Scaffold-Forming Collagen and Motor-Endplate Expressing Muscle Cells for Porcine Laryngoplasty.

OBJECTIVE: Vocal fold paralysis impairs quality of life, and no curative injectable therapy exists. We evaluated injection of a novel in situ polymerizing (scaffold-forming) collagen in the presence and absence of muscle-derived motor-endplate expressing cells (MEEs) to promote medialization and recurrent laryngeal nerve (RLN) regeneration in a porcine model of unilateral vocal fold paralysis. METHODS: Twelve Yucatan minipigs underwent right RLN transection. Autologous muscle progenitor cells were isolated from muscle biopsies, differentiated, and induced to MEEs. Three weeks after RLN injury, animals received injections of collagen, collagen containing MEEs, or saline into the paralyzed right vocal fold. Stimulated laryngeal electromyography and acoustic vocalization were used for function assessments. Larynges were harvested and underwent histologic, gene expression, and further quantitative analyses. RESULTS: Injections were well-tolerated, with the collagen scaffold showing immunotolerance and collagen-encapsulated MEEs remaining viable. Collagen-treated paralyzed vocal folds showed increased laryngeal adductor muscle volumes relative to that of the uninjured side, with those receiving MEEs and collagen showing the highest volumes. Muscles injected with MEEs and collagen demonstrated increased expression of select neurotrophic (BDNF and NTN1), motor-endplate (DOK7, CHRNA1, and MUSK), and myogenic (MYOG and MYOD) related genes relative to saline controls. CONCLUSION: In a porcine model of unilateral vocal fold paralysis, injection of in situ polymerizing collagen in the absence and presence of MEEs enhanced laryngeal adductor muscle volume, modulated expression of neurotrophic and myogenic factors, and avoided adverse material-mediated immune responses. Further study is needed to determine long-term functional outcomes with this novel therapeutic approach. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Early Changes in Porcine Larynges Following Injection of Motor-Endplate Expressing Muscle Cells for the Treatment of Unilateral Vocal Fold Paralysis.

OBJECTIVES: No curative injectable therapy exists for unilateral vocal fold paralysis. Herein, we explore the early implications of muscle-derived motor-endplate expressing cells (MEEs) for injectable vocal fold medialization after recurrent laryngeal nerve (RLN) injury. METHODS: Yucatan minipigs underwent right RLN transection (without repair) and muscle biopsies. Autologous muscle progenitor cells were isolated, cultured, differentiated, and induced to form MEEs. Three weeks after the injury, MEEs or saline were injected into the paralyzed right vocal fold. Outcomes including evoked laryngeal electromyography (LEMG), laryngeal adductor pressure, and acoustic vocalization data were analyzed up to 7 weeks post-injury. Harvested porcine larynges were examined for volume, gene expression, and histology. RESULTS: MEE injections were tolerated well, with all pigs demonstrating continued weight gain. Blinded analysis of videolaryngoscopy post-injection revealed infraglottic fullness, and no inflammatory changes. Four weeks after injection, LEMG revealed on average higher right distal RLN activity retention in MEE pigs. MEE-injected pigs on average had vocalization durations, frequencies, and intensities higher than saline pigs. Post-mortem, the MEE-injected larynges revealed statistically greater volume on quantitative 3D ultrasound, and statistically increased expression of neurotrophic factors (BDNF, NGF, NTF3, NTF4, NTN1) on quantitative PCR. CONCLUSIONS: Minimally invasive MEE injection appears to establish an early molecular and microenvironmental framework to encourage innate RLN regeneration. Longer follow-up is needed to determine if early findings will translate into functional contraction. LEVEL OF EVIDENCE: NA Laryngoscope, 134:272-282, 2024.

Treatment of post-tonsillectomy hemorrhage with nebulized tranexamic acid: A retrospective study.

