Nanodepots Encapsulating a Latency Reversing Agent and Broadly Neutralizing Antibody Enhance Natural Killer Cell Cytotoxicity Against an in vitro Model of Latent HIV.

Purpose: Current antiretroviral therapies (ART) for human immunodeficiency virus (HIV) are not curative, as the virus persists in latent reservoirs, requiring lifelong adherence to ART and increasing the risk of co-morbidities. "Shock and kill" approaches to reactivate HIV from latent reservoirs followed by administration of anti-HIV drugs represent a promising strategy for eradicating latent HIV. To achieve effective shock and kill, we describe a strategy to eradicate the HIV reservoir that combines latency reversing agents (LRAs), broadly neutralizing antibodies (bnAbs), and natural killer (NK) cells. This strategy utilizes a polymer nanodepot (ND) that co-encapsulates the LRA and bnAb to reactivate latent infection and elicit enhanced cytotoxicity from co-administered NK cells. Methods: Poly(lactic-co-glycolic acid) (PLGA) NDs were synthesized using the nanoprecipitation method to co-encapsulate an LRA (TNF-α) and a bnAb (3BNC117) (TNF-α-3BNC117-NDs). ACH-2 cells were used as a cellular model of latent HIV infection. An NK92 subline, genetically modified to constitutively express the Fc receptor CD16, was administered to ACH-2 cells in combination with TNF-α-3BNC117-NDs. ACH-2 cell death and extracellular p24 were measured via flow cytometry and ELISA, respectively. Results: Stable PLGA NDs co-encapsulated TNF-α and 3BNC117 with high efficiencies and released these agents in physiological conditions. NK92 phenotype remained similar in the presence of TNF-α-3BNC117-NDs. TNF-α released from NDs efficiently reactivated HIV in ACH-2 cells, as measured by a 3.0-fold increase in the frequency of intracellular p24 positive cells. Released 3BNC117 neutralized and bound reactivated virus, targeting 57.5% of total ACH-2 cells. Critically, TNF-α-3BNC117-NDs significantly enhanced NK92 cell-mediated killing of ACH-2 cells (1.9-fold) and reduced extracellular levels of p24 to baseline. Conclusion: These findings suggest the therapeutic potential of our novel ND-based tripartite strategy to reactivate HIV from latently infected cells, generate an HIV-specific site for bnAb binding, and enhance the killing of reactivated HIV-infected target cells by NK92 cells.

Vestibular reflexes in essential tremor: abnormalities of ocular and cervical vestibular-evoked myogenic potentials are associated with the cerebellum and brainstem involvement.

This study utilized cervical vestibular-evoked myogenic potentials tests (cVEMP) and ocular vestibular-evoked myogenic potentials tests (oVEMP) to investigate the vestibulocollic and vestibuloocular reflex arcs and to evaluate cerebellar and brainstem involvement) in essential tremor (ET). Eighteen cases with ET and 16 age- and gender-matched healthy control subjects (HCS) were included in the present study. Otoscopic and neurologic examinations were performed on all participants, and both cervical and ocular VEMP tests were performed. Pathological cVEMP results were increased in the ET group (64.7%) compared to the HCS (41,2%; p > 0.05). The latencies of P1 and N1 waves were shorter in the ET group than in HCS (p = 0.01 and p = 0.001). Pathological oVEMP responses were significantly higher in the ET group (72.2%) compared to the HCS (37.5%; p = 0.01). There was no statistically significant difference in oVEMP N1-P1 latencies between groups (p > 0.05). Because the ET group had high pathological responses to the oVEMP, but not the cVEMP, the upper brainstem pathways may be more affected by ET.

Limb positioning and magnitude of postural tremor ratings: A study of 100 essential tremor cases.

