Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate.

Clonal hematopoiesis of indeterminate potential (CHIP), whereby somatic mutations in hematopoietic stem cells confer a selective advantage and drive clonal expansion, not only correlates with age but also confers increased risk of morbidity and mortality. Here, we leverage genetically predicted traits to identify factors that determine CHIP clonal expansion rate. We used the passenger-approximated clonal expansion rate method to quantify the clonal expansion rate for 4,370 individuals in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) cohort and calculated polygenic risk scores for DNA methylation aging, inflammation-related measures and circulating protein levels. Clonal expansion rate was significantly associated with both genetically predicted and measured epigenetic clocks. No associations were identified with inflammation-related lab values or diseases and CHIP expansion rate overall. A proteome-wide search identified predicted circulating levels of myeloid zinc finger 1 and anti-Müllerian hormone as associated with an increased CHIP clonal expansion rate and tissue inhibitor of metalloproteinase 1 and glycine N-methyltransferase as associated with decreased CHIP clonal expansion rate. Together, our findings identify epigenetic and proteomic patterns associated with the rate of hematopoietic clonal expansion.

User experience of a family health history chatbot: A quantitative analysis.

OBJECTIVE: Family health history (FHx) is an important tool in assessing one's risk towards specific health conditions. However, user experience of FHx collection tools is rarely studied. ItRunsInMyFamily.com (ItRuns) was developed to assess FHx and hereditary cancer risk. This study reports a quantitative user experience analysis of ItRuns. METHODS: We conducted a public health campaign in November 2019 to promote FHx collection using ItRuns. We used software telemetry to quantify abandonment and time spent on ItRuns to identify user behaviors and potential areas of improvement. RESULTS: Of 11,065 users who started the ItRuns assessment, 4305 (38.91%) reached the final step to receive recommendations about hereditary cancer risk. Highest abandonment rates were during Introduction (32.82%), Invite Friends (29.03%), and Family Cancer History (12.03%) subflows. Median time to complete the assessment was 636 s. Users spent the highest median time on Proband Cancer History (124.00 s) and Family Cancer History (119.00 s) subflows. Search list questions took the longest to complete (median 19.50 s), followed by free text email input (15.00 s). CONCLUSION: Knowledge of objective user behaviors at a large scale and factors impacting optimal user experience will help enhance the ItRuns workflow and improve future FHx collection.

Morbidity and mortality after antireflux and hiatal hernia surgery across a spectrum of ages.

BACKGROUND: Antireflux surgery (ARS) and hiatal hernia repair (HHR) are common surgical procedures with modest morbidity. Increasing age is a risk factor for complications; however, details regarding acute morbidity are lacking. This study aimed to describe the incidence rates and types of morbidities across the spectrum of ages. METHODS: A total of 2342 consecutive cases were retrospectively reviewed from 2003 to 2020 for 30-day complications. All complications were assessed using the Clavien-Dindo (CD) grading system. Patients were divided into 5 age groups: ≤59, 60 to 69, 70 to 79, 80 to 89, and ≥90 years. RESULTS: The numbers per age group were 1100 patients aged ≤59 years, 684 patients aged 60 to 69 years, 458 patients aged 70 to 79 years, 458 patients aged 80 to 89 years, and 6 patients aged ≥90 years. A total of 427 complications (18.2%) occurred, including 2 mortalities, each in the 60- to 69-year age group and the 70- to 79-year age group, for a mortality rate of 0.2%. The complication rate increased from 13.5% (149) in patients aged ≤59 years to 35.0% (35) in patients aged ≥80 years (P = .006), with CD grades I and II accounting for >70% of complications, except in patients aged ≥80 years (57.1%). CD grades IIIa and IIIb were higher in patients aged ≥80 years (26.5% [P = .001] and 11.8% [P = .021], respectively). CD grade IVa and IVb complications were rare overall. CONCLUSION: There is a modest rate of morbidity that increases as patients age, regardless of hernia type, elective or primary surgery, with most being minor complications (CD grade≤II). Our data should help patients, referring physicians, and surgeons counsel patients regarding the effect of increasing age in ARS and HHR.

Thirty- and 90-Day Morbidity and Mortality by Clavien-Dindo 30 and 90 Days after Surgery for Antireflux and Hiatal Hernia.