OBJECTIVE: To evaluate the association of treatment with nebulized tranexamic acid (TXA) with rates of operative intervention in post-tonsillectomy hemorrhage (PTH). METHODS: Single tertiary-referral center and satellite hospitals, retrospective cohort of adult and pediatric patients who were diagnosed with PTH in 2015-2022 and treated with nebulized TXA and standard care, compared with an age- and gender-matched control cohort treated with standard care. Patients were typically treated in the emergency department with a single dose of 500mg/5 mL TXA delivered via nebulizer. RESULTS: 1110 total cases of PTH were observed, and 83 were treated with nebulized TXA. Compared to 249 age- and gender-matched PTH controls, TXA-treated patients had a rate of operating room (OR) intervention of 36.1% versus 60.2% (p < 0.0001) and a rate of repeat bleeding of 4.9% versus 14.2% (p < 0.02). The odds ratio for OR intervention with TXA treatment was 0.37 (95% CI 0.22, 0.63). There were no adverse effects identified with an average follow-up time of 586 days. CONCLUSION: Treatment of PTH with nebulized TXA is associated with lower rates of operative intervention and lower rates of repeat bleeding events. Prospective studies are needed to further characterize efficacy and optimal treatment protocols.

Inequalities in Life Expectancy Across North Carolina: A Spatial Analysis of the Social Determinants of Health and the Index of Concentration at Extremes.

Health inequalities are characterized by spatial patterns of social, economic, and political factors. Life expectancy (LE) is a commonly used indicator of overall population health and health inequalities that allows for comparison across different spatial and temporal regions. The objective of this study was to examine geographic inequalities in LE across North Carolina census tracts by comparing the performance of 2 popular geospatial health indices: Social Determinants of Health (SDoH) and the Index of Concentration at Extremes (ICE). A principal components analysis (PCA) was used to address multicollinearity among variables and aggregate data into components to examine SDoH, while the ICE was constructed using the simple subtraction of geospatial variables. Spatial regression models were employed to compare both indices in relation to LE to evaluate their predictability for population health. For individual SDoH and ICE components, poverty and income had the strongest positive correlation with LE. However, the common spatial techniques of adding PCA components together for a final SDoH aggregate measure resulted in a poor relationship with LE. Results indicated that both metrics can be used to determine spatial patterns of inequities in LE and that the ICE metric has similar success to the more computationally complex SDoH metric. Public health practitioners may find the ICE metric's high predictability matched with lower data requirements to be more feasible to implement in population health monitoring.

Pedicled Cervical Lymphoadipose Tissue for Volume Reconstruction after Superficial Parotidectomy.

Volume restoration is often required after parotidectomy due to the resultant facial contour deformity. Common procedures include local pedicled flaps, such as the sternocleidomastoid muscle flap, fat grafting, and even autologous free flaps, for more extensive defects. Local pedicled flaps have the advantage of a single surgical site, which spares the patient the added morbidity of a separate fat graft donor site, while simultaneously reducing the operative time. We report two cases of a novel reconstructive option using pedicled level I and II cervical lymphoadipose tissue for volume restoration after superficial parotidectomy. This reconstruction would be useful for patients with benign parotid lesions and inferior parotid defects. In addition, with maintained blood supply to this tissue, it would likely provide sustained bulk over time.

Systematic Observation of Physical Distancing Behaviors of Trail Users During the COVID-19 Pandemic.

During the early months of the COVID-19 pandemic, opportunities for indoor and sometimes outdoor recreation were restricted across the world. Despite restrictions, many greenways and rail-trails saw increased use. Messaging from the federal and state public health authorities stressed the importance of social distancing and other preventive measures in reducing spread of the coronavirus. Little is known about actual behaviors of individuals and groups using these outdoor recreational opportunities. This study used passive infrared cameras to systematically observe physical distancing behaviors on multi-user trails in Boone, North Carolina, and Morgantown, West Virginia, to assess safety implications of trail use during June 2020. Most interactions (72.2%) occurred with the recommended six feet of distance between users. Maintaining six feet of distance is more likely to occur when a single individual passes another single individual (88.2%), users pass while traveling in opposite directions (75.9%), and trails are wider (76.8% on 12 ft width trail vs. 62.6% on a 10 ft width trail). Messaging on multi-user trails should target how groups pass other groups, such as "keep six feet" and "pass single file."

Bacteriome and mycobiome and bacteriome-mycobiome interactions in head and neck squamous cell carcinoma.

