Fluorescence guidance improves the accuracy of radiological imaging-guided surgical navigation.

BACKGROUND: Imaging-based navigation technologies require static referencing between the target anatomy and the optical sensors. Imaging-based navigation is therefore well suited to operations involving bony anatomy; however, these technologies have not translated to soft-tissue surgery. We sought to determine if fluorescence imaging complement conventional, radiological imaging-based navigation to guide the dissection of soft-tissue phantom tumors. METHODS: Using a human tissue-simulating model, we created tumor phantoms with physiologically accurate optical density and contrast concentrations. Phantoms were dissected using all possible combinations of computed tomography (CT), magnetic resonance, and fluorescence imaging; controls were included. The data were margin accuracy, margin status, tumor spatial alignment, and dissection duration. RESULTS: Margin accuracy was higher for combined navigation modalities compared to individual navigation modalities, and accuracy was highest with combined CT and fluorescence navigation (p = 0.045). Margin status improved with combined CT and fluorescence imaging. CONCLUSIONS: At present, imaging-based navigation has limited application in guiding soft-tissue tumor operations due to its inability to compensate for positional changes during surgery. This study indicates that fluorescence guidance enhances the accuracy of imaging-based navigation and may be best viewed as a synergistic technology, rather than a competing one.

Treatment Guideline Nonadherence Pretransport Associated With Need for Higher Level of Care in Children Transferred to a Pediatric Tertiary Care Center for Status Epilepticus.

OBJECTIVES: We sought to investigate the association between adherence to the American Epilepsy Society (AES) 2016 guidelines for management of convulsive status epilepticus (SE) and clinical outcomes among children requiring interhospital transport for SE. We hypothesized that pretransport guideline nonadherence would be associated with needing higher level of care posttransfer. METHODS: This was a retrospective cohort study of children aged 30 days to 18 years transferred to our pediatric tertiary center from 2017 to 2019 for management of SE. Their care episodes were classified as 2016 American Epilepsy Society guideline adherent or nonadherent. There were 40 referring hospitals represented in this cohort. RESULTS: Of 260 care episodes, 55 (21%) were guideline adherent, 184 (71%) were guideline nonadherent, and 21 (8%) had insufficient data to determine guideline adherence. Compared with the adherent group, patients in the nonadherent care group had longer hospitalizations (32 hours [17-68] vs 21 hours [7-48], P = 0.006), were more likely to require intensive care unit admission (47% vs 31%), and less likely to be discharged home from the emergency department (16% vs 35%; χ 2 test, P = 0.01). Intubation rates did not differ significantly between groups (25% vs 18%, P = 0.37). When we fit a multivariable model to adjust for confounding variables, guideline nonadherence was associated with need for higher level of care (odds ratio, 2.04; 95% confidence interval, 1.04-3.99). Treatment guideline adherence did not improve over the 3-year study period (2017: 22%, 2018: 19%, 2019: 29% [χ 2 test for differences between any 2 years, P = 0.295]). CONCLUSIONS: Guideline nonadherence pretransport was associated with longer hospitalizations and need for higher level of care among children transferred for SE at our institution. These findings suggest a need to improve SE guideline adherence through multifaceted quality improvement efforts targeting both the prehospital and community hospital settings.

Diagnostic Discordance in Pediatric Critical Care Transport: A Single-Center Experience.