BACKGROUND: The historic morbidity and mortality rates of anti-reflux and hiatal hernia surgery are reported as 3-21% and 0.2-0.5%, respectively. These data come from either large national/population level or small institutional studies, with the former focusing on broad 30-day outcomes while lacking granular data on complications and their severity. Institutional studies tend to focus on long-term and quality of life outcomes. Our objective is to describe and evaluate the incidence of 30 and 90-day morbidity and mortality in a large, single institution dataset. STUDY DESIGN: We retrospectively reviewed 2342 cases of anti-reflux and hiatal hernia surgery from 2003-2020 for intra-operative complications causing post-operative sequelae, as well as morbidity and mortality within 90 days. All complications were graded using the Clavien-Dindo (CD) Grading System. The highest-grade of complication was used per patient during 30-day and 31-90-day intervals. RESULTS: Out of 2342 patients, the overall 30-day morbidity and mortality rates were 18.2% (427/2342) and 0.2% (4/2342), respectively. Most of the complications were CD<3a at 13.1% (306/2342). In the 31-90-day post-operative period, morbidity and mortality rates decreased to 3.1% (78/2338) and 0.09% (2/2338). CD<3a complications accounted for 1.9% (42/2338). CONCLUSIONS: Anti-reflux and hiatal hernia surgery are safe operations with rare mortality and modest rates of morbidity. However, the majority of complications patients experience are minor (CD<3a) and are easily managed. A minority of patients will experience major complications (CD≥3a) that require additional procedures and management to secure a safe outcome. These data are helpful to inform patients of the risks of surgery, and guide physicians for optimal consent.

ATRX and Its Prognostic Significance in Soft Tissue Sarcoma.

Purpose: Recently, the association between ATRX and a more aggressive sarcoma phenotype has been shown. We performed a retrospective study of sarcomas from an individual institution to evaluate ATRX as a prognosticator in soft tissue sarcoma. Experimental Design. 128 sarcomas were collected from a single institution and stained for ATRX. The prognostic significance of these markers was evaluated in a smaller cohort of primary soft tissue sarcomas (n = 68). Kaplan-Meier curves were created for univariate analysis, and Cox regression was utilized for multivariate analysis. Results: High expression of ATRX was found to be a positive prognostic indicator for overall survival and metastasis-free survival in our group of soft tissue sarcomas both in univariate analysis and multivariate analysis (HR: 0.38 (0.17-0.85), P=0.02 and HR: 0.49 (0.24-0.99), P=0.05, respectively). Conclusions: High expression of ATRX is a positive prognostic indicator of overall survival and metastasis-free survival in patients with STS. This is consistent with studies in osteosarcoma, which indicate possible mechanisms through which loss of ATRX leads to more aggressive phenotypes. Future prospective clinical studies are required to validate the prognostic significance of these findings.

Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2.

Neurofibromatosis Type 2 (NF-2) is a dominantly inherited genetic disorder that results from mutations in the tumor suppressor gene, neurofibromin 2 (NF2) gene. Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by an inducible genetic knockout of nf2a/b, the zebrafish homolog of human NF2. Analysis of nf2a and nf2b expression reveals ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, nf2a displays lower expression levels. Induction of nf2a/b knockout at early stages increases the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, nf2a/b knockout triggers the development of a spectrum of tumors, including vestibular schwannomas, spinal schwannomas, meningiomas, and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.

Sweetened Beverage Tax Implementation and Change in Body Mass Index Among Children in Seattle.