The etiology of head and neck squamous cell carcinoma (HNSCC) is not fully understood. While risk factors such as positive human papilloma virus (HPV) status, smoking and tobacco use have been identified, they do not account for all cases of the disease. We aimed to characterize the bacteriome, mycobiome and mycobiome-bacteriome interactions of oral wash in HNSCC patients and to determine if they are distinct from those of the oral wash of matched non-HNSCC patients. Oral wash samples were collected from 46 individuals with HNSCC and 46 controls for microbiome analyses. We identified three fungal phyla and eleven bacterial phyla of which Ascomycota (fungi, 72%) and Firmicutes (bacteria, 39%) were the most dominant, respectively. A number of organisms were identified as being differentially abundant between oral wash samples from patients with HNSCC and oral wash samples from those without HNSCC. Of note, strains of Candida albicans and Rothia mucilaginosa were differentially abundant and Schizophyllum commune was depleted in those with HNSCC compared to oral wash from those without HNSCC. Our results suggest that the oral cavity of HNSCC patients harbors unique differences in the mycobiome, bacteriome, and microbiome interactions when compared to those of control patients.

Exercise-induced laryngeal obstruction (EILO) in children and young adults: From referral to diagnosis.

OBJECTIVE: To identify different presentations, referral patterns, comorbidities, and laryngoscopy findings in children and young adults with exercise-induced laryngeal obstruction (EILO). METHODS: We performed a retrospective chart review of 112 patients, age <26 years, with EILO between 2013 and 2016. RESULTS: Of the 112 patients who met criteria, 91 were female and 21 were male. Patients were most frequently referred by pulmonologists (60.7%). The majority of patients (93%) participated in organized sports, most of them at a competitive level. The mean age at symptom onset was 13.8 ± 3.3 years, and the mean age of diagnosis was 15.4 ± 3.0 years. Sixty-seven (59.8%) patients presented with a prior diagnosis of asthma, the majority of whom had failed asthma treatment. The most common symptoms reported were dyspnea (93.8%), wheezing/stridor (78.6%), and throat tightness (48.2%). Ninety-one (81.3%) patients had spirometry performed, with 46 (51.1%) showing inspiratory loop flattening. On flexible laryngoscopy, 87 (78.4%) of 111 patients had paradoxical vocal fold motion. Supraglottic involvement was observed to obstruct the airway in 26 (23.9%) patients, with patterns of obstruction similar to those observed in children with laryngomalacia. CONCLUSION: Most patients participated in competitive sports, were female, and presented with exertional dyspnea. Most patients were diagnosed with exercise-induced asthma but treated unsuccessfully. Almost one-quarter of our patients showed supraglottic collapse obstructing the airway. Exercise-induced laryngeal obstruction is a more descriptive term than paradoxical vocal fold motion or vocal cord dysfunction, which only describe vocal fold involvement. The time to diagnosis of EILO was shorter than previously reported, suggesting that awareness of this condition is increasing. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E400-E406, 2020.

Impact of perforation size and predictive factors for successful pediatric gelfoam myringoplasty.

OBJECTIVES: Rates of success with pediatric myringoplasty range from 35 to 95%. The objective of this study is to evaluate the impact of perforation size on successful closure of the tympanic membrane (TM) after gelfoam myringoplasty. We also aim to identify variables that affect perforation closure rates and define predictive factors for successful TM closure. METHODS: A retrospective chart review of all patients that underwent gelfoam myringoplasty by a single surgeon from August 2008 through January 2015 was performed. RESULTS: One hundred fifty-nine patients met inclusion criteria and underwent a total of 219 procedures. Overall, gelfoam myringoplasty had an 83.1% rate of successful closure. Average perforation size was 15.31%. Classification tree analysis separated our cohort into three groups based on perforation size: Group 1 (<16.25%) had a 91% closure rate, group 2 (16.25% to <31.25%) had a 66.0% closure rate and group 3 (≥31.25%) had a 30.0% closure rate. Smaller perforations (P ≤0.001) were associated with increased success rates. Other factors associated with successful closure of the TM included younger age at the time of myringoplasty (P ≤0.001), fewer number of prior tympanostomy tubes (P = 0.016), and lesser duration of tube retention (P = 0.003). CONCLUSION: Gelfoam myringoplasty provides good overall TM closure rates and may be considered as a potential first-line option for repair of perforations, including those involving up to 40% of the TM. Younger patients with smaller perforations, fewer sets of tubes, shorter length of tube retention are more likely to have successful closure of the tympanic membrane.

