Search

Importance: An emergency medicine (EM) handoff note generated by a large language model (LLM) has the potential to reduce physician documentation burden without compromising the safety of EM-to-inpatient (IP) handoffs., Objective: To develop LLM-generated EM-to-IP handoff notes and evaluate their accuracy and safety compared with physician-written notes., Design, Setting, and Participants: This cohort study used EM patient medical records with acute hospital admissions that occurred in 2023 at NewYork-Presbyterian/Weill Cornell Medical Center. A customized clinical LLM pipeline was trained, tested, and evaluated to generate templated EM-to-IP handoff notes. Using both conventional automated methods (ie, recall-oriented understudy for gisting evaluation [ROUGE], bidirectional encoder representations from transformers score [BERTScore], and source chunking approach for large-scale inconsistency evaluation [SCALE]) and a novel patient safety-focused framework, LLM-generated handoff notes vs physician-written notes were compared. Data were analyzed from October 2023 to March 2024., Exposure: LLM-generated EM handoff notes., Main Outcomes and Measures: LLM-generated handoff notes were evaluated for (1) lexical similarity with respect to physician-written notes using ROUGE and BERTScore; (2) fidelity with respect to source notes using SCALE; and (3) readability, completeness, curation, correctness, usefulness, and implications for patient safety using a novel framework., Results: In this study of 1600 EM patient records (832 [52%] female and mean [SD] age of 59.9 [18.9] years), LLM-generated handoff notes, compared with physician-written ones, had higher ROUGE (0.322 vs 0.088), BERTScore (0.859 vs 0.796), and SCALE scores (0.691 vs 0.456), indicating the LLM-generated summaries exhibited greater similarity and more detail. As reviewed by 3 board-certified EM physicians, a subsample of 50 LLM-generated summaries had a mean (SD) usefulness score of 4.04 (0.86) out of 5 (compared with 4.36 [0.71] for physician-written) and mean (SD) patient safety scores of 4.06 (0.86) out of 5 (compared with 4.50 [0.56] for physician-written). None of the LLM-generated summaries were classified as a critical patient safety risk., Conclusions and Relevance: In this cohort study of 1600 EM patient medical records, LLM-generated EM-to-IP handoff notes were determined superior compared with physician-written summaries via conventional automated evaluation methods, but marginally inferior in usefulness and safety via a novel evaluation framework. This study suggests the importance of a physician-in-loop implementation design for this model and demonstrates an effective strategy to measure preimplementation patient safety of LLM models.

Primary brain tumours are rare but carry a significant morbidity and mortality burden. Malignant gliomas are the most common subtype and their incidence is increasing within our ageing population. The diagnosis and treatment of gliomas involves substantial interplay between multiple specialties, including general medical physicians, radiologists, pathologists, surgeons, oncologists and allied health professionals. At any point along this pathway, patients can present to acute medicine with complications of their cancer or anti-cancer therapy. Increasing the awareness of malignant gliomas among general physicians is paramount to delivering prompt radiological and histopathological diagnoses, facilitating access to earlier and individualised treatment options and allows for effective recognition and management of anticipated complications. This article discusses evidence-based real-world practice for malignant gliomas, encompassing patient presentation, diagnostic pathways, treatments and their complications, and prognosis to guide management outside of specialist centres., Competing Interests: Declaration of competing interest Nil to declare, (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Trypsin is a very common enzyme used in cell culture to harvest cells by cleaving the proteins responsible for cell adhesion. However, trypsin also induces undesirable effects on cells, such as altering membrane proteins and the cytoskeleton, changing the composition of the cytoplasm and the cell volume, and even leading to cell death when used improperly. Using attenuated total reflection in the terahertz domain, confocal microscopy, and the propidium iodide test, we quantified in real time the change in cytoplasmic content induced by trypsin proteolysis on Madin-Darby canine kidney epithelial cells. We have observed a cytoplasmic modification from the very first seconds of trypsinization, following the change of cell volume due to mechanical re-equilibrium of the membrane. We found that the cytoplasmic alteration is associated with a transfer of small solutes: electrolytes and metabolites. We also found a very good nonlinear correlation between the side effects monitored by terahertz sensing and the cell height, regardless of the dependence of the cell height on trypsin concentration and exposure time., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Large language models (LLMs) hold great promise in summarizing medical evidence. Most recent studies focus on the application of proprietary LLMs. Using proprietary LLMs introduces multiple risk factors, including a lack of transparency and vendor dependency. While open-source LLMs allow better transparency and customization, their performance falls short compared to proprietary ones. In this study, we investigated to what extent fine-tuning open-source LLMs can further improve their performance in summarizing medical evidence. Utilizing a benchmark dataset, MedReview, consisting of 8,161 pairs of systematic reviews and summaries, we fine-tuned three broadly-used, open-sourced LLMs, namely PRIMERA, LongT5, and Llama-2. Overall, the fine-tuned LLMs obtained an increase of 9.89 in ROUGE-L (95% confidence interval: 8.94-10.81), 13.21 in METEOR score (95% confidence interval: 12.05-14.37), and 15.82 in CHRF score (95% confidence interval: 13.89-16.44). The performance of fine-tuned LongT5 is close to GPT-3.5 with zero-shot settings. Furthermore, smaller fine-tuned models sometimes even demonstrated superior performance compared to larger zero-shot models. The above trends of improvement were also manifested in both human and GPT4-simulated evaluations. Our results can be applied to guide model selection for tasks demanding particular domain knowledge, such as medical evidence summarization., Competing Interests: Competing Interests The authors declare no competing interests.

