Biomechanical evaluation of a fixation technique with a modified hemicerclage for tibial tuberosity transposition: an ex vivo cadaveric study.

Objectives: (1) To determine stiffness, load at failure, and mode of failure of a novel fixation method with a tension modified-hemicerclage (MH) for tibial tuberosity transposition, and (2) to compare the biomechanical properties of this novel fixation technique to 2 pins (2Pins) and 2 pins and tension band wire fixation (2Pins + TBW). Study design: Thirty cadaveric stifles from dogs between 5.2 and 13.1 kg were assigned to 3 treatment groups: Group 1: fixation technique with MH; Group 2: 2Pins; Group 3: 2Pins + TBW. Biomechanical testing was performed with the tibia positioned at an angle of 135° relative to vertical position. Tensile force was applied to the patellar ligament until catastrophic failure was observed. The mode of failure, the load at failure, and the stiffness were compared among treatment groups. Results: The mean stiffness of the novel fixation (38.1 N/mm ± 7.1) and the 2Pins + TBW (40.2 N/mm ± 9.3) were greater than the 2Pins (26.7 N/mm ± 6.7). There was no significant difference between the novel fixation technique and 2Pins + TBW in stiffness and maximum load to failure. The 2Pins (284.3 N ± 70.5) failed at a significantly lower load than the tension modified-hemicerclage (555.7 N ± 225.9 N) and 2Pins + TBW (715.3 N ± 339.8 N). Conclusion: A fixation technique using a modified hemicerclage had the same strength and stiffness as the 2Pins + TBW and was stronger and stiffer than the 2 Pins technique in a cadaveric model.

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound.

Triple negative breast cancer (TNBC) represents a subtype of breast cancer that does not express the three major prognostic receptors of human epidermal growth factor receptor 2 (HER2), progesterone (PR), and estrogen (ER). This limits treatment options and results in a high rate of mortality. We have reported previously on the efficacy of a water-soluble, cationic organometallic compound (Ru-IM) in a TNBC mouse xenograft model with impressive tumor reduction and targeted tumor drug accumulation. Ru-IM inhibits cancer hallmarks such as migration, angiogenesis, and invasion in TNBC cells by a mechanism that generates apoptotic cell death. Ru-IM displays little interaction with DNA and appears to act by a P53-independent pathway. We report here on the mitochondrial alterations caused by Ru-IM treatment and detail the inhibitory properties of Ru-IM in the PI3K/AKT/mTOR pathway in MDA-MB-231 cells. Lastly, we describe the results of an efficacy study of the TNBC xenografted mouse model with Ru-IM and Olaparib monotherapy and combinatory treatments. We find 59% tumor shrinkage with Ru-IM and 65% with the combination. Histopathological analysis confirmed no test-article-related toxicity. Immunohistochemical analysis indicated an inhibition of the angiogenic marker CD31 and increased levels of apoptotic cleaved caspase 3 marker, along with a slight inhibition of p-mTOR. Taken together, the effects of Ru-IM in vitro show similar trends and translation in vivo. Our investigation underscores the therapeutic potential of Ru-IM in addressing the challenges posed by TNBC as evidenced by its robust efficacy in inhibiting key cancer hallmarks, substantial tumor reduction, and minimal systemic toxicity.

Safety and Effectiveness of Portal Vein Embolization after Hepatic Arterial Infusion Therapy.

Portal vein embolization (PVE) is a tool potentially useful for inducing future liver remnant (FLR) hypertrophy in patients with advanced hepatic malignancies who are at high risk of hepatic insufficiency if treated with surgical resection. However, the safety and effectiveness of PVE in the context of patients who have undergone hepatic arterial infusion (HAI) are unknown. This retrospective, single-center study identified 9 patients who underwent PVE after HAI between January 2015 and December 2022. There were no major adverse events, including biliary injury or high-grade liver failure. Analysis showed an increase in standardized FLR from 21.1% (SEM ± 2.4) to 34.8% (SEM ± 2.1) over 9.8 weeks (SEM ± 1.2), with a mean kinetic growth rate of 1.9% (interquartile range, 0.9%-2.4%). Patients who have undergone HAI therapy should not be excluded from consideration of PVE as part of their operative clearance strategy.

