Airway disease decreases the therapeutic potential of epithelial stem cells.

BACKGORUND: Tissue-engineered tracheal grafts (TETG) can be recellularized by the host or pre-seeded with host-derived cells. However, the impact of airway disease on the recellularization process is unknown. METHODS: In this study, we determined if airway disease alters the regenerative potential of the human tracheobronchial epithelium (hTBE) obtained by brushing the tracheal mucosa during clinically-indicated bronchoscopy from 48 pediatric and six adult patients. RESULTS: Our findings revealed that basal cell recovery and frequency did not vary by age or region. At passage 1, all samples produced enough cells to cellularize a 3.5 by 0.5 cm2 graft scaffold at low cell density (~ 7000 cells/cm2), and 43.75% could cellularize a scaffold at high cell density (~ 100,000 cells/cm2). At passage 2, all samples produced the number of cells required for both recellularization models. Further evaluation revealed that six pediatric samples (11%) and three (50%) adult samples contained basal cells with a squamous basal phenotype. These cells did not form a polarized epithelium or produce differentiated secretory or ciliated cells. In the pediatric population, the squamous basal cell phenotype was associated with degree of prematurity (< 28 weeks, 64% vs. 13%, p = 0.02), significant pulmonary history (83% vs. 34%, p = 0.02), specifically with bronchopulmonary dysplasia (67% vs. 19%, p = 0.01), and patients who underwent previous tracheostomy (67% vs. 23%, p = 0.03). CONCLUSIONS: In summary, screening high-risk pediatric or adult population based on clinical risk factors and laboratory findings could define appropriate candidates for airway reconstruction with tracheal scaffolds. LEVEL OF EVIDENCE: Level III Cohort study.

Validation of presence-only models for conservation planning and the application to whales in a multiple-use marine park.

Identification of species' Biologically Important Areas (BIAs) is fundamental to conservation planning and species distribution models (SDMs) are a powerful tool commonly used to do this. Presence-only data are increasingly being used to develop SDMs to aid the conservation decision-making process. The application of presence-only SDMs for marine species' is particularly attractive due to often logistical and economic costs of obtaining systematic species' distribution data. However, robust model validation is important for conservation management applications that require accurate and reliable species' occurrence data (e.g., spatially explicit risk assessments). This is commonly done using a random subset of the data and less commonly with fully independent test data. Here, we apply a spatial block cross-validation (CV) approach to validate a MaxEnt presence-only model using independent presence/absence survey data for a highly mobile, marine species (humpback whale, Megaptera novaengliae) in the Great Barrier Reef (GBR). A MaxEnt model was developed using opportunistic whale sightings (2003-2007) and then used to identify areas differing in habitat suitability (low, medium, high) to conduct a systematic, line-transect, aerial survey (2012) and derive a density surface model. A spatial block CV buffering strategy was used to validate the MaxEnt model, using the opportunistic sightings as training data and independent aerial survey sightings data as test data. Moderate performance measures indicate MaxEnt was reliable in identifying the distribution patterns of a mobile whale species on their breeding ground, indicated by areas of high density aligned to areas of high habitat suitability. Furthermore, we demonstrate that MaxEnt models can be useful and cost-effective for designing a sampling scheme to undertake systematic surveys that significantly reduces sampling effort. In this study, higher quality information on whale reproductive class (calf vs. non-calf groups) was obtained that the presence-only data lacked, while sampling only 18% of the GBR World Heritage Area. The validation approach using fully independent data provides greater confidence in the MaxEnt model, which indicates significant overlap with the main breeding ground of humpback whales and the inner shipping route. This is important when evaluating presence-only models within certain conservation management applications, such as spatial risk assessments.

Adaptation of an Intervention to Reduce Disparities in School HRQOL for Latino Childhood Cancer Survivors.

