Effective targeted therapies for small-cell lung cancer (SCLC), the most aggressive form of lung cancer, remain urgently needed. Here we report evidence of preclinical efficacy evoked by targeting the overexpressed cell-cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacologic blockade with the novel second-generation CHK1 inhibitor prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the effects of cisplatin or the PARP inhibitor olaparib, and improved the response of platinum-resistant models. Proteomic analysis identified CHK1 and MYC as top predictive biomarkers of LY2606368 sensitivity, suggesting that CHK1 inhibition may be especially effective in SCLC with MYC amplification or MYC protein overexpression. Our findings provide a preclinical proof of concept supporting the initiation of a clinical efficacy trial in patients with platinum-sensitive or platinum-resistant relapsed SCLC.

Deciphering the massive volume of complex electronic data that has been compiled by hospital systems over the past decades has the potential to revolutionize modern medicine, as well as present significant challenges. Deep learning is uniquely suited to address these challenges, and recent advances in techniques and hardware have poised the field of medical machine learning for transformational growth. The clinical neurosciences are particularly well positioned to benefit from these advances given the subtle presentation of symptoms typical of neurologic disease. Here we review the various domains in which deep learning algorithms have already provided impetus for change-areas such as medical image analysis for the improved diagnosis of Alzheimer's disease and the early detection of acute neurologic events; medical image segmentation for quantitative evaluation of neuroanatomy and vasculature; connectome mapping for the diagnosis of Alzheimer's, autism spectrum disorder, and attention deficit hyperactivity disorder; and mining of microscopic electroencephalogram signals and granular genetic signatures. We additionally note important challenges in the integration of deep learning tools in the clinical setting and discuss the barriers to tackling the challenges that currently exist.

Study Design: Cross sectional database study. Objective: To develop a fully automated artificial intelligence and computer vision pipeline for assisted evaluation of lumbar lordosis. Methods: Lateral lumbar radiographs were used to develop a segmentation neural network (n = 629). After synthetic augmentation, 70% of these radiographs were used for network training, while the remaining 30% were used for hyperparameter optimization. A computer vision algorithm was deployed on the segmented radiographs to calculate lumbar lordosis angles. A test set of radiographs was used to evaluate the validity of the entire pipeline (n = 151). Results: The U-Net segmentation achieved a test dataset dice score of 0.821, an area under the receiver operating curve of 0.914, and an accuracy of 0.862. The computer vision algorithm identified the L1 and S1 vertebrae on 84.1% of the test set with an average speed of 0.14 seconds/radiograph. From the 151 test set radiographs, 50 were randomly chosen for surgeon measurement. When compared with those measurements, our algorithm achieved a mean absolute error of 8.055° and a median absolute error of 6.965° (not statistically significant, P > .05). Conclusion: This study is the first to use artificial intelligence and computer vision in a combined pipeline to rapidly measure a sagittal spinopelvic parameter without prior manual surgeon input. The pipeline measures angles with no statistically significant differences from manual measurements by surgeons. This pipeline offers clinical utility in an assistive capacity, and future work should focus on improving segmentation network performance.

The field of image analysis has seen large gains in recent years due to advances in deep convolutional neural networks (CNNs). Work in biomedical imaging domains, however, has seen more limited success primarily due to limited training data, which is often expensive to collect. We propose a framework that leverages deep CNNs pretrained on large, non-biomedical image data sets. Our hypothesis, which we affirm empirically, is that these pretrained networks learn cross-domain features that improve low-level interpretation of images. We evaluate our model on brain imaging data to show our approach improves the ability to diagnose Alzheimer's Disease from patient brain MRIs. Importantly, our results show that pretraining and the use of deep residual networks are crucial to seeing large improvements in diagnosis accuracy.