Constructing synthetic datasets with generative artificial intelligence to train large language models to classify acute renal failure from clinical notes.

OBJECTIVES: To compare performances of a classifier that leverages language models when trained on synthetic versus authentic clinical notes. MATERIALS AND METHODS: A classifier using language models was developed to identify acute renal failure. Four types of training data were compared: (1) notes from MIMIC-III; and (2, 3, and 4) synthetic notes generated by ChatGPT of varied text lengths of 15 (GPT-15 sentences), 30 (GPT-30 sentences), and 45 (GPT-45 sentences) sentences, respectively. The area under the receiver operating characteristics curve (AUC) was calculated from a test set from MIMIC-III. RESULTS: With RoBERTa, the AUCs were 0.84, 0.80, 0.84, and 0.76 for the MIMIC-III, GPT-15, GPT-30- and GPT-45 sentences training sets, respectively. DISCUSSION: Training language models to detect acute renal failure from clinical notes resulted in similar performances when using synthetic versus authentic training data. CONCLUSION: The use of training data derived from protected health information may not be needed.

mSigSDK - private, at scale, computation of mutation signatures.

In our previous work, we demonstrated that it is feasible to perform analysis on mutation signature data without the need for downloads or installations and analyze individual patient data at scale without compromising privacy. Building on this foundation, we developed an in-browser Software Development Kit (a JavaScript SDK), mSigSDK, to facilitate the orchestration of distributed data processing workflows and graphic visualization of mutational signature analysis results. We strictly adhered to modern web computing standards, particularly the modularization standards set by the ECMAScript ES6 framework (JavaScript modules). Our approach allows for the computation to be entirely performed by secure delegation to the computational resources of the user's own machine (in-browser), without any downloads or installations. The mSigSDK was developed primarily as a companion library to the mSig Portal resource of the National Cancer Institute Division of Cancer Epidemiology and Genetics (NIH/NCI/DCEG), with a focus on FAIR extensibility as components of other researchers' own data science constructs. Anticipated extensions include the programmatic operation of other mutation signature API ecosystems such as SIGNAL and COSMIC, advancing towards a data commons for mutational signature research (Grossman et al., 2016).

"What We're Doing Now Is More Than Water Cooler": Perspectives of Primary Care Leaders on Leading Through (and Beyond) COVID-19.

BACKGROUND: COVID-19 presented numerous challenges to primary care, but little formal research has explored the experience of practice leaders and their strategies for managing teams as the crisis unfolded. OBJECTIVE: Describe the experience of leaders in US primary care delivery organizations, and their strategies for leading teams during COVID-19 and beyond. DESIGN: Qualitative study using semi-structured interviews performed between 9/15/2020 and 8/31/2021. PARTICIPANTS: Purposive sample of 17 clinical leaders in a range of US primary care organizations. APPROACH: An iterative grounded review of interview transcripts was performed, followed by immersion/crystallization analysis. KEY RESULTS: Early in the pandemic, practice leaders reported facing rapid change and the need for constant decision-making, amidst an environment of stress, fear, and uncertainty, but this was buffered by a strong sense of purpose. Later, leaders noted the emergence of layered crises, and evolving challenges including fatigue, burnout, and strained relationships within their organizations and with the communities they serve. Leaders described four interrelated strategies for supporting their teams: (1) Being intentionally present, physically and emotionally; (2) Frequent and transparent communication; (3) Deepening and broadening relationships; (4) Increasing adaptive decision-making, alternating between formal hierarchical and flexible participatory processes. These strategies were influenced by individual leaders' perceived autonomy, which was impacted by the leader's specific role, and organizational size, complexity, and funding model. CONCLUSIONS: As the burnout and workforce crises have accelerated, the identified strategies can be useful to leaders to support teams and build organizational resilience in primary care moving forward.

The impacts of relational organizing for health system and community collaboration: Early evidence from a rapid multisite qualitative study.