OBJECTIVES: The aims of the study were to describe diagnostic discordance rates at our pediatric tertiary care center between the reason for transfer of critically ill/injured children (determined by the referring institution) and the inpatient admission diagnosis (determined by our accepting institution), to identify potential factors associated with discordance, and to determine its impact on patient outcomes. METHODS: We conducted a retrospective chart review of all critically ill/injured children transferred to the Johns Hopkins Children's Center between July 1, 2017, and June 30, 2018. All patients whose initial inpatient disposition was the pediatric intensive care unit were included. RESULTS: Six hundred forty-three children (median age, 51 months) from 57 institutions (median pediatric capability level: 3) met inclusion criteria: 46.8% were transported during nighttime, 86.5% by ground, and 21.2% accompanied by a physician. Nearly half (43.4%) had respiratory admission diagnoses. The rest included surgical/neurosurgical (14.2%), neurologic (11.2%), cardiovascular/shock (8.7%), endocrine (8.2%), infectious disease (6.8%), poisoning (3.1%), hematology-oncology (2.2%), gastrointestinal/metabolic (1.9%), and renal (0.3%). Forty-six (7.2%) had referral-to-admission diagnostic discordance: 25 of 46 had discordance across different diagnostic groups and 21 of 46 had clinically significant discordance within the same diagnostic group. The discordant group had higher need for respiratory support titration in transport (43.9% vs 27.9%, p = 0.02); more invasive procedures and vasopressor needs during the day of admission (26.1% vs 11.6%, P = 0.008; 19.6% vs 7%, P = 0.006); and longer intensive care unit (ICU) and hospital stays (5 vs 2 days; 11 vs 3 days, P < 0.001). When compared with respiratory admission diagnoses, patients with cardiovascular/shock and neurologic diagnoses were more likely to have discordant diagnoses (odds ratio [95% confidence interval], 13.24 [5.41-35.05]; 6.47 [2.48-17.75], P < 0.001). CONCLUSIONS: Seven percent of our critically ill/injured pediatric cohort had clinically significant referral-to-admission diagnostic discordance. Patients with cardiovascular/shock and neurologic diagnoses were particularly at risk. Those with discordant diagnoses had more in-transit events; a higher need for ICU interventions postadmission; and significantly longer ICU stays and hospitalizations, deserving further investigation.

Dual-agent fluorescent labeling of soft-tissue sarcomas improves the contrast based upon targeting both interstitial and cellular components of the tumor milieu.

BACKGROUND: Current practices for fluorescence-guided cancer surgery utilize a single fluorescent agent, but homogeneous distribution throughout the tumor is difficult to achieve. We hypothesize that administering a perfusion and a molecular-targeted agent at their optimal administration-to-imaging time will improve whole-tumor contrast. EXPERIMENTAL DESIGN: Mice bearing subcutaneous xenograft human synovial sarcomas were administered indocyanine green (ICG) (3 mg/kg) or ABY-029 (48.7 µg/kg)-an epidermal growth factor receptor-targeted Affibody molecule-alone or in combination. Fluorescence contrast and signal distribution were compared between treatment groups. Two commercial fluorescence imaging systems were tested for simultaneous imaging of ICG and ABY-029. RESULTS: ABY-029 has a moderate positive correlation with viable tumor (ρ = 0.2 ± 0.4), while ICG demonstrated a strong negative correlation (ρ = -0.6 ± 0.1). The contrast-to-variance ratio was highest in the ABY-029 +ICG (2.5 ± 0.8), compared to animals that received ABY-029 (2.3 ± 0.8) or ICG (2.0 ± 0.5) alone. Moreover, the combination of ABY-029 + ICG minimizes the correlation between viable tumor and fluorescence intensity (ρ = -0.1 ± 0.2) indicating the fluorescence signal distribution is more homogeneous throughout the tumor milieu. CONCLUSION: Dual-agent imaging utilizing a single channel in a commercial fluorescence-guided imaging system tailored for IRDye 800CW is a promising method to increase tumor contrast in a clinical setting.

Superficial malignant ossifying fibromyxoid tumors harboring the rare and recently described ZC3H7B-BCOR and PHF1-TFE3 fusions.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation and intermediate biologic potential. Up to 85% of OFMTs, including benign, atypical, and malignant forms, harbor fusion genes. Most commonly, the PHF1 gene localized to 6p21 is fused with EP400, but other fusion partners, such as MEAF6, EPC1, and JAZF1 have also been described. Herein, we present two rare cases of superficial OFMTs with ZC3H7B-BCOR and the very recently described PHF1-TFE3 fusions. The latter also exhibited moderate to strong diffuse immunoreactivity for TFE3. Reciprocally, this finding expands the entities with TFE3 rearrangements. Accumulation of additional data is necessary to determine if OFMTs harboring these rare fusions feature any reproducible clinicopathologic findings or carry prognostic and/or predictive implications.

Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and viral epitranscriptomes during infection.

More than 140 post-transcriptional modifications (PTMs) are known to decorate cellular RNAs, but their incidence, identity and significance in viral RNA are still largely unknown. We have developed an agnostic analytical approach to comprehensively survey PTMs on viral and cellular RNAs. Specifically, we used mass spectrometry to analyze PTMs on total RNA isolated from cells infected with Zika virus, Dengue virus, hepatitis C virus (HCV), poliovirus and human immunodeficiency virus type 1. All five RNA viruses significantly altered global PTM landscapes. Examination of PTM profiles of individual viral genomes isolated by affinity capture revealed a plethora of PTMs on viral RNAs, which far exceeds the handful of well-characterized modifications. Direct comparison of viral epitranscriptomes identified common and virus-specific PTMs. In particular, specific dimethylcytosine modifications were only present in total RNA from virus-infected cells, and in intracellular HCV RNA, and viral RNA from Zika and HCV virions. Moreover, dimethylcytosine abundance during viral infection was modulated by the cellular DEAD-box RNA helicase DDX6. By opening the Pandora's box on viral PTMs, this report presents numerous questions and hypotheses on PTM function and strongly supports PTMs as a new tier of regulation by which RNA viruses subvert the host and evade cellular surveillance systems.

Pediatric Transport Triage: Development and Assessment of an Objective Tool to Guide Transport Planning.

OBJECTIVES: We developed a Pediatric Transport Triage Tool (PT3) to objectively guide selection of team composition and transport mode, thereby standardizing transport planning. Previously, modified Pediatric Early Warning Score for transport has been used to assess illness severity but not to guide transport decision making. METHODS: The PT3 was created for pediatric transport by combining objective evaluations of neurologic, cardiovascular, and respiratory systems with a systems-based medical condition list to identify diagnoses requiring expedited transport and/or advanced team composition not captured by neurologic, cardiovascular, and respiratory systems alone. A scoring algorithm was developed to guide transport planning. Transport data (mode, team composition, time to dispatch, patient disposition, and complications) were collected before and after PT3 implementation at a single tertiary care center over an 18-month period. RESULTS: We reviewed 2237 inbound pediatric transports. Transport mode, patient disposition, and dispatch time were unchanged over the study period. Fewer calls using a transport nurse were noted after PT3 implementation (33.9% vs 30%, P = 0.05), with a trend toward fewer rotor-wing transports and transports requiring physicians. The majority of users, regardless of experience level, reported improved transport standardization with the tool. Need to upgrade team composition or mode during transport was not different during the study period. No adverse patient safety events occurred with PT3 use. CONCLUSIONS: The PT3 represents an objective triage tool to reduce variability in transport planning. The PT3 decreased resource utilization and was not associated with adverse outcomes. Teams with dynamic staffing models, various experience levels, and multiple transport modes may benefit from this standardized assessment tool.

Preclinical imaging of epidermal growth factor receptor with ABY-029 in soft-tissue sarcoma for fluorescence-guided surgery and tumor detection.

BACKGROUND AND OBJECTIVES: Fluorescence-guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY-029 (anti-EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small-molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft-tissue sarcomas with varying levels of EGFR expression and vascularization. METHODS: Five xenograft soft-tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY-029 and IRDye 700DX were each administered at 4.98 µM. Fluorescence from in vivo and ex vivo (fresh and formalin-fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues. RESULTS: ABY-029 is retained longer within tumor tissue and achieves higher tumor-to-background ratios both in vivo and ex vivo than IRDye 700DX. ABY-029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast-to-noise ratio, but all systems have individual advantages. CONCLUSIONS: ABY-029 demonstrates promise to assist in wide local excision of soft-tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.

Trauma Bay Disposition of Infants and Young Children With Mild Traumatic Brain Injury and Positive Head Imaging.