BACKGROUND: Essential tremor (ET) is a highly prevalent movement disorder. As the diagnosis is purely clinical, it is important for clinicians to develop a reliable taxonomy of signs and symptoms of ET. Here, we investigate two common clinical maneuvers for determining the presence and severity of postural tremor in ET cases: the evaluation of tremor observed when arms are held in the outstretched and wing posture positions. METHODS: Two movement disorders neurologists assessed tremor severity from videotaped neurological evaluations of 100 ET cases displaying outstretched and wing posture positions. These raters also completed a forced choice measure indicating whether upper limb tremor was more severe in the outstretched position, the wing posture position, or equivalent in the two positions. RESULTS: Our raters judged tremor observed in the wing posture position to be more severe than tremor observed in the outstretched position (average ratings of 1.17 and 1.03, respectively, p's <0.05). This finding replicated across the two independent neurologists' ratings of tremor severity. Analyses of the forced choice measure revealed parallel results, with tremor observed in the wing posture position more often identified as more severe than tremor observed in the outstretched position (37.5% versus 14.5%, respectively, p < 0.05). CONCLUSION: Our data reveal that ET cases generally display more severe upper limb tremor in the wing posture position than in the outstretched position. These findings having potential clinical and research implications, suggesting that postural tremor in ET may be more easily identified from observations of the wing posture than the outstretched position.

Novel treatment for hypotonic airway obstruction and severe obstructive sleep apnea using a nasopharyngeal airway device with 3D printing innovation.

STUDY OBJECTIVES: Pediatric obstructive sleep apnea impacts child and familial well-being. Airway management in patients with hypotonic pharyngeal conditions is complex. Some patients may benefit from continuous positive airway pressure or bilevel positive airway pressure, others may require further invasive measures for treatment. There is critical need for treatment alternatives for patients with pharyngeal hypotonia. METHODS: This is a retrospective case series. Collaboratively with patients, families, biomedical engineers, and medical professionals, a long-term nasopharyngeal airway (NPA) was created to bypass upper airway obstruction. Two patients used a safety pin and tape attachment, and two patients used a novel 3D-printed, self-supporting nasal securement. All 4 patients had polysomnography before and during NPA use. Paired 1-tailed t-tests were conducted to compare apnea-hypopnea index, hypopnea index, obstructive index, and oxygen nadir. RESULTS: Compared to baseline polysomnography, repeat polysomnography with the NPA in place demonstrated statistically significant improvement for apnea-hypopnea index (75.8 ± 36.6 events/h to 8.9 ± 2.9 events/h, P = .03), hypopnea index (45.4 ± 25.8 events/h to 7.7 ± 3.2 events/h, P = .04), and oxygen saturation nadir (60.3 ± 13.0% to 79.3 ± 8.7%, P = .01). The NPA had been used for over 1 year in 3 of the 4 children. Those using the safety pin and tape did report skin irritation due to adhesive required to keep device in place. CONCLUSIONS: Current management of severe upper airway obstruction and obstructive sleep apnea in hypotonic pharyngeal conditions requires a team-based approach to care. A long-term NPA device may be an alternative or temporizing option to continuous positive airway pressure, upper airway surgery, or tracheostomy in children with pharyngeal hypotonia and severe obstructive sleep apnea. Larger studies of this approach are underway to assess efficacy in a range of obstructive sleep apnea severity in this population. CITATION: Powell AR, Srinivasan S, Helman JL, et al. Novel treatment for hypotonic airway obstruction and severe obstructive sleep apnea using a nasopharyngeal airway device with 3D printing innovation. J Clin Sleep Med. 2022;18(10):2497-2502.

The generation and application of antigen-specific T cell therapies for cancer and viral-associated disease.