Study Design Retrospective database study. Objectives The goal of this study was to assess the influence of weekend admission on patients undergoing elective thoracolumbar spinal fusion by investigating hospital readmission outcomes and analyzing differences in demographics, comorbidities, and postoperative factors. Methods The 2016-2018 Nationwide Readmission Database was used to identify adult patients who underwent elective thoracolumbar spinal fusion. The sample was divided into weekday and weekend admission patients. Demographics, comorbidities, complications, and discharge status data were compiled. The primary outcomes were 30-day and 90-day readmission. Univariate logistic regression analyzed the relationship between weekday or weekend admission and 30- or 90-day readmission, and multivariate regression determined the impact of covariates. Results 177,847 patients were identified in total, with 176,842 in the weekday cohort and 1005 in the weekend cohort. Multivariate regression analysis found that 30-day readmissions were significantly greater for the weekend cohort after adjusting for sex, age, Medicare or Medicaid status, and comorbidity status (OR 2.00, 95% CI: 1.60-2.48; P < .001), and 90-day readmissions were also greater for the weekend cohort after adjustment (OR 2.01, 95% CI: 1.68-2.40, P < .001). Conclusions Patients undergoing elective thoracolumbar spinal fusion surgery who are initially admitted on weekends are more likely to experience hospital readmission. These patients have increased incidence of deep vein thrombosis, postoperative infection, and non-routine discharge status. These factors are potential areas of focus for reducing the impact of the “weekend effect” and improving outcomes for elective thoracolumbar spinal fusion.

Machine learning and artificial intelligence have seen tremendous growth in recent years and have been applied in numerous studies in the field of orthopaedics.Machine learning will soon become critical in the day-to-day operations of orthopaedic practice; therefore, it is imperative that providers become accustomed to and familiar with not only the terminology but also the fundamental techniques behind the technology.A foundation of knowledge regarding machine learning is critical for physicians so they can begin to understand the details in the algorithms that are being developed, which provide improved accuracy compared with clinicians, decreased time required, and a heightened ability to triage patients.

Real-time seizure detection is a resource intensive process as it requires continuous monitoring of patients on stereoelectroencephalography. This study improves real-time seizure detection in drug resistant epilepsy (DRE) patients by developing patient-specific deep learning models that utilize a novel self-supervised dynamic thresholding approach. Deep neural networks were constructed on over 2000 h of high-resolution, multichannel SEEG and video recordings from 14 DRE patients. Consensus labels from a panel of epileptologists were used to evaluate model efficacy. Self-supervised dynamic thresholding exhibited improvements in positive predictive value (PPV; difference: 39.0%; 95% CI 4.5–73.5%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.03) with similar sensitivity (difference: 14.3%; 95% CI − 21.7 to 50.3%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.42) compared to static thresholds. In some models, training on as little as 10 min of SEEG data yielded robust detection. Cross-testing experiments reduced PPV (difference: 56.5%; 95% CI 25.8–87.3%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.002), while multimodal detection significantly improved sensitivity (difference: 25.0%; 95% CI 0.2–49.9%; Wilcoxon–Mann–Whitney test; N = 14; p < 0.05). Self-supervised dynamic thresholding improved the efficacy of real-time seizure predictions. Multimodal models demonstrated potential to improve detection. These findings are promising for future deployment in epilepsy monitoring units to enable real-time seizure detection without annotated data and only minimal training time in individual patients.

Vision impairment continues to be a major global problem, as the WHO estimates 2.2 billion people struggling with vision loss or blindness. One billion of these cases, however, can be prevented by expanding diagnostic capabilities. Direct global healthcare costs associated with these conditions totaled $255 billion in 2010, with a rapid upward projection to $294 billion in 2020. Accordingly, WHO proposed 2030 targets to enhance integration and patient-centered vision care by expanding refractive error and cataract worldwide coverage. Due to the limitations in cost and portability of adapted vision screening models, there is a clear need for new, more accessible vision testing tools in vision care. This comparative, systematic review highlights the need for new ophthalmic equipment and approaches while looking at existing and emerging technologies that could expand the capacity for disease identification and access to diagnostic tools. Specifically, the review focuses on portable hardware- and software-centered strategies that can be deployed in remote locations for detection of ophthalmic conditions and refractive error. Advancements in portable hardware, automated software screening tools, and big data-centric analytics, including machine learning, may provide an avenue for improving ophthalmic healthcare.