Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

Online video resources pertaining to cerebral palsy: A YouTube-based quality control study.

Aim: To assess the content and quality of YouTube videos related to cerebral palsy to provide insights into the online video resources available for individuals affected by cerebral palsy and suggest strategies for improvement. Methods: YouTube videos were analyzed based on interaction parameters, content characteristics/category, and video source. Video reliability and quality were assessed using the Journal of American Medical Association benchmark, Global Quality Scale, and cerebral palsy-specific score. Statistical analyses examined associations between video characteristics and reliability/quality scores. Results: The average video (n = 48) length was 6.8 min, with 29 informational and 19 experiential videos. The mean Journal of American Medical Association score was 2.0, indicating moderate reliability. The Global Quality Scale suggested good quality content (average: 3.5), but only 14% were rated as good via cerebral palsy-specific score. Higher views were associated with higher Journal of American Medical Association score and cerebral palsy-specific score (p = 0.002 and p = 0.006), and nonphysician medical expert videos had lower Journal of American Medical Association scores than academic videos (p = 0.042). Video content was not significantly associated with either score. Conclusion: YouTube provides moderate to good quality information on cerebral palsy. Critical evaluation of video sources and content is essential. Findings can guide strategies to enhance the quality of cerebral palsy-related YouTube content, benefiting individuals with cerebral palsy, health care providers, and caregivers.

3D CT modeling demonstrates the anatomic feasibility of S1AI screw trajectory for spinopelvic fixation in neuromuscular scoliosis.

PURPOSE: In patients with neuromuscular scoliosis undergoing posterior spinal fusion, the S2 alar iliac (S2AI) screw trajectory is a safe and effective method of lumbopelvic fixation but can lead to implant prominence. Here we use 3D CT modeling to demonstrate the anatomic feasibility of the S1 alar iliac screw (S1AI) compared to the S2AI trajectory in patients with neuromuscular scoliosis. METHODS: This retrospective study used CT scans of 14 patients with spinal deformity to create 3D spinal reconstructions and model the insertional anatomy, max length, screw diameter, and potential for implant prominence between 28 S2AI and 28 S1AI screw trajectories. RESULTS: Patients had a mean age of 14.42 (range 8-21), coronal cobb angle of 85° (range 54-141), and pelvic obliquity of 28° (range 4-51). The maximum length and diameter of both screw trajectories were similar. S1AI screws were, on average, 6.3 ± 5 mm less prominent than S2AI screws relative to the iliac crests. S2AI screws were feasible in all patients, while in two patients, posterior elements of the lumbar spine would interfere with S1AI screw insertion. CONCLUSION: In this cohort of patients with neuromuscular scoliosis, we demonstrate that the S1AI trajectory offers comparable screw length and diameter to an S2AI screw with less implant prominence. An S1AI screw, however, may not be feasible in some patients due to interference from the posterior elements of the lumbar spine.

Use of Peripheral Nerve Blocks Is Not Associated With Decreased Postoperative Opioid Prescription After ACL Reconstruction in Adolescents.

The rate of anterior cruciate ligament (ACL) injuries and reconstruction in pediatric patients is increasing. Perioperative peripheral nerve blocks (PNBs) are widely used for pain management in this population. We used a multi-state administrative claims database to describe the effect of PNB after ACL reconstruction on postoperative opioid consumption. We identified patients 10 to 18 years old undergoing primary ACL reconstruction between 2014 and 2016 in an administrative claims database. Patients filling an outpatient perioperative prescription for opioids with at least 1 year of follow-up were included. We stratified patients based on PNB. Our primary outcome was opioid prescription patterns (in morphine milligram equivalents [MMEs]) and incidence of opioid represcription. Of the 4459 cases, 2432 (54.5%) of the patients were given a PNB during ACL reconstruction while 2027 (45.5%) were not. Patients with PNB were prescribed more MMEs per day (76.1±41.7 vs 62.7±35.7 MMEs, P<.001), more pills (63.6±53.1 vs 54.4±40.6 pills, P<.001), higher MMEs per pill (10.0±9.5 vs 8.3±5.0 MMEs, P<.001), and more total MMEs (460.6±259.4 vs 355.7±215.1 MMEs, P<.001) than patients without PNB. Adjusting for prescription patterns and demographic variables with logistic regression, PNBs were associated with a 60% increase in the odds of opioid represcription within 30 days and a 32% increase in the odds of opioid represcription within 90 days. We demonstrated an increase in postoperative opioid prescription rates with PNB after ACL reconstruction. [Orthopedics. 2024;47(2):83-88.].