The oral and suprahyoid muscles are responsible for movements of swallowing. Our study aimed to determine the reproducibility of static and dynamic measurements of these muscles using bedside ultrasound equipment. Forty healthy participants were recruited prospectively. Primary outcomes were evaluation of mass measurements of the anterior bellies of the digastric, mylohyoid, geniohyoid and tongue in B-mode ultrasound. Secondary outcomes were evaluation of geniohyoid muscle layer thickness and function using M-mode. Muscle mass measurements demonstrated little within-participant variability. Coefficient of Variance (CoV) across muscles were: anterior belly digastric (5.0%), mylohyoid (8.7%), geniohyoid (5.0%) and tongue (3.2%). A relationship between sex (r 2  = 0.131 p = 0.022) was demonstrated for the geniohyoid muscle, with males having higher transverse Cross Sectional Area (CSA) (14.3 ± 3.6 mm vs. 11.9 ± 2.5 mm, p = 0.002). Tongue size was correlated with weight (r 2  = 0.356, p = 0.001), height (r 2  = 0.156, p = 0.012) and sex (r 2  = 0.196, p = 0.004). Resting thickness of the geniohyoid muscle layer changed with increasing bolus sizes (f = 3.898, p = 0.026). Velocity increased with bolus size (p =  < 0.001, F = 8.974). However swallow time and slope distance did not, potentially influenced by higher coefficients of variation. Oral and suprahyoid muscle mass are easily assessed using bedside ultrasound. Ultrasound may provide new information about muscle mass and function during swallowing., (© 2024. Crown.)

Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood., Objectives: To explore whether clinical and/or paraclinical baseline characteristics, including the degree of lymphocyte reduction, drug dose and lesions on magnetic resonance imaging (MRI) are associated with re-emerging disease activity., Design: Service evaluation in pwMS undergoing subcutaneous cladribine (SClad) treatment., Methods: Demographics, clinical, laboratory and MRI data of pwMS receiving two courses of SClad were extracted from health records. To assess associations of predictor variables with re-emerging disease activity, a series of Cox proportional hazards models was fitted (one for each predictor variable)., Results: Of n  = 264 pwMS 236 received two courses of SClad and were included in the analysis. Median follow-up was 4.5 years (3.9, 5.3) from the first, and 3.5 years (2.9, 4.3) from the last SClad administration. Re-emerging disease activity occurred in 57/236 pwMS (24%); 22/236 received further cladribine doses (SClad or cladribine tablets) at 36.7 months [median; interquartile range (IQR): 31.7, 42.1], and 22/236 other immunotherapies 18.9 months (13.0, 30.2) after their second course of SClad, respectively. Eligibility was based on MRI activity in 29, relapse in 5, both in 13, elevated cerebrospinal fluid neurofilament light chain level in 3, deterioration unrelated to relapse in 4 and other in 3. Only 36/57 of those eligible for additional immunotherapy had received a reduced dose of SClad for their second treatment course. Association was detected between re-emerging disease activity and (i) high baseline MRI activity and (ii) low second dose of SClad., Conclusion: Re-emerging disease activity was associated with baseline MRI activity and low dose second course of SClad., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: KA-P, SDT, AMD, AA, LB, TC and DWH have no conflicts of interest to declare. GG has received honoraria and meeting support from AbbVie Biotherapeutics, Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, Roche, Sanofi Genzyme, Synthon, Teva and Vertex. He also serves as a chief editor for Multiple Sclerosis and Related Disorders. SG has received honoraria from Biogen Idec, Sanofi Genzyme, Janssen Cilag, Merck, Neurodiem, Novartis, Roche and Teva, and grant support from ECTRIMS, Genzyme, Merck, National MS Society, Takeda, UK MS Society, NIHR and NHSx. MM has received travel support and speaker honoraria from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva, and consultation for Celgene, Merck Serono, Novartis and Roche. JM has received honoraria and meeting support from Arvelle, Biogen, Novartis, Merck Serono, Roche, Sanofi Genzyme, Jazz Pharmaceuticals, Janssen and Novartis. BPT has received honoraria, travel grants, and has been a member of advisory boards for Biogen, Merck Serono, Novartis, Sanofi Genzyme and Roche. DB has received compensation from InMuneBio, Lundbeck, Merck, Novartis, Rock and Teva. KS has received research support, through Queen Mary University of London, from Biogen, Merck KGaA and Novartis, speaking honoraria from, and/or served in an advisory role for, Biogen, EMD Serono, Merck KGaA, Novartis, Roche, Sanofi-Genzyme and Teva; and remuneration for teaching activities from AcadeMe, Medscape and the Neurology Academy., (© The Author(s), 2023.)

