88]; P = 0.037) and 12 month post-CRT TMDD-free rate (90.9 vs. 57.1%) were also significantly higher in the low NLR patients. CONCLUSIONS: Durvalumab consolidation treatment in real-world patients showed substantial efficacy and the correlation with the NLR level warrants further investigation.

Front-line treatment of ceritinib improves efficacy over crizotinib for Asian patients with anaplastic lymphoma kinase fusion NSCLC: The role of systemic progression control.

BACKGROUND: Approximately 3%-5% of lung adenocarcinoma is driven by anaplastic lymphoma kinase (ALK) fusion oncogene, whose activity can be suppressed by multiple ALK inhibitors. Crizotinib and ceritinib have demonstrated superior efficacy to platinum-based chemotherapy as front-line treatment for patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the direct comparison between them in the front-line setting remains lacking. METHODS: A total of 48 patients with ALK-positive, previously untreated advanced NSCLC, who received crizotinib and ceritinib as front-line treatment were retrospectively investigated. The efficacy and pattern of disease progression were analyzed. RESULTS: Patients receiving ceritinib treatment were significantly younger than those receiving crizotinib treatment (52.0 vs. 63.0, P = 0.016). The median progression-free survival (PFS) was significantly longer with ceritinib than with crizotinib treatment (32.3 vs. 12.9 months; log-rank P = 0.020); the hazard ratio for disease progression or death, 0.27 (95% CI, 0.08-0.90; P = 0.033). An objective response was noted in all patients in the ceritinib group and in 23 patients in the crizotinib group (74.2%; 95% CI, 59.0 to 88.5). The rate of systemic progression was significantly lower over time with ceritinib treatment compared to crizotinib treatment (cause-specific hazard ratio, 0.21; 95% CI 0.06-0.73; P = 0.014). Serious adverse events were noted in one (2.9%) patient showing elevated liver function in the crizotinib group and three (23.1%) patients showing diarrhea in the ceritinib group. Dose reduction was needed in five out of 13 (38.5%) patients receiving ceritinib treatment. CONCLUSION: Ceritinib showed higher efficacy associated with a better control of systemic progression compared to crizotinib for the front-line treatment of ALK-positive advanced NSCLCs.

Full Reference Quality Assessment for Image Retargeting Based on Natural Scene Statistics Modeling and Bi-Directional Saliency Similarity.

Image retargeting technology has been widely studied to adapt images for the devices with heterogeneous screen resolutions. Meanwhile effective objective retargeting quality assessment algorithms are also very important for optimizing and selecting favorable retargeting methods. Unlike previous assessment algorithms which rely on image local structure features and unidirectional prediction of information loss, we propose a bi-directional natural salient scene distortion model (BNSSD) including image natural scene statistics (NSS) measurement, salient global structure distortion measurement, and bi-directional salient information loss measurement. First, we propose a new NSS model in log-Gabor domain and verify its effectiveness in reflecting nature scene statistical distortions introduced during the retargeting process. Second, the concept of salient global structure distortion is proposed to measure the global structure uniformity in the corresponding salient regions between original and retargeted images. Finally, we propose a bidirectional salient information loss metric to measure the information loss between salient areas in original image and retargeted image. The effectiveness of the BNSSD model is verified on two widely recognized public databases, and the experimental results show that our method outperforms the state-of-the-art algorithms under different statistical assessment criteria.

Sparse Representation With Spatio-Temporal Online Dictionary Learning for Promising Video Coding.

Classical dictionary learning methods for video coding suffer from high computational complexity and interfered coding efficiency by disregarding its underlying distribution. This paper proposes a spatio-temporal online dictionary learning (STOL) algorithm to speed up the convergence rate of dictionary learning with a guarantee of approximation error. The proposed algorithm incorporates stochastic gradient descents to form a dictionary of pairs of 3D low-frequency and high-frequency spatio-temporal volumes. In each iteration of the learning process, it randomly selects one sample volume and updates the atoms of dictionary by minimizing the expected cost, rather than optimizes empirical cost over the complete training data, such as batch learning methods, e.g., K-SVD. Since the selected volumes are supposed to be independent identically distributed samples from the underlying distribution, decomposition coefficients attained from the trained dictionary are desirable for sparse representation. Theoretically, it is proved that the proposed STOL could achieve better approximation for sparse representation than K-SVD and maintain both structured sparsity and hierarchical sparsity. It is shown to outperform batch gradient descent methods (K-SVD) in the sense of convergence speed and computational complexity, and its upper bound for prediction error is asymptotically equal to the training error. With lower computational complexity, extensive experiments validate that the STOL-based coding scheme achieves performance improvements than H.264/AVC or High Efficiency Video Coding as well as existing super-resolution-based methods in rate-distortion performance and visual quality.