Immunotherapy with antigen-specific T cells is a promising, targeted therapeutic option for patients with cancer as well as for immunocompromised patients with virus infections. In this review, we characterize and compare current manufacturing protocols for the generation of T cells specific to viral and non-viral tumor-associated antigens. Specifically, we discuss: (1) the different methodologies to expand virus-specific T cell and non-viral tumor-associated antigen-specific T cell products, (2) an overview of the immunological principles involved when developing such manufacturing protocols, and (3) proposed standardized methodologies for the generation of polyclonal, polyfunctional antigen-specific T cells irrespective of donor source. Ex vivo expanded cells have been safely administered to treat numerous patients with virus-associated malignancies, hematologic malignancies, and solid tumors. Hence, we have performed a comprehensive review of the clinical trial results evaluating the safety, feasibility, and efficacy of these products in the clinic. In summary, this review seeks to provide new insights regarding antigen-specific T cell technology to benefit a rapidly expanding T cell therapy field.

The Michigan Plan for Appropriate Tailored Healthcare in Pregnancy Prenatal Care Recommendations.

OBJECTIVE: To describe MiPATH (the Michigan Plan for Appropriate Tailored Healthcare in pregnancy) panel process and key recommendations for prenatal care delivery. METHODS: We conducted an appropriateness study using the RAND Corporation and University of California Los Angeles Appropriateness Method, a modified e-Delphi process, to develop MiPATH recommendations using sequential steps: 1) definition and scope of key terms, 2) literature review and data synthesis, 3) case scenario development, 4) panel selection and scenario revisions, and 5) two rounds of panel appropriateness ratings with deliberation. Recommendations were developed for average-risk pregnant individuals (eg, individuals not requiring care by maternal-fetal medicine specialists). Because prenatal services (eg, laboratory tests, vaccinations) have robust evidence, panelists considered only how services are delivered (eg, visit frequency, telemedicine). RESULTS: The appropriateness of key aspects of prenatal care delivery across individuals with and without common medical and pregnancy complications, as well as social and structural determinants of health, was determined by the panel. Panelists agreed that a risk assessment for medical, social, and structural determinants of health should be completed as soon as individuals present for care. Additionally, the panel provided recommendations for: 1) prenatal visit schedules (care initiation, visit timing and frequency, routine pregnancy assessments), 2) integration of telemedicine (virtual visits and home devices), and 3) care individualization. Panelists recognized significant gaps in existing evidence and the need for policy changes to support equitable care with changing practices. CONCLUSION: The MiPATH recommendations offer more flexible prenatal care delivery for average-risk individuals.

A Review of Prenatal Care Delivery to Inform the Michigan Plan for Appropriate Tailored Healthcare in Pregnancy Panel.

OBJECTIVE: To perform a literature review of key aspects of prenatal care delivery to inform new guidelines. DATA SOURCES: A comprehensive review of Ovid MEDLINE, Elsevier's Scopus, Google Scholar, and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We included studies addressing components of prenatal care delivery (visit frequency, routine pregnancy assessments, and telemedicine) that assessed maternal and neonatal health outcomes, patient experience, or care utilization in pregnant individuals with and without medical conditions. Quality was assessed using the RAND/UCLA Appropriateness Methodology approach. Articles were independently reviewed by at least two members of the study team for inclusion and data abstraction. TABULATION, INTEGRATION, AND RESULTS: Of the 4,105 published abstracts identified, 53 studies met inclusion criteria, totaling 140,150 participants. There were no differences in maternal and neonatal outcomes among patients without medical conditions with reduced visit frequency schedules. For patients at risk of preterm birth, increased visit frequency with enhanced prenatal services was inconsistently associated with improved outcomes. Home monitoring of blood pressure and weight was feasible, but home monitoring of fetal heart tones and fundal height were not assessed. More frequent weight measurement did not lower rates of excessive weight gain. Home monitoring of blood pressure for individuals with medical conditions was feasible, accurate, and associated with lower clinic utilization. There were no differences in health outcomes for patients without medical conditions who received telemedicine visits for routine prenatal care, and patients had decreased care utilization. Telemedicine was a successful strategy for consultations among individuals with medical conditions; resulted in improved outcomes for patients with depression, diabetes, and hypertension; and had inconsistent results for patients with obesity and those at risk of preterm birth. CONCLUSION: Existing evidence for many components of prenatal care delivery, including visit frequency, routine pregnancy assessments, and telemedicine, is limited.

