Osteochondral Allograft Transplantation to the Capitellum: Technical Considerations of a Mega Osteochondritis Dissecans Technique.

Osteochondritis dissecans of the elbow is a rare but debilitating pathology typically found in the adolescent repetitive overhead athlete. In the setting of unstable lesions, mechanical symptoms, or deteriorating function despite appropriate conservative management, surgical osteochondral allograft transplantation of the capitellum is a viable option for even large lesions (>10 mm), with minimal morbidity and good return of function. We describe a technique for performing a large osteochondral allograft transplantation of the capitellum.

A Month of Vestibular Migraine: Symptom Characterization Using Ecological Momentary Assessment.

OBJECTIVE(S): This study investigated the frequency and intensity of vestibular migraine (VM) symptoms using Ecological Momentary Assessment (EMA). This approach was intended to provide insights into the day-to-day experiences of individuals with VM, contributing to a more comprehensive understanding of this condition. METHODS: Participants reported symptoms to an automated text system, rating their dizziness over the prior 24 h as none, mild, moderate, or severe. Definitive Dizzy Days (DDDs) were defined as days with moderate or severe dizziness. A student's independent group t-test was used to compare the number of DDDs between VM and probable VM subjects. RESULTS: Sixty-six subjects were included, with an average of 29 days of pre-intervention data (SD = 1.4). The average number of days with no dizziness was 3.5 (SD = 6.5), mild dizziness was 9.1 (SD = 6.7), moderate dizziness was 11 (SD = 6.1), and severe dizziness was 5.4 (SD = 6.3). Out of the 66 patients, 52 were classified as VM and 14 as pVM. The average number of DDDs was not significantly different between VM (17.0, SD = 8.3) and pVM (15.3, SD = 10.0) patients, with a two-tailed p-value of 0.44. CONCLUSION: With EMA, we found that the average subject with VM had some degree of dizziness almost every day, and more than 15 DDDs per month. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

Piloting Home Produce Delivery to Improve Food Security, Budget, and Diet in Families with Children: A Mixed-Methods Study.

BACKGROUND: Few children in food insecure (FI) households meet dietary recommendations for fruit and vegetables ("produce"). Barriers include affordability, accessibility, and desirability. Home produce delivery may reduce FI, increase produce consumption, and decrease budget tradeoffs. OBJECTIVE: Evaluate the acceptability and potential impact of delivering produce through home visiting programs on FI, diet, and budget tradeoffs. METHODS: In this prospective pre/post mixed methods study, 51 parents engaged in home visiting programs were enrolled. Participants completed pre- and post-program surveys on FI (18-item Food Security Scale), produce consumption, and budget tradeoffs. Pre- and post-surveys were compared using McNemar's test and weighted kappas. Interview guides were based on Social Cognitive Theory and a previously published framework. Interviews were conducted in English or Spanish; thematic analysis was completed. RESULTS: Twenty-nine (56.9%) participants completed both surveys. Most were female (96.3%) and Hispanic (79.3%) (Table 1). Food security improved in the post-period, with more participants reporting high food security (pre: 6.9%, post: 31.0%) and fewer reporting very low food security (pre: 20.7%, post: 6.9%, p<0.01) (Table 2). Budgetary tradeoffs decreased in the post-program period (pre: 71.4%, post: 48.1%, p=0.03). Fifteen participants were interviewed. Themes included 1) saved money, 2) increased fruit and vegetable consumption, and 3) interest in future participation. CONCLUSION: This pilot study found that an intervention for delivery of produce through home visiting programs was acceptable to participants and resulted in potential improvements in FI and household budgets. This supports future studies to further explore the impact of this novel intervention. WHAT'S NEW: In this prospective mixed-methods pilot, home delivered produce was acceptable and feasible with potentially improved food security and household budgets; evidence of potential change in produce consumption was mixed. Changes in budget tradeoffs is a novel outcome in food programs.

Time to Functional Loss as an Endpoint in Huntington's Disease Trials: Enrichment and Sample Size.