Long-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, Heligmosomoides polygyrus , down-modulates the host immune system through release of an immunosuppressive TGF-β mimic, TGM1, which is a divergent member of the CCP (Sushi) protein family. TGM1 comprises 5 domains, of which domains 1-3 (D1/2/3) bind mammalian TGF-β receptors, acting on T cells to induce Foxp3 + regulatory T cells; however, the roles of domains 4 and 5 (D4/5) remain unknown. We noted that truncated TGM1, lacking D4/5, showed reduced potency. Combination of D1/2/3 and D4/5 as separate proteins did not alter potency, suggesting that a physical linkage is required and that these domains do not deliver an independent signal. Coprecipitation from cells treated with biotinylated D4/5, followed by mass spectrometry, identified the cell surface protein CD44 as a coreceptor for TGM1. Both full-length and D4/5 bound strongly to a range of primary cells and cell lines, to a greater degree than D1/2/3 alone, although some cell lines did not respond to TGM1. Ectopic expression of CD44 in nonresponding cells conferred responsiveness, while genetic depletion of CD44 abolished enhancement by D4/5 and ablated the ability of full-length TGM1 to bind to cell surfaces. Moreover, CD44-deficient T cells showed attenuated induction of Foxp3 by full-length TGM1, to levels similar to those induced by D1/2/3. Hence, a parasite protein known to bind two host cytokine receptor subunits has evolved a third receptor specificity, which serves to raise the avidity and cell type-specific potency of TGF-β signaling in mammalian cells.

Type 2-high asthma is a chronic inflammatory disease of the airways which is increasingly prevalent in countries where helminth parasite infections are rare, and characterized by T helper 2 (Th2)-dependent accumulation of eosinophils in the lungs. Regulatory cytokines such as TGF-β can restrain inflammatory reactions, dampen allergic Th2 responses, and control eosinophil activation. The murine helminth parasite Heligmosomoides polygyrus releases a TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β despite bearing no structural similarity to the mammalian protein. Here, we investigated if Hp-TGM could alleviate allergic airway inflammation in mice exposed to Alternaria alternata allergen, house dust mite (HDM) extract or alum-adjuvanted ovalbumin protein (OVA). Intranasal administration of Hp-TGM during Alternaria exposure sharply reduced airway and lung tissue eosinophilia along with bronchoalveolar lavage fluid IL-5 and lung IL-33 cytokine levels at 24 h. The protective effect of Hp-TGM on airway eosinophilia was also obtained in the longer T-cell mediated models of HDM or OVA sensitisation with significant inhibition of eotaxin-1, IL-4 and IL-13 responses depending on the model and time-point. Hp-TGM was also protective when administered parenterally either when given at the time of allergic sensitisation or during airway allergen challenge. This project has taken the first steps in identifying the role of Hp-TGM in allergic asthma and highlighted its ability to control lung inflammation and allergic pathology. Future research will investigate the mode of action of Hp-TGM against airway allergic eosinophilia, and further explore its potential to be developed as a biotherapeutic in allergic asthma., (© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)

