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"Lee, Ki H"
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Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer
Relapse is common in patients with locally advanced unresectable lung cancer after concurrent chemotherapy and radiation therapy. In a randomized study, addition of the anti–PD-L1 antibody durvalumab every 2 weeks for 12 months increased relapse-free survival by 47%.
Journal Article
Deep Learning Provides Exceptional Accuracy to ECoG-Based Functional Language Mapping for Epilepsy Surgery
The success of surgical resection in epilepsy patients depends on preserving functionally critical brain regions, while removing pathological tissues. Being the gold standard, electro-cortical stimulation mapping (ESM) helps surgeons in localizing the function of eloquent cortex through electrical stimulation of electrodes placed directly on the cortical brain surface. Due to the potential hazards of ESM, including increased risk of provoked seizures, electrocorticography based functional mapping (ECoG-FM) was introduced as a safer alternative approach. However, ECoG-FM has a low success rate when compared to the ESM. In this study, we address this critical limitation by developing a new algorithm based on deep learning for ECoG-FM and thereby we achieve an accuracy comparable to ESM in identifying eloquent language cortex. In our experiments, with 11 epilepsy patients who underwent presurgical evaluation (through deep learning-based signal analysis on 637 electrodes), our proposed algorithm obtained an accuracy of 83.05% in identifying language regions, an exceptional 23% improvement with respect to the conventional ECoG-FM analysis (∼60%). Our findings have demonstrated, for the first time, that deep learning powered ECoG-FM can serve as a stand-alone modality and avoid likely hazards of the ESM in epilepsy surgery. Hence, reducing the potential for developing post-surgical morbidity in the language function.
Journal Article
Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC
In patients with locally advanced non–small-cell lung cancer who have undergone concurrent chemotherapy and radiation therapy, the use of durvalumab in the year after completing treatment significantly prolonged disease-free and overall survival as compared with placebo.
Journal Article
Physical Feature Encoding and Word Recognition Abilities Are Altered in Children with Intractable Epilepsy: Preliminary Neuromagnetic Evidence
Objective evaluation of language function is critical for children with intractable epilepsy under consideration for epilepsy surgery. The purpose of this preliminary study was to evaluate word recognition in children with intractable epilepsy by using magnetoencephalography (MEG). Ten children with intractable epilepsy (M/F 6/4, mean ± SD 13.4 ± 2.2 years) were matched on age and sex to healthy controls. Common nouns were presented simultaneously from visual and auditory sensory inputs in “match” and “mismatch” conditions. Neuromagnetic responses M1, M2, M3, M4, and M5 with latencies of ~100 ms, ~150 ms, ~250 ms, ~350 ms, and ~450 ms, respectively, elicited during the “match” condition were identified. Compared to healthy children, epilepsy patients had both significantly delayed latency of the M1 and reduced amplitudes of M3 and M5 responses. These results provide neurophysiologic evidence of altered word recognition in children with intractable epilepsy.
Journal Article
Corpus Callosotomy for Treatment of Pediatric Epilepsy in the Modern Era
Objective: The purpose of this study was to evaluate seizure outcome in children with intractable secondary generalized epilepsy without a resectable focus who underwent complete corpus callosotomy and compare these results to those of anterior two-third callosotomy. Method: Data were obtained for all patients who underwent a corpus callosotomy from 2000 to 2005. The study involved 37 patients. Eleven patients had anterior two-third corpus callosotomy compared with 28patients who underwent complete corpus callosotomy. Two of these patients had completion of their callosotomy following initial partial callosotomy. Seizure type, seizure frequency, and family satisfaction were evaluated for all patients pre- and postoperatively. Results: A reduction of ≧75% in seizures occurred in 75% of the total-callosotomy patients compared to 55% of the partial-callosotomy patients. Family satisfaction for complete and partial callosotomy was 89 and 73%, respectively. No prolonged neurologic deficits were observed in either group. Conclusion: Complete corpus callosotomy is the most effective treatment for secondary generalized intractable seizures not amenable to focal resection in children.