OBJECTIVE: To understand the ways relational organizing practices impacted collaborations between independent or health system-affiliated community health clinics, public health offices, and community groups during the early COVID-19 pandemic. DATA SOURCES AND STUDY SETTING: Between November 2020 and June 2021, we interviewed clinical and public health workers, clinic-based community organizers, and staff and volunteers at community organizations who participated in three COVID-19 response collaborations in the Northwestern United States. STUDY DESIGN: This was a qualitative study employing participatory and rapid data collection and analysis methods. DATA COLLECTION: Research team members invited key participants in organizing efforts to a semi-structured virtual interview conducted by an independent health services researcher. A sensemaking team that included project participants analyzed interview data using an iterative, thematic approach and conducted a ripple effect mapping exercise to supplement interview data. A total of 19 people contributed data for analysis. Analysis was guided by the underlying research questions: whether and how relational organizing practices contributed to successful collaboration, and what challenges were encountered. PRINCIPAL FINDINGS: Relational organizing was perceived to contribute to multiple positive project outcomes, including greater self-efficacy in a time of crisis and enhanced sense of connection; these outcomes contributed to a sense of successful collaboration. Four mechanisms were identified that explained relational organizing's collaborative efficacy: (1) mobilizing existing relationships for rapid community engagement; (2) bringing concrete skills for enhancing trust among cross-sector partners; (3) recognizing and addressing power dynamics; and (4) creating vehicles for exercising collective community power. Lack of trust and unsurfaced power dynamics were perceived as common challenges to sustained collaboration, which relational organizing could sometimes mitigate. CONCLUSIONS: Our findings suggest relational organizing practices can be protective against common "pain points" faced by cross-sectoral partnerships, especially in times of crisis. Further piloting of clinic-based relational organizing is recommended, as is research on longer-term impacts.

Improving Pediatric Ovarian Torsion Evaluation in the Pediatric Emergency Department: A Quality Improvement Initiative.

Background: Transabdominal pelvic ultrasound (TPUS) is the diagnostic test of choice for the evaluation of ovarian torsion, a time-sensitive surgical emergency. A full bladder is required to visualize the ovaries. Bladder filling is a time-consuming process leading to delays to TPUS, poor visualization of ovaries requiring repeat studies, and prolonged emergency department length of stay (ED LOS). The primary objective was to decrease the time to TPUS by standardizing the bladder filling process. Methods: This quality improvement initiative occurred at a single, academic, quaternary-care children's hospital ED and utilized the Institute for Healthcare Improvement Model for Improvement with sequential plan-do-study-act cycles. The first set of interventions implemented in August 2021 included a new electronic order set and bladder scan by ED nurses. Subsequent plan-do-study-act cycles aimed to decrease the time to intravenous fluid, decrease fluid requirement, and decrease the need for intravenous fluid. The primary outcome measure was the monthly mean time to TPUS. Secondary outcome measures included monthly mean ED LOS and percentage of repeat TPUS. We performed data analysis with statistical process control charts to assess for system change over time. Results: The preintervention baseline included 292 ED encounters more than 10 months, and postintervention analysis included 526 ED encounters more than 16 months. Time to TPUS decreased (138-120 min), ED LOS decreased (372-335 min), and repeat TPUS decreased (18% to 4%). All changes met the rules for special cause variation. Conclusions: Standardizing the bladder filling process was associated with decreased time to TPUS, ED LOS, and repeat TPUS.

Virtual and Augmented Reality in Interventional Radiology: Current Applications, Challenges, and Future Directions.

Virtual reality (VR) and augmented Reality (AR) are emerging technologies with the potential to revolutionize Interventional radiology (IR). These innovations offer advantages in patient care, interventional planning, and educational training by improving the visualization and navigation of medical images. Despite progress, several challenges hinder their widespread adoption, including limitations in navigation systems, cost, clinical acceptance, and technical constraints of AR/VR equipment. However, ongoing research holds promise with recent advancements such as shape-sensing needles and improved organ deformation modeling. The development of deep learning techniques, particularly for medical imaging segmentation, presents a promising avenue to address existing accuracy and precision issues. Future applications of AR/VR in IR include simulation-based training, preprocedural planning, intraprocedural guidance, and increased patient engagement. As these technologies advance, they are expected to facilitate telemedicine, enhance operational efficiency, and improve patient outcomes, marking a new frontier in interventional radiology.