BACKGROUND: Clinical trial scenarios can be modeled using data from observational studies, providing critical information for design of real-world trials. The Huntington's Disease Integrated Staging System (HD-ISS) characterizes disease progression over an individual's lifespan and allows for flexibility in the design of trials with the goal of delaying progression. Enrichment methods can be applied to the HD-ISS to identify subgroups requiring smaller estimated sample sizes. OBJECTIVE: Investigate time to the event of functional decline (HD-ISS Stage 3) as an endpoint for trials in HD and present sample size estimates after enrichment. METHODS: We classified individuals from observational studies according to the HD-ISS. We assessed the ability of the prognostic index normed (PIN) and its components to predict time to HD-ISS Stage 3. For enrichment, we formed groups from deciles of the baseline PIN distribution for HD-ISS Stage 2 participants. We selected enrichment subgroups closer to Stage 3 transition and estimated sample sizes, using delay in the transition time as the effect size. RESULTS: In predicting time to HD-ISS Stage 3, PIN outperforms its components. Survival curves for each PIN decile show that groups with PIN from 1.48 to 2.74 have median time to Stage 3 of approximately 2 years and these are combined to create enrichment subgroups. Sample size estimates are presented by enrichment subgroup. CONCLUSIONS: PIN is predictive of functional decline. A delay of 9 months or more in the transition to Stage 3 for an enriched sample yields feasible sample size estimates, demonstrating that this approach can aid in planning future trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical Utility of Plasma Microbial Cell-Free DNA Sequencing Among Immunocompromised Patients With Pneumonia.

Background: Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit. Methods: We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies. This is a secondary analysis of an expanded cohort that evaluated the clinical utility of plasma mcfDNA sequencing across prespecified and adjudicated outcomes. We examined the percentage of participants for whom plasma mcfDNA sequencing identified a probable cause of pneumonia or clinically relevant nonpneumonia infection. We then assessed potential changes in antimicrobial therapy based on plasma mcfDNA sequencing results and the potential for early mcfDNA testing to avoid bronchoscopy and its associated adverse events. Results: Of 223 participants, at least 1 microbial detection by plasma mcfDNA sequencing was adjudicated as a probable cause of pneumonia in 57 (25.6%) and a clinically relevant nonpneumonia infection in 88 (39.5%). A probable cause of pneumonia was exclusively identified by plasma mcfDNA sequencing in 23 (10.3%) participants. Antimicrobial therapy would have changed for 41 (18.4%) participants had plasma mcfDNA results been available in real time. Among the 57 participants with a probable cause of pneumonia identified by plasma mcfDNA sequencing, bronchoscopy identified no additional probable cause of pneumonia in 52 (91.2%). Conclusions: Plasma mcfDNA sequencing could improve management of both pneumonia and other concurrent infections in immunocompromised patients with suspected pneumonia.

Initial experience and patient tolerance of proton stereotactic body radiotherapy.

Purpose: To review our initial experience with proton-based SBRT to evaluate the planning outcomes and initial patient tolerance of treatment. Patients and methods: From Sep. 2019 to Dec. 2020, 52 patients were treated with proton SBRT to 62 lesions. Fractionation varied by indication and site with a median of 5 fractions and median fractional dose of 8 Gy. Planning outcomes, including plan heterogeneity, conformity, and PTV volume receiving 100% of the prescription dose (PTV V100%) were evaluated. Acute toxicities were prospectively recorded, and patient reported outcomes were assessed prior to and at completion of treatment using the MD Anderson Symptom Inventory (MDASI) and EQ-5D5L visual analogue score (VAS). Results: All treated patients completed their course of proton-based SBRT. The mean conformity index was 1.05 (range 0.51-1.48). R50% values were comparable to ideal photon parameters. PTV V100% was 89.9% on average (40.44% - 99.76%). 5 patients (10%) required plan modification due to setup or tumor changes. No patients developed a new grade 3 or greater toxicity during treatment. Comparing pretreatment to end of treatment timepoints, there was a significant improvement in the mean VAS (65 to 75, p = 0.014), with no significant change in the mean MDASI symptom (1.7, 1.8; p = 0.79) or interference (2.3, 2.4; p = 0.452) scores. Conclusion: Proton-based SBRT can achieve dosimetric goals required by major clinical photon trials. It was well-tolerated with no decrement in patient reported outcomes and a mean 10-point improvement in VAS at the conclusion of SBRT. Further follow-up is necessary for tumor control and late effects analysis.

Feasibility of intentional bioprosthetic valve fracture in the tricuspid position.