Symptom Prevalence and Genotype-Phenotype Correlations in Patients With TANGO2-Related Metabolic Encephalopathy and Arrhythmias (TRMEA).

BACKGROUND: TANGO2-related metabolic encephalopathy and arrhythmias (TRMEA) is a rare, phenotypically heterogeneous, neurological disease affecting children. METHODS: We conducted a chart review of five children with molecularly confirmed TRMEA diagnosed at our institution and compiled pathogenic variant frequency and symptom prevalence from cases previously reported in the literature. RESULTS: Including those patients in our case series, 76 patients with TRMEA have been described. Developmental delay (93%) and/or regression (71%), spasticity (78%), and seizures (57%) are common in TRMEA and frequently precede life-threatening symptoms such as metabolic decompensation with lactic acidosis (83%), cardiomyopathy (38%), and cardiac arrhythmias (68%). Deletion of exons 3 to 9 is the most common pathogenic variant (39% of alleles). The majority of reported intragenic variants (17 of 27) result in disruption of the reading frame, and no clear genotype-phenotype correlations could be identified for those variants wherein the reading frame is maintained, highlighting instead the variable expressivity of the disease. CONCLUSIONS: Patients with TRMEA frequently experience life-threatening complications that are preceded by common neurological symptoms underscoring the need for pediatric neurologists to be familiar with this condition. Additional work pertaining to disease pathophysiology and potential therapeutics is needed.

Simulation of Cerebrospinal Fluid Leak Repair Using a 3-Dimensional Printed Model.

BACKGROUND: Acquiring proficiency for the repair of a cerebrospinal fluid (CSF) leak is challenging in great part due to its relative rarity, which offers a finite number of training opportunities. OBJECTIVE: The purpose of this study was to evaluates the use of a 3-dimensional (3D) printed, anatomically accurate model to simulate CSF leak closure. METHODS: Volunteer participants completed two simulation sessions. Questionnaires to assess their professional qualifications and a standardized 5-point Likert scale to estimate the level of confidence, were completed before and after each session. Participants were also queried on the overall educational utility of the simulation. RESULTS: Thirteen otolaryngologists and 11 neurosurgeons, met the inclusion criteria. A successful repair of the CSF leak was achieved by 20/24 (83.33%), and 24/24 (100%) during the first and second simulation sessions respectively (average time 04:04 ± 1.39 and 02:10 ± 01:11). Time-to-close-the-CSF-leak during the second session was significantly shorter than the first (p < 0.001). Confidence scores increased across the training sessions (3.3 ± 1.0, before the simulation, 3.7 ± 0.6 after the first simulation, and 4.2 ± 0.4 after the second simulation; p < 0.001). All participants reported an increase in confidence and believed that the model represented a valuable training tool. CONCLUSIONS: Despite significant differences with varying clinical scenarios, 3D printed models for cerebrospinal leak repair offer a feasible simulation for the training of residents and novice surgeons outside the constrictions of a clinical environment.

Addressing the Pandemic Training Deficiency: Filling the Void with Simulation in Facial Reconstruction.

OBJECTIVE/HYPOTHESIS: To assess the use of a three-dimensional (3D) printed, multilayer facial flap model for use in trainee education as an alternative method of teaching surgical techniques of facial reconstruction. STUDY DESIGN: Cohort study. METHODS: A 3D printed facial flap simulator was designed from a computed tomography scan and manufactured out of silicone for low-cost, high-fidelity simulation. This simulator was tested by a group of Otolaryngology-Head and Neck Surgery trainees at a single institution. The simulator group was compared to a control group who completed an exercise on a traditional paper facial flap exercise. Both groups underwent didactic lectures prior to completing their respective exercises. Pre- and post-exercise Likert scale surveys measuring experience, understanding, effectiveness, and realism were completed by both groups. Central tendency, variability, and confidence intervals were measured to evaluate the outcomes. RESULTS: Trainees completing the facial flap simulator reported a statistically significant (p < 0.05) improvement in overall expertise in facial flap procedures, design of facial flaps, and excision of standing cutaneous deformities. No statistically significant improvement was seen in the control group. CONCLUSIONS: Trainees found the facial flap simulator to be an effective and useful training tool with a high level of realism in surgical education of facial reconstruction. Surgical simulators can serve as an adjunct to trainee education, especially during extraordinary times such as the novel coronavirus disease 2019 pandemic, which significantly impacted surgical training. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2444-E2448, 2021.