Importance: Sweetened beverage taxes have been associated with reduced purchasing of taxed beverages. However, few studies have assessed the association between sweetened beverage taxes and health outcomes. Objective: To evaluate the association between the Seattle sweetened beverage tax and change in body mass index (BMI) among children. Design, Setting, and Participants: In this longitudinal cohort study, anthropometric data were obtained from electronic medical records of 2 health care systems (Kaiser Permanente Washington [KP] and Seattle Children's Hospital Odessa Brown Children's Clinic [OBCC]). Children were included in the study if they were aged 2 to 18 years (between January 1, 2014, and December 31, 2019); had at least 1 weight measurement every year between 2015 and 2019; lived in Seattle or in urban areas of 3 surrounding counties (King, Pierce, and Snohomish); had not moved between taxed (Seattle) and nontaxed areas; received primary health care from KP or OBCC; did not have a recent history of cancer, bariatric surgery, or pregnancy; and had biologically plausible height and BMI (calculated as weight in kilograms divided by height in meters squared). Data analysis was conducted between August 5, 2022, and March 4, 2024. Exposure: Seattle sweetened beverage tax (1.75 cents per ounce on sweetened beverages), implemented on January 1, 2018. Main Outcomes and Measures: The primary outcome was BMIp95 (BMI expressed as a percentage of the 95th percentile; a newly recommended metric for assessing BMI change) of the reference population for age and sex, using the Centers for Disease Control and Prevention growth charts. In the primary (synthetic difference-in-differences [SDID]) model used, a comparison sample was created by reweighting the comparison sample to optimize on matching to pretax trends in outcome among 6313 children in Seattle. Secondary models were within-person change models using 1 pretax measurement and 1 posttax measurement in 22 779 children and fine stratification weights to balance baseline individual and neighborhood-level confounders. Results: The primary SDID analysis included 6313 children (3041 female [48%] and 3272 male [52%]). More than a third of children (2383 [38%]) were aged 2 to 5 years); their mean (SE) age was 7.7 (0.6) years. With regard to race and ethnicity, 789 children (13%) were Asian, 631 (10%) were Black, 649 (10%) were Hispanic, and 3158 (50%) were White. The primary model results suggested that the Seattle tax was associated with a larger decrease in BMIp95 for children living in Seattle compared with those living in the comparison area (SDID: -0.90 percentage points [95% CI, -1.20 to -0.60]; P < .001). Results from secondary models were similar. Conclusions and Relevance: The findings of this cohort study suggest that the Seattle sweetened beverage tax was associated with a modest decrease in BMIp95 among children living in Seattle compared with children living in nearby nontaxed areas who were receiving care within the same health care systems. Taken together with existing studies in the US, these results suggest that sweetened beverage taxes may be an effective policy for improving children's BMI. Future research should test this association using longitudinal data in other US cities with sweetened beverage taxes.

Activity standard and calibrations for 227Th with ingrowing progeny.

Thorium-227 was separated from its progeny and standardized for activity by the triple-to-double coincidence ratio (TDCR) method of liquid scintillation counting. Confirmatory liquid scintillation-based measurements were made using efficiency tracing with 3H and live-timed anticoincidence counting (LTAC). The separation time and the efficiency of the separation were confirmed by gamma-ray spectrometry. Calibrations for reentrant pressurized ionization chambers, including commercial radionuclide calibrators, and a well-type NaI(Tl) detector are discussed.

Anterior vertebral tethering for adolescent idiopathic scoliosis: our initial ten year clinical experience.

BACKGROUND: Anterior vertebral tethering (AVT) is a minimally invasive alternative to fusion surgery for adolescent idiopathic scoliosis (AIS) that offers the potential for definitive scoliosis treatment with the possibility of preservation of the growth, motion, function and overall health of the spine. This study represents our first ten years using AVT to treat AIS. METHODS: In this retrospective review we analyzed our first 74 AIS patients treated with AVT 2010-2020. Multiple Lenke curve types 33-70° were treated with skeletal maturity spanning Risser -1 to 5. RESULTS: Of 74 consecutive AIS patients treated with AVT, 52 patients (47 female, 5 male) had sufficient 2-year follow-up for inclusion. Forty-six of these 52 patients (88%) with 65 curves (35T, 30TL/L) were satisfactorily treated with AVT demonstrating curve correction from 48.6° pre-op (range 33°-70°) at age 15.1 years (range 9.2-18.8) and skeletal maturity of Risser 2.8 (range -1 to 5) to 23.2° post-op (range 0°-54°) and 24.0° final (range 0°-49°) at 3.3 years follow-up (range 2-10 years). Curve corrections from pre-op to post-op and pre-op to final were both significant (p < 0.001). The 0.8° change from post-op to final was not significant but did represent good control of scoliosis correction over time. Thoracic kyphosis and lumbar lordosis were maintained in a normal range throughout while axial rotation demonstrated a slight trend toward improvement. Skeletal maturity of Risser 4 or greater was achieved in all but one patient. Four of the 52 patients (8%) required additional procedures for tether rupture (3 replacements) or overcorrection (1 removal) to achieve satisfactory treatment status after AVT. An additional 6 of the 52 patients (12%), however, were not satisfactorily treated with AVT, requiring fusion for overcorrection (2) or inadequate correction (4). CONCLUSIONS: In this study, AIS was satisfactorily treated with AVT in the majority of patients over a broad range of curve magnitudes, curve types, and skeletal maturity. Though late revision surgery for overcorrection, inadequate correction, or tether rupture was not uncommon, the complication of overcorrection was eliminated after our first ten patients by a refinement of indications. LEVEL OF EVIDENCE: IV.