OBJECTIVE: Survivors of childhood leukemia, especially those from low socioeconomic status households, often experience persistent neurocognitive and academic impairment. This study adapted an existing parent training intervention to improve outcomes for low-acculturated, Spanish-speaking Latino parents of children with leukemia and pilot tested that intervention for feasibility. METHODS: Semistructured interviews were conducted with a focus group of 20 Latino parents of children treated for leukemia. Ten Latino families participated in a pilot study of the adapted parenting intervention, consisting of eight sessions over 6 months. RESULTS: Focus groups revealed that parents unanimously supported a parenting intervention but barriers to participation included time constraints, transportation issues, and anxiety in the hospital environment. The parents also highlighted cultural factors that could contribute to the health disparity, such as lack of knowledge and efficacy in facilitating their child's progress with learning and school. In the pilot study, adherence was 90%, establishing feasibility, and the adapted intervention was considered beneficial. The median parenting efficacy scores improved from preintervention to postintervention (median 3.40 vs. 3.94; p < .011), as did parent-reported school functioning of the child (median 50.00 vs. 60.00; p = .088). CONCLUSIONS: This study addressed a health disparity by culturally adapting a parenting intervention, which was designed to improve school functioning, to meet the needs and preferences of low-acculturated, Spanish-speaking families of children with leukemia in Southern California. The pilot study demonstrated that the adapted intervention is feasible and acceptable in the target population. A larger trial is underway to test the efficacy of this adapted parenting intervention.

Improving the echocardiographic assessment of pulmonary pressure using the tricuspid regurgitant signal-The "chin" vs the "beard".

AIM: Transthoracic echocardiography (TTE) is a fundamental investigation for the noninvasive assessment of pulmonary hemodynamics and right heart function. The aim of this study was to assess the correlation and agreement of Doppler calculation of right ventricular systolic pressure (RVSP) and pulmonary vascular resistance (PVR) using "chin" and "beard" measurements of tricuspid regurgitant velocity (TRVmax ), with invasive pulmonary artery systolic pressure (PASP) and PVR. METHODS: One hundred patients undergoing right heart catheterisation (RHC) and near simultaneous transthoracic echocardiography were studied. TRVmax was recorded for "chin" measurement (distinct peak TRVmax signal) and where available (63 patients), "beard" measurement (higher indistinct peak TRVmax signal). RESULTS: Measurable TRV signal was obtained in 96 patients. Mean RVSPchin 54.7 ± 22.7 mm Hg and RVSPbeard 68.6 = 23 ± 26.3 mm Hg (P < .001). There was strong correlation between both RVSPchin and RVSPbeard with invasive PASP (Pearson's r = .9, R2  = 0.82, P < .001 - r = .88, R = .78, P < .001, respectively.). Bland-Altman analysis for RVSPchin and RVSPbeard showed a mean bias of -0.5 mm Hg (95% limits of agreement -21.4 to 20.5 mm Hg) and -10.7 (95% LOA -35.5 to 14.2 mm Hg), respectively. Receiver operator characteristics of TRVmax "chin" and "beard" for diagnosis of pulmonary hypertension was assessed with optimal cut-offs being 2.8 m/s (sensitivity 93%, specificity 87%) and 3.2 m/s (sensitivity 91%, specificity 82%), respectively. There was similar correlation between PVRchin and PVRbeard (r = .87, R2  = 0.75, P < .001 and r = .86, R2  = 0.74, P < .001, respectively). At higher PVR, there was overestimation of calculated PVR using PVRbeard . CONCLUSION: The accuracy of noninvasive measurement of right heart pressures is increased using the "chin" in estimation of both RVSP and PVR.

Unmanned aerial vehicles for surveying marine fauna: assessing detection probability.