Activity-induced gene expression in the human brain.

Activity-induced gene expression underlies synaptic plasticity and brain function. Here, using molecular sequencing techniques, we define activity-dependent transcriptomic and epigenomic changes at the tissue and single-cell level in the human brain following direct electrical stimulation of the anterior temporal lobe in patients undergoing neurosurgery. Genes related to transcriptional regulation and microglia-specific cytokine activity displayed the greatest induction pattern, revealing a precise molecular signature of neuronal activation in the human brain.

The Impacts of Slc19a3 Deletion and Intestinal SLC19A3 Insertion on Thiamine Distribution and Brain Metabolism in the Mouse.

The Thiamine Transporter 2 (THTR2) encoded by SLC19A3 plays an ill-defined role in the maintenance of tissue thiamine, thiamine monophosphate, and thiamine diphosphate (TDP) levels. To evaluate the impact of THTR2 on tissue thiamine status and metabolism, we expressed the human SLC19A3 transgene in the intestine of total body Slc19a3 knockout (KO) mice. Male and female wildtype (WT) and transgenic (TG) mice were fed either 17 mg/kg (1×) or 85 mg/kg (5×) thiamine hydrochloride diet, while KOs were only fed the 5× diet. Thiamine vitamers in plasma, red blood cells, duodenum, brain, liver, kidney, heart, and adipose tissue were measured. Untargeted metabolomics were performed on the brain tissues of groups with equivalent plasma thiamine. KO mice had ~two- and ~three-fold lower plasma and brain thiamine levels than WT on the 5× diet. Circulating vitamers were sensitive to diet and equivalent in TG and WT mice. However, TG had 60% lower thiamine but normal brain TDP levels regardless of diet, with subtle differences in the heart and liver. The loss of THTR2 reduced levels of nucleic acid and amino acid derivatives in the brain. Therefore, mutation or inhibition of THTR2 may alter the brain metabolome and reduce the thiamine reservoir for TDP biosynthesis.

Pediatric Toxidrome Simulation Curriculum: Jimson Weed Toxicity.

Introduction: Jimson weed is a poisonous plant containing tropane alkaloids that can cause anticholinergic toxicity. Recognition of anticholinergic toxidrome is important for prevention and management of potentially life-threatening complications of severe toxicity, including dysrhythmia and seizure. Methods: Designed for pediatric emergency medicine (PEM) fellows, this simulation featured a 15-year-old female presenting to the emergency department (ED) with agitation and hallucinations. The team was required to perform a primary survey of the critically ill patient, recognize anticholinergic toxidrome from jimson weed intoxication, and treat complications of severe anticholinergic toxicity. Learners practiced critical resuscitation skills such as management of generalized tonic-clonic seizure, endotracheal intubation, synchronized cardioversion, and external cooling measures. A debriefing guide and participant evaluation forms were utilized. This simulation was created as both an in-person and a virtual simulation experience to accommodate COVID-19 social distancing guidelines. Results: Seventeen PEM fellows completed this simulation across three institutions (two in person, one virtual). Using 5-point Likert scales (with 5 being the most relevant or effective), participants rated the simulation as relevant to their work (M = 4.8, SD = 0.5) as well as effective in teaching basic resuscitation skills (M = 4.7, SD = 0.5), management of generalized tonic-clonic seizure (M = 4.8, SD = 0.5), and treatment of ventricular tachycardia with appropriate interventions (M = 4.6, SD = 0.5). Discussion: This simulation scenario allows pediatric medicine trainees in the ED to practice recognition and management of anticholinergic toxicity and its severe complications secondary to jimson weed ingestion.

Pediatric Emergency Medicine Didactics and Simulation: JumpSTART Secondary Triage for Mass Casualty Incidents.