Does Tranexamic Acid Reduce the Need for Hypotensive Anesthesia Within Orthognathic Surgery? A Retrospective Study.

Background: Tranexamic acid (TXA) is utilized frequently in orthognathic surgery to limit blood loss and improve surgical field visualization. This antifibrinolytic has been proven effective with use of concomitant hypotensive anesthesia. Despite proven efficacy, there is a recent push to avoid perioperative hypotensive anesthesia due to risks of organ hypoperfusion, cardiac ischemia and postoperative nausea. Aims: The aim is to study the efficacy and safety of utilizing TXA without controlled hypotensive anesthesia. Methods: The authors identified two cohorts of subjects that underwent bimaxillary orthognathic surgery both with and without TXA administration and compared operative and perioperative variables. A retrospective analysis was completed evaluating intraoperative MAP measurements in subjects treated both with and without TXA using descriptive and bivariate analysis. Results and conclusion: Sixty-three subjects met inclusion criteria. The TXA cohort experienced 11.5% less time under hypotensive anesthesia when compared to the group that did not receive TXA. Additionally, surgical length was decreased by more than 28 min when subjects received TXA. No subjects required a blood transfusion or experienced any TXA-related complications. Given the recommendations to limit hypotensive anesthesia perioperatively, TXA is a useful adjunct in orthognathic surgery to limit controlled hypotensive anesthesia.

Bitter taste receptor activation by cholesterol and an intracellular tastant.

Bitter taste sensing is mediated by type 2 taste receptors (TAS2Rs (also known as T2Rs)), which represent a distinct class of G-protein-coupled receptors1. Among the 26 members of the TAS2Rs, TAS2R14 is highly expressed in extraoral tissues and mediates the responses to more than 100 structurally diverse tastants2-6, although the molecular mechanisms for recognizing diverse chemicals and initiating cellular signalling are still poorly understood. Here we report two cryo-electron microscopy structures for TAS2R14 complexed with Ggust (also known as gustducin) and Gi1. Both structures have an orthosteric binding pocket occupied by endogenous cholesterol as well as an intracellular allosteric site bound by the bitter tastant cmpd28.1, including a direct interaction with the α5 helix of Ggust and Gi1. Computational and biochemical studies validate both ligand interactions. Our functional analysis identified cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator with direct agonist activity at TAS2R14. Moreover, the orthosteric pocket is connected to the allosteric site via an elongated cavity, which has a hydrophobic core rich in aromatic residues. Our findings provide insights into the ligand recognition of bitter taste receptors and suggest activities of TAS2R14 beyond bitter taste perception via intracellular allosteric tastants.

Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease.