Aerial surveys are conducted for various fauna to assess abundance, distribution, and habitat use over large spatial scales. They are traditionally conducted using light aircraft with observers recording sightings in real time. Unmanned Aerial Vehicles (UAVs) offer an alternative with many potential advantages, including eliminating human risk. To be effective, this emerging platform needs to provide detection rates of animals comparable to traditional methods. UAVs can also acquire new types of information, and this new data requires a reevaluation of traditional analyses used in aerial surveys; including estimating the probability of detecting animals. We conducted 17 replicate UAV surveys of humpback whales (Megaptera novaeangliae) while simultaneously obtaining a 'census' of the population from land-based observations, to assess UAV detection probability. The ScanEagle UAV, carrying a digital SLR camera, continuously captured images (with 75% overlap) along transects covering the visual range of land-based observers. We also used ScanEagle to conduct focal follows of whale pods (n = 12, mean duration = 40 min), to assess a new method of estimating availability. A comparison of the whale detections from the UAV to the land-based census provided an estimated UAV detection probability of 0.33 (CV = 0.25; incorporating both availability and perception biases), which was not affected by environmental covariates (Beaufort sea state, glare, and cloud cover). According to our focal follows, the mean availability was 0.63 (CV = 0.37), with pods including mother/calf pairs having a higher availability (0.86, CV = 0.20) than those without (0.59, CV = 0.38). The follows also revealed (and provided a potential correction for) a downward bias in group size estimates from the UAV surveys, which resulted from asynchronous diving within whale pods, and a relatively short observation window of 9 s. We have shown that UAVs are an effective alternative to traditional methods, providing a detection probability that is within the range of previous studies for our target species. We also describe a method of assessing availability bias that represents spatial and temporal characteristics of a survey, from the same perspective as the survey platform, is benign, and provides additional data on animal behavior.

An Evolving Ecosystem for Natural Language Processing in Department of Veterans Affairs.

In an ideal clinical Natural Language Processing (NLP) ecosystem, researchers and developers would be able to collaborate with others, undertake validation of NLP systems, components, and related resources, and disseminate them. We captured requirements and formative evaluation data from the Veterans Affairs (VA) Clinical NLP Ecosystem stakeholders using semi-structured interviews and meeting discussions. We developed a coding rubric to code interviews. We assessed inter-coder reliability using percent agreement and the kappa statistic. We undertook 15 interviews and held two workshop discussions. The main areas of requirements related to; design and functionality, resources, and information. Stakeholders also confirmed the vision of the second generation of the Ecosystem and recommendations included; adding mechanisms to better understand terms, measuring collaboration to demonstrate value, and datasets/tools to navigate spelling errors with consumer language, among others. Stakeholders also recommended capability to: communicate with developers working on the next version of the VA electronic health record (VistA Evolution), provide a mechanism to automatically monitor download of tools and to automatically provide a summary of the downloads to Ecosystem contributors and funders. After three rounds of coding and discussion, we determined the percent agreement of two coders to be 97.2% and the kappa to be 0.7851. The vision of the VA Clinical NLP Ecosystem met stakeholder needs. Interviews and discussion provided key requirements that inform the design of the VA Clinical NLP Ecosystem.

Designing an effective mark-recapture study of Antarctic blue whales.

To properly conserve and manage wild populations, it is important to have information on abundance and population dynamics. In the case of rare and cryptic species, especially in remote locations, surveys can be difficult and expensive, and run the risk of not producing sample sizes large enough to produce precise estimates. Therefore, it is crucial to conduct preliminary analysis to determine if the study will produce useable estimates. The focus of this paper is a proposed mark-recapture study of Antarctic blue whales (Balaenoptera musculus intermedia). Antarctic blue whales were hunted to near extinction up until the mid- 1960s, when commercial exploitation of this species ended. Current abundance estimates are a decade old. Furthermore, at present, there are no formal circumpolar-level cetacean surveys operating in Antarctic waters and, specifically, there is no strategy to monitor the potential recovery of Antarctic blue whales. Hence the work in this paper was motivated by the need to inform decisions on strategies for future monitoring of Antarctic blue whale population. The paper describes a model to predict the precision and bias of estimates from a proposed survey program. The analysis showed that mark-recapture is indeed a suitable method to provide a circumpolar abundance estimate of Antarctic blue whales, with precision of the abundance, at the midpoint of the program, predicted to be between 0.2 and 0.3. However, this was only if passive acoustic tracking was utilized to increase the encounter rate. The analysis also provided guidance on general design for an Antarctic blue whale program, showing that it requires a 12-year duration; although surveys do not necessarily need to be run every year if multiple vessels are available to clump effort. Mark-recapture is based on a number of assumptions; it was evident from the analysis that ongoing analysis and monitoring of the data would be required to check such assumptions hold (e.g., test for heterogeneity), with the modeling adjusted as needed.

Does preoperative calcium and 1, 25 OH vitamin D supplementation impact postoperative hypocalcemia and length of stay following pediatric thyroidectomy?