The mouse intestinal helminth Heligmosomoides polygyrus modulates host immune responses by secreting a transforming growth factor (TGF)-β mimic (TGM), to expand the population of Foxp3 + T regs . TGM comprises five complement control protein (CCP)-like domains, designated D1-D5. Though lacking homology to TGF-β, TGM binds directly to the TGF-β receptors TβRI and TβRII and stimulates the differentiation of naïve T-cells into T regs . However, the molecular determinants of binding are unclear. Here, we used surface plasmon resonance, isothermal calorimetry, NMR spectroscopy, and mutagenesis to investigate how TGM binds the TGF-β receptors. We demonstrate that binding is modular, with D1-D2 binding to TβRI and D3 binding to TβRII. D1-D2 and D3 were further shown to compete with TGF-β(TβRII) 2 and TGF-β for binding to TβRI and TβRII, respectively. The solution structure of TGM-D3 revealed that TGM adopts a CCP-like fold but is also modified to allow the C-terminal strand to diverge, leading to an expansion of the domain and opening potential interaction surfaces. TGM-D3 also incorporates a long structurally ordered hypervariable loop, adding further potential interaction sites. Through NMR shift perturbations and binding studies of TGM-D3 and TβRII variants, TGM-D3 was shown to occupy the same site of TβRII as bound by TGF-β using both a novel interaction surface and the hypervariable loop. These results, together with the identification of other secreted CCP-like proteins with immunomodulatory activity in H. polygyrus, suggest that TGM is part of a larger family of evolutionarily plastic parasite effector molecules that mediate novel interactions with their host., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Daclizumab is an anti-CD25 monoclonal antibody developed for the treatment of relapsing remitting multiple sclerosis, which was withdrawn worldwide in March 2018, due to emerging serious immune-mediated systemic andcentral nervous system adverse events. We report a case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis occurring 14 weeks after stopping daclizumab, which responded to the proteasome inhibitor bortezomib., Methods: Following lack of effective clinical response to first line (corticosteroid, plasma exchange, intravenous immunoglobulin) and second line (rituximab) treatments, bortezomib therapy was commenced. The patient received six cycles of bortezomib treatment., Results: Clinical improvement was noted 4 weeks after the first of six cycles of bortezomib and the patient experienced sustained clinical improvement., Conclusion: Our case provides further class IV evidence of the use of bortezomib therapy for treatment refractory anti-NMDAR encephalitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The olfactory pathway is composed of peripheral sinonasal and central sensorineural components. The wide variety of different pathologies that can affect the olfactory pathway reflect this complex anatomical relationship. Localising olfactory pathology can present a challenge to the reporting radiologist. This imaging review will illustrate the normal anatomy of the olfactory system and describe a systematic approach to considering olfactory dysfunction. Key concepts in image interpretation will be demonstrated using examples of olfactory pathway pathologies.

Background and Purpose: A large spectrum of neurologic disease has been reported in patients with coronavirus disease 2019 (COVID-19) infection. Our aim was to investigate the yield of neuroimaging in patients with COVID-19 undergoing CT or MR imaging of the brain and to describe associated imaging findings., Materials and Methods: We performed a retrospective cohort study involving 2054 patients with laboratory-confirmed COVID-19 presenting to 2 hospitals in New York City between March 4 and May 9, 2020, of whom 278 (14%) underwent either CT or MR imaging of the brain. All images initially received a formal interpretation from a neuroradiologist within the institution and were subsequently reviewed by 2 neuroradiologists in consensus, with disputes resolved by a third neuroradiologist., Results: The median age of these patients was 64 years (interquartile range, 50-75 years), and 43% were women. Among imaged patients, 58 (21%) demonstrated acute or subacute neuroimaging findings, the most common including cerebral infarctions (11%), parenchymal hematomas (3.6%), and posterior reversible encephalopathy syndrome (1.1%). Among the 51 patients with MR imaging examinations, 26 (51%) demonstrated acute or subacute findings; notable findings included 6 cases of cranial nerve abnormalities (including 4 patients with olfactory bulb abnormalities) and 3 patients with a microhemorrhage pattern compatible with critical illness-associated microbleeds., Conclusions: Our experience confirms the wide range of neurologic imaging findings in patients with COVID-19 and suggests the need for further studies to optimize management for these patients., (© 2020 by American Journal of Neuroradiology.)

Background: Pareidolic associations are commonly used in medical education to enhance perception of radiological abnormalities. A number of animal-inspired neuroradiological pareidolias have been defined which should alert clinicians to specific movement disorder diagnoses., Methods: A review of the published literature detailing neuroradiological abnormalities in movement disorder syndromes was conducted, looking specifically for established animal-inspired pareidolic associations., Results: A number of animal-inspired neuroradiological patterns with specific movement disorder associations have been defined. These include eye of the tiger sign, face of the panda sign, swallow tail sign, hummingbird sign, Mickey Mouse sign, ears of the lynx sign, dragonfly cerebellum, tadpole sign, tigroid/leopard skin sign, and bat wing sign., Conclusion: Pareidolias represent a quick and easy way of enhancing perception, thereby improving the efficiency and accuracy of image analysis. Movement disorder physicians should keep in mind these associations, given that they will likely facilitate scan analysis.