Mass casualty incidents (MCI), particularly involving pediatric patients, are high-risk, low-frequency occurrences that require exceptional emergency arrangements and advanced preparation. In the aftermath of an MCI, it is essential for medical personnel to accurately and promptly triage patients according to their acuity and urgency for care. As first responders bring patients from the field to the hospital, medical personnel are responsible for prompt secondary triage of these patients to appropriately delegate hospital resources. The JumpSTART triage algorithm (a variation of the Simple Triage and Rapid Treatment, or START, triage system) was originally designed for prehospital triage by prehospital providers but can also be used for secondary triage in the emergency department setting. This technical report describes a novel simulation-based curriculum for pediatric emergency medicine residents, fellows, and attendings involving the secondary triage of patients in the aftermath of an MCI in the emergency department. This curriculum highlights the importance of the JumpSTART triage algorithm and how to effectively implement it in the MCI setting.

Impact of Surgical Lights on the Performance of Fluorescence-Guided Surgery Systems: A Pilot Study.

Fluorescence-guided surgery can aid in the intraoperative visualization of target tissues, with promising applications in human and veterinary surgical oncology. The aim of this study was to evaluate the performances of two fluoresce camera systems, IC-FlowTM and VisionsenseTM VS3 Iridum, for the detection of two non-targeted (ICG and IRDye-800) and two targeted fluorophores (AngiostampTM and FAP-Cyan) under different room light conditions, including ambient light, new generation LED, and halogen artificial light sources, which are commonly used in operating theaters. Six dilutions of the fluorophores were imaged in phantom kits using the two camera systems. The limit of detection (LOD) and mean signal-to-background ratio (mSBR) were determined. The highest values of mSBR and a lower LOD were obtained in dark conditions for both systems. Under room lights, the capabilities decreased, but the mSBR remained greater than 3 (=clearly detectable signal). LOD and mSBR worsened under surgical lights for both camera systems, with a greater impact from halogen bulbs on VisionsenseTM VS3 Iridium and of the LED lights on IC-Flow due to a contribution of these lights in the near-infrared spectrum. When considering implementing FGS into the clinical routine, surgeons should cautiously evaluate the spectral contribution of the lights in the operating theater.

Surgical outcomes and risk factors for recurrence of myxopapillary ependymoma: a single-center experience.

OBJECTIVE: Myxopapillary ependymomas (MPEs) are low-grade, well-circumscribed tumors that often involve the conus medullaris, cauda equina, or filum terminale. They account for up to 5% of all tumors of the spine and 13% of spinal ependymomas, with a peak incidence between 30 and 50 years of age. Because of the rarity of MPEs, their clinical course and optimal management strategy are not well defined, and long-term outcomes remain difficult to predict. The objective of this study was to review long-term clinical outcomes of spinal MPEs and identify factors that may predict tumor resectability and recurrence. METHODS: Pathologically confirmed cases of MPE at the authors' institution were identified and medical records were reviewed. Demographics, clinical presentation, imaging characteristics, surgical technique, follow-up, and outcome data were noted. Two groups of patients-those who underwent gross-total resection (GTR) and those who underwent subtotal resection (STR)-were compared using the Mann-Whitney U-test for continuous and ordinal variables and the Fisher exact test for categorical variables. Differences were considered statistically significant at p ≤ 0.05. RESULTS: Twenty-eight patients were identified, with a median age of 43 years at the index surgery. The median postoperative follow-up duration was 107 months (range 5-372 months). All patients presented with pain. Other common presenting symptoms were weakness (25.0%), sphincter disturbance (21.4%), and numbness (14.3%). GTR was achieved in 19 patients (68%) and STR in 9 (32%). Preoperative weakness and involvement of the sacral spinal canal were more common in the STR group. Tumors were larger and spanned more spinal levels in the STR group compared with the GTR cohort. Postoperative modified McCormick Scale grades were significantly higher in the STR cohort compared with the GTR group (p = 0.00175). Seven of the 9 STR patients (77.8%) underwent reoperation for recurrence at a median of 32 months from the index operation, while no patients required reoperation after GTR, for an overall reoperation rate of 25%. CONCLUSIONS: Findings of this study emphasize the importance of tumor size and location-particularly involvement of the sacral canal-in determining resectability. Reoperation for recurrence was necessary in 78% of patients with subtotally resected tumors; none of the patients who underwent GTR required reoperation. Most patients had stable neurological status postoperatively.