OBJECTIVE: To investigate whether perioperative calcium and 1,25 OH vitamin D supplementation (PCDS) influences the rates of postoperative hypocalcemia and length of stay (LOS) following pediatric thyroidectomy. STUDY DESIGN: Retrospective Cohort Review. SETTING: Tertiary children's hospital. METHODS: 94 patients who underwent completion or total thyroidectomy with or without concomitant neck dissection from 2010 to 2020 at a single institution were included. Patients with pre-existing hypocalcemia or preoperative vitamin D insufficiency were excluded. Rates of postoperative hypocalcemia and LOS were compared for patients receiving PCDS to those receiving no supplementation. RESULTS: Thirty percent of patients with PCDS had documented postoperative hypocalcemia compared to 64% of patients without PCDS (p = 0.01). Patients with PCDS had a median LOS of 30 h compared to 36 h (p = 0.002). Multivariable analyses confirmed that patients with PCDS had lower odds of postoperative hypocalcemia (OR: 0.32, CI: 0.11, 0.89) and shorter LOS by 17 h (SE: 8, p = 0.04) after adjustment for confounders. CONCLUSION: PCDS is associated with significantly lower risk of hypocalcemia and shorter LOS. Standardizing preoperative care for pediatric patients undergoing thyroidectomy may decrease variability and improve outcomes following surgery.

Dynamic Volumetric Computed Tomography Angiography is an Effective Method to Evaluate Tracheomalacia in Children.

OBJECTIVE: Standard methods to evaluate tracheal pathology in children, including bronchoscopy, may require general anesthesia. Conventional dynamic proximal airway imaging in noncooperative children requires endotracheal intubation and/or medically induced apnea, which may affect airway mechanics and diagnostic performance. We describe a technique for unsedated dynamic volumetric computed tomography angiography (DV-CTA) of the proximal airway and surrounding vasculature in children and evaluate its performance compared to the reference-standard of rigid bronchoscopy. METHODS: Children who had undergone DV-CTA and bronchoscopy in one-year were retrospectively identified. Imaging studies were reviewed by an expert reader blinded to the bronchoscopy findings of primary or secondary tracheomalacia. Airway narrowing, if present, was characterized as static and/or dynamic, with tracheomalacia defined as >50% collapse of the tracheal cross-sectional area in exhalation. Pearson correlation was used for comparison. RESULTS: Over a 19-month period, we identified 32 children (median age 8 months, range 3-14 months) who had undergone DV-CTA and bronchoscopy within a 90-day period of each other. All studies were unsedated and free-breathing. The primary reasons for evaluation included noisy breathing, stridor, and screening for tracheomalacia. There was excellent agreement between DV-CTA and bronchoscopy for diagnosis of tracheomalacia (κ = 0.81, p < 0.001), which improved if children (n = 25) had the studies within 30 days of each other (κ = 0.91, p < 0.001). CTA provided incremental information on severity, and cause of secondary tracheomalacia. CONCLUSION: For most children, DV-CTA requires no sedation or respiratory manipulation and correlates strongly with bronchoscopy for the diagnosis of tracheomalacia. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:410-416, 2023.

Association of Vibrotactile Biofeedback With Reduced Ergonomic Risk for Surgeons During Tonsillectomy.

