Planned Dental Extractions After Radiation Therapy.

Importance: Nonrestorable teeth are recommended to be extracted prior to radiation therapy (RT). Occasionally, preradiation extractions introduce unacceptable delays in treatment initiation. Planned dental extractions immediately postradiation presents an alternative strategy, though outcomes are uncertain. Objective: To evaluate the feasibility and safety of dental extractions immediately postradiation. Design, Setting, and Participants: A prospective cohort study including patients planned for curative-intent RT but unable or unwilling to proceed with 1 or more extractions recommended pretreatment was carried out. From January 2020 to September 2022, 58 patients were screened and 50 enrolled. The dental care was performed at a single academic department and the cancer care at regional centers. Analysis took place between September 22, 2023, and June 10, 2024. Exposure: On completion of RT, patients were recommended to complete extractions as soon as feasible, and ideally within 4 months. Main Outcomes and Measures: The primary end point was the actuarial cumulative incidence of exposed alveolar bone noted by any practitioner at any time after extraction, calculated using Gray method with death as a competing risk. As a pilot study, no formal power calculation was performed; resources allowed for 50 evaluable patients. Results: Among the 50 participants enrolled, RT was nonoperative for 32 patients (64%) and postoperative for 18 patients (36%). Intensity-modulated RT (IMRT) was delivered in all patients. Of the 50 patients, 20 (40%) declined dental extractions immediately postradiation and the remaining 30 (60%) underwent a median (range) of 8.5 (1-28) extractions at a median (range) of 64.5 (13-152) days after RT. The median (IQR) follow-up for survivors without exposed bone was 26 (17-35) months from the end of RT. The 2-year cumulative incidence of any exposed bone was 27% (95% CI, 14%-40%). The 2-year incidence of exposed bone for those who underwent dental extractions immediately postradiation was 40% (95% CI, 22%-58%) and 7% (95% CI, 0%-22%) for those who did not. Of the 13 who developed exposed bone: 4 resolved, 1 was lost to follow-up, and 8 were confirmed as osteoradionecrosis. Conclusions and Relevance: This cohort study found that postradiation dental extractions incur considerable risk, even if performed within a 4-month window.

Prospective validation of a hospital triage predictive model to decrease undertriage: an EAST multicenter study.

Background: Tiered trauma team activation (TTA) allows systems to optimally allocate resources to an injured patient. Target undertriage and overtriage rates of <5% and <35% are difficult for centers to achieve, and performance variability exists. The objective of this study was to optimize and externally validate a previously developed hospital trauma triage prediction model to predict the need for emergent intervention in 6 hours (NEI-6), an indicator of need for a full TTA. Methods: The model was previously developed and internally validated using data from 31 US trauma centers. Data were collected prospectively at five sites using a mobile application which hosted the NEI-6 model. A weighted multiple logistic regression model was used to retrain and optimize the model using the original data set and a portion of data from one of the prospective sites. The remaining data from the five sites were designated for external validation. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were used to assess the validation cohort. Subanalyses were performed for age, race, and mechanism of injury. Results: 14 421 patients were included in the training data set and 2476 patients in the external validation data set across five sites. On validation, the model had an overall undertriage rate of 9.1% and overtriage rate of 53.7%, with an AUROC of 0.80 and an AUPRC of 0.63. Blunt injury had an undertriage rate of 8.8%, whereas penetrating injury had 31.2%. For those aged ≥65, the undertriage rate was 8.4%, and for Black or African American patients the undertriage rate was 7.7%. Conclusion: The optimized and externally validated NEI-6 model approaches the recommended undertriage and overtriage rates while significantly reducing variability of TTA across centers for blunt trauma patients. The model performs well for populations that traditionally have high rates of undertriage. Level of evidence: 2.

Arsenic Exposure in Well Water From the Perspective of Patients and Providers.

BACKGROUND: Arsenic is a well-known toxin which may contaminate household water. It is harmful when ingested over prolonged periods of time. As a result, public health experts recommend that water should be screened and treated to prevent arsenic ingestion. In the United States, the responsibility of testing and treatment of private wells falls on homeowners. Despite recommendations for routine screening, this is rarely done. OBJECTIVES: To assess the prevalence of well water use in a Midwestern patient population, how patients and clinicians perceive the risks of arsenic in well water, and whether additional resources on well water testing are desired. These findings will be used to influence tools for clinicians regarding symptom and examination findings of chronic arsenic exposure and potentiate the distribution of informational resources on well water testing. METHODS: Surveys were sent via email to all actively practicing primary care clinicians at the Mayo Clinic in the United States Midwest, and all active adult patients at the Mayo Clinic in the same region. Our team analyzed survey data to determine whether both patients and clinicians are aware of the health effects of chronic arsenic toxicity from well water, the need for routine well water testing and whether each group wants more information on the associated risks. RESULTS: Both patients and primary care clinicians worry about arsenic exposure. Patients with well water are concerned about their water safety yet feel uninformed about testing options. Clinicians do not know how prevalent well water use is among their patients, feel uninformed about the chronic risks of arsenic exposure and the physical examination associated with it. Both groups unanimously want more information on testing options. CONCLUSIONS: Our findings show a significant reliance on well water use in the American Midwest, and unanimous support for the need for further well water testing information and resources for patients and their clinicians.

Neutrophil-dependent hepatic platelet accumulation and liver injury revealed by acetaminophen dose-response studies.