Development of a novel mandibular distraction osteogenesis simulator using Computer Aided Design and 3D printing.

INTRODUCTION: Micrognathia, a component of Robin Sequence, can cause glossoptosis, failure of palatal fusion, and critical obstruction of the airway. Mandibular distraction osteogenesis (MDO) is at times offered to anteriorly translate the mandible and tongue, relieving airway obstruction. MDO is an intricate reconstructive procedure that may be ideal for teaching using a high-fidelity educational simulator, allowing early hands-on experience in a zero-risk environment. OBJECTIVES: To design a novel, low-cost, high-fidelity neonatal MDO simulator that can be used for trainee education and refinement of surgical technique. METHODS: A novel MDO simulator was developed using additive manufacturing techniques. Three experts in MDO surgery completed a 20-item survey, rating the simulator's physical attributes, the realism of experience, the simulator's value, its relevance to practice and the surgeon's ability to perform tasks on a 4-point Likert scale. RESULTS: Computer Aided Design (CAD) and 3D printing allowed for the production of a realistic surgical simulator that emulates important aspects of MDO surgery. This preliminary evaluation indicated adequate means across the five domains relevant to the simulator's fidelity and usability (M = 3.33 to 3.75) out of a maximum of 4 points. Lowest rated items were consistent with expert comments allowing future refinement on subsequent iterations. Consumable material costs per model were $9.39 USD. CONCLUSIONS: The MDO model demonstrated adequate fidelity and holds promise as a skill-development tool for surgeons in training. Further studies are planned to determine its utility as a training and assessment tool.

Simulation of Pediatric Anterior Skull Base Anatomy Using a 3D Printed Model.

OBJECTIVE: The pediatric skull base may present anatomic challenges to the skull base surgeon, including limited sphenoid pneumatization and a narrow nasal corridor. The rare nature of pediatric skull base pathology makes it difficult to gain experience with these anatomic challenges. The objective of this study was to create a 3-dimensionally (3D) printed model of the pediatric skull base and assess its potential as a training tool. METHODS: Twenty-eight participants at various stages of training and practice were included in our study. They completed a pre- and postdissection questionnaire assessing challenges with endoscopic endonasal skeletonization of the carotid arteries and sella face using the 3D printed model. RESULTS: The majority of participants had completed a skull base surgery fellowship (60.7%), were <5 years into practice (60.7%), and had <10 cases of pediatric skull base experience (82.1%). Anticipated challenges included limitation of maneuverability of instruments (71.4%), narrow nasal corridor and nonpneumatized bone (57.1%). On a scale of 0-10, 10 being very difficult, the average participant expected level of difficulty with visualization was 6.89 and expected level of difficulty with instrumentation was 7.3. On postdissection assessment, there was a nonstatistically significant change to 6.93 and 7.5, respectively. Participants endorsed on a scale of 0-10, 10 being very realistic, an overall model realism of 7.0 and haptic realism of 7.1. CONCLUSIONS: A 3D printed model of the pediatric skull base may provide a realistic model to help participants gain experience with anatomic limitations characteristic of the pediatric anterior skull base.

Multi-institutional Comparison of Temporal Bone Models: A Collaboration of the AAO-HNSF 3D-Printed Temporal Bone Working Group.