Importance: Work-related musculoskeletal disorders are common among otolaryngologists and can be associated with decreased productivity, missed workdays, and reduced quality of life. Ergonomic risk for surgeons is elevated during common otolaryngology procedures; current ergonomic interventions lack the ability to provide real-time feedback. The ability to quantify and mitigate ergonomic risk during surgery may reduce work-related musculoskeletal disorders. Objective: To quantify the association of vibrotactile biofeedback with intraoperative ergonomic risk to surgeons during tonsillectomy. Design, Setting, and Participants: This cross-sectional study was conducted between June 2021 and October 2021 at a freestanding tertiary care children's hospital and included 11 attending pediatric otolaryngologists. Data analysis was conducted from August to October 2021. Interventions: Real-time quantification of ergonomic risk during tonsillectomy and the use of a vibrotactile biofeedback posture monitor. Main Outcomes and Measures: Association of vibrotactile biofeedback with objective measures of ergonomic risk. Assessment tools included the Rapid Upper Limb Assessment, craniovertebral angle, and time spent in an at-risk posture. Results: Eleven surgeons (mean [SD] age 42 [7] years; 2 women [18%]) performed 126 procedures with continuous posture monitoring in the presence (80 [63%]) and absence (46 [37%]) of vibrotactile biofeedback. No complications or delays associated with the device were reported. Intraoperative vibrotactile biofeedback was associated with improved Rapid Upper Limit Assessment neck, trunk, and leg scores by 0.15 (95% CI, 0.05-0.25), improved craniovertebral angle by 1.9 (95% CI, 0.32-3.40), and decreased overall time spent in an at-risk posture by 30% (95% CI, 22%-39%). Conclusions and Relevance: The results of this cross-sectional study suggest that use of a vibrotactile biofeedback device to quantify and mitigate ergonomic risk for surgeons is feasible and safe while performing surgery. Vibrotactile biofeedback was associated with reduced ergonomic risk during tonsillectomy and may have a role in improving surgical ergonomics and preventing work-related musculoskeletal disorders.

Dynamic contact mechanics of radial tears of the lateral meniscus: implications for treatment.

PURPOSE: To characterize the effect of radial tears (RTs) of the lateral meniscus and their subsequent treatment (inside-out repair, partial meniscectomy) on joint contact mechanics during simulated gait. METHODS: Six human cadaveric knees were mounted on a simulator programmed to mimic human gait. A sensor was inserted below the lateral meniscus to measure peak joint contact pressure location, magnitude, and contact area. The following conditions were compared: intact meniscus, 30% RT (at the popliteal hiatus), 60% RT, 90% RT, repair, and partial meniscectomy. Data were analyzed in the midstance phase of gait (14% and 45%) when axial force was at its highest (2,100 N). RESULTS: Intact knees had peak contact pressures of 5.9 ± 0.9 MPa and 6.4 ± 1.1 MPa at 14% and 45% of gait, respectively. RTs of up to and including 60% had no effect on pressure magnitude or location. RTs of 90% resulted in significantly increased peak pressure (8.4 ± 1.1 MPa) in the postero-peripheral aspect of the tibial plateau and reduced contact area versus the intact knee, at 45% of gait. Repair resulted in a significant decrease in peak pressure (7.7 ± 1.0 MPa) relative to 90% RT but had no effect on contact area. Partial lateral meniscectomy resulted in areas and pressures that were not significantly different from 90% tears (8.7 ± 1.5 MPa). CONCLUSIONS: Simulated large RTs of the lateral meniscus in the region of the popliteal hiatus show unfavorable dynamic contact mechanics that are not significantly different from those resulting from a partial lateral meniscectomy. Pressure was significantly reduced with inside-out repair but was not affected by partial meniscectomy; contact area was not restored to that of the intact condition for either procedure. CLINICAL RELEVANCE: Large RTs in the region of the popliteal hiatus show unfavorable dynamic contact mechanics.

Assessing the use of telehealth for the surgical management of recurrent otitis media.

OBJECTIVE: To compare the incidence of middle ear effusion (MEE) at the time of bilateral tympanostomy tube insertion (BTI) for recurrent acute otitis media (rAOM) patients initially seen in-office or via telehealth. METHODS: After obtaining IRB approval from Nationwide Children's Hospital, a total of 524 patients evaluated for rAOM were retrospectively reviewed after being divided into two cohorts: those seen via a telehealth visit from April to June of 2020 (n = 140), and those seen via an in-person visit from April to June of 2019 (n = 384). Recommendation for BTI was captured for each patient following their visit. Clinical characteristics documented at the time of the visit, such as history of intramuscular (IM) antibiotic use and hearing or speech concerns were also captured to determine whether both telehealth and in-person cohorts were similar in clinical presentation. For BTI patients, the presence or absence of MEE in either ear at the time of BTI was recorded. Patients with cleft palate or prior BTI were excluded. RESULTS: 51.43% (72/140) of patients in the telehealth cohort were recommended for BTI. Of those recommended, 87.50% (63/72) underwent BTI. Of these, 31.75% (20/63) had a MEE at the time of BTI. In the in-office cohort, 69.01% (265/384) of patients were recommended for BTI. Of those recommended, 92.83% (246/265) underwent BTI. Of these, 69.92% (172/246) had a MEE at the time of BTI. CONCLUSION: There were significantly less middle ear effusions in the telehealth cohort compared to the in-office cohort (p < 0.0001). It is well understood that telehealth is limited in its physical exam capabilities. It is possible that the use of telehealth for the surgical management of rAOM may lead to more procedures on patients without MEE.

