Recycled melanoma-secreted melanosomes regulate tumor-associated macrophage diversification.

Extracellular vesicles (EVs) are important mediators of communication between cells. Here, we reveal a new mode of intercellular communication by melanosomes, large EVs secreted by melanocytes for melanin transport. Unlike small EVs, which are disintegrated within the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell as "second-hand" EVs. We show that melanoma-secreted melanosomes passaged through epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. This process leads to macrophage polarization into pro-tumor or pro-immune cell infiltration phenotypes. Melanosomes that are transferred through fibroblasts can carry AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in vivo. In melanoma patients, macrophages that are co-localized with AKT1 are correlated with disease aggressiveness, and immunotherapy non-responders are enriched in macrophages containing melanosome markers. Our findings suggest that interactions mediated by second-hand extracellular vesicles contribute to the formation of the metastatic niche, and that blocking the melanosome cues of macrophage diversification could be helpful in halting melanoma progression.

Using ChatGPT-4 to Create Structured Medical Notes From Audio Recordings of Physician-Patient Encounters: Comparative Study.

BACKGROUND: Medical documentation plays a crucial role in clinical practice, facilitating accurate patient management and communication among health care professionals. However, inaccuracies in medical notes can lead to miscommunication and diagnostic errors. Additionally, the demands of documentation contribute to physician burnout. Although intermediaries like medical scribes and speech recognition software have been used to ease this burden, they have limitations in terms of accuracy and addressing provider-specific metrics. The integration of ambient artificial intelligence (AI)-powered solutions offers a promising way to improve documentation while fitting seamlessly into existing workflows. OBJECTIVE: This study aims to assess the accuracy and quality of Subjective, Objective, Assessment, and Plan (SOAP) notes generated by ChatGPT-4, an AI model, using established transcripts of History and Physical Examination as the gold standard. We seek to identify potential errors and evaluate the model's performance across different categories. METHODS: We conducted simulated patient-provider encounters representing various ambulatory specialties and transcribed the audio files. Key reportable elements were identified, and ChatGPT-4 was used to generate SOAP notes based on these transcripts. Three versions of each note were created and compared to the gold standard via chart review; errors generated from the comparison were categorized as omissions, incorrect information, or additions. We compared the accuracy of data elements across versions, transcript length, and data categories. Additionally, we assessed note quality using the Physician Documentation Quality Instrument (PDQI) scoring system. RESULTS: Although ChatGPT-4 consistently generated SOAP-style notes, there were, on average, 23.6 errors per clinical case, with errors of omission (86%) being the most common, followed by addition errors (10.5%) and inclusion of incorrect facts (3.2%). There was significant variance between replicates of the same case, with only 52.9% of data elements reported correctly across all 3 replicates. The accuracy of data elements varied across cases, with the highest accuracy observed in the "Objective" section. Consequently, the measure of note quality, assessed by PDQI, demonstrated intra- and intercase variance. Finally, the accuracy of ChatGPT-4 was inversely correlated to both the transcript length (P=.05) and the number of scorable data elements (P=.05). CONCLUSIONS: Our study reveals substantial variability in errors, accuracy, and note quality generated by ChatGPT-4. Errors were not limited to specific sections, and the inconsistency in error types across replicates complicated predictability. Transcript length and data complexity were inversely correlated with note accuracy, raising concerns about the model's effectiveness in handling complex medical cases. The quality and reliability of clinical notes produced by ChatGPT-4 do not meet the standards required for clinical use. Although AI holds promise in health care, caution should be exercised before widespread adoption. Further research is needed to address accuracy, variability, and potential errors. ChatGPT-4, while valuable in various applications, should not be considered a safe alternative to human-generated clinical documentation at this time.

How Providers Can Optimize Effective and Safe Scribe Use: a Qualitative Study.