OBJECTIVES: To describe the disposition of infants and young children with isolated mild traumatic brain injury and neuroimaging findings evaluated at a level 1 pediatric trauma center, and identify factors associated with their need for ICU admission. DESIGN: Retrospective cohort. SETTING: Single center. PATIENTS: Children less than or equal to 4 years old with mild traumatic brain injury (Glasgow Coma Scale 13-15) and neuroimaging findings evaluated between January 1, 2013, and December 31, 2015. Polytrauma victims and patients requiring intubation or vasoactive infusions preadmission were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-hundred ten children (median age/weight/Glasgow Coma Scale: 6 mo/7.5 kg/15) met inclusion criteria. Most neuroimaging showed skull fractures with extra-axial hemorrhage/no midline shift (30%), nondisplaced skull fractures (28%), and intracranial hemorrhage without fractures/midline shift (19%). Trauma bay disposition included ICU (48%), ward (38%), intermediate care unit and home (7% each). Overall, 1% required intubation, 4.3% seizure management, and 4.3% neurosurgical procedures; 15% were diagnosed with nonaccidental trauma. None of the ward/intermediate care unit patients were transferred to ICU. Median ICU/hospital length of stay was 2 days. Most patients (99%) were discharged home without neurologic deficits. The ICU subgroup included all patients with midline shift, 62% patients with intracranial hemorrhage, and 20% patients with skull fractures. Across these imaging subtypes, the only clinical predictor of ICU admission was trauma bay Glasgow Coma Scale less than 15 (p = 0.018 for intracranial hemorrhage; p < 0.001 for skull fractures). A minority of ICU patients (18/100) required neurocritical care and/or neurosurgical interventions; risk factors included neurologic deficit, loss of consciousness/seizures, and extra-axial hemorrhage (especially epidural hematoma). CONCLUSIONS: Nearly half of our cohort was briefly monitored in the ICU (with disposition mostly explained by trauma bay imaging, rather than clinical findings); however, less than 10% required ICU-specific interventions. Although ICU could be used for close neuromonitoring to prevent further neurologic injury, additional research should explore if less conservative approaches may preserve patient safety while optimizing healthcare resource utilization.

Application of Fluorescence-Guided Surgery to Subsurface Cancers Requiring Wide Local Excision: Literature Review and Novel Developments Toward Indirect Visualization.

The excision of tumors by wide local excision is challenging because the mass must be removed entirely without ever viewing it directly. Positive margin rates in sarcoma resection remain in the range of 20% to 35% and are associated with increased recurrence and decreased survival. Fluorescence-guided surgery (FGS) may improve surgical accuracy and has been utilized in other surgical specialties. ABY-029, an anti-epidermal growth factor receptor Affibody molecule covalently bound to the near-infrared fluorophore IRDye 800CW, is an excellent candidate for future FGS applications in sarcoma resection; however, conventional methods with direct surface tumor visualization are not immediately applicable. A novel technique involving imaging through a margin of normal tissue is needed. We review the past and present applications of FGS and present a novel concept of indirect FGS for visualizing tumor through a margin of normal tissue and aiding in excising the entire lesion as a single, complete mass with tumor-free margins.

Sex and gender differences in upper extremity prosthesis rejection: A review of literature.

Prosthesis rejection is a significant barrier to rehabilitation of persons with upper limb difference. Many individual factors can affect device rejection, including a person's sex or gender. The objective of this narrative review was to explore the reported differences between the sexes and genders in upper limb prosthesis rejection. This review considered peer-reviewed, published research studies in which the study population were adults (aged 18 and older) who had unilateral or bilateral limb difference (any level) of any etiology with current, past, or no history of prosthetic device usage. Using identified keywords, index terms, and a peer-reviewed search filter, the literature was searched in MEDLINE, Embase, and PsycInfo. The reasons for rejection, disuse, or abandonment of prosthetic devices were extracted, with the focus on reported differences between sex and genders. After searching, 29 articles were selected for full-text review and 15 were included. Only 5 of 15 articles examined differences between the sexes. Women tend to reject upper extremity prostheses more than men both before and after being fit with a device; device characteristics, such as weight and cosmesis, do not appear to be appropriately designed for women; and there may not be adequate consideration of the goals for women with limb difference(s). There is inadequate reporting of sex and gender in the literature on prosthesis rejection; future studies should report and explore these factors to determine whether the needs of the full population with limb loss are being met.