Using the Craniovertebral Angle to Quantify Intraoperative Ergonomic Risk.

OBJECTIVE: To measure the craniovertebral angle during tonsillectomy, assess the interrater reliability of our methodology, and investigate the correlations of the Rapid Upper Limb Assessment and the craniovertebral angle to quantify ergonomic risk. STUDY DESIGN: Prospective, observational study. SETTING: Tertiary care pediatric institution. METHODS: Neck posture was evaluated for 92 images with 7 surgeons. Lateral images of the surgeon were captured every minute in a standardized method. Images were assessed by 3 raters, measuring the craniovertebral angle, defined as the angle between a horizontal line through the C7 vertebrae and another line through C7 and the tragus of the ear. Interrater reliability of the craniovertebral angle was evaluated using the κ statistic. Per prior publications, reports of neck pain were frequent when the craniovertebral angle value was <50°; thus, we defined an abnormal posture if the craniovertebral angle was <50°. RESULTS: Mean (SD) craniovertebral angle during tonsillectomy was 26.0° (11.3°). One hundred percent of procedures had at least 1 assessment of abnormal posture. The lowest interrater reliability was 0.77 (CI: 0.67-0.87). Rapid Upper Limb Assessment and craniovertebral angle (CA) correlation was -0.12 (P = .27) and, therefore, null. CONCLUSION: Poor posture during tonsillectomy places otolaryngologists at intraoperative ergonomic risk. The craniovertebral angle is a predictor of future neck pain, and a pathologic neck position during tonsillectomy was identified. Given the high interrater reliability, our approach to assessing intraoperative surgical ergonomics was validated. Overall, RULA and the CA are not a substitute for one another but complementary.

Organotypic stromal cells impact endothelial cell transcriptome in 3D microvessel networks.

Endothelial cells line all major blood vessels and serve as integral regulators of many functions including vessel diameter, cellular trafficking, and transport of soluble mediators. Despite similar functions, the phenotype of endothelial cells is highly organ-specific, yet our understanding of the mechanisms leading to organ-level differentiation is incomplete. We generated 3D microvessel networks by combining a common naïve endothelial cell with six different stromal cells derived from the lung, skin, heart, bone marrow, pancreas, and pancreatic cancer. Single cell RNA-Seq analysis of the microvessel networks reveals five distinct endothelial cell populations, for which the relative proportion depends on the stromal cell population. Morphologic features of the organotypic vessel networks inversely correlate with a cluster of endothelial cells associated with protein synthesis. The organotypic stromal cells were each characterized by a unique subpopulation of cells dedicated to extracellular matrix organization and assembly. Finally, compared to cells in 2D monolayer, the endothelial cell transcriptome from the 3D in vitro heart, skin, lung, and pancreas microvessel networks are more similar to the in vivo endothelial cells from the respective organs. We conclude that stromal cells contribute to endothelial cell and microvessel network organ tropism, and create an endothelial cell phenotype that more closely resembles that present in vivo.

Biobanked tracheal basal cells retain the capacity to differentiate.