OBJECTIVE: The American Academy of Otolaryngology-Head and Neck Surgery Foundation's (AAO-HNSF's) 3D-Printed Temporal Bone Working Group was formed with the goal of sharing information and experience relating to the development of 3D-printed temporal bone models. The group conducted a multi-institutional study to directly compare several recently developed models. STUDY DESIGN: Expert opinion survey. SETTING: Temporal bone laboratory. METHODS: The working group convened in 2018. The various methods in which 3D virtual models had been created and printed in physical form were then shared and recorded. This allowed for comparison of the advantages, disadvantages, and costs of each method. In addition, a drilling event was held during the October 2018 AAO-HNSF Annual Meeting. Each model was drilled and evaluated by attending-level working group members using an 15-question Likert scale questionnaire. The models were graded on anatomic accuracy as well as their suitability as a simulation of both cadaveric and operative temporal bone drilling. RESULTS: The models produced for this study demonstrate significant anatomic detail and a likeness to human cadaver specimens for drilling and dissection. Models printed in standard resin material with a stereolithography printer scored highest in the evaluation, though the margin of difference was negligible in several categories. CONCLUSION: Simulated 3D temporal bones created through a number of printing methods have potential benefit in surgical training, preoperative simulation for challenging otologic cases, and the standardized testing of temporal bone surgical skills.

Patient and provider perspectives of a new prenatal care model introduced in response to the coronavirus disease 2019 pandemic.

BACKGROUND: Randomized controlled trials document the safety and efficacy of reduced frequency prenatal visit schedules and virtual visits, but real-world data are lacking. Our institution created a prenatal care delivery model incorporating these alternative approaches to continue safely providing prenatal care during the coronavirus disease 2019 pandemic. OBJECTIVE: To evaluate institutional-level adoption and patient and provider experiences with the coronavirus disease 2019 prenatal care model. STUDY DESIGN: We conducted a single-site evaluation of a coronavirus disease 2019 prenatal care model incorporating a reduced frequency visit schedule and virtual visits deployed at a suburban academic institution on March 20, 2020. We used electronic health record data to evaluate institution-level model adoption, defined as changes in overall visit frequency and proportion of virtual visits in the 3 months before and after implementation. To evaluate the patient and provider experience with the coronavirus disease 2019 model, we conducted an online survey of all pregnant patients (>20 weeks' gestation) and providers in May 2020. Of note, 3 domains of care experience were evaluated: (1) access, (2) quality and safety, and (3) satisfaction. Quantitative data were analyzed with basic descriptive statistics. Free-text responses coded by the 3 survey domains elucidated drivers of positive and negative care experiences. RESULTS: After the coronavirus disease 2019 model adoption, average weekly prenatal visit volume fell by 16.1%, from 898 to 761 weekly visits; the average weekly proportion of prenatal visits conducted virtually increased from 10.8% (97 of 898) to 43.3% (330 of 761); and the average visit no-show rate remained stable (preimplementation, 4.3%; postimplementation, 4.2%). Of those eligible, 74.8% of providers (77 of 103) and 15.0% of patients (253 of 1690) participated in the surveys. Patient respondents were largely white (180 of 253; 71.1%) and privately insured (199 of 253; 78.7%), reflecting the study site population. The rates of chronic conditions and pregnancy complications also differed from national prevalence. Provider respondents were predominantly white (44 of 66; 66.7%) and female (50 of 66; 75.8%). Most patients and almost all providers reported that virtual visits improved access to care (patients, 174 of 253 [68.8%]; providers, 74 of 77 [96.1%]). More than half of respondents (patients, 124 of 253 [53.3%]; providers, 41 of 77 [62.1%]) believed that virtual visits were safe. Nearly all believed that home blood pressure cuffs were important for virtual visits (patients, 213 of 231 [92.2%]; providers, 63 of 66 [95.5%]). Most reported satisfaction with the coronavirus disease 2019 model (patients, 196 of 253 [77.5%]; providers, 64 of 77 [83.1%]). In free-text responses, drivers of positive care experiences were similar for patients and providers and included perceived improved access to care through decreased barriers (eg, transportation, childcare), perceived high quality of virtual visits for low-risk patients and increased safety during the pandemic, and improved satisfaction through better patient counseling. Perceived drivers of negative care experience were also similar for patients and providers, but less common. These included concerns that unequal access to virtual visits could deepen existing maternity care inequities, concerns that the lack of home devices (eg, blood pressure cuffs) would affect care quality and safety, and dissatisfaction with poor patient-provider continuity and inadequate expectation setting for the virtual visit experience. CONCLUSION: Reduced visit schedules and virtual visits were rapidly integrated into real-world care, with positive experiences for many patients and providers. Future research is needed to understand the health outcomes and care experience associated with alternative approaches to prenatal care delivery across more diverse patient populations outside of the coronavirus disease 2019 pandemic to inform broader health policy decisions.