Distinct neural mechanisms underlying conceptual knowledge of manner and instrument verbs.

Studies on the organization of conceptual knowledge have examined categories of concrete nouns extensively. Less is known about the neural basis of verb categories suggested by linguistic theories. We used functional MRI to examine the differences between manner verbs, which encode information about the manner of an action, versus instrument verbs, which encode information about an object as part of their meaning. Using both visual and verbal stimuli and a combination of univariate and multivariate pattern analyses, our results show that accessing conceptual representations of instrument class involves brain regions typically associated with complex action and object perception, including the anterior inferior parietal cortex and occipito-temporal cortex. On the other hand, accessing conceptual representations of the manner class involves regions that are commonly associated with the processing of visual and biological motion, in the posterior superior temporal sulcus. These findings support the idea that the semantics of manner and instrument verbs are supported by distinct neural mechanisms.

Natural history of silent aspiration on modified barium swallow studies in the pediatric population.

OBJECTIVES: To investigate the natural history of silent aspiration in the pediatric population. METHODS: Retrospective chart review of patients (age < 3 years) who underwent modified barium swallow studies (MBSS), between January 1, 2007, to December 31, 2017, were studied to compare comorbidities and determine course of resolution in those with silent aspiration. RESULTS: A total of 148 charts were reviewed. Patients that underwent surgical intervention for laryngeal anomalies causing silent aspiration and those with overt aspiration or oral aversion were excluded. Of the 56 patients in the study, 25 had silent aspiration and 31 demonstrated no silent aspiration on MBSS. There was a higher rate of overall comorbidities amongst silent aspirators (96.0% vs. 48.4%, p=0.003) in comparison to patients with no silent aspiration on MBSS. Silent aspirators had higher rates of cerebral palsy (16.0% vs. 0%, p=0.034), and seizures (36.0% vs. 3.2%, p=0.003). Of the 20 patients with silent aspiration with an MBSS completed beyond the initial one, 13 (65.0%) experienced resolution, 5 (20.0%) did not experience resolution by age 5, and 2 (10.0%) had unknown resolution due to being lost to follow up or not yet reaching age 5. No statistically significant associations were found between comorbidities, gender, presence of a gastrostomy tube and resolution. CONCLUSIONS: Silent aspiration in children is associated with neurological comorbidities, particularly cerebral palsy and seizures. More than half of the patients with silent aspiration spontaneously resolve over time. Expectant management, close surveillance, and clinical assessments can be considered in these patients on an individual basis.

Decoding intransitive actions in primary motor cortex using fMRI: toward a componential theory of 'action primitives' in motor cortex.

Multivoxel pattern analysis (MVPA) over functional MRI data can distinguish neural representational states that do not differ in their overall amplitude of BOLD contrast. Here we used MVPA to test whether simple intransitive actions can be distinguished in primary motor cortex. Participants rotated and flexed each of their extremities (hands and feet) during fMRI scanning. The primary motor cortex for the hand/wrist was functionally defined in each hemisphere in each subject. Within those subject-specific ROIs, we found that the average amplitude of BOLD contrast for two different movements of the contralateral hand (rotation, flexion) were higher than for the ipsilateral hand, as well as movements by both feet; however, there was no difference in amplitude between the two different types of movements for the contralateral hand. Using multivoxel pattern analysis (linear correlation), we were able to distinguish the two movements for the contralateral hand. These findings demonstrate that simple intransitive actions can be distinguished in primary motor areas using multivoxel pattern analysis.

Trends in Breast Reconstruction by Ethnicity: An Institutional Review Centered on the Treatment of an Urban Population.