BACKGROUND: The use of electronic health records has generated an increase in after-hours and weekend work for providers. To alleviate this situation, the hiring of medical scribes has rapidly increased. Given the lack of scribe industry standards and the wide variance in how providers and scribes work together, it could potentially create new patient safety-related risks. OBJECTIVE: The purpose of this paper was to identify how providers can optimize the effective and safe use of scribes. DESIGN: The research team conducted a secondary analysis of qualitative data where we reanalyzed data from interview transcripts, field notes, and transcribed group discussions generated by four previous projects related to medical scribes. PARTICIPANTS: Purposively selected participants included subject matter experts, providers, informaticians, medical scribes, medical assistants, administrators, social scientists, medical students, and qualitative researchers. APPROACH: The team used NVivo12 to assist with the qualitative analysis. We used a template method followed by word queries to identify an optimum level of scribe utilization. We then used an inductive interpretive theme-generation process. KEY RESULTS: We identified three themes: (1) communication aspects, (2) teamwork efforts, and (3) provider characteristics. Each theme contained specific practices so providers can use scribes safely and in a standardized way. CONCLUSION: We utilized a secondary qualitative data analysis methodology to develop themes describing how providers can optimize their use of scribes. This new knowledge could increase provider efficiency and safety and be incorporated into further and future training tools for them.

Epidemiology, clinical characteristics and outcomes of multisystem inflammatory syndrome in children.

BACKGROUND: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia. METHODS: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes. RESULTS: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement. CONCLUSION: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities.

Emerging roles of ECM remodeling processes in cancer.

Extracellular matrix (ECM) plays a central and dynamic role in the creation of tumor microenvironment. Herein we discuss the emerging biophysical and biochemical aspects of ECM buildup and proteolysis in cancer niche formation. Dysregulated ECM remodeling by cancer cells facilitate irreversible proteolysis and crosslinking, which in turn influence cell signaling, micro environmental cues, angiogenesis and tissue biomechanics. Further, we introduce the emerging roles of cancer microbiome in aberrant tumor ECM remodeling and membrane bound nano-sized vesicles called exosomes in creation of distant pre-metastatic niches. A detailed molecular and biophysical understanding of the ECM morphologies and its components such as key enzymes, structural and signaling molecules are critical in identifying the next generation of therapeutic and diagnostic targets in cancer.

The future of medical scribes documenting in the electronic health record: results of an expert consensus conference.

BACKGROUND: With the use of electronic health records (EHRs) increasing and causing unintended negative consequences, the medical scribe profession has burgeoned, but it has yet to be regulated. The purpose of this study was to describe scribe workflow as well as identify the threats and opportunities for the future of the scribe industry. METHODS: The first phase of the study used ethnographic methods consisting of interviews and observations by a multi-disciplinary team of researchers at five United States sites. In April 2019, a two-day conference of experts representing different stakeholder perspectives was held to discuss the results from site visits and to predict the future of medical scribing. An interpretive content analysis approach was used to discover threats and opportunities for the future of medical scribes. RESULTS: Threats facing the medical scribe industry were related to changes in the documentation model, EHR usability, different payment structures, the need to acquire disparate data during clinical encounters, and workforce-related changes relevant to the scribing model. Simultaneously, opportunities for medical scribing in the future included extension of their role to include workflow analysis, acting as EHR-related subject-matter-experts, and becoming integrated more effectively into the clinical care delivery team. Experts thought that if EHR usability increases, the need for medical scribes might decrease. Additionally, the scribe role could be expanded to allow scribes to document more or take on more informatics-related tasks. The experts also anticipated an increased use of alternative models of scribing, like tele-scribing. CONCLUSION: Threats and opportunities for medical scribing were identified. Many experts thought that if the scribe role could be expanded to allow scribes to document more or take on more informatics activities, it would be beneficial. With COVID-19 continuing to change workflows, it is critical that medical scribes receive standardized training as tele-scribing continues to grow in popularity and new roles for scribes as medical team members are identified.

Intravital imaging of vascular anomalies and extracellular matrix remodeling in orthotopic pancreatic tumors.