Engineered Antigen-Specific T Cells Secreting Broadly Neutralizing Antibodies: Combining Innate and Adaptive Immune Response against HIV.

While antiretroviral therapy (ART) can completely suppress viremia, it is not a cure for HIV. HIV persists as a latent reservoir of infected cells, able to evade host immunity and re-seed infection following cessation of ART. Two promising immunotherapeutic strategies to eliminate both productively infected cells and reactivated cells of the reservoir are the adoptive transfer of potent HIV-specific T cells and the passive administration of HIV-specific broadly neutralizing antibodies also capable of mediating antibody-dependent cellular cytotoxicity (ADCC). The simultaneous use of both as the basis of a single therapeutic has never been explored. We therefore sought to modify HIV-specific T cells from HIV-naive donors (to allow their use in the context of allotransplant, a promising platform for sterilizing cures) so they are able to secrete a broadly neutralizing antibody (bNAb) directed against the HIV envelope to elicit ADCC. We designed an antibody construct comprising bNAb 10-1074 heavy and light chains, fused to IgG3 Fc to elicit ADCC, with truncated cluster of differentiation 19 (CD19) as a selectable marker. HIV-specific T cells were expanded from HIV-naive donors by priming with antigen-presenting cells expressing overlapping HIV antigens in the presence of cytokines. T cells retained specificity against Gag, Nef, and Pol peptides (218.55 ± 300.14 interferon γ [IFNγ] spot-forming cells [SFC]/1 × 105) following transduction (38.92 ± 25.30) with the 10-1074 antibody constructs. These cells secreted 10-1074 antibodies (139.04 ± 114.42 ng/mL). The HIV-specific T cells maintained T cell function following transduction, and the secreted 10-1074 antibody bound HIV envelope (28.13% ± 19.42%) and displayed ADCC activity (10.47% ± 4.11%). Most critically, the 10-1074 antibody-secreting HIV-specific T cells displayed superior in vitro suppression of HIV replication. In summary, HIV-specific T cells can be engineered to produce antibodies mediating ADCC against HIV envelope-expressing cells. This combined innate/adaptive approach allows for synergy between the two immune arms, broadens the target range of the immune therapy, and provides further insight into what defines an effective anti-HIV response.

Three-dimensional modeling of the scapular tip for anterolateral and lateral mandibular defects.

OBJECTIVE: Three-dimensional (3D) computational modeling represents an invaluable surgical tool for complex reconstructive cases. There exists limited data on 3D imaging to evaluate the use of the scapular tip free flap in complex, anterolateral mandibular reconstructions. The purpose of this study is to radiographically assess the scapular tip free flap in anterolateral defects of the mandible. METHODS: A retrospective case series of 50 patients was performed on head and neck cancer patients treated at Michigan Medicine from 2013 to 2018. Patients who had pre-operative computed tomography neck and thorax for review were included. RESULTS: The scapular tip was able to cover defects from the ipsilateral mandibular angle to the symphysis in all cases. On average, the bone extended to cover defects from the mandibular angle to 17 mm (SD ± 3.6 mm) beyond the mandibular symphysis, which equates to 70% (95% CI 0.66-0.74) of the distance from the symphysis to the contralateral mental foramen. CONCLUSION: Use of the scapular tip as a donor site for reconstruction of the mandibular body can be evaluated pre-operatively utilizing 3D imaging. All patients were able to achieve posterior coverage to the vertical plane of the mandibular condyle and contralateral extension across the symphysis on average extends almost three-fourths of the distance to the mandibular foramen. The extent of contralateral coverage can be more accurately delineated utilizing the patient's pre-operative imaging.