Objective: While airway epithelial biorepositories have established roles in the study of bronchial progenitor stem (basal) cells, the utility of a bank of tracheal basal cells from pediatric patients, who have or are suspected of having an airway disease, has not been established. In vitro study of these cells can enhance options for tracheal restoration, graft design, and disease modeling. Development of a functional epithelium in these settings is a key measure. The aim of this study was the creation a tracheal basal cell biorepository and assessment of recovered cells. Methods: Pediatric patients undergoing bronchoscopy were identified and endotracheal brush (N = 29) biopsies were collected. Cells were cultured using the modified conditional reprogramming culture (mCRC) method. Samples producing colonies by day 14 were passaged and cryopreserved. To explore differentiation potential, cells were thawed and differentiated using the air-liquid interface (ALI) method. Results: No adverse events were associated with biopsy collection. Of 29 brush biopsies, 16 (55%) were successfully cultured to passage 1/cryopreserved. Samples with higher initial cell yields were more likely to achieve this benchmark. Ten unique donors were then thawed for analysis of differentiation. The average age was 2.2 ± 2.2 years with five donors (50%) having laryngotracheal pathology. Nine donors (90%) demonstrated differentiation capacity at 21 days of culture, as indicated by detection of ciliated cells (ACT+) and mucous cells (MUC5B+). Conclusion: Pediatric tracheal basal cells can be successfully collected and cryopreserved. Recovered cells retain the ability to differentiate into epithelial cell types in vitro. Level of Evidence: Level 3.

Reduction of Distress and Attrition in a 6-Week Psychoeducational Group: A Pilot Study.

Purpose: The distress and unique needs of AYAs (adolescent/young adults) with an oncology diagnosis have been well explored and documented in the literature. However, effective means of reducing distress and meeting needs has been more elusive. This study explored the impact of a 6-week psychoeducational pilot group on AYA distress. Methods: Patient surveys and literature review were conducted to develop content for a 6-week psychoeducational group to reduce AYA distress through peer support and increased knowledge related to symptom management, physician communication, body image, family relationships, autonomy, sexuality, fertility, and coping skills. Distress was measured using the Hospital Anxiety and Depression Scale (HADS). Results: Twenty-one AYAs receiving oncology treatment enrolled in the group. Thirteen completed the program. Reasons for attrition included transportation, severity of symptoms, procedures, disinterest, and death. A correlated t-test demonstrated a significant decrease in HADS total score from pre- to post-test. Conclusion: This pilot study suggests that providing AYAs with information relative to their unique developmental needs and opportunities to process those needs in an environment of peers is challenging but can have benefit. nCT01817335.

Bone mass and adaptation to mechanical loading are sexually dimorphic in adult osteoblast-specific ERα knockout mice.

Estrogen receptor-alpha (ERα) regulates bone mass and is implicated in bone tissue's response to mechanical loading. The effects of ERα deletion in mice depend on sex, anatomical location, and the cellular stage at which ERα is removed. Few studies have investigated the effect of age on the role of ERα in skeletal maintenance and functional adaptation. We previously demonstrated that bone mass and adaptation to loading were altered in growing 10-week-old female and male mice lacking ERα in mature osteoblasts and osteocytes (pOC-ERαKO). Here our goal was to determine the effects of ERα and mechanical loading in skeletally-mature adult mice. We subjected 26-week-old skeletally-mature adult pOC-ERαKO and littermate control (LC) mice of both sexes to two weeks of in vivo cyclic tibial loading. ERα deletion in male mice did not alter bone mass or the response to loading. Adult female pOC-ERαKO mice had reduced cancellous and cortical bone mass and increased adaptation to high-magnitude mechanical loading compared to LC mice. Thus, ERα deletion from mature osteoblasts reduced the bone mass and increased the mechanoadaptation of adult female but not male mice. Additionally, compared to our previous work in young mice, adult female mice had greatly reduced mechanoadaptation and adult male mice retained most of their mechanoadaptation with age.

Lumbar spine intervertebral disc gene delivery of BMPs induces anterior spine fusion in lewis rats.