Background: Acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure (ALF). Neutrophil activation has been associated with poor outcomes in patients with ALF and is proposed to amplify coagulation in this context. However, the precise role of neutrophils in APAP-induced liver injury is not known. Methods: We used a dual antibody-mediated neutrophil depletion strategy to determine the role of neutrophils in mice challenged with different doses of APAP (300 or 600 mg/kg) that produce hepatotoxicity and ALF-like pathology. Results: Flow cytometry confirmed depletion of neutrophils in whole blood prior to APAP challenge. Mice given isotype control and challenged with 300 mg/kg APAP developed marked hepatocellular necrosis and showed an increase in biomarkers of coagulation cascade activation. Neutrophil depletion (anti-Ly6G) did not affect either liver injury or coagulation activation in mice challenged with 300 mg/kg APAP. Mice given isotype control and challenged with 600 mg/kg APAP developed hepatic necrosis alongside marked hemorrhage and congestion indicative of vascular injury. Interestingly, hepatic neutrophil and platelet accumulation were increased in mice given 600 mg/kg APAP compared with those given the lower APAP dose. Neutrophil depletion significantly reduced the severity of liver necrosis in mice challenged with 600 mg/kg APAP, without significantly impacting biomarkers of coagulation activity. Notably, neutrophil depletion significantly reduced hepatic platelet accumulation in mice challenged with 600 mg/kg APAP. Conclusion: The results indicate a role of neutrophils in APAP-induced liver injury that is dependent on the APAP dose and suggest involvement of neutrophil-platelet interactions in promoting hepatic injury in experimental APAP-induced ALF.

A Metabolic-Epigenetic Mechanism Directs Cell Fate and Therapeutic Sensitivity in Breast Cancer.

Over the past decade, studies have increasingly shed light on a reciprocal relationship between cellular metabolism and cell fate, meaning that a cell's lineage both drives and is governed by its specific metabolic features. A recent study by Zhang and colleagues, published in Cell Metabolism, describes a novel metabolic-epigenetic regulatory axis that governs lineage identity in triple-negative breast cancer (TNBC). Among the key findings, the authors demonstrate that the metabolic enzyme pyruvate kinase M2 (PKM2) directly binds to the histone methyltransferase enhancer of zeste homolog 2 (EZH2) in the nucleus to silence expression of a set of genes that includes the mitochondrial carnitine transporter SLC16A9. Perturbation of this metabolic-epigenetic regulatory mechanism induces a metabolic shift away from glycolysis and toward fatty acid oxidation. The ensuing influx of carnitine facilitates the deposition of the activating epigenetic mark H3K27Ac onto the promoter of GATA3, driving a committed luminal lineage state. Importantly, this metabolic-epigenetic axis represents a potentially targetable vulnerability for the treatment of TNBC, a subtype that currently lacks effective therapeutic strategies. These findings lend further support for the paradigm shift underlying our understanding of cancer metabolism: that a cellular fuel source functions not only to provide energy but also to direct the epigenetic regulation of cell fate.

Fragmenting projectiles: a case report and literature review of the G2 Radically Invasive Projectile.

Innovations in projectile design present unique challenges for trauma surgeons when treating gunshot victims. The G2 Radically Invasive Projectile (G2 Research, Winder, Georgia, USA) (G2RIP) is a frangible, rapidly expanding bullet resulting in a distinct pattern of injury consisting of diffuse hemorrhage with multicavity trauma as well as unique radiographic features of the projectile. To efficiently manage patients injured by the G2RIP, trauma surgeons must be aware of these distinct characteristics, and of previous patterns in effective management such as liberal damage control and extensive use of CT. Understanding previous presentation and management of patients injured by the G2RIP can aid in improving patient care in the trauma center.

Provider Perspectives on Artificial Intelligence-Guided Screening for Low Ejection Fraction in Primary Care: Qualitative Study.

BACKGROUND: The promise of artificial intelligence (AI) to transform health care is threatened by a tangle of challenges that emerge as new AI tools are introduced into clinical practice. AI tools with high accuracy, especially those that detect asymptomatic cases, may be hindered by barriers to adoption. Understanding provider needs and concerns is critical to inform implementation strategies that improve provider buy-in and adoption of AI tools in medicine. OBJECTIVE: This study aimed to describe provider perspectives on the adoption of an AI-enabled screening tool in primary care to inform effective integration and sustained use. METHODS: A qualitative study was conducted between December 2019 and February 2020 as part of a pragmatic randomized controlled trial at a large academic medical center in the United States. In all, 29 primary care providers were purposively sampled using a positive deviance approach for participation in semistructured focus groups after their use of the AI tool in the randomized controlled trial was complete. Focus group data were analyzed using a grounded theory approach; iterative analysis was conducted to identify codes and themes, which were synthesized into findings. RESULTS: Our findings revealed that providers understood the purpose and functionality of the AI tool and saw potential value for more accurate and faster diagnoses. However, successful adoption into routine patient care requires the smooth integration of the tool with clinical decision-making and existing workflow to address provider needs and preferences during implementation. To fulfill the AI tool's promise of clinical value, providers identified areas for improvement including integration with clinical decision-making, cost-effectiveness and resource allocation, provider training, workflow integration, care pathway coordination, and provider-patient communication. CONCLUSIONS: The implementation of AI-enabled tools in medicine can benefit from sensitivity to the nuanced context of care and provider needs to enable the useful adoption of AI tools at the point of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04000087; https://clinicaltrials.gov/ct2/show/NCT04000087.