Multicenter Advanced Pediatric Otolaryngology Fellowship Prep Surgical Simulation Course with 3D Printed High-Fidelity Models.

OBJECTIVE: To assess the effect of 3-dimensional (3D)-printed surgical simulators used in an advanced pediatric otolaryngology fellowship preparatory course on trainee education. STUDY DESIGN: Quasi-experimental pre/postsurvey. SETTING: Multicenter collaborative course conducted at a contract research organization prior to a national conference. SUBJECTS AND METHODS: A 5-station, 7-simulator prep course was piloted for 9 pediatric otolaryngology fellows and 17 otolaryngology senior residents, with simulators for airway graft carving, microtia ear framework carving, and cleft lip/palate repair. Prior to the course, trainees were provided educational materials electronically along with presurveys rating confidence, expertise, and attitude around surgical simulators. In October 2018, surgeons engaged in simulation stations with direction from 2 attending faculty per station, then completed postsurveys for each simulator. RESULTS: Statistically significant increases (P < .05) in self-reported confidence (average, 53%; range, 18%-80%) and expertise (average, 68%; range, 9%-95%) were seen across all simulators, corresponding to medium to large effect sizes as measured by Cohen's d statistic (0.41-1.71). Positive attitudes around 3D printing in surgical education also demonstrated statistically significant increases (average, 10%; range, 8%-13%). Trainees commented positively on gaining such broad exposure, although consistently indicated a preference for more practice time during the course. CONCLUSION: We demonstrate the benefit of high-fidelity, 3D-printed simulators in exposing trainees to advanced procedures, allowing them hands-on practice in a zero-risk environment. In the future, we hope to refine this course design, develop standardized tools to assess their educational value, and explore opportunities for integration into use in milestone assessment and accreditation.

Comparing medication histories obtained by pharmacy technicians and nursing staff in the emergency department.

BACKGROUND: An accurate medication history is crucial for maintaining continuity of care. There are numerous opportunities for discrepancies to occur, such as medication omissions, commissions, incorrect dosing, incorrect frequencies, or incorrect formulations. Medication discrepancies may prolong hospital length of stay, increase the number of future emergency department (ED) visits, and increase hospital readmissions. Numerous studies have established the advantages of utilizing pharmacy technicians to complete medication histories. This study aimed to compare the accuracy of obtaining medication histories through pharmacy technicians compared to nursing staff. OBJECTIVE: To compare the accuracy of obtaining medication histories through pharmacy technicians compared to nursing staff in the emergency department. METHODS: This was a single-center, retrospective, observational analysis of patients presenting to the ED between December 2018 through January 2019. A pharmacy technician received on-site training on how to properly obtain a medication history and performed medication histories on the days the pharmacy resident was present between 10:00 and 18:00. Medication histories were obtained by nurses on the days the pharmacy technician was not present. All study medication histories were reviewed for discrepancies by the pharmacy resident. RESULTS: Medication histories conducted by a pharmacy technician (n = 102) resulted in a greater number of accurate medication histories [96 (94.1%) versus 59 (57.8%); p < 0.01] when compared to those conducted by nurses (n = 102). A total of seven discrepancies were found in the pharmacy technician group compared to 131 in the nursing group (p < 0.01). There was also a statistically significant lower amount of high impact discrepancies in the pharmacy technician group compared to nursing (1 versus 15; p < 0.01). CONCLUSIONS: Pharmacy technicians in the ED provided more accurate medication histories when compared to nursing staff, thereby reducing potential medication errors.