BACKGROUND: Transcatheter tricuspid valve-in-valve (ViV) replacement has yielded good hemodynamic outcomes in the treatment of dysfunctional bioprosthetic valves (BPVs). Intentional fracture of certain rigid BPV frames, if feasible, allows a larger implanted valve when compared with implant into an unfractured BPV. There remains limited data on the feasibility of tricuspid valve frame fracture. AIMS: Evaluate the feasibility of transcatheter tricuspid ViV replatement with fracture of the underlying BPV ring. METHODS: An international multicenter registry of tricuspid ViV replacement with intentional tricuspid valve frame fracture was created. Demographic data along with procedural characteristics, outcomes, and follow-up data were collected. Comparison was made to the pre- and post-ViV replacement with fracture of the tricuspid valve frame conditions. RESULTS: Ten patients from six centers were included with a median age and weight of 29 years and 67.3 kg respectively. Tricuspid valve frame fracture was performed using a median balloon diameter 3 mm (IQR 3-5) larger than the true inner diameter (ID). The final ID was a mean of 1.5 mm (95% CI: 0.35, 2.64: p < 0.05), and median 1.1 mm (0.5, 2.1) larger than the reported true ID of the surgical BPV after ViV replacement. The mean tricuspid inflow gradient by echocardiogram decreased by 6.65 mmHg (95% CI: 4.14, 9.15: p < 0.001). All procedures were without complication, specifically there was no heart block, pericardial effusion, or right coronary disruption. CONCLUSION: Intentional tricuspid valve frame fracture with tricuspid ViV replacement is feasible and can increase the valve orifice potentially reducing the risk of ViV patient prosthesis mismatch and is not associated with significant complications.

Bioabsorbable, subcutaneous naltrexone implants mitigate fentanyl-induced respiratory depression at 3 months-A pilot study in male canines.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 µg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 µg/kg, 60 µg/kg, 90 µg/kg, and 120 µg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 µg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 µg/kg and especially at 120 µg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.

Mafic slab melt contributions to Proterozoic massif-type anorthosites.

Massif-type anorthosites, enormous and enigmatic plagioclase-rich cumulate intrusions emplaced into Earth's crust, formed in large numbers only between 1 and 2 billion years ago. Conflicting hypotheses for massif-type anorthosite formation, including melting of upwelling mantle, lower crustal melting, and arc magmatism above subduction zones, have stymied consensus on what parental magmas crystallized the anorthosites and why the rocks are temporally restricted. Using B, O, Nd, and Sr isotope analyses, bulk chemistry, and petrogenetic modeling, we demonstrate that the magmas parental to the Marcy and Morin anorthosites, classic examples from North America's Grenville orogen, require large input from mafic melts derived from slab-top altered oceanic crust. The anorthosites also record B isotopic signatures corresponding to other slab lithologies such as subducted abyssal serpentinite. We propose that anorthosite massifs formed underneath convergent continental margins wherein a subducted or subducting slab melted extensively and link massif-type anorthosite formation to Earth's thermal and tectonic evolution.

Alteration of Neuropilin-1 and Heparan Sulfate Interaction Impairs Murine B16 Tumor Growth.

Neuropilin-1 acts as a coreceptor with vascular endothelial growth factor receptors to facilitate binding of its ligand, vascular endothelial growth factor. Neuropilin-1 also binds to heparan sulfate, but the functional significance of this interaction has not been established. A combinatorial library screening using heparin oligosaccharides followed by molecular dynamics simulations of a heparin tetradecasaccharide suggested a highly conserved binding site composed of amino acid residues extending across the b1 and b2 domains of murine neuropilin-1. Mutagenesis studies established the importance of arginine513 and lysine514 for binding of heparin to a recombinant form of Nrp1 composed of the a1, a2, b1, and b2 domains. Recombinant Nrp1 protein bearing R513A,K514A mutations showed a significant loss of heparin-binding, heparin-induced dimerization, and heparin-dependent thermal stabilization. Isothermal calorimetry experiments suggested a 1:2 complex of heparin tetradecasaccharide:Nrp1. To study the impact of altered heparin binding in vivo, a mutant allele of Nrp1 bearing the R513A,K514A mutations was created in mice (Nrp1D) and crossbred to Nrp1+/- mice to examine the impact of altered heparan sulfate binding. Analysis of tumor formation showed variable effects on tumor growth in Nrp1D/D mice, resulting in a frank reduction in tumor growth in Nrp1D/- mice. Expression of mutant Nrp1D protein was normal in tissues, suggesting that the reduction in tumor growth was due to the altered binding of heparin/heparan sulfate to neuropilin-1. These findings suggest that the interaction of neuropilin-1 with heparan sulfate modulates its stability and its role in tumor formation and growth.

Demographics, utilization, workflow and outcomes based on observational data from the RSNA-ACR 3D Printing Registry.