Journal Article
Interaction Between Akt1-Positive Neurons and Age at Surgery Is Associated With Surgical Outcome in Children With Isolated Focal Cortical Dysplasia
ABSTRACTTo identify pathologic characteristics that are associated with outcome, we performed a retrospective analysis of the clinical, radiologic, and pathologic features of 44 children with isolated focal cortical dysplasia (FCD) after epilepsy surgery. Based on the International League Against Epilepsy Classification, 16 patients had FCD Type I and 28 subjects had FCD Type II. A significantly higher percentage of subjects with FCD Type IIb versus Types I and IIa were seizure-free after surgery. Akt (also known as protein kinase B) is the main downstream target of phosphatidylinositol 3′-kinase and has been implicated in epilepsy pathogenesis. Semiquantitative analysis of cortical gliosis and quantitation of Akt1-immunoreactive neurons indicated that individuals with FCD Type II were more likely to have diffuse astrogliosis and higher counts of Akt1-positive neurons versus those with FCD Type I. A logistic regression model, including Akt1-positive neurons, age at surgery, and the interaction of these factors, was significantly associated with seizure-free outcome. This study provides evidence that astrogliosis and overexpression of neuronal Akt1 protein may be important factors in the pathogenesis of FCD and suggests that the pathogenesis of FCD Type I may differ from that of FCD Type II in children.
Journal Article
Real-Time Functional Mapping With Electrocorticography in Pediatric Epilepsy
SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection) software provides real-time functional mapping (RTFM) of eloquent cortex for epilepsy patients preparing to undergo resective surgery. This study presents the first application of paradigms used in functional magnetic resonance (fMRI) and electrical cortical stimulation mapping (ESM) studies for shared functional cortical mapping in the context of RTFM. Results from the 3 modalities are compared. A left-handed 13-year-old male with intractable epilepsy participated in functional mapping for localization of eloquent language cortex with fMRI, ESM, and RTFM. For RTFM, data were acquired over the frontal and temporal cortex. Several paradigms were sequentially presented: passive (listening to stories) and active (picture naming and verb generation). For verb generation and story processing, fMRI showed atypical right lateralizing language activation within temporal lobe regions of interest and bilateral frontal activation with slight right lateralization. Left hemisphere ESM demonstrated no eloquent language areas. RTFM procedures using story processing and picture naming elicited activity in the right lateral and basal temporal regions. Verb generation elicited strong right lateral temporal lobe activation, as well as left frontal lobe activation. RTFM results confirmed atypical language lateralization evident from fMRI and ESM. We demonstrated the feasibility and usefulness of a new RTFM stimulation paradigm during presurgical evaluation. Block design paradigms used in fMRI may be optimal for this purpose. Further development is needed to create age-appropriate RTFM test batteries.
Journal Article
Porcine testicular extract inhibits T cell proliferation by blocking cell cycle transition from G1 phase to S phase
Since T cells express diverse sex steroid hormone receptors, they might be a good model to evaluate the effects of sex steroid hormones on immune modulation. Porcine testicular extract contains several sex steroid hormones and may be useful to study the effects of sex steroid hormones during T cell activation. We have examined the effects of the porcine testicular extract on T cell activation: proliferation and secretion of cytokines (IL-2 and IFN-γ) by activated T cells were severely decreased after treatment with porcine testicular extract. The extract produced an immunosuppressive effect and inhibited the proliferation of activated T cells by blocking the cell cycle transition from the G
1
phase to S phase. These effects were mediated by a decrease in the expression of cyclin D1 and cyclin E and constitutive expression of p27
KIP1
after T cell activation.
Journal Article
Deep Learning provides exceptional accuracy to ECoG-based Functional Language Mapping for epilepsy surgery
The success of surgical resection in epilepsy patients depends on preserving functionally critical brain regions, while removing pathological tissues. Being the gold standard, electro-cortical stimulation mapping (ESM) helps surgeons in localizing the function of eloquent cortex through electrical stimulation of electrodes placed directly on the cortical brain surface. Due to the potential hazards of ESM, including increased risk of provoked seizures, electrocorticography based functional mapping (ECOG-FM) was introduced as a safer alternative approach. However, ECoG-FM has a low success rate when compared to the ESM. In this study, we address this critical limitation by developing a new algorithm based on deep learning for ECoG-FM and thereby we achieve an accuracy comparable to ESM in identifying eloquent language cortex. In our experiments, with 11 epilepsy patients who underwent presurgical evaluation (through deep learning-based signal analysis on 637 electrodes), our proposed algorithm made an exceptional 23% improvement with respect to the conventional ECoG-FM analysis (~60%). We obtained the state-of-the-art accuracy of 83.05% in identifying language regions, which has never been achieved before. Our findings have demonstrated, for the first time, that deep learning powered ECoG-FM can serve as a stand-alone modality and avoid likely hazards of the ESM in epilepsy surgery. Hence, reducing the potential for developing post-surgical morbidity in the language function. Footnotes * The article has been updated to reflect new architectures and features analyzed in the channel classification process.
Paper