A Common Longitudinal Intensive Care Unit data Format (CLIF) to enable multi-institutional federated critical illness research.

Background: Critical illness, or acute organ failure requiring life support, threatens over five million American lives annually. Electronic health record (EHR) data are a source of granular information that could generate crucial insights into the nature and optimal treatment of critical illness. However, data management, security, and standardization are barriers to large-scale critical illness EHR studies. Methods: A consortium of critical care physicians and data scientists from eight US healthcare systems developed the Common Longitudinal Intensive Care Unit (ICU) data Format (CLIF), an open-source database format that harmonizes a minimum set of ICU Data Elements for use in critical illness research. We created a pipeline to process adult ICU EHR data at each site. After development and iteration, we conducted two proof-of-concept studies with a federated research architecture: 1) an external validation of an in-hospital mortality prediction model for critically ill patients and 2) an assessment of 72-hour temperature trajectories and their association with mechanical ventilation and in-hospital mortality using group-based trajectory models. Results: We converted longitudinal data from 94,356 critically ill patients treated in 2020-2021 (mean age 60.6 years [standard deviation 17.2], 30% Black, 7% Hispanic, 45% female) across 8 health systems and 33 hospitals into the CLIF format, The in-hospital mortality prediction model performed well in the health system where it was derived (0.81 AUC, 0.06 Brier score). Performance across CLIF consortium sites varied (AUCs: 0.74-0.83, Brier scores: 0.06-0.01), and demonstrated some degradation in predictive capability. Temperature trajectories were similar across health systems. Hypothermic and hyperthermic-slow-resolver patients consistently had the highest mortality. Conclusions: CLIF facilitates efficient, rigorous, and reproducible critical care research. Our federated case studies showcase CLIF's potential for disease sub-phenotyping and clinical decision-support evaluation. Future applications include pragmatic EHR-based trials, target trial emulations, foundational multi-modal AI models of critical illness, and real-time critical care quality dashboards.

Acinar cell carcinoma with PRKAR1A and PTEN alterations and paraneoplastic panniculitis.

Pancreatic acinar cell carcinoma is a rare type of pancreatic malignancy, which can be confused with pancreatic neuroendocrine neoplasm. Here, we describe a woman in her 80s who presented with abdominal pain and bilateral lower extremity panniculitis. She underwent surgery for a presumed diagnosis of neuroendocrine tumour with PTEN and PRKAR1A alterations; 19 months, later, a recurrence of her pancreatic malignancy was discovered. The patient underwent repeat resection and this time immunohistochemical staining confirmed the diagnosis of acinar cell carcinoma. Staining for acinar cell carcinoma should be prompted based on clinical suspicion in context of PTEN or PRKAR1A mutation when appropriate.

Longitudinal associations between internalizing symptoms and driving avoidance in newly licensed adolescents.

BACKGROUND: Extensive literature assesses risky adolescent driving, but nothing examines what makes teens avoid driving. Many assume teenagers are eager to drive, but evidence suggests internalizing symptoms lead some to avoid driving. AIMS: This study tested whether depressive and anxious symptomology predicted longitudinal driving avoidance in novice teen drivers. MATERIALS AND METHODS: N = 56 16-year-olds (52% female; 48% Black/African American) completed three observations over 6 months. At Time 1, participants reported depressive (Center for Epidemiological Studies Depression 10-item Scale) and anxious (Generalized Anxiety Disorder 7-item Scale) symptomologies, and driving avoidance (Driving Habits Questionnaire [DHQ]), repeating DHQ at Times 2 and 3. Multiple linear regression tested whether symptomologies predicted avoidance at licensure. Linear mixed models tested associations between symptomologies and avoidance over time. RESULTS: High anxiety predicted greater avoidance at baseline and over 6 months. Depressive symptoms did not predict avoidance. DISCUSSION: Findings warrant an assessment of anxious adolescents' barriers to driving and avoidance impacts on crash risk.

Demographic, driving experience, and psychosocial predictors of adolescent distracted driving beliefs.