Previous studies have investigated reconstructive decisions after mastectomy and such studies document a preference among African American women for autologous tissue-based procedures and among Latin American women for implant-based reconstructions, however, there is a paucity of studies evaluating the current relationship between ethnicity and reconstructive preferences. This institutional review provides a unique, up-to-date evaluation of an understudied urban population composed of majority ethnic minority patients and explores reconstructive trends. Consecutive breast reconstruction patients were entered into a prospectively maintained database at the University of Illinois at Chicago and affiliate hospitals between July 2010 and October 2013. Demographics and oncologic characteristics including tumor stage, pathology, BRCA status, and adjuvant treatment were reviewed, and reconstructive trends were assessed by racial group with a focus on reconstructive procedure, mastectomy volume, and implant characteristics. Statistical analysis was performed using SAS (version 9.2). One-hundred and sixty breast reconstructions were performed in 105 women; of which 50 per cent were African American, 26 per cent Hispanic, 22 per cent Caucasian, and 2 per cent Asian. Age, tumor stage, prevalence of triple negative disease, chemotherapy, and radiation treatment was comparable between groups. Rates of obesity, hypertension, and diabetes mellitus were slightly higher in African American and Hispanic cohorts, with more African American patients having one or more of these comorbidities as compared with the Caucasian and Hispanic cohorts (P = 0.047). Despite comparable positive BRCA testing rates, significant differences were seen in the percentage of bilateral mastectomy; 68 per cent African American, 48 per cent Caucasian, and 30 per cent Hispanic (P = 0.004). Hispanics predominantly underwent flap-based reconstruction (56%), while African American (74%) and Caucasian (60%) patients had a preference toward tissue expander reconstruction (P = 0.04 across all groups). African American and Hispanic presented with increased mastectomy weights and thus required higher implant volumes as compared with Caucasians that approached significance (P = 0.06 and P = 0.06). Implant size utilization followed a unimodal distribution for Caucasians, peaking at 500 cc; while African American and Hispanic demonstrated a bimodal distribution, peaking once at 550 cc and again at the max implant volume of 800 cc. This study of a large proportion of minority patients in an urban geographic setting offers an evolving understanding of breast reconstruction patterns. The data demonstrated unique findings of increased rates of bilateral implant-based reconstruction in African American women and unilateral flap-based reconstructions in Hispanic patients. Reconstructive decision-making seems to be greatly influenced by cultural and geographically driven preferences.

Recalcitrant Hidradenitis Suppurativa: An Investigation of Demographics, Surgical Management, Bacterial Isolates, Pharmacologic Intervention, and Patient-reported Health Outcomes.

Hidradenitis suppurativa (HS) is characterized by chronic inflammation, recurrent abscesses, and scarring. Surgery is performed when medical management and antibiotic therapy fails. This study sought to evaluate the demographics, surgical procedures, bacteriology, pharmacologic intervention, and quality of life of patients with recalcitrant HS requiring surgical intervention. A retrospective chart review was performed of 76 recalcitrant HS patients at the University of Illinois Medical Center. Patient demographics, bacterial culture, and surgery data were reviewed. Quality of life was assessed using the 36-item short-form health survey. Patients were mostly female (73.7%) and African American (81.6%) with a mean duration of symptoms of 8.6 years before surgery. Patients underwent at least one surgical procedure, most often to the axillae (57.6%) and 73.7 per cent received antibiotics. The most common culture isolates were Corynebacterium species (14.0%), Staphylococcus epidermidis (13.1%), and Staphylococcus aureus (10.4%) with varying resistance patterns. Surveyed patients had depressed 36-item short-form health survey physical functioning and social functioning scores. Recalcitrant HS patients with progressive symptomology over approximately nine years before surgical intervention were more likely to be African American women with axillary HS. Quality of life was diminished. We recommend initial treatment of HS with clindamycin and trimethoprim-sulfamethoxazole in clindamycin refractory cases.

Use of Dog Parks and the Contribution to Physical Activity for Their Owners.