Real-time identification of life-threatening necrotizing soft-tissue infections using indocyanine green fluorescence imaging.

Significance: Necrotizing soft-tissue infections (NSTIs) are life-threatening infections with a cumulative case fatality rate of 21%. The initial presentation of an NSTI is non-specific, frequently leading to misdiagnosis and delays in care. No current strategies yield an accurate, real-time diagnosis of an NSTI. Aim: A first-in-kind, observational, clinical pilot study tested the hypothesis that measurable fluorescence signal voids occur in NSTI-affected tissues following intravenous administration and imaging of perfusion-based indocyanine green (ICG) fluorescence. This hypothesis is based on the established knowledge that NSTI is associated with local microvascular thrombosis. Approach: Adult patients presenting to the Emergency Department of a tertiary care medical center at high risk for NSTI were prospectively enrolled and imaged with a commercial fluorescence imager. Single-frame fluorescence snapshot and first-pass perfusion kinetic parameters-ingress slope (IS), time-to-peak (TTP) intensity, and maximum fluorescence intensity (IMAX)-were quantified using a dynamic contrast-enhanced fluorescence imaging technique. Clinical variables (comorbidities, blood laboratory values), fluorescence parameters, and fluorescence signal-to-background ratios (SBRs) were compared to final infection diagnosis. Results: Fourteen patients were enrolled and imaged (six NSTI, six cellulitis, one diabetes mellitus-associated gangrene, and one osteomyelitis). Clinical variables demonstrated no statistically significant differences between NSTI and non-NSTI patient groups (p-value≥0.22). All NSTI cases exhibited prominent fluorescence signal voids in affected tissues, including tissue features not visible to the naked eye. All cellulitis cases exhibited a hyperemic response with increased fluorescence and no distinct signal voids. Median lesion-to-background tissue SBRs based on snapshot, IS, TTP, and IMAX parameter maps ranged from 3.2 to 9.1, 2.2 to 33.8, 1.0 to 7.5, and 1.5 to 12.7, respectively, for the NSTI patient group. All fluorescence parameters except TTP demonstrated statistically significant differences between NSTI and cellulitis patient groups (p-value<0.05). Conclusions: Real-time, accurate discrimination of NSTIs compared with non-necrotizing infections may be possible with perfusion-based ICG fluorescence imaging.

Neoadjuvant Therapies Do Not Reduce Epidermal Growth Factor Receptor (EGFR) Expression or EGFR-Targeted Fluorescence in a Murine Model of Soft-Tissue Sarcomas.

PURPOSE: ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for fluorescence-guided surgery of sarcomas. To date, studies using ABY-029 have occurred in tumors naïve to chemotherapy (CTx) and radiation therapy (RTx), although these neoadjuvant therapies are frequently used for sarcoma treatment in humans. The goal of this study was to evaluate the impact of CTx and RTx on tumor EGFR expression and ABY-029 fluorescence of human soft-tissue sarcoma xenografts in a murine model. PROCEDURES: Immunodeficient mice (n = 98) were divided into five sarcoma xenograft groups and three treatment groups - CTx only, RTx only, and CTx followed by RTx, plus controls. Four hours post-injection of ABY-029, animals were sacrificed followed by immediate fluorescence imaging of ex vivo adipose, muscle, nerve, and tumor tissues. Histological hematoxylin and eosin staining confirmed tumor type, and immunohistochemistry staining determined EGFR, cluster of differentiation 31 (CD31), and smooth muscle actin (SMA) expression levels. Correlation analysis (Pearson's correlation coefficients, r) and linear regression (unstandardized coefficient estimates, B) were used to determine statistical relationships in molecular expression and tissue fluorescence between xenografts and treatment groups. RESULTS: Neoadjuvant therapies had no broad impact on EGFR expression (|B|≤ 7.0, p ≥ 0.4) or on mean tissue fluorescence (any tissue type, (|B|≤ 2329.0, p ≥ 0.1). Mean tumor fluorescence was significantly related to EGFR expression (r = 0.26, p = 0.01), as expected. CONCLUSION: Results suggest that ABY-029 as an EGFR-targeted, fluorescent probe is not negatively impacted by neoadjuvant soft-tissue sarcoma therapies, although validation in humans is required.