The Cardiotoxicity of Chemotherapy Knowledgebase (CATCH-KB) contains information extracted from articles investigating an association between germline genetic polymorphisms and the development of chemotherapy-induced cardiotoxicity (CIC) in cancer patients receiving antineoplastic treatments. CATCH-KB also contains integrated gene and drug information from open biomedical resources such as PharmGKB 1 and SIDER 2 . Furthermore, the genetic polymorphisms, drugs, and cancer types detailed in CATCH-KB are standardized according to appropriate biomedical ontologies, such as SNOMED-CT 3 and RxNorm 4 . CATCH-KB currently contains information on 49 research papers published between 2004 and 2017 investigating a total of 2,210 variants in over 280 genes for an association with CIC. By centralizing this information and linking it to external open-access biomedical resources, CATCH-KB will facilitate hypothesis generation and meta-analysis efforts and will ultimately accelerate the use of genetic screening in preventing CIC. CATCH-KB is publicly accessible via http://catchkb.org.

While imaging appearances of pseudomembranous colitis are commonly recognised, radiological manifestations of Clostridium difficile -associated enteritis are poorly understood which, combined with the rarity of this infection involving small bowel, makes establishing the correct diagnosis challenging. Therefore, in order to encourage awareness of readers, we present a case of C. difficile enteritis that manifested as abdominal sepsis complicating the postoperative period in a middle-aged woman with fistulating Crohn's disease and defunctioning ileostomy. Radiological appearances are described based on three consecutive CT studies performed 5 days prior to onset of symptoms, during the peak of enteritis, corresponding with the patient's clinical deterioration, and also 35 days later following treatment and resolution., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Relevant patient information is frequently difficult to obtain in emergency department (ED) visits. Improved provider access to previously inaccessible patient information may improve the quality of care and reduce hospital admissions. Health information exchange (HIE) systems enable access to longitudinal, community-wide patient information at the point of care. However, the ability of HIE to avert admissions is not well demonstrated. We sought to determine if HIE system usage is correlated with a reduction in admissions via the ED., Methods: We identified 15,645 adults from New York State with an ED visit during a 6-month period, all of whom consented to have their information accessible in the HIE system, and were continuously enrolled in two area health plans. Using claims we determined if the ED encounter resulted in an admission. We used the HIE's system log files to determine usage during the encounter. We determined the association between HIE system use and the likelihood of admission to the hospital from the ED and potential cost savings., Results: The HIE system was accessed during 2.4% of encounters. The odds of an admission were 30% lower when the system was accessed after controlling for confounding (odds ratio = 0.70; 95%C I= 0.52, 0.95). The annual savings in the sample was $357,000., Conclusion: These findings suggest that the use of an HIE system may reduce hospitalizations from the ED with resultant cost savings. This is an important outcome given the substantial financial investment in interventions designed to improve provider access to patient information in the US.

The use of prostacyclin (PGI2) infusions has been recommended in the management of patients with severe distal arteriopathy, who are not candidates for conventional bypass procedures. Further clarification regarding the route of administration and the optimal dose of this potent vasodilator, however, is needed before controlled clinical trials are initiated. We measured bilateral femoral arterial blood flow electromagnetically in seven anesthetized adult mongrel dogs. Systemic arterial pressure and cardiac output were also measured. Central venous and femoral arterial injections of PGI2 were administered in five doses ranging from 10(-4) to 10(0) micrograms X kg-1 to study the dose response. PGI2 was also infused intravenously and intra-arterially for 20 minutes at a dose of 10(-1) micrograms X kg-1 X min-1. Femoral arterial injections of PGI2 in doses from 10(-4) through 10(0) micrograms X kg-1 caused significant (p less than 0.05) and dose-dependent increases in ipsilateral femoral arterial blood flow. Intravenous injections of PGI2 caused no significant changes in the dose range from 10(-4) to 10(-2) micrograms X kg-1 but resulted in a significant (p less than 0.05) reduction in femoral arterial flow and systemic arterial pressure at doses of 10(-1) and 10(0) micrograms X kg-1. The femoral arterial infusion of PGI2 produced a significant and sustained increase in femoral arterial flow that was not observed during the intravenous infusion. Arterial pressure was unchanged with intra-arterial PGI2 but was significantly reduced during the intravenous infusion. The beneficial hemodynamic effects of intra-arterial PGI2 suggest that further clinical trials should employ this route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)