Background: Radiolabeled antibody 131I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance. This development bears broader implications for analogous therapies within the pediatric patient demographic. Methods: Intraventricular radioimmunotherapy (RIT) with 925-1850 MBq (25-50 mCi) of 131I-omburtamab was administered via the Ommaya reservoir, in designated rooms within the pediatric ambulatory care center. Dosimeters were provided to staff involved in patient care to evaluate exposure during injection and post-administration. Post-administration exposure rate readings from the patient on contact, at 0.3 m, and at 1 m were taken within the first 30 minutes, and the room was surveyed after patient discharge. Duration of radiation exposure was calculated using standard U.S. Nuclear Regulatory Commission (US NRC) regulatory guidance recommendations combined with mean exposure rates and whole-body clearance estimates. Exposure rate measurements and clearance data provided patient-specific precautions for four cohorts by age: < 3 y/o, 3-10 y/o, 10-18 y/o, and 18+. Results: Post-administration exposure rates for patients ranged from 0.16-0.46 µSv/hr/MBq at 1 ft and 0.03-0.08 µSv/hr/MBq at 1 m. Radiation exposure duration ranged from 1-10 days after release for the four evaluated cohorts. Based on the highest measured exposure rates and slowest whole-body clearance, the longest precautions were approximately 78% lower than the regulatory guidance recommendations. Radiation exposure to staff associated with 131I-omburtamab per administration was substantially below the annual regulatory threshold for individual exposure monitoring. Conclusion: 131I-omburtamab can be administered on an outpatient basis, using appropriate patient-based radiation safety precautions that employ patient-specific exposure rate and biological clearance parameters. This trial is registered with the National Library of Medicine's ClinicalTrials.gov. The registration number is NCT03275402, and it was registered on 7 September 2017. The web link is included here. https://clinicaltrials.gov/study/NCT03275402.

Dynamic Stress Ultrasound Assessment of Professional Baseball Players' Elbows After Ulnar Collateral Ligament Reconstruction.

BACKGROUND: There is a paucity of data analyzing dynamic stress ultrasound (SUS) findings in elite pitchers who have undergone ulnar collateral ligament (UCL) reconstruction (UCLR) and returned to sport. PURPOSE: To identify longitudinal, perioperative changes in the elbows of professional baseball pitchers who have undergone UCLR and to compare these findings with a matched cohort of healthy pitchers. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study used prospectively collected data from dynamic elbow SUS analyses of professional baseball pitchers within a single Major League Baseball organization. Pitchers were divided into 2 cohorts: a UCLR cohort and healthy cohort. The UCLR cohort eligibility included availability of (1) SUS from preseason of injury/UCLR and (2) SUS from ≥2 years after surgery. These players were 1:1 matched to players with no history of upper extremity injury to form the healthy cohort. Ligament thickness and ulnohumeral joint space at rest and under stress were directly measured. Joint laxity was calculated by subtracting joint space at rest from joint space under stress. The term "relative" was used to describe calculated differences where nondominant measurements were subtracted from dominant-side measurements. RESULTS: Eight pitchers were included in the UCLR group and matched to 8 healthy pitchers (mean age at initial SUS examination, 19.6 years). At a minimum follow-up of 2 years, there were no significant differences between groups in terms of relative or dominant arm rest space, stress space, or laxity. Longitudinally (final measurements - baseline measurements), the mean relative ulnohumeral rest space decreased in the UCLR group and increased in the healthy group (-0.36 mm vs +0.50 mm; P = .032). The finding of increased UCL thickness in the UCLR group was expected, as UCL grafts are typically thicker than native ligaments. CONCLUSION: Ulnhohumeral joint stability was achieved after UCLR as indicated by similar rest space, stress space, and joint laxity in dominant arms compared with a matched healthy cohort. A significant decrease in relative rest space after UCLR may represent the achievement of stability in surgery patients. Alternatively, the increase in ulnohumeral rest space seen in the healthy cohort may represent adaptive changes from pitching at a professional level.

Prefusion stabilization of the Hendra and Langya virus F proteins.

Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the Henipavirus genus, NiV and HeV use an attachment (G) glycoprotein and a class I fusion (F) glycoprotein to invade host cells. The F protein rearranges from a metastable prefusion form to an extended postfusion form to facilitate host cell entry. Prefusion NiV F elicits higher neutralizing antibody titers than postfusion NiV F, indicating that stabilization of prefusion F may aid vaccine development. A combination of amino acid substitutions (L104C/I114C, L172F, and S191P) is known to stabilize NiV F in its prefusion conformation, although the extent to which substitutions transfer to other henipavirus F proteins is not known. Here, we perform biophysical and structural studies to investigate the mechanism of prefusion stabilization in F proteins from three henipaviruses: NiV, HeV, and Langya virus (LayV). Three known stabilizing substitutions from NiV F transfer to HeV F and exert similar structural and functional effects. One engineered disulfide bond, located near the fusion peptide, is sufficient to stabilize the prefusion conformations of both HeV F and LayV F. Although LayV F shares low overall sequence identity with NiV F and HeV F, the region around the fusion peptide exhibits high sequence conservation across all henipaviruses. Our findings indicate that substitutions targeting this site of conformational change might be applicable to prefusion stabilization of other henipavirus F proteins and support the use of NiV as a prototypical pathogen for henipavirus vaccine antigen design.IMPORTANCEPathogenic henipaviruses such as Nipah virus (NiV) and Hendra virus (HeV) cause respiratory symptoms, with severe cases resulting in encephalitis, seizures, and coma. The work described here shows that the NiV and HeV fusion (F) proteins share common structural features with the F protein from an emerging henipavirus, Langya virus (LayV). Sequence alignment alone was sufficient to predict which known prefusion-stabilizing amino acid substitutions from NiV F would stabilize the prefusion conformations of HeV F and LayV F. This work also reveals an unexpected oligomeric interface shared by prefusion HeV F and NiV F. Together, these advances lay a foundation for future antigen design targeting henipavirus F proteins. In this way, Nipah virus can serve as a prototypical pathogen for the development of protective vaccines and monoclonal antibodies to prepare for potential henipavirus outbreaks.

What Is Health Literacy Among Orthognathic Surgery Patients?

BACKGROUND: Health literacy of orthognathic surgery patients has not been thoroughly evaluated. PURPOSE: The purpose of this study was to estimate health literacy and identify risk factors associated with inadequate health literacy in orthognathic surgery patients. STUDY DESIGN, SETTING, SAMPLE: A cross-sectional study was implemented utilizing patients ages 14-80 years who presented for orthognathic surgery evaluation between September 2021 and December 2022. Subjects were excluded from the study if they did not complete the orthognathic surgery evaluation, were not between the ages of 14-80 years old, or did not complete the Brief Health Literacy Screening Tool (BRIEF) questionnaire during intake. Subjects who have not undergone orthognathic surgery but completed the initial evaluation for orthognathic surgery were included in the study. PREDICTOR VARIABLES: The predictor variables were a set of risk factors for inadequate health literacy: age, sex, primary language, race, estimated household income, and diagnosis. MAIN OUTCOME VARIABLE: The main outcome variable was health literacy assessed using the BRIEF questionnaire. During intake, subjects completed the BRIEF questionnaire consisting of four questions scored on an ordinal scale of 1-5. Inadequate health literacy was defined as a BRIEF score ≤16. COVARIATES: Not applicable. ANALYSES: Bivariate and multivariate analyses were performed. P < .05 was considered statistically significant. RESULTS: Of 150 patients presenting for orthognathic surgery, fifteen percent of patients had inadequate health literacy via the BRIEF test. The mean age of those with adequate health literacy was 27.9 years (standard deviation, ±12.5) compared to 18.5 years (standard deviation, ±5.7) for those with inadequate health literacy (P = <.001). After adjusting for sex, language, race, estimated household income, and diagnosis via multivariate analysis, increasing age was associated with decreased odds of inadequate health literacy (adjusted odds ratio = 0.81; confidence interval, 0.72-0.92; P = <.001). CONCLUSION AND RELEVANCE: In the complex process of orthognathic surgery, it is essential to identify patients with inadequate health literacy that may require additional health literacy interventions. Ultimately, 15% of orthognathic surgery subjects had inadequate health literacy, and younger patients were the most susceptible as the odds of inadequate health literacy decreased with increasing age.

Association Between Draft Order and Stress Sonography of the Ulnar Collateral Ligament of the Elbow in Professional Baseball Pitchers: An 18-Year Study.