Pancreatic cancers, both adenocarcinomas and endocrine tumors are characterized by varying levels of aberrant angiogenesis and fibrotic microenvironment. The difficulty to deliver drugs and treat the disease has been attributed in part to the vascular architecture and tissue/ECM density. Here we present longitudinal three-dimensional intravital imaging of vascular and tumor microenvironment remodeling in spontaneous transgenic tumors (RIP1-Tag2 insulinomas) and orthotopically injected tumors (KPC adenocarcinomas). Analysis of the data acquired in insulinomas revealed major differences in tumor blood vessel branching, fraction volume, number of branch points segments, vessel straightness and length compared to the normal tissue. The aggressive adenocarcinoma presented widespread peritumoral vascular remodeling and heterogeneous vascular distribution. Longitudinal imaging was used to acquire sequential vascular remodeling data during tumor progression. This work demonstrates the potential for using a pancreatic intravital imaging window for direct visualization of the tumor heterogenic microenvironments during tumor progression.

Exosomes as a storehouse of tissue remodeling proteases and mediators of cancer progression.

Rapidly increasing scientific reports of exosomes and their biological effects have improved our understanding of their cellular sources and their cell-to-cell communication. These nano-sized vesicles act as potent carriers of regulatory bio-macromolecules and can induce regulatory functions by delivering them from its source to recipient cells. The details of their communication network are less understood. Recent studies have shown that apart from delivering its cargo to the cells, it can directly act on extracellular matrix (ECM) proteins and growth factors and can induce various remodeling events. More importantly, exosomes carry many surface-bound proteases, which can cleave different ECM proteins and carbohydrates and can shed cell surface receptors. These local extracellular events can modulate signaling cascades, which consequently influences the whole tissue and organ. This review aims to highlight the critical roles of exosomal proteases and their mechanistic insights within the cellular and extracellular environment.

Data Omission by Physician Trainees on ICU Rounds.

OBJECTIVES: Incomplete patient data, either due to difficulty gathering and synthesizing or inappropriate data filtering, can lead clinicians to misdiagnosis and medical error. How completely ICU interprofessional rounding teams appraise the patient data set that informs clinical decision-making is unknown. This study measures how frequently physician trainees omit data from prerounding notes ("artifacts") and verbal presentations during daily rounds. DESIGN: Observational study. SETTING: Tertiary academic medical ICU with an established electronic health record and where physician trainees are the primary presenters during daily rounds. SUBJECTS: Presenters (medical student or resident physician), interprofessional rounding team. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We quantified the amount and types of patient data omitted from photocopies of physician trainees' artifacts and audio recordings of oral ICU rounds presentations when compared with source electronic health record data. An audit of 157 patient presentations including 6,055 data elements across nine domains revealed 100% of presentations contained omissions. Overall, 22.9% of data were missing from artifacts and 42.4% from presentations. The interprofessional team supplemented only 4.1% of additional available data. Frequency of trainee data omission varied by data type and sociotechnical factors. The strongest predictor of trainee verbal omissions was a preceding failure to include the data on the artifact. Passive data gathering via electronic health record macros resulted in extremely complete artifacts but paradoxically predicted greater likelihood of verbal omission when compared with manual notation. Interns verbally omitted the most data, whereas medical students omitted the least. CONCLUSIONS: In an academic rounding model reliant on trainees to preview and select data for presentation during ICU rounds, verbal appraisal of patient data was highly incomplete. Additional trainee oversight and education, improved electronic health record tools, and novel academic rounding paradigms are needed to address this potential source of medical error.

Use of a Novel, Electronic Health Record-Centered, Interprofessional ICU Rounding Simulation to Understand Latent Safety Issues.

