Periprocedural management of type 2N von Willebrand disease with efanesoctocog alfa.

Type 2 Normandy von Willebrand disease (type 2N VWD) is a rare qualitative defect in von Willebrand factor (VWF) that results in impaired factor VIII (FVIII) binding and consequently reduced FVIII levels. Current perioperative strategies require VWF concentrates to attain durable hemostatic FVIII levels. This case highlights the successful perioperative management of a 78-year-old female with type 2N VWD and coronary artery disease utilizing efanesoctocog alfa, a novel long-acting recombinant FVIII product approved for hemophilia A. By decoupling the FVIII-VWF interaction, efanesoctocog alfa achieves prolonged FVIII circulation independent of VWF. A single administration targeting 90% FVIII levels yielded sustained FVIII elevation without achieving supraphysiologic VWF levels, thus mitigating potential cardiovascular risks. This is the first report of efanesoctocog alfa use in type 2N VWD. Further clinical studies are necessary to corroborate its efficacy and safety for this indication.

Natural Language Processing of Serum Protein Electrophoresis Reports in the Veterans Affairs Health Care System.

PURPOSE: Serum protein electrophoresis (SPEP) is a clinical tool used to screen for monoclonal gammopathy, thus it is a critical tool in the evaluation of patients with multiple myeloma. However, SPEP laboratory results are usually returned as short text reports, which are not amenable to simple computerized processing for large-scale studies. We applied natural language processing (NLP) to detect monoclonal gammopathy in SPEP laboratory results and compared its performance at multiple hospitals using both a rules-based manual system and a machine-learning algorithm. METHODS: We used the data from the VA Corporate Data Warehouse, which comprises data from 20 million unique individuals. SPEP reports were collected from July to December 2015 at 5 Veterans Affairs Medical Centers. Of these reports, we annotated the presence or absence of monoclonal gammopathy in 300 reports. We applied a machine learning-based NLP and a manual rules-based NLP to detect monoclonal gammopathy in SPEP reports at each of the hospitals, then applied the model from 1 hospital to each of the other hospitals. RESULTS: The learning system achieved an area under the receiver operating characteristic curve of 0.997, and the rules-based system achieved an accuracy of 0.99. When a model trained on 1 hospital's data was applied to a different hospital, however, accuracy varied greatly, and the learning-based models performed better than the rules-based model. CONCLUSION: Binary classification of short clinical texts such as SPEP reports may be a particularly attractive target on which to train highly accurate NLP systems.

Readability of Spine-Related Patient Education Materials From Leading Orthopedic Academic Centers.

STUDY DESIGN: Cross-sectional analysis of online spine-related patient education materials from leading academic centers. OBJECTIVE: To assess the readability levels of spine surgery-related patient education materials available on the websites of academic orthopedic surgery departments. SUMMARY OF BACKGROUND DATA: The Internet is becoming an increasingly popular resource for patient education. Yet many previous studies have found that Internet-based orthopedic-related patient education materials from subspecialty societies are written at a level too difficult for the average American; however, no prior study has assessed the readability of spine surgery-related patient educational materials from leading academic centers. METHODS: All spine surgery-related articles from the online patient education libraries of the top five US News & World Report-ranked orthopedic institutions were assessed for readability using the Flesch-Kincaid (FK) readability test. Mean readability levels of articles amongst the five academic institutions and articles were compared. We also determined the number of articles with readability levels at or below the recommended sixth- or eight-grade levels. Intraobserver and interobserver reliability of readability assessment were assessed. RESULTS: A total of 122 articles were reviewed. The mean overall FK grade level was 11.4; the difference in mean FK grade level between each department varied significantly (range, 9.3-13.4; P < 0.0001). Twenty-three articles (18.9%) had a readability level at or below the eighth grade level, and only one (0.8%) was at or below the sixth grade level. Intraobserver and interobserver reliability were both excellent (intraclass correlation coefficient of 1 for both). CONCLUSION: Online patient education materials related to spine from academic orthopedic centers are written at a level too high for the average patient, consistent with spine surgery-related patient education materials provided by the American Academy of Orthopaedic Surgeons and spine subspecialty societies. This study highlights the potential difficulties patients might have in reading and comprehending the information in publicly available education materials related to spine. LEVEL OF EVIDENCE: N/A.

PTPMT1 Inhibition Lowers Glucose through Succinate Dehydrogenase Phosphorylation.

Virtually all organisms seek to maximize fitness by matching fuel availability with energy expenditure. In vertebrates, glucose homeostasis is central to this process, with glucose levels finely tuned to match changing energy requirements. To discover new pathways regulating glucose levels in vivo, we performed a large-scale chemical screen in live zebrafish and identified the small molecule alexidine as a potent glucose-lowering agent. We found that alexidine inhibits the PTEN-like mitochondrial phosphatase PTPMT1 and that other pharmacological and genetic means of inactivating PTPMT1 also decrease glucose levels in zebrafish. Mutation of ptpmt1 eliminates the effect of alexidine, further confirming it as the glucose-lowering target of alexidine. We then identified succinate dehydrogenase (SDH) as a substrate of PTPMT1. Inactivation of PTPMT1 causes hyperphosphorylation and activation of SDH, providing a possible mechanism by which PTPMT1 coordinates glucose homeostasis. Therefore, PTPMT1 appears to be an important regulator of SDH phosphorylation status and glucose concentration.

Induced and sustained hypernatremia for the prevention and treatment of cerebral edema following brain injury.

Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm.

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure.

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.