Resolving bony abnormality evolves to diffuse large B-cell lymphoma.

Primary lymphoma of bone is a rare malignancy that can mimic infection and benign bone lesions radiographically. Malignant conversion of osseous lesions has been reported; evolution to lymphoma has not. We describe an adolescent male diagnosed with atypical osteoid osteoma who, despite near resolution of bony changes involving the anterior tibia, was diagnosed with monostotic diffuse large B-cell lymphoma four years later. Indolent lymphoma of the initial lesion is unlikely. This case highlights the importance of clinical suspicion of malignancy even with recurrence of similar clinical presentation and hints at possible osseous microenvironment abnormalities predisposing to the development of lymphoma.

Is there a role for knee arthrodesis with modular endoprostheses for tumor and revision of failed endoprostheses?

BACKGROUND: Knee arthrodeses are performed to treat infection after arthroplasty and tumors requiring extensive soft tissue resection. Many techniques have been described, but most have important disadvantages. Currently, endoprosthetic arthrodesis implants are available, but little is known about them. QUESTIONS/PURPOSES: Our objective was to analyze a series of knee arthrodeses with a modular prosthetic system to evaluate (1) survivorship of the implant, (2) complications, (3) whether survivorship differed between arthrodeses done for primary tumor resection and revision reconstructions, and (4) whether survivorship differed based on the presence of previous infection or the use of a gastrocnemius flap. METHODS: We present 32 patients with modular knee arthrodeses; arthrodeses were performed in 25 patients with tumors and in seven patients without tumors. There were 14 implants done at the time of tumor resection and 18 for revision of failed implants. Survivorship and complications were analyzed with Kaplan-Meier curves. Log-rank test was used for comparison between primary and revision implants, not infected and previously infected implants, and use or nonuse of a gastrocnemius flap. RESULTS: Survivorship of arthrodeses with modular endoprostheses was 50% and 25% at 5 and 10 years, respectively. There were nine infections (29%) and one implant fracture (3%). Amputation as final surgery was required in 8 patients (six owing to infection and two to oncologic failures). There was no significant difference in survivorship between arthrodeses done for primary tumor resection and as a salvage procedure for failed implants. No differences were found between patients with and without prior infection or with and without a gastrocnemius flap. CONCLUSIONS: Survivorship of a modular arthrodesis implant was 50% at 5 years owing to a high complication rate. Infection is the most common cause of failure of oncologic and revision implants. Implant fracture is a rare occurrence. Modular segmental arthrodesis provides a stable construct for patients in whom limb preservation is possible but a hinged device is contraindicated as a result of major muscle resection. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Size-dependent absolute quantum yields for size-separated colloidally-stable silicon nanocrystals.

Size-selective precipitation was used to successfully separate colloidally stable allylbenzene-capped silicon nanocrystals into several visible emitting monodisperse fractions traversing the quantum size effect range of 1-5 nm. This enabled the measurement of the absolute quantum yield and lifetime of photoluminescence of allylbenzene-capped silicon nanocrystals as a function of size. The absolute quantum yield and lifetime are found to monotonically decrease with decreasing nanocrystal size, which implies that nonradiative vibrational and surface defect effects overwhelm spatial confinement effects that favor radiative relaxation. Visible emission absolute quantum yields as high as 43% speak well for the development of "green" silicon nanocrystal color-tunable light emitting diodes that can potentially match the performance of their toxic heavy metal chalcogenide counterparts.

In vitro transcription of self-assembling DNA nanoparticles.

Nucleic acid nanoparticles are playing an increasingly important role in biomolecular diagnostics and therapeutics as well as a variety of other areas. The unique attributes of self-assembling DNA nanoparticles provide a potentially valuable addition or alternative to the lipid-based nanoparticles that are currently used to ferry nucleic acids in living systems. To explore this possibility, we have assessed the ability of self-assembling DNA nanoparticles to be constructed from complete gene cassettes that are capable of gene expression in vitro. In the current report, we describe the somewhat counter-intuitive result that despite extensive crossovers (the stereochemical analogs of Holliday junctions) and variations in architecture, these DNA nanoparticles are amenable to gene expression as evidenced by T7 RNA polymerase-driven transcription of a reporter gene in vitro. These findings, coupled with the vastly malleable architecture and chemistry of self-assembling DNA nanoparticles, warrant further investigation of their utility in biomedical genetics.