Concentrated Economic Disadvantage Predicts Resource Utilization After Total Knee Arthroplasty.

BACKGROUND: The Index of Concentration at the Extremes (ICE), a measure of geographic socioeconomic polarization, predicts several health outcomes but has not been evaluated concerning total knee arthroplasty (TKA). This study evaluates ICE as a predictor of post-TKA resource utilization. METHODS: Using the Healthcare Cost and Utilization Project's New York State database from 2016 to 2017, we retrospectively evaluated 57,426 patients ≥50 years undergoing primary TKA. The ICE values for extreme concentrations of income and race were calculated using United States Census Bureau data with the formula ICEi = (Pi-Di)/Ti where Pi, Di, and Ti are the number of households in the most privileged extreme, disadvantaged extreme, and total population in zip code i, respectively. Extremes of privilege and disadvantage were defined as ≥$150,000 versus <$25,000 for income and non-Hispanic White versus non-Hispanic Black for race. Association of ICE values, demographics, and comorbidities with 90-day readmission and 90-day emergency department (ED) visits was examined using multivariable analysis. RESULTS: Overall 90-day readmission and ED visit rates were 12.8% and 9.4%, respectively. On multivariable analysis, the lowest ICEIncome quintile (concentrated poverty) predicted 90-day readmission (odds ratio 1.17, 95% confidence interval 1.05 to 1.30, P = .005) and 90-day ED visit (odds ratio 1.22, 95% confidence interval 1.08 to 1.38, P = .001). The ICERace was not predictive of either outcome. CONCLUSION: Patients in communities with the lowest ICEIncome values use more inpatient and ED resources after primary TKA. Incorporating ICEIncome into risk-adjusted payment models may help align incentives for equitable care.

Effectiveness of an early operating room start time in managing pediatric trauma.

BACKGROUND: The timing of operative treatment for pediatric supracondylar humerus fractures (SCHF) and femoral shaft fractures (FSF) remains controversial. Many fractures previously considered to be surgical emergencies, such as SCHF and open fractures, are now commonly being treated the following day. When presented with an urgent fracture overnight needing operative treatment, the on-call surgeon must choose whether to mobilize resources for a late-night case or to add the case to an elective schedule of the following day. AIM: To describe the effect of a program allowing an early operating room (OR) start for uncomplicated trauma prior to an elective day of surgery to decrease wait times for surgery for urgent fractures admitted overnight. METHODS: Starting in October 2017, patients were eligible for the early slot in the OR at the discretion of the surgeon if they were admitted after 21:00 the previous night and before 05:00. We compared demographics and timing of treatment of SCHF and FSF treated one year before and after implementation as well as the survey responses from the surgical team. RESULTS: Of the 44 SCHF meeting inclusion criteria, 16 received treatment before implementation while 28 were treated after. After implementation, the mean wait time for surgery decreased by 4.8 h or 35.4% (13.4 h vs 8.7 h; P = 0.001). There were no significant differences in the operative duration, time in the post anesthesia care unit, and wait time for discharge. Survey results demonstrated decreased popularity of the program among nurses and anesthesiologists relative to surgeons. Whereas 57% of the surgeons believed that the program was effective, only 9% of anesthesiologists and 16% of nurses agreed. The program was ultimately discontinued given the dissatisfaction. CONCLUSION: Our findings demonstrate significantly reduced wait times for surgery for uncomplicated SCHF presenting overnight while discussing the importance of shared decision-making with the stakeholders. Although the program produced promising results, it also created new conflicts within the OR staff that led to its discontinuation at our institution. Future implementations of such programs should involve stakeholders early in the planning process to better address the needs of the OR staff.

Spinal fusion is an aerosol generating procedure.