PURPOSE: The current study had three aims: 1) describe distracted driving beliefs among adolescents by various distraction types (i.e., talking on a hands-free/hands-held cell phone, texting or emailing, taking "selfies," and updating/checking social media); 2) examine the factor structure of distracted driving beliefs; and 3) test whether individual difference factors, shown in prior work to be related to distracted driving behavior, significantly predicted factors of distracted driving beliefs. METHODS: Three hundred seventy-nine high school students enrolled in non-mandatory Driver's Education courses completed surveys of distracted driving beliefs, sensation seeking, and demographics. RESULTS: A factor analysis revealed four factors of distracted driving beliefs: 1) self-acceptance of interacting with a cell phone while driving; 2) perceived peer acceptance of interacting with a cell phone while driving; 3) perceived threat of distracted driving to personal safety; and 4) self- and peer- acceptance of talking on a cell phone while driving. Adolescents perceived a greater threat to safety and less self- and peer-acceptance of interacting with cell phones while driving (i.e., texting/emailing, updating/posting to social media, taking selfies) than talking on a cell phone while driving. In general, men, those with more driving experience, higher in sensation seeking, and those placing more importance on checking notifications on a phone had riskier beliefs about distracted driving. CONCLUSION: Findings suggest adolescent distracted driving beliefs are influenced by individual difference factors, providing some knowledge about the motivations for distracted driving. Future work should consider novel strategies for intervening to reduce this common yet extremely dangerous behavior among adolescents.

Reassessing mechanism as a predictor of pediatric injury mortality.

BACKGROUND: The use of mechanism of injury as a predictor of injury outcome presents practical challenges because this variable may be missing or inaccurate in many databases. The purpose of this study was to determine the importance of mechanism of injury as a predictor of mortality among injured children. METHODS: The records of children (<15-y-old) sustaining a blunt injury were obtained from the National Trauma Data Bank. Models predicting injury mortality were developed using mechanism of injury and injury coding using either abbreviated injury scale post-dot values (low-dimensional injury coding) or injury International Classification of Diseases, Ninth Revision codes and their two-way interactions (high-dimensional injury coding). Model performance with and without inclusion of mechanism of injury was compared for both coding schemes, and the relative importance of mechanism of injury as a variable in each model type was evaluated. RESULTS: Among 62,569 records, a mortality rate of 0.9% was observed. Inclusion of mechanism of injury improved model performance when using low-dimensional injury coding but was associated with no improvement when using high-dimensional injury coding. Mechanism of injury contributed to 28% of model variance when using low-dimensional injury coding and <1% when high-dimensional injury coding was used. CONCLUSIONS: Although mechanism of injury may be an important predictor of injury mortality among children sustaining blunt trauma, its importance as a predictor of mortality depends on the approach used for injury coding. Mechanism of injury is not an essential predictor of outcome after injury when coding schemes are used that better characterize injuries sustained after blunt pediatric trauma.

Tubulin-destabilizing agent BPR0L075 induces vascular-disruption in human breast cancer mammary fat pad xenografts.

BPR0L075, 6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole, is a tubulin-binding agent that inhibits tubulin polymerization by binding to the colchicine-binding site. BPR0L075 has shown antimitotic and antiangiogenic activity in vitro. The current study evaluated the vascular-disrupting activity of BPR0L075 in human breast cancer mammary fat pad xenografts using dynamic bioluminescence imaging. A single dose of BPR0L075 (50 mg/kg, intraperitoneally (i.p.)) induced rapid, temporary tumor vascular shutdown (at 2, 4, and 6 hours); evidenced by rapid and reproducible decrease of light emission from luciferase-expressing orthotopic MCF7 and MDA-MB-231 breast tumors after administration of luciferin substrate. A time-dependent reduction of tumor perfusion after BPR0L075 treatment was confirmed by immunohistological staining of the perfusion marker Hoechst 33342 and tumor vasculature marker CD31. The vasculature showed distinct recovery within 24 hours post therapy. A single i.p. injection of 50 mg/kg of BPR0L075 initially produced plasma concentrations in the micromolar range within 6 hours, but subsequent drug distribution and elimination caused BPR0L075 plasma levels to drop rapidly into the nanomolar range within 24 h. Tests with human umbilical vein endothelial (HUVEC) cells and tumor cells in culture showed that BPR0L075 was cytotoxic to both tumor cells and proliferating endothelial cells, and disrupted pre-established vessels in vitro and ex vivo. In conclusion, BPR0L075 caused rapid, albeit, temporary tumor vascular shutdown and led to reduction of tumor perfusion in orthotopic human breast cancer xenografts, suggesting that this antimitotic agent may be useful as a vascular-disrupting cancer therapy.