Detection of early cognitive impairment using AD8 in a young patient with stroke with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome: a case report.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome is a hereditary disease resulting from NOTCH3 gene mutation. The clinical presentations include migraine, recurrent stroke, and cognitive impairment. The severity of cognitive impairment varies in different stages, and early recognition poses a challenge. A 47-year-old lady presented with chronic migraine and sudden onset of hemiparesis. Magnetic resonance imaging revealed compatible findings of CADASIL, which was confirmed by mutation analysis of NOTCH3 gene. Early cognitive impairment was detected by her score of 3 in Ascertain Dementia 8 (AD8) questionnaire and confirmed by detailed neuropsychological assessments. After 21 months of follow-up, deterioration in her cognition and ability to perform instrumental activities of daily living were significant with a follow-up AD8 score of 7. Ascertain Dementia 8 questionnaire is an easy and valid screening tool for early cognitive impairment in patients with CADASIL syndrome.

Real-time electrocardiogram transmission from Mount Everest during continued ascent.

The feasibility of a real-time electrocardiogram (ECG) transmission via satellite phone from Mount Everest to determine a climber's suitability for continued ascent was examined. Four Taiwanese climbers were enrolled in the 2009 Mount Everest summit program. Physiological measurements were taken at base camp (5300 m), camp 2 (6400 m), camp 3 (7100 m), and camp 4 (7950 m) 1 hour after arrival and following a 10 minute rest period. A total of 3 out of 4 climbers were able to summit Mount Everest successfully. Overall, ECG and global positioning system (GPS) coordinates of climbers were transmitted in real-time via satellite phone successfully from base camp, camp 2, camp 3, and camp 4. At each camp, Resting Heart Rate (RHR) was transmitted and recorded: base camp (54-113 bpm), camp 2 (94-130 bpm), camp 3 (98-115 bpm), and camp 4 (93-111 bpm). Real-time ECG and GPS coordinate transmission via satellite phone is feasible for climbers on Mount Everest. Real-time RHR data can be used to evaluate a climber's physiological capacity to continue an ascent and to summit.

Effect of acetazolamide for long-lasting paroxysmal dystonia in a patient with multiple sclerosis: a case report and review of literature.

Dystonia is a rare manifestation of multiple sclerosis (MS), but it always interferes with the functional performance and quality of life. We report a rare case of long-lasting paroxysmal dystonia associated with MS. The patient was a 40-year-old woman with relapsing- remitting MS for 6 years. During the latest attack of MS, she suffered from long-lasting paroxysmal dystonia in her left hand. Despite treatment with pulse high-dose intravenous methylprednisolone, interferon, and baclofen, along with occupational therapy, the dystonia persisted and significantly bothered her daily activities. Finally, she was treated with oral acetazolamide (250 mg, three times a day for 4 days), which was very effective for the control of her dystonia. The dystonic movement subsided without recurrence in a follow-up of 17 months. We advocate this effective and safe treatment for patients with paroxysmal dystonia associated with MS.

Therapeutic effects of lidocaine patch on myofascial pain syndrome of the upper trapezius: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The aim of this study was to compare topical 5% lidocaine patch with placebo patch in the treatment of myofascial pain syndrome of the upper trapezius. DESIGN: In this prospective, randomized, double-blind, placebo-controlled study, 60 participants were randomly assigned, placing 31 subjects in the 5% lidocaine patch group and 29 subjects in the placebo patch group. We used the Verbal Rating Scale (VRS), the Pressure Pain Threshold, the ranges of motion of the neck, and the Neck Disability Index to evaluate the subjective pain intensity, objective pain intensity, ranges of motion, and disability of the neck, respectively. Outcome measures were performed before (day 0) the treatment course, 12 hrs after removal of the final patch on the seventh day (day 7), and 1 wk (day 14) and 3 wks (day 28) after the completion of treatment course. RESULTS: The characteristics of the participants did not differ at baseline. Pain intensity assessed by the VRS decreased at day 7 in both the lidocaine patch and placebo patch groups. There was no significant difference between the two groups in the VRS, the Pressure Pain Threshold, the ranges of motion, and the Neck Disability Index. At day 14, the experimental group continued to improve in the VRS (1.06), but the pain of the placebo group aggravated (VRS, 1.5). The difference is significant (P = 0.03). In addition, the Neck Disability Index in the lidocaine patch group decreased significantly as compared to that in the placebo group. The pain-relieving effect of the lidocaine patch attenuated, and it was not significantly different between the two groups at day 28 in the VRS and the Neck Disability Index. Neither the Pressure Pain Threshold nor the ranges of motion were significantly different through the periods of this study. CONCLUSIONS: The application of the 5% lidocaine patch is probably superior to the placebo patch in relieving pain and in reducing associated neck disability for a period of longer than 1 wk for treating patients with myofascial pain syndrome of the upper trapezius.