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 can occur during aerosol generating procedures. Several steps in spinal fusion may aerosolize blood but little data exists to quantify the risk this may confer upon surgeons. Aerosolized particles containing infectious coronavirus are typically 0.5-8.0 µm. AIM: To measure the generation of aerosols during spinal fusion using a handheld optical particle sizer (OPS). METHODS: We quantified airborne particle counts during five posterior spinal instrumentation and fusions (9/22/2020-10/15/2020) using an OPS near the surgical field. Data were analyzed by 3 particle size groups: 0.3-0.5 µm/m3, 1.0-5.0 µm/m3, and 10.0 µm/m3. We used hierarchical logistic regression to model the odds of a spike in aerosolized particle counts based on the step in progress. A spike was defined as a > 3 standard deviation increase from average baseline levels. RESULTS: Upon univariate analysis, bovie (P < 0.0001), high speed pneumatic burring (P = 0.009), and ultrasonic bone scalpel (P = 0.002) were associated with increased 0.3-0.5 µm/m3 particle counts relative to baseline. Bovie (P < 0.0001) and burring (P < 0.0001) were also associated with increased 1-5 µm/m3 and 10 µm/m3 particle counts. Pedicle drilling was not associated with increased particle counts in any of the size ranges measured. Our logistic regression model demonstrated that bovie (OR = 10.2, P < 0.001), burring (OR = 10.9, P < 0.001), and bone scalpel (OR = 5.9, P < 0.001) had higher odds of a spike in 0.3-0.5 µm/m3 particle counts. Bovie (OR = 2.6, P < 0.001), burring (OR = 5.8, P < 0.001), and bone scalpel (OR = 4.3, P = 0.005) had higher odds of a spike in 1-5 µm/m3 particle counts. Bovie (OR = 0.3, P < 0.001) and drilling (OR = 0.2, P = 0.011) had significantly lower odds of a spike in 10 µm/m3 particle counts relative to baseline. CONCLUSION: Several steps in spinal fusion are associated with increased airborne particle counts in the aerosol size range. Further research is warranted to determine if such particles have the potential to contain infectious viruses. Previous research has shown that electrocautery smoke may be an inhalation hazard for surgeons but here we show that usage of the bone scalpel and high-speed burr also have the potential to aerosolize blood.

Pediatric meniscus morphology varies with age: a cadaveric study.

PURPOSE: In adolescent patients, meniscal tear injury can occur either in isolation (e.g., discoid lateral meniscus tears) or in association with other traumatic injuries including tibial eminence fracture or ACL tear. Damage to meniscal integrity has been shown to increase contact pressure in articular cartilage, increasing risk of early onset osteoarthritis. In symptomatic patients failing conservative management, surgical intervention via meniscus repair or meniscus transplant is indicated. The purpose of this study was to evaluate the radial dimensions of pediatric menisci throughout development. The hypothesis was that the average radial meniscus dimensions will increase as specimen age increases, and mean medial and lateral region measurements will increase at a linear rate. METHODS: Seventy-eight skeletally immature knee cadaver specimens under age 12 years were included in this study. The meniscal specimens were photographed in the axial view with ruler in the plane of the tibial plateau and analyzed using computer-aided design (CAD) software (Autodesk Fusion 360). Measurements were taken from inner to outer meniscus rims at five 45 degree intervals using the clockface as a reference (12:00, 1:30, 3:00, 4:30, 6:00), and total area of meniscus and tibial plateau was recorded. Generalized linear models were used to evaluate the associations of radial width measurements with age, tibial coverage, and lateral vs. medial meniscus widths. RESULTS: All radial width measurements increased significantly with specimen age (p ≤ 0.002), and all lateral-medial meniscal widths increased (p < 0.001). The anterior zones of the meniscus were found to increase at the slowest rate compared to other regions. Tibial plateau coverage was found to not significantly vary with age. CONCLUSIONS: Meniscus radial width and lateral-medial meniscus width are related to age. The anterior width of the meniscus varied least with age. Improved anatomic understanding may help surgeons more effectively plan for meniscus repair, discoid resection/saucerization/repair, and also support appropriate selection of meniscus allograft for transplantation.

Does spinal deformity affect adolescents' quality of life before we tell them it should?

PURPOSE: The Scoliosis Research Society 22r Questionnaire(SRS-22r) is the standard for assessing health-related quality of life(HRQoL) in patients with adolescent idiopathic scoliosis. Here we investigate whether patients' perceptions of their HRQoL are influenced by knowledge of scoliosis and counseling by an orthopedic surgeon. METHODS: Patients ages 10-18 years referred for their first visit with an orthopaedic surgeon for scoliosis were enrolled from 9/30/19 to 10/22/20. Patients completed the SRS-22r pre- and post-visit. A Wilcoxon signed-rank test was used to analyze the SRS-22r scores. RESULTS: 52 patients participated in the study at a mean age of 14.3 years (95% CI 13.8-14.8 years) with an average major curve magnitude of 23.2 degrees (95% CI 19.4-27.0 degrees). SRS-22r scores were not correlated to curve magnitude pre- or post-visit. The SRS-22r Satisfaction with care domain exhibited a small increase from pre- to post-visit (pre: 3.3, post: 3.6). All other SRS-22r domains and total scores did not exhibit clinically significant differences. CONCLUSION: Among new adolescent referrals for scoliosis, it is unlikely that counseling by a surgeon influences perceptions of HRQoL as measured by the SRS-22r. LEVEL OF EVIDENCE: III.

