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.

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.

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.

Development and Multidisciplinary Preliminary Validation of a 3-Dimensional-Printed Pediatric Airway Model for Emergency Airway Front-of-Neck Access Procedures.

BACKGROUND: Pediatric-specific difficult airway guidelines include algorithms for 3 scenarios: unanticipated difficult tracheal intubation, difficult mask ventilation, and cannot intubate/cannot ventilate. While rare, these instances may require front-of-neck access (FONA) to secure an airway until a definitive airway can be established. The aim of this study was to develop a pediatric FONA simulator evaluated by both anesthesiology and otolaryngology providers, promoting multidisciplinary airway management. METHODS: A 3-dimensional-printed tracheal model was developed using rescaled, anatomically accurate dimensions from a computerized tomography scan using computer-aided design software. The medical grade silicone model was incorporated into a mannequin to create a low-cost, high-fidelity simulator. A multidisciplinary team of anesthesiology, otolaryngology, and simulation experts refined the model. Experts in airway management were recruited to rate the realism of the model's characteristics and features and their own ability to complete specific FONA-related tasks. RESULTS: Six expert raters (3 anesthesiology and 3 otolaryngology) were identified for multidisciplinary evaluation of model test content validity. Analysis of response data shows null variance within 1 or both specialties for a majority of the content validity tool elements. High and consistent absolute ratings for each domain indicate that the tested experts perceived this trainer as a realistic and highly valuable tool in its current state. CONCLUSIONS: The ability to practice front-of-neck emergency airway procedures safely and subsequently demonstrate proficiency on a child model has great implications regarding both quality of physician training and patient outcomes. This model may be incorporated into curricula to teach needle cricothyroidotomy and other FONA procedures to providers across disciplines.

Medulloblastoma rendered susceptible to NK-cell attack by TGFß neutralization.

BACKGROUND: Medulloblastoma (MB), the most common pediatric brain cancer, presents with a poor prognosis in a subset of patients with high risk disease, or at recurrence, where current therapies are ineffective. Cord blood (CB) natural killer (NK) cells may be promising off-the-shelf effector cells for immunotherapy due to their recognition of malignant cells without the need for a known target, ready availability from multiple banks, and their potential to expand exponentially. However, they are currently limited by immune suppressive cytokines secreted in the MB tumor microenvironment including Transforming Growth Factor ß (TGF-ß). Here, we address this challenge in in vitro models of MB. METHODS: CB-derived NK cells were modified to express a dominant negative TGF-ß receptor II (DNRII) using retroviral transduction. The ability of transduced CB cells to maintain function in the presence of medulloblastoma-conditioned media was then assessed. RESULTS: We observed that the cytotoxic ability of nontransduced CB-NK cells was reduced in the presence of TGF-ß-rich, medulloblastoma-conditioned media (21.21 ± 1.19% killing at E:T 5:1 in the absence vs. 14.98 ± 2.11% in the presence of medulloblastoma-conditioned media, n = 8, p = 0.02), but was unaffected in CB-derived DNRII-transduced NK cells (21.11 ± 1.84% killing at E:T 5:1 in the absence vs. 21.81 ± 3.37 in the presence of medulloblastoma-conditioned media, n = 8, p = 0.85. We also observed decreased expression of CCR2 in untransduced NK cells (mean CCR2 MFI 826 ± 117 in untransduced NK + MB supernatant from mean CCR2 MFI 1639.29 ± 215 in no MB supernatant, n = 7, p = 0.0156), but not in the transduced cells. Finally, we observed that CB-derived DNRII-transduced NK cells may protect surrounding immune cells by providing a cytokine sink for TGF-ß (decreased TGF-ß levels of 610 ± 265 pg/mL in CB-derived DNRII-transduced NK cells vs. 1817 ± 342 pg/mL in untransduced cells; p = 0.008). CONCLUSIONS: CB NK cells expressing a TGF-ß DNRII may have a functional advantage over unmodified NK cells in the presence of TGF-ß-rich MB, warranting further investigation on its potential applications for patients with medulloblastoma.

Human papilloma virus-specific T cells can be generated from naïve T cells for use as an immunotherapeutic strategy for immunocompromised patients.

Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers. Most protocols for generating virus-specific T cells require prior exposure of the donor to the targeted virus and, because the seroprevalence of high-risk HPV types varies greatly by age and ethnicity, manufacturing of donor-derived HPV-specific T cells has proven challenging. We, therefore, made systematic changes to our current Good Manufacturing Practice (GMP)-compliant protocols to improve antigen presentation, priming and expansion for the manufacture of high-efficacy HPV-specific T cells. Like others, we found that current methodologies fail to expand HPV-specific T cells from most healthy donors. By optimizing dendritic cell maturation and function with lipopolysaccharide (LPS) and interferon (IFN)γ, adding interleukin (IL)-21 during priming and depleting memory T cells, we achieved reliable expansion of T cells specific for oncoproteins E6 and E7 to clinically relevant amounts (mean, 578-fold expansion; n = 10), which were polyfunctional based on cytokine multiplex analysis. In the third-party setting, such HPV-specific T-cell products might serve as a potent salvage therapy for patients with HPV-associated diseases.

Cord blood natural killer cells expressing a dominant negative TGF-ß receptor: Implications for adoptive immunotherapy for glioblastoma.

Cord blood (CB) natural killer (NK) cells are promising effector cells for tumor immunotherapy but are currently limited by immune-suppressive cytokines in the tumor microenvironment, such as transforming growth factor (TGF-ß). We observed that TGF-ß inhibits expression of activating receptors such as NKG2D and DNAM1 and decreases killing activity against glioblastoma tumor cells through inhibition of perforin secretion. To overcome the detrimental effects of TGF-ß, we engrafted a dominant negative TGF-ß receptor II (DNRII) on CB-derived NK cells by retroviral transduction and evaluated their ability to kill glioblastoma cells in the presence of TGF-ß. After manufacture using Good Manufacturing Practice-compliant methodologies and transduction with DNRII, CB-derived DNRII-transduced NK cells expanded to clinically relevant numbers and retained both their killing ability and their secretion of interferon-γ upon activation. More important, these cells maintained both perforin expression and NKG2D/DNMA1 expression in the presence of TGF-ß allowing for recognition and killing of glioblastoma tumor cells. Hence, NK cells expressing a DNRII should have a functional advantage over unmodified NK cells in the presence of TGF-ß-secreting tumors and may be an important therapeutic approach for patients with cancer.

Human parainfluenza virus-3 can be targeted by rapidly ex vivo expanded T lymphocytes.

BACKGROUND AIMS: Human parainfluenza virus-3 (HPIV) is a common cause of respiratory infection in immunocompromised patients and currently has no effective therapies. Virus-specific T-cell therapy has been successful for the treatment or prevention of viral infections in immunocompromised patients but requires determination of T-cell antigens on targeted viruses. METHODS: HPIV3-specific T cells were expanded from peripheral blood of healthy donors using a rapid generation protocol targeting four HPIV3 proteins. Immunophenotyping was performed by flow cytometry. Viral specificity was determined by interferon (IFN)-γ ELISpot, intracellular cytokine staining and cytokine measurements from culture supernatants by Luminex assay. Cytotoxic activity was tested by 51Cr release and CD107a mobilization assays. Virus-specific T cells targeting six viruses were then produced by rapid protocol, and the phenotype of HPIV3-specific T cells was determined by immunomagnetic sorting for IFN-γ-producing cells. RESULTS: HPIV3-specific T cells were expanded from 13 healthy donors. HPIV3-specific T cells showed a CD4+ predominance (mean CD4:CD8 ratio 2.89) and demonstrated specificity for multiple HPIV3 antigens. The expanded T cells were polyfunctional based on cytokine production but only had a minor cytotoxic component. T cells targeting six viruses in a single product similarly showed HPIV3 specificity, with a predominant effector memory phenotype (CD3+/CD45RA-/CCR7-) in responder cells. DISCUSSION: HPIV3-specific T cells can be produced using a rapid ex vivo protocol from healthy donors and are predominantly CD4+ T cells with Th1 activity. HPIV3 epitopes can also be successfully targeted alongside multiple other viral epitopes in production of six-virus T cells, without loss of HPIV3 specificity. These products may be clinically beneficial to combat HPIV3 infections by adoptive T-cell therapy in immune-compromised patients.

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.

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.

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.

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.

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.

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.

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.

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.

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.