BACKGROUND: The Major League Baseball (MLB) draft is a common route for players to enter professional baseball in the United States. Players taken in earlier rounds are typically higher-performing players. When looking at pitchers specifically, higher performance at the amateur level may be associated with an increased frequency of adaptive change in the throwing elbow. PURPOSE: To determine whether pitchers taken in earlier rounds of the MLB draft have a greater frequency or extent of pathological change in the elbow, as measured by dynamic stress ultrasound. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Dynamic stress ultrasounds (SUSs) were performed over 18 years on the dominant and nondominant arms of 651 professional pitchers. The 383 drafted players were grouped according to the round in which they were drafted (rounds 1-5, 6-10, 11-20, 21+). Groups were compared with respect to "relative" ulnar collateral ligament (UCL) thickness (dominant-nondominant), relative ulnohumeral joint laxity (joint space distance under stress minus joint space at rest), and the presence of pathology (calcifications, tears, hypoechoic foci, osteophytes). In addition, a subgroup analysis was done to compare the progression of SUS findings over 3 years in players for which data were available. RESULTS: Draft round groups did not differ by age, number of previous spring training, or handedness. Comparing baseline measurements, there was no significant relationship between draft round and relative UCL thickness (P = .932), relative laxity (P = .996), or presence of pathology detectable on SUS (P = .642). However, increased relative UCL thickness was significantly associated with the presence of pathology on SUS (odds ratio, 1.45; 95% CI, 1.26-1.69; P < .001). Longitudinally, there was no significant relationship between draft round and 3-year progression of relative laxity, relative UCL thickness, or clinical progression of pathology. CONCLUSION: Higher-performing pitchers are drafted earlier in the MLB draft. This may be attributable to peak pitch velocity, in-game performance, visibility gained during player showcases, or any number of other sport-specific variables. However, despite this, there was no significant relationship between draft round and adaptive changes to the elbow or specific properties of the UCL on stress ultrasound.

COVID-19 in the Clinic: Trial of an Aerosol Containment Mask for Endoscopic Clinic Procedures.

OBJECTIVE: Create an aerosol containment mask (ACM) for common otolaryngologic endoscopic procedures which also provides nanoparticle-level protection to patients. STUDY DESIGN: Prospective feasibility study. SETTING: In-person testing with a novel ACM. METHODS: The mask was designed in Solidworks and 3-dimensional printed. Measurements were made on 100 consecutive clinic patients who underwent medically necessarily endoscopy, 50 rigid nasal and 50 flexible, by 9 surgeons. RESULTS: Of the 50 patients who underwent rigid nasal endoscopy with the ACM, 0 of 25 patients with the suction off and 0 of 25 patients with the suction on had evidence of leakage of 0.3 µm particles. Of the 50 patients who underwent flexible endoscopy with the ACM, 0 of 25 patients with the suction off and 0 of 25 patients with the suction on had evidence of leakage of 0.3 µm particles. In terms of comfort, 73% of patients found the ACM somewhat or very comfortable without suction, compared to 86% with the suction on. Surgeons were able to visualize all necessary anatomic areas in 98% of procedures. In 97% of procedures, the masks were able to be placed easily. CONCLUSION: ACM can accommodate rigid nasal and flexible endoscopes and may prevent leakage of patient-generated aerosols, thus avoiding contamination of the room and protecting health care workers from airborne contagions. LEVEL OF EVIDENCE: The level of evidence is 2.

Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques.

Adeno-associated virus (AAV) vector gene therapy is a promising approach to treat rare genetic diseases; however, an ongoing challenge is how to best modulate host immunity to improve transduction efficiency and therapeutic outcomes. This report presents two studies characterizing multiple prophylactic immunosuppression regimens in male cynomolgus macaques receiving an AAVrh10 gene therapy vector expressing human coagulation factor VIII (hFVIII). In study 1, no immunosuppression was compared with prednisolone, rapamycin (or sirolimus), rapamycin and cyclosporin A in combination, and cyclosporin A and azathioprine in combination. Prednisolone alone demonstrated higher mean peripheral blood hFVIII expression; however, this was not sustained upon taper. Anti-capsid and anti-hFVIII antibody responses were robust, and vector genomes and transgene mRNA levels were similar to no immunosuppression at necropsy. Study 2 compared no immunosuppression with prednisolone alone or in combination with rapamycin or methotrexate. The prednisolone/rapamycin group demonstrated an increase in mean hFVIII expression and a mean delay in anti-capsid IgG development until after rapamycin taper. Additionally, a significant reduction in the plasma cell gene signature was observed with prednisolone/rapamycin, suggesting that rapamycin's tolerogenic effects may include plasma cell differentiation blockade. Immunosuppression with prednisolone and rapamycin in combination could improve therapeutic outcomes in AAV vector gene therapy.

Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: Two-Year Results from a Randomized, Multicenter Study.

PURPOSE: To compare the effectiveness and safety of the MicroShunt (Santen Inc) versus trabeculectomy in patients with primary open-angle glaucoma (POAG). DESIGN: Prospective, randomized, multicenter trial conducted in the United States and Europe. PARTICIPANTS: Adult patients (aged 40-85 years) with mild to severe POAG inadequately controlled on maximum tolerated medical therapy and intraocular pressure (IOP) ≥ 15 mmHg and ≤ 40 mmHg. METHODS: Patients were randomized 3:1 to stand-alone MicroShunt implantation (n = 395) or trabeculectomy (n = 132), both augmented with mitomycin C (MMC) 0.2 mg/ml for 2 minutes. MAIN OUTCOME MEASURES: The primary effectiveness end point was surgical success, defined as ≥ 20% reduction in mean diurnal IOP from baseline with no increase in glaucoma medications. Secondary end points included changes in mean IOP and medication use from baseline and the need for postoperative interventions. RESULTS: At 2 years, the rate of surgical success was lower in the MicroShunt group than in the trabeculectomy group (50.6% vs. 64.4%, P = 0.005). Mean diurnal IOP was reduced from 21.1 ± 4.9 mmHg at baseline to 13.9 ± 3.9 mmHg at 24 months in the MicroShunt group and from 21.1 ± 5.0 mmHg at baseline to 10.7 ± 3.7 mmHg at 24 months in the trabeculectomy group (P < 0.001 compared with baseline in both groups). Mean medication use decreased from 3.1 to 0.9 in the MicroShunt group and from 2.9 to 0.4 in the trabeculectomy group (P < 0.001 compared with baseline in both groups). Adverse events at 2 years were generally similar in the 2 groups, except that hypotony was more common in eyes undergoing trabeculectomy (51.1% vs. 30.9%, P < 0.001). Repositioning or explantation of the implant occurred in 6.8% of MicroShunt patients. The majority of these patients had device removal at the time of subsequent glaucoma surgery. Vision-threatening complications were uncommon in both groups. CONCLUSION: At 2 years, both the MicroShunt and trabeculectomy provided significant reductions in IOP and medication use, with trabeculectomy continuing to have greater surgical success. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Two-Year Performance and Safety Results of the MINIject Supraciliary Implant in Patients With Primary Open-Angle Glaucoma: Meta-Analysis of the STAR-I, II, III Trials.

PURPOSE: To evaluate the performance and safety of minimally invasive glaucoma surgery with a supraciliary drainage device (MINIject; iSTAR Medical, Wavre, Belgium) in primary open-angle glaucoma (POAG) as a stand-alone procedure. DESIGN: Meta-analysis. METHODS: At 11 sites in Colombia, France, Germany, India, Panama, and Spain, 82 patients were treated in 3 prospective, multicenter, interventional, nonrandomized trials (STAR-I, II, III). Data were pooled in a meta-analysis of up to 2 years of follow-up postimplantation. The main outcome measures were mean relative and absolute reduction in diurnal intraocular pressure (IOP) compared to baseline. Secondary outcomes included patients with IOP ≤18 mmHg, patients with IOP reduction ≥20%, number of IOP-lowering medications, adverse events, and endothelial cell density loss. RESULTS: At the 2-year follow-up (n = 66), mean IOP was reduced from 23.8 ± 3.3 mmHg at baseline to 14.4 ± 4.5 mmHg (-39.3%; P < 0.0001). An IOP reduction of ≥20% was achieved in 89.4% of patients, with 84.8% having an IOP ≤18 mmHg. IOP-lowering medications were reduced from a mean of 2.4 ± 1.1 to 1.4 ± 1.4 (P < 0.0001), with 37.9% of patients being medication-free at 2 years. Mean endothelial cell density loss at 2 years was 6.2 ± 9.1% compared to baseline and no patient had a loss >30%. CONCLUSIONS: This meta-analysis demonstrates the favorable safety and efficacy profile of a supraciliary device implanted in a stand-alone, ab-interno procedure in patients with mild-to-moderate POAG. The data demonstrate that MINIject is a safe and effective, bleb-free treatment option for patients requiring low target IOP up to 2 years.