Extraneuraxial Hemangioblastoma: An Unusual Soft Tissue Neoplasm that Mimics More Common Entities but Carries Distinct Clinical Implications.

Hemangioblastoma, one of the characteristic tumors associated with Von Hippel-Lindau (VHL) disease, most often presents in the central nervous system (CNS) but can uncommonly arise in extraneuraxial, or previously referred to as peripheral, locations. Without the clinical context of known VHL disease, hemangioblastoma may not enter the differential for a soft tissue mass outside the CNS. Here, we present two patients with diagnostically challenging extraneuraxial hemangioblastoma to highlight the importance of considering this entity within the differential diagnosis of soft tissue neoplasms containing clear cells and delicate vasculature. We review the relevant diagnostic features, including a suggested immunohistochemical panel, along with the potential associated clinical implications of making this diagnosis. It is recommended that affected patients be offered genetic counseling to assess for underlying VHL disease.

Pathologic Femur Fracture in an Immunocompetent Healthy Young Adult due to Acute Osteomyelitis.

An immunocompetent 33-year-old woman presented with a pathologic femur fracture after one month of progressively worsening right thigh pain. Open biopsy demonstrated acute suppurative osteomyelitis despite the lack of clinical risk factors. The polymicrobial infection was successfully treated with three operative procedures and culture-specific antibiotic agents. Acute osteomyelitis, while an uncommon cause of pathologic fracture, must always be on the differential diagnosis, even when no obvious predisposing factors are present. When investigating for an infectious etiology in cases such as our own, considering immunodeficiency syndromes alongside the more typical causes of osteomyelitis is encouraged.

Cardiopulmonary Resuscitation During Simulated Pediatric Interhospital Transport: Lessons Learned From Implementation of an Institutional Curriculum.

INTRODUCTION: Little is known about cardiopulmonary resuscitation (CPR) quality during pediatric interhospital transport; hence, our aim was to investigate its feasibility. METHODS: After implementing an institutional education curriculum on pediatric resuscitation during ambulance transport, we conducted a 4-year prospective observational study involving simulation events. Simulated scenarios were (1) interhospital transport of a child retrieved in cardiac arrest (Sim1) and (2) unanticipated cardiac arrest of a child during transport (Sim2). Cardiopulmonary resuscitation data were collected via Zoll RSeries defibrillators. Performance was evaluated using age-appropriate American Heart Association (AHA) Guidelines. Video recordings were reviewed for qualitative thematic analysis. RESULTS: Twenty-six simulations were included: 16 Sim1 [mannequins: Laerdal SimMan 3G (n = 13); Gaumard 5-year-old HAL (n = 3)] and 10 Sim2 [Gaumard 1-year-old HAL (n = 8); Laerdal SimBaby (n = 2)]. Median (IQR) CPR duration was 18 minutes 23 seconds (14-22 minutes), chest compression rate was 112 per minute (106-118), and fraction (CCF) was 1 (0.9-1). Five hundred eight 60-second resuscitation epochs were evaluated (Sim1: 356; Sim2: 152); 73% were AHA compliant for rate and 87.8% for CCF. Twenty-four minutes (4.7%) had pauses more than 10 seconds. One hundred fifty seven Sim1 epochs (44.1%) met criteria for excellent CPR (AHA-compliant for rate, depth, and CCF). Rates of excellent CPR were higher for learner groups with increased simulation and transport experience (59.1% vs. 35.3%, P < 0.001). Thematic analysis identified performance-enhancing strategies, stemming from anticipating challenges, planning solutions, and ensuring team's shared mental model. CONCLUSIONS: High-quality CPR may be achievable during pediatric interhospital transport. Certain transport-specific strategies may enhance resuscitation quality. Learners' performance improved with simulation and transport experience, highlighting ongoing education's role.