OBJECTIVE: To report data from the first three years of operation of the RSNA-ACR 3D Printing Registry. METHODS: Data from June 2020 to June 2023 was extracted, including demographics, indications, workflow and user assessments. Clinical indications were stratified by 12 organ systems. Imaging modalities, printing technologies and number of parts per case were assessed. Effort data was analyzed, dividing staff into provider and non-provider categories. The opinions of clinical users were evaluated through a Likert-scale questionnaire, and estimates of procedure time saved were collected. RESULTS: A total of 20 sites and 2,637 cases were included, consisting of 1,863 anatomic models and 774 anatomic guides. Mean patient age for models and guides was 42.4 ± 24.5 years and 56.3 ± 18.5 years respectively. Cardiac models were the most common type of models (27.2%), and neurologic guides were the most common type of guides (42.4%). Material jetting, vat photopolymerization and material extrusion were the most common printing technologies used overall (85.6% of all cases). On average, providers spent 92.4 minutes and non-providers spent 335.0 minutes per case. Providers spent most time on consultation (33.6 minutes), while non-providers focused most on segmentation (148.0 minutes). Confidence in treatment plans increased after using 3D printing (p<.001). Estimated procedure time savings for 155 cases was 40.5 ± 26.1 minutes. CONCLUSION: 3D printing is performed in healthcare facilities for many clinical indications. The registry provides insight into the technologies and workflows used to create anatomic models and guides, and the data shows clinical benefits from 3D printing.

Use of Hybrid Stage I to Stratify Between Single Ventricle Palliation and Biventricular Repair.

Background: Hybrid stage I palliation (HS1P) has been utilized for patients with single ventricle (SV) congenital heart disease (CHD). To date, reports on the use of HS1P for other indications including biventricular (BiV) CHD have been limited. Methods: We performed a single-center retrospective cohort study of patients who underwent HS1P with an anticipated physiologic outcome of BiV repair, or with an undetermined SV versus BiV outcome. Patient characteristics and outcomes from birth through definitive repair or palliation were collected and reported with descriptive statistics. Results: Nineteen patients underwent HS1P with anticipated BiV repair. Extracardiac and intracardiac risk factors (ICRF) were common. Ultimately, 13 (68%) patients underwent BiV repair, 1 (5%) underwent SV palliation, and 5 (26%) died prior to further palliation or repair. Resolution of ICRF tracked with BiV outcome (6/6, 100%), persistence of ICRF tracked with SV outcome or death (3/3, 100%). Twenty patients underwent HS1P with an undetermined outcome. Ultimately, 13 (65%) underwent BiV repair, 6 (30%) underwent SV palliation, and 1 (5%) underwent transplant. There were no deaths. Intracardiac risk factors were present in 15 of 20 patients (75%); BiV repair only occurred when all ICRF resolved (67%). Post-HS1P complications and reinterventions occurred frequently in both groups, through all phases of care. Conclusions: Hybrid stage 1 palliation can be used to defer BiV repair and to delay decision between SV palliation and BiV repair. Resolution of ICRF was associated with ultimate outcome. In this high-risk group, complications are common, and mortality especially in the marginal BiV patient is high.

Localized intratumoral delivery of immunomodulators for oral cancer and oral potentially malignant disorders.

Immunotherapy has developed into an important modality of modern cancer treatment. Unfortunately, checkpoint inhibitor immunotherapies are currently delivered systemically and require frequent administration, which can result in toxicity and severe, sometimes fatal, adverse events. Localized delivery of immunomodulators for oral cancer and oral potentially malignant disorders offers the promise of maximum therapeutic potential and reduced systemic adverse effects. This review will discuss the limitations of current standard-of-care systemic therapies and highlight research advances in localized, intratumoral delivery platforms for immunotherapy for oral cancer and oral potentially malignant disorders.

Gait Training Interventions for Individuals with Chronic Ankle Instability: A Systematic Review & Meta-Analysis.