Opioid Represcriptions After ACL Reconstruction in Adolescents Are Associated With Subsequent Opioid Use Disorder.

INTRODUCTION: Postoperative opioid prescriptions may confer a risk for subsequent opioid use disorders (OUDs). For many children, postoperative analgesia is often the first opioid exposure. The rates of anterior cruciate ligament (ACL) reconstruction in pediatric populations are rising. Here, we use an administrative claims database to describe opioid prescription patterns after ACL reconstruction and their effect on subsequent risk of OUD. METHODS: Using International Classification of Diseases (ICD)-9, ICD-10, and CPT codes, we identified patients, with ages 10 to 18, undergoing primary ACL reconstruction between 2014 and 2016 with minimum 1 year follow-up in the Optum Clinformatics Data Mart, which is a nationally representative administrative claims database. Demographic variables and prescription patterns (in morphine milligram equivalents [MMEs]) were analyzed using univariate tests and multivariable logistic regression to determine any potential association with the appearance of anew an ICD-9 or ICD-10 code for OUD within 1 year of the initial procedure. RESULTS: A total of 4459 cases were included and 29 (0.7%) of these patients were diagnosed with an OUD within 1 year of surgery. Upon univariate analysis, opioid represcriptions within 6 weeks were significantly more common among patients with OUD; 27.6% vs. 9.7% of patients that did not develop a new diagnosis of OUD ( P =0.005). Multivariable logistic regression indicated an independent significant relationship between total MMEs initially prescribed and the odds of a subsequent OUD diagnosis: for each additional 100 MMEs prescribed in total, the odds of OUD increased by 13% ( P =0.002). Patients with a represcription within 6 weeks of surgery had an average increase in the odds of OUD by 161% ( P =0.027). CONCLUSIONS: In this cohort of patient ages 10 to 18 undergoing primary isolated ACL reconstruction, we found substantial variability in opiate prescribing patterns and higher initial opioid prescription volume, as well as opioid represcription within 6 weeks were predictive of the subsequent development of OUD. LEVEL OF EVIDENCE: Level III.

Potential biomechanical risk factors on developing lead knee osteoarthritis in the golf swing.

The load on the lead knee joint during a golf swing is greater than that observed during gait. However, current evidence regarding golf swing biomechanics for risks associated with knee osteoarthritis (OA) is limited. Therefore, this study investigated golf swing styles associated with knee adduction and abduction moments, which are considered to be crucial loading regions of the medial and lateral compartments of knee OA, respectively. Thirteen professional male golfers performed five shots using a 5-iron club, and their swings were recorded using a motion capture system with two force platforms for the feet. A regression analysis was performed to calculate the correlation coefficients between the peak knee adduction and abduction moments of the lead leg and varus/valgus angle, toe-out angle, stance width, weight transfer, and shoulder sway. Swinging with a narrower stance width at address (r = - 0.62, p = 0.02) with more weight shift (r = 0.66, p = 0.014) and shoulder sway (r = 0.79, p = 0.001) towards the target during the downswing were associated with a higher peak knee adduction of the lead leg, whereas a greater valgus angle at address (r = 0.60, p = 0.03) was associated with a higher peak knee abduction of the lead leg. Based on these findings, we anticipate future research to support postural changes, particularly a wider stance width and restricted shoulder sway for golfers who are classified to be at high risk of developing medial compartment knee OA, as well as a lower valgus (tibial medial tilt) angle at address for those classified to be at high risk of developing lateral compartment knee OA.

Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells.

Sensory hair cells are mechanoreceptors required for hearing and balance functions. From embryonic development, hair cells acquire apical stereociliary bundles for mechanosensation, basolateral ion channels that shape receptor potential, and synaptic contacts for conveying information centrally. These key maturation steps are sequential and presumed coupled; however, whether hair cells emerging postnatally mature similarly is unknown. Here, we show that in vivo postnatally generated and regenerated hair cells in the utricle, a vestibular organ detecting linear acceleration, acquired some mature somatic features but hair bundles appeared nonfunctional and short. The utricle consists of two hair cell subtypes with distinct morphological, electrophysiological and synaptic features. In both the undamaged and damaged utricle, fate-mapping and electrophysiology experiments showed that Plp1+ supporting cells took on type II hair cell properties based on molecular markers, basolateral conductances and synaptic properties yet stereociliary bundles were absent, or small and nonfunctional. By contrast, Lgr5+ supporting cells regenerated hair cells with type I and II properties, representing a distinct hair cell precursor subtype. Lastly, direct physiological measurements showed that utricular function abolished by damage was partially regained during regeneration. Together, our data reveal a previously unrecognized aberrant maturation program for hair cells generated and regenerated postnatally and may have broad implications for inner ear regenerative therapies.