OBJECTIVES: The electronic health record is a primary source of information for all professional groups participating in ICU rounds. We previously demonstrated that, individually, all professional groups involved in rounds have significant blind spots in recognition of patient safety issues in the electronic health record. However, it is unclear how team dynamics impacts identification and verbalization of viewed data. Therefore, we created an ICU rounding simulation to assess how the interprofessional team recognized and reported data and its impact on decision-making. DESIGN: Each member of the ICU team reviewed a simulated ICU chart in the electronic health record which contained embedded patient safety issues. The team conducted simulated rounds according to the ICU's existing rounding script and was assessed for recognition of safety issues. SETTING: Academic medical center. SUBJECTS: ICU residents, nurses, and pharmacists. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Twenty-eight teams recognized 68.6% of safety issues with only 50% teams having the primary diagnosis in their differential. Individually, interns, nurses, and pharmacists recognized 30.4%, 15.6%, and 19.6% of safety items, respectively. However, there was a negative correlation between the intern's performance and the nurse's or the pharmacist's performance within a given team. The wide variance in recognition of data resulted in wide variance in orders. Overall, there were 21.8 orders requested and 21.6 orders placed per case resulting in 3.6 order entry inconsistencies/case. Between the two cases, there were 145 distinct orders place with 43% being unique to a specific team and only 2% placed by all teams. CONCLUSIONS: Although significant blind spots exist in the interprofessional team's ability to recognize safety issues in the electronic health record, the inclusion of other professional groups does serve as a partial safety net to improve recognition. Electronic health record-based, ICU rounding simulations can serve as a test-bed for innovations in ICU rounding structure and data collection.

Accuracy of Laboratory Data Communication on ICU Daily Rounds Using an Electronic Health Record.

OBJECTIVES: Accurately communicating patient data during daily ICU rounds is critically important since data provide the basis for clinical decision making. Despite its importance, high fidelity data communication during interprofessional ICU rounds is assumed, yet unproven. We created a robust but simple methodology to measure the prevalence of inaccurately communicated (misrepresented) data and to characterize data communication failures by type. We also assessed how commonly the rounding team detected data misrepresentation and whether data communication was impacted by environmental, human, and workflow factors. DESIGN: Direct observation of verbalized laboratory data during daily ICU rounds compared with data within the electronic health record and on presenters' paper prerounding notes. SETTING: Twenty-six-bed academic medical ICU with a well-established electronic health record. SUBJECTS: ICU rounds presenter (medical student or resident physician), interprofessional rounding team. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During 301 observed patient presentations including 4,945 audited laboratory results, presenters used a paper prerounding tool for 94.3% of presentations but tools contained only 78% of available electronic health record laboratory data. Ninty-six percent of patient presentations included at least one laboratory misrepresentation (mean, 6.3 per patient) and 38.9% of all audited laboratory data were inaccurately communicated. Most misrepresentation events were omissions. Only 7.8% of all laboratory misrepresentations were detected. CONCLUSION: Despite a structured interprofessional rounding script and a well-established electronic health record, clinician laboratory data retrieval and communication during ICU rounds at our institution was poor, prone to omissions and inaccuracies, yet largely unrecognized by the rounding team. This highlights an important patient safety issue that is likely widely prevalent, yet underrecognized.

Medical Record Closure Practices of Physicians Before and After the Use of Medical Scribes.

This study uses electronic health record data to evaluate medical record closure outcomes before and after the use of medical scribes at a large academic medical center.

Hydroxytyrosol, a dietary phenolic compound forestalls the toxic effects of methylmercury-induced toxicity in IMR-32 human neuroblastoma cells.