OBJECTIVE: This review aimed to determine if gait training interventions influence lower extremity biomechanics during walking in individuals with chronic ankle instability (CAI). METHODS: A literature search was conducted in PubMed, CINAHL, SPORTDiscus, and MEDLINE to identify English-language studies from inception through September 2022. Eligible studies included randomized control trials, repeated measures design, and descriptive laboratory studies measuring the effects during or following a gait training intervention on biomechanical outcomes (kinematics, kinetics, electromyography) during walking in individuals with CAI. Gait training interventions were broadly categorized into devices (destabilization devices, novel gait training device) and biofeedback (visual, auditory, and haptic delivery modes). Meta-analyses were conducted when appropriate using random-effects to compare pre-and post- gait training intervention mean differences and standard deviations. RESULTS: Thirteen studies were included. Meta-analyses were conducted for single session gait training studies only. Eleven studies reported kinetic outcomes. Our meta-analyses showed location of center of pressure (COP) was shifted medially from 0-90% (Effect Size [ES] range=0.35-0.82) of stance, contact time was decreased in medial forefoot (ES=0.43), peak pressure was decreased for lateral midfoot (ES=1.18) and increased for hallux (ES=0.59), pressure time integral was decreased for lateral heel (ES=0.33) and lateral midfoot (ES=1.22) and increased for hallux (ES=0.63). Three studies reported kinematic outcomes. Seven studies reported electromyography outcomes. Our meta-analyses revealed increased activity following initial contact (IC) for fibularis longus (ES=0.83). CONCLUSIONS: Gait training protocols improved some lower extremity biomechanical outcomes in individuals with CAI. Plantar pressure outcome measures seem to be most impacted by gait training programs with improvements in decreasing lateral pressure associated with increased risk for lateral ankle sprains. Gait training increased EMG activity post-IC for the fibularis longus. Few studies have assessed the impact of multi-session gait training on biomechanical outcome measures. Targeted gait trainning should be considered when treating patients with CAI.

Observed declines in body size have differential effects on survival and recruitment, but no effect on population growth in tropical birds.

Declines in body size can be an advantageous physiological response to warming temperatures, or a result of physiological and nutritional stress. Either way, studies often assume that these climate-induced trait changes have important implications for fitness and demography. We leveraged almost three decades of capture-mark-recapture data of 51 bird species in Panama to examine if body size has changed through time, how sensitive body size is to changes in weather, and if body size impacts population demography. We evaluated two metrics of body size, structural size (wing length), and body condition (residual body mass). Over the study, wing length changed in varying directions for 88% of species (23 decrease, 22 increase), but the effects were weak, and change was only significant for two species. Conversely, body condition declined for 88% of species (45), effects were stronger, and that change was significant for 22% of species (11). This suggests that nutritional stress is likely the cause of changes in body size, not an adaptive response to warming. Precipitation metrics impacted body condition across three of our four feeding guilds, while wing length was only impacted by weather metrics for two guilds. This suggests that body condition is more sensitive to change in weather metrics compared to wing length. Lastly, we found that the impact of changes in body size on survival and recruitment was variable across species, but these relationships were in the opposite direction, ultimately resulting in no change in population growth for all but one species. Thus, while different stages (adult survival and recruitment) of populations may be impacted by body size, populations appear to be buffered from changes. The lack of an effect on population growth rate suggests that populations may be more resilient to changes in body size, with implications for population persistence under expected climate change.

The Effects of Slow Breathing during Inter-Set Recovery on Power Performance in the Barbell Back Squat.

Slow breathing (SB) reduces sympathetic nervous system activity, the heart rate (HR), and blood pressure (BP) and increases parasympathetic nervous system activity, HR variability, and oxygen saturation which may lead to quicker recovery between bouts of exercise. Therefore, the purpose of this study was to examine whether a SB technique using the 4-7-8 method between sets of barbell back squats (SQs) would attenuate drops in power and bar velocity. In a randomized, crossover design, 18 healthy resistance-trained college-aged males (age: 20.7 ± 1.4 years, body height: 178.6 ± 6.4 cm, body mass: 82.2 ± 15.0 kg, 4.5 ± 2.4 years of experience) performed 5 sets of 3 repetitions of SQs with normal breathing (CON) or SB during the 3-min recovery between sets. Peak and average power and bar velocity were assessed using a linear positioning transducer. HR recovery (RHR), systolic BP recovery (RBP), the rating of perceived exertion (RPE) and the rating of perceived recovery score (RS) were assessed after each set. There were no significant differences between conditions for peak and average power and bar velocity, RBP, RPE, and RS (p > 0.211). SB led to a greater RHR after set 2 (SB: 51.0 ± 14.9 bpm vs. CON: 44.5 ± 11.5 bpm, p = 0.025) and 3 (SB: 48.3 ± 13.5 bpm vs. CON: 37.7 ± 11.7 bpm, p = 0.006) compared to the CON condition. SB was well tolerated, did not hinder nor improve training performance and improved RHR after the middle sets of SQs. Further investigations are warranted to examine the effects of other SB techniques and to determine SB's effects on different training stimuli as well as its effects over an entire workout and post-workout recovery metrics.