Small-Scale Perfusion Bioreactor of Red Blood Cells for Dynamic Studies of Cellular Pathways: Proof-of-Concept.

To date, the development of bioreactors for the study of red blood cells (RBCs, daily transfused in the case of disease or hemorrhage) has focused on hematopoietic stem cells. Despite the fact that mature RBCs are enucleated and do not expand, they possess complex cellular and metabolic pathways, as well as post-translation modification signaling and gas-exchange regulation. In order to dynamically study the behavior of RBCs and their signaling pathways under various conditions, a small-scale perfusion bioreactor has been developed. The most advanced design developed here consists of a fluidized bed of 7.6 mL containing 3·10(9) cells and perfused at 8.5 µL/min. Mimicking RBC storage conditions in transfusion medicine, as a proof-of-concept, we investigated the ex vivo aging of RBCs under both aerobic and anaerobic conditions. Hence, RBCs stored in saline-adenine-glucose-mannitol (SAGM) were injected in parallel into two bioreactors and perfused with a modified SAGM solution over 14 days at room temperature under air or argon. The formation of a fluidized bed enabled easy sampling of the extracellular medium over the storage period used for the quantitation of glucose consumption and lactate production. Hemolysis and microvesiculation increased during aging and were reduced under anaerobic (argon) conditions, which is consistent with previously reported findings. Glucose and lactate levels showed expected trends, i.e., decreased and increased during the 2-week period, respectively; whereas extracellular glucose consumption was higher under aerobic conditions. Metabolomics showed depletion of glycolsis and pentose phosphate pathway metabolites, and an accumulation of purine metabolite end-products. This novel approach, which takes advantage of a fluidized bed of cells in comparison to traditional closed bags or tubes, does not require agitation and limit shear stress, and constantly segragates extracellular medium from RBCs. It thus gives access to several difficult-to-obtain on- and off-line parameters in the extracellular medium. This dynamic bioreactor system does not only allow us to probe the behavior of RBCs under different storage conditions, but it also could be a powerful tool to study physiological or pathological RBCs exposed to various conditions and stimuli.

Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle.

Recruitment of endogenous progenitors is critical during tissue repair. The inner ear utricle requires mechanosensory hair cells (HCs) to detect linear acceleration. After damage, non-mammalian utricles regenerate HCs via both proliferation and direct transdifferentiation. In adult mammals, limited transdifferentiation from unidentified progenitors occurs to regenerate extrastriolar Type II HCs. Here we show that HC damage in neonatal mouse utricle activates the Wnt target gene Lgr5 in striolar supporting cells. Lineage tracing and time-lapse microscopy reveal that Lgr5+ cells transdifferentiate into HC-like cells in vitro. In contrast to adults, HC ablation in neonatal utricles in vivo recruits Lgr5+ cells to regenerate striolar HCs through mitotic and transdifferentiation pathways. Both Type I and II HCs are regenerated, and regenerated HCs display stereocilia and synapses. Lastly, stabilized ß-catenin in Lgr5+ cells enhances mitotic activity and HC regeneration. Thus Lgr5 marks Wnt-regulated, damage-activated HC progenitors and may help uncover factors driving mammalian HC regeneration.

Relationship between visual-motor integration and spatial organization of written language and math.

PURPOSE: The relationship between visual-motor integration and academic achievement is not clearly understood. The purpose of this study was to assess the type and frequency of errors made by children with poor visual-motor integration during a written language and math task. METHODS: Eighteen children with normal visual-motor integration (> or =36%) and 19 children with low visual-motor integration (< or =16%) participated in the study. The two groups had similar ages, gender profiles, and cognitive and reading levels. Each group copied and solved math problems and copied a written passage. The errors for the math and writing task were combined into a total error score, and the time taken to complete each task was combined into a total time score. RESULTS: The low visual-motor integration group made more errors than the normal visual-motor integration group. However, the time taken to copy both tasks was not different between the two groups. A secondary analysis of the errors revealed that alignment of numbers (p = 0.02), organization of math problems (p = 0.05), and spacing errors of letters and words (p = 0.01) were more common in the low visual-motor integration group. CONCLUSIONS: The results suggest that reduced visual-motor integration may contribute to poor spatial organization of written work.