This study demonstrates the protective potential of hydroxytyrosol (HT), an olive oil phenol, against methylmercury (MeHg)-induced neurotoxicity using IMR-32 human neuroblastoma cell line. HT inhibited MeHg-induced cytotoxicity and genotoxicity as confirmed by MTT, micronucleus, and comet assays. Cells preconditioned with HT showed reduction of MeHg-induced cellular oxidative stress along with the maintenance of glutathione, superoxide dismutase, glutathione-S-tranferase, and catalase. Fluorescence microscopy and DNA ladder assays indicated the inhibitory effect of HT against MeHg-induced apoptosis, which was further established by Western blotting. An effective concentration of 5 µM HT caused downregulation of p53, bax, cytochrome c, and caspase 3 and upregulation of prosurvival proteins including nuclear factor erythroid 2-related factor 2 (Nrf2) and metallothionein. This work indicates the cytoprotective potential of HT against MeHg-induced toxicity primarily by the lowering of oxidative stress, which may be endorsed to its antigenotoxic and antiapoptotic potential, in addition to its free radical scavenging ability. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1264-1275, 2016.

Professional and interprofessional differences in electronic health records use and recognition of safety issues in critically ill patients.

During interprofessional intensive care unit (ICU) rounds each member of the interprofessional team is responsible for gathering and interpreting information from the electronic health records (EHR) to facilitate effective team decision-making. This study was conducted to determine how each professional group reviews EHR data in preparation for rounds and their ability to identify patient safety issues. Twenty-five physicians, 29 nurses, and 20 pharmacists participated. Individual participants were given verbal and written sign-out and then asked to review a simulated record in our institution's EHR, which contained 14 patient safety items. After reviewing the chart, subjects presented the patient and the number of safety items recognised was recorded. About 40%, 30%, and 26% of safety issues were recognised by physicians, nurses, and pharmacists, respectively (p = 0.0006) and no item recognised 100% of the time. There was little overlap between the three groups with only 50% of items predicted to be recognised 100% of the time by the team. Differential recognition was associated with marked differences in EHR use, with only 3/152 EHR screens utilised by all three groups and the majority of screens used exclusively only by one group. There were significant and non-overlapping differences in individual profession recognition of patient safety issues in the EHR. Preferential identification of safety issues by certain professional groups may be attributed to differences in EHR use. Future studies will be needed to determine if shared decision-making during rounds can improve recognition of safety issues.

Multiple perspectives on clinical decision support: a qualitative study of fifteen clinical and vendor organizations.

BACKGROUND: Computerized clinical decision support (CDS) can help hospitals to improve healthcare. However, CDS can be problematic. The purpose of this study was to discover how the views of clinical stakeholders, CDS content vendors, and EHR vendors are alike or different with respect to challenges in the development, management, and use of CDS. METHODS: We conducted ethnographic fieldwork using a Rapid Assessment Process within ten clinical and five health information technology (HIT) vendor organizations. Using an inductive analytical approach, we generated themes from the clinical, content vendor, and electronic health record vendor perspectives and compared them. RESULTS: The groups share views on the importance of appropriate manpower, careful knowledge management, CDS that fits user workflow, the need for communication among the groups, and for mutual strategizing about the future of CDS. However, views of usability, training, metrics, interoperability, product use, and legal issues differed. Recommendations for improvement include increased collaboration to address legal, manpower, and CDS sharing issues. CONCLUSIONS: The three groups share thinking about many aspects of CDS, but views differ in a number of important respects as well. Until these three groups can reach a mutual understanding of the views of the other stakeholders, and work together, CDS will not reach its potential.

Integrating the Electronic Health Record into high-fidelity interprofessional intensive care unit simulations.

With the rapid adoption of electronic health records (EHR), there is a growing appreciation for the central role they play in clinical decision making and team communication, with many studies documenting new safety issues with integration of the EHR into the clinical enterprise. To study these issues, we created a high-fidelity simulation instance of our clinical EHR. In this paper, we describe the impact of integrating the EHR into high-fidelity, interprofessional intensive care unit (ICU) simulations, and the errors induced. We found a number of safety issues directly related to the EHR including alert fatigue, negative impacts on interprofessional communication, and problems with selective data gathering, and these issues were present for all members of the interprofessional team. Through successful integration of the EHR into high-fidelity team-based simulations, we now have an infrastructure to focus educational initiative and deploy informatics solutions to mitigate these safety issues.