Connected-sea partons.

According to the path-integral formalism of the hadronic tensor, the nucleon sea contains two distinct components called the connected sea (CS) and the disconnected sea (DS). We discuss how the CS and DS are accessed in the lattice QCD calculation of the moments of the parton distributions. We show that the CS and DS components of u(x) + d(x) can be extracted by using recent data on the strangeness parton distribution, the CT10 global fit, and the lattice result of the ratio of the strange to u(d) moments in the disconnected insertion. The extracted CS and DS for u(x) + d(x) have a distinct Bjorken x dependence in qualitative agreement with expectation. The analysis also shows that the momentum fraction of u(x) + d(x) is about equally divided between the CS and DS at Q(2) = 2.5 GeV(2). Implications for the future global analysis of parton distributions are presented.

Flavor asymmetry of the nucleon sea and the five-quark components of the nucleons.

The existence of the five-quark Fock states for the intrinsic charm quark in the nucleons was suggested some time ago, but conclusive evidence is still lacking. We generalize the previous theoretical approach to the light-quark sector and study possible experimental signatures for such five-quark states. In particular, we compare the d-u and u + d-s-s data with the calculations based on the five-quark Fock states. The qualitative agreement between the data and the calculations is interpreted as evidence for the existence of the intrinsic light-quark sea in the nucleons. The probabilities for the |uuduu and |uuddd Fock states are also extracted.

Coincidence planar imaging for dynamic [18F]FDG uptake in nude mice with tumors and inflammation: correlated with histopathology and micro-autoradiography.

The Institute of Nuclear Energy Research of Taiwan has developed a dynamic coincidence detection device for positron emitted radiotracer pharmacodynamic study in small mice models. In this study, we set up an experimental paradigm by determining [fluorine-18]-2-deoxy-2-fluoro-D-glucose ([18F]FDG) dynamic uptake in tumors and inflammations in nude mice as the foundation for future applications in therapy development. Histopathology and micro-autoradiography of these tumors and inflammations were obtained for confirmation. Dynamic coincidence planar images of six tumors and two inflammations in nude mice were acquired over 4 hours immediately after injection of 25.9 MBq of [18F]FDG into the right thigh of each animal. After image reconstruction, the lesion-to-background ratios were calculated in regions of interest over the lesion and contralateral thigh to determine the equilibrium status of the radiotracer. All mice were sacrificed for histopathologic examination and six of the mice were examined with micro-autoradiography. [18F]FDG uptake in tumors and inflammations both reached equilibrium about 3 hours after injection. At equilibrium, [18F]FDG uptake into tumors was two to four times higher than the background. Uptake into the 4-day and 8-day inflammations was 2.3 and 5.5 times higher than the background, respectively. Histopathology showed macrophage and neutrophil infiltration around the tumors and in the inflammations. Micro-autoradiography showed dense silver grains in the granulation tissue surrounding the tumors and inflammations. The preliminary results suggested that dynamic [18F]FDG coincidence planar imaging can help in determining the suitable time for static [18F]FDG imaging in nude mice models. The optimal time for static [18F]FDG positron emission tomography imaging was around 3 hours after injection. The paradigm for determining a dynamic [18F]FDG uptake pattern was demonstrated for future new therapeutic drug experimental use.

Lymphoscintigraphy and intraoperative gamma probe-directed sentinel lymph node mapping in patients with malignant melanoma.

BACKGROUND AND PURPOSE: Lymphoscintigraphy has been considered a useful tool for sentinel lymph node (SLN) mapping for malignant melanoma. This study evaluated the usefulness of SLN detection by lymphoscintigraphy and excision with intraoperative gamma probe in Taiwanese patients with malignant melanoma. METHODS: Thirty six malignant melanoma patients in clinical stage I and II were enrolled. The Breslow thickness of the primary melanomas was /= 4 mm in 3 patients, and unknown in 4 patients who were transferred from other hospitals and had no nodal or distant metastasis. SLN lymphoscintigraphy was performed with filtered 99mTc-sulfur colloid. An intraoperative gamma probe was used to identify the SLN for dissection. RESULTS: A total of 44 SLNs were detected in 36 patients, with a mean of 1.22 SLNs per patient. The SLN detection rate by lymphoscintigraphy was 100%. During surgery, 39 of the 44 SLNs (88.6%) in 33 of 36 patients (91.7%) were identified. SLN metastasis was found in 8 of 39 dissected SLNs (20.5%) or in 8 of 36 patients (22.2%). The SLN metastatic rate in the patients with primary melanoma with Breslow thickness 2.0 mm was 41.7% (5/12). CONCLUSIONS: Lymphoscintigraphy and intraoperative gamma probe are useful in localizing and dissecting SLN in patients with malignant melanoma. SLN mapping changed the clinical stage in 22.2% of melanoma patients.