Minimally invasive techniques and biological autograft alternatives such as the bone morphogenetic proteins (BMPs) can reduce morbidity associated with spinal fusions. This study was a proof-of-concept for gene-therapy-mediated anterior spine fusion that could be adapted to percutaneous technique for clinical use. Isogeneic bone marrow stromal cells genetically programmed to express b-galactosidase (LACZ, a marker gene), BMP2, BMP7, a mixture of BMP2 and BMP7 infected cells (homodimers, HM), or BMP2/7 heterodimers (HT) were implanted into the discs between lumbar vertebrae 4 and 5 (L4/5) and L5/6 of male Lewis rats. Spine stiffening was monitored at 4, 8 and 12 weeks using noninvasive-induced angular displacement (NIAD) testing. At 12 weeks isolated spines were assessed for fusion and bone formation by palpation, biomechanical testing [four-point bending stiffness, moment to failure in extension, and in vitro angular displacement (IVAD)], faxitron x-rays, microCT, and histology. Progressive loss of NIAD occurred in only the HT group (p < 0.001), and biomechanical tests correlated with the NIAD results. Significant fusion occurred only in the HT group (94% of animals with one or both levels) as assessed by palpation (p < 0.001), which predicted HT bone production assessed by faxitron (p ≤ 0.001) or microCT (p < 0.023). Intervertebral bridging bone was consistently observed only in HT-treated specimens. Induced bone was located anterior and lateral to the disc space, with no bone formation noted within the disc. Percutaneous anterior spine fusions may be possible clinically, but induction of bone inside the disc space remains a challenge.

Retrieved highly crosslinked UHMWPE acetabular liners have similar wear damage as conventional UHMWPE.

BACKGROUND: Highly crosslinked UHMWPE is associated with increased wear resistance in hip simulator and clinical studies. Laboratory and case studies, however, have described rim fracture in crosslinked acetabular liners. Controversy exists, therefore, on the relative merits of crosslinked liners over conventional liners in terms of wear performance versus resistance to fatigue cracking. QUESTIONS/PURPOSES: We asked whether crosslinked liners would show less surface damage than conventional liners but would be more susceptible to fatigue damage. METHODS: We examined 36 conventional UHMWPE and 39 crosslinked UHMWPE retrieved implants with similar patient demographics and identical design for evidence of wear damage, including articular surface damage, impingement, screw-hole creep, and rim cracks. RESULTS: We observed no difference in wear damage scores for the two liners. Conventional liners more frequently impinged but were more often elevated with smaller head sizes. We observed creep in approximately 70% of both types of liners. Incipient rim cracks were found in five crosslinked liners, and one liner had a rim fracture. Only one conventional liner had an incipient rim crack. CONCLUSIONS: Contrary to our expectation, damage was similar between crosslinked and conventional UHMWPE liners. Moreover, the 15% occurrence (six of 39) of incipient or complete fractures in crosslinked liners as compared with a 3% occurrence (one of 36) in conventional liners may have implications for the long-term performance of crosslinked liners. Longer-term studies will be necessary to establish the fate of rim cracks and thus the overall clinical fatigue performance of crosslinked liners.

Implant design influences tibial post wear damage in posterior-stabilized knees.

BACKGROUND: The tibial post in posterior-stabilized total knees is a potential source of polyethylene wear debris, but the relationship between the shape and location of the tibial post in relation to the tibiofemoral bearing surfaces and the subsequent wear damage patterns remains unknown. QUESTIONS/PURPOSES: We used observations made on retrieved implant components from three contemporary posterior-stabilized knee designs to examine how differences in tibial post design affected wear damage on the post. METHODS: We examined 113 retrieved Zimmer NexGen(®), 103 Exactech Optetrak(®), and 58 Smith and Nephew Genesis(®) II posterior-stabilized inserts using a subjective scale to grade post damage. RESULTS: All 274 inserts demonstrated wear damage. Total wear scores and scores for wear damage on the anterior post differed among designs: Optetrak(®) 20 ± 4 and 5 ± 1, NexGen(®) 13 ± 4 and 3 ± 1, and Genesis(®) II 8 ± 3 and 1 ± 1, respectively. The Optetrak(®) had predominantly anterior wear damage, the NexGen(®) had more global wear damage, and the Genesis(®) II had predominantly posterior wear damage. Tibial post wear damage and anterior post wear damage were primarily determined by implant design and to a lesser extent by length of implantation and revision diagnosis. CONCLUSIONS: Although tibial post wear damage is multifactorial, the primary determinant of wear damage, and specifically anterior wear damage, is implant design. CLINICAL RELEVANCE: The constraint provided by the posterior-stabilized post-cam contact in modern knee arthroplasties is reflected in the wear damage patterns that occur during in vivo use. Unintended constraint such as anterior impingement should be addressed through design modifications for future posterior-stabilized knee arthroplasties.