Participation in EHR based simulation improves recognition of patient safety issues.

BACKGROUND: Electronic health records (EHR) are becoming increasingly integrated into the clinical environment. With the rapid proliferation of EHRs, a number of studies document an increase in adverse patient safety issues due to the EHR-user interface. Because of these issues, greater attention has been placed on novel educational activities which incorporate use of the EHR. The ICU environment presents many challenges to integrating an EHR given the vast amounts of data recorded each day, which must be interpreted to deliver safe and effective care. We have used a novel EHR based simulation exercise to demonstrate that everyday users fail to recognize a majority of patient safety issues in the ICU. We now sought to determine whether participation in the simulation improves recognition of said issues. METHODS: Two ICU cases were created in our EHR simulation environment. Each case contained 14 safety issues, which differed in content but shared common themes. Residents were given 10 minutes to review a case followed by a presentation of management changes. Participants were given an immediate debriefing regarding missed issues and strategies for data gathering in the EHR. Repeated testing was performed in a cohort of subjects with the other case at least 1 week later. RESULTS: 116 subjects have been enrolled with 25 subjects undergoing repeat testing. There was no difference between cases in recognition of patient safety issues (39.5% vs. 39.4%). Baseline performance for subjects who participated in repeat testing was no different than the cohort as a whole. For both cases, recognition of safety issues was significantly higher among repeat participants compared to first time participants. Further, individual performance improved from 39.9% to 63.6% (p = 0.0002), a result independent of the order in which the cases were employed. The degree of improvement was inversely related to baseline performance. Further, repeat participants demonstrated a higher rate of recognition of changes in vitals, misdosing of antibiotics and oversedation compared to first time participants. CONCLUSION: Participation in EHR simulation improves EHR use and identification of patient safety issues.

Axial Imaging in Spondyloarthritis.

Imaging plays a crucial role in diagnosing and forecasting treatment outcomes in axial spondyloarthritis. Conventional radiography may overlook patients in the initial stages of the disease, while MRI is sensitive in identifying inflammation early on. Computed tomography reliably detects structural abnormalities. Practicing rheumatologists must possess a fundamental understanding of interpreting both active inflammatory and structural lesions in axial spondyloarthritis.

Variable Impact of Medical Scribes on Physician Electronic Health Record Documentation Practices: A Quantitative Analysis Across a Large, Integrated Health-System.

BACKGROUND: Medical scribes have been utilized to reduce electronic health record (EHR) associated documentation burden. Although evidence suggests benefits to scribes, no large-scale studies have quantitatively evaluated scribe impact on physician documentation across clinical settings. This study aimed to evaluate the effect of scribes on physician EHR documentation behaviors and performance. METHODS: This retrospective cohort study used EHR audit log data from a large academic health system to evaluate clinical documentation for all ambulatory encounters between January 2014 and December 2019 to evaluate the effect of scribes on physician documentation behaviors. Scribe services were provided on a first-come, first-served basis on physician request. Based on a physician's scribe use, encounters were grouped into 3 categories: never using a scribe, prescribe (before scribe use), or using a scribe. Outcomes included chart closure time, the proportion of delinquent charts, and charts closed after-hours. RESULTS: Three hundred ninety-five physicians (23% scribe users) across 29 medical subspecialties, encompassing 1,132,487 encounters, were included in the analysis. At baseline, scribe users had higher chart closure time, delinquent charts, and after-hours documentation than physicians who never used scribes. Among scribe users, the difference in outcome measures postscribe compared with baseline varied, and using a scribe rarely resulted in outcome measures approaching a range similar to the performance levels of nonusing physicians. In addition, there was variability in outcome measures across medical specialties and within similar subspecialties. CONCLUSION: Although scribes may improve documentation efficiency among some physicians, not all will improve EHR-related documentation practices. Different strategies may help to optimize documentation behaviors of physician-scribe dyads and maximize outcomes of scribe implementation.