PURPOSE: This study described the use of dog parks in several diverse locations and explored the contribution dog parks made to physical activity of the dog owners. METHOD: The Systematic Observation of Play and Recreation in Communities (SOPARC) tool was used to count the number and characteristics of people using parks. Observations were conducted 4 times per day, 4 days per week during for 1 week in 6 urban/suburban parks during different seasons. Collection sites included 3 dog parks in Chapel Hill/Durham, NC; 2 dog parks in Los Angeles, CA; and 1 dog park in Philadelphia, PA. Interviews at the NC and PA parks were conducted among 604 adults. RESULTS: We counted 2,124 people (11.9%) in the dog park area compared with 15,672 people in the remaining park areas. Based on observations, dog park visitors were more likely to be female and White or Other race/ethnicity compared with Hispanics, and were less likely to be children or engaged in walking or vigorous activity. Park interviews revealed that compared with other park activities, reporting walking/watching a dog at the park was more common among those who visited the park more frequently ( ≥ 1 time per week), stayed at the park for a shorter time ( ≤  1 hr), or visited the park alone. CONCLUSION: Although dog parks may be an important destination for dog owners and contribute to physical activity, the contribution of dog parks to participants' moderate-to-vigorous physical activity was limited.

Identifying walking trips from GPS and accelerometer data in adolescent females.

BACKGROUND: Studies that have combined accelerometers and global positioning systems (GPS) to identify walking have done so in carefully controlled conditions. This study tested algorithms for identifying walking trips from accelerometer and GPS data in free-living conditions. The study also assessed the accuracy of the locations where walking occurred compared with what participants reported in a diary. METHODS: A convenience sample of high school females was recruited (N = 42) in 2007. Participants wore a GPS unit and an accelerometer, and recorded their out-of-school travel for 6 days. Split-sample validation was used to examine agreement in the daily and total number of walking trips with Kappa statistics and count regression models, while agreement in locations visited by walking was examined with geographic information systems. RESULTS: Agreement varied based on the parameters of the algorithm, with algorithms exhibiting moderate to substantial agreement with self-reported daily (Kappa = 0.33-0.48) and weekly (Kappa = 0.41-0.64) walking trips. Comparison of reported locations reached by walking and GPS data suggest that reported locations are accurate. CONCLUSIONS: The use of GPS and accelerometers is promising for assessing the number of walking trips and the walking locations of adolescent females.

Hemangiogenesis and lymphangiogenesis in corneal pathology.

PURPOSE: We characterized the presence of hemangiogenesis (HA) and lymphangiogenesis (LA) in human corneal specimens exhibiting 13 underlying pathologies. METHODS: Human corneal specimens were obtained from consenting subjects (n = 2 or n = 3 for each pathology; total sample size, n = 35). The pathological specimens were stained with hematoxylin and eosin (H&E) to determine the presence or absence of corneal neovascularization (NV) and superficial or deep stromal distribution of NV. Immunohistochemical staining was then performed to differentiate HA (positive for CD31) from LA (positive for lymphatic vessel endothelial hyaluronan receptor-1 [LYVE-1]). RESULTS: The double-negative (CD31(-)/LYVE-1(-)) immunostaining, indicating the absence of NV, was exhibited by 21 specimens (60%). CD31(-)/LYVE-1(-), indicating the presence of HA and absence of LA, was exhibited by 12 specimens (34%). The double-positive (CD31(+)/LYVE-1(+)) phenotype, indicating both HA and LA, was exhibited by 2 specimens (6%). Notably, the CD31(-)/LYVE-1(-) phenotype, indicating the presence of LA and absence of HA, was not detected among the specimens. Deep stromal NV was exhibited in a 4:3 ratio to superficial stromal NV. The double-negative immunostaining was more prevalent in noninflammatory pathologies, particularly in comparison with combined neovascular phenotypes (ie, CD31(+) or LYVE-1(+)). Among the neovascular phenotypes, HA was 7 times more common than LA. Specimens exhibiting LA presented only with the double-positive phenotype. CONCLUSIONS: HA is the predominant component of NV in corneal pathologies. LA accompanies HA; however, isolated LA (from lymphatics in the conjunctiva) does not occur in these corneal pathologies. Our results suggest the potential therapeutic utility of targeting antineovascular therapies specifically for corneal HA and/or LA pathology.

Inhibition of angiogenesis by HC·HA, a complex of hyaluronan and the heavy chain of inter-α-inhibitor, purified from human amniotic membrane.

PURPOSE: To determine whether antiangiogenic action of the amniotic membrane (AM) can be mediated by HC·HA, a covalent complex of hyaluronan (HA) and the heavy chain (HC) of inter-α-inhibitor, purified from AM soluble extract. METHODS: HC·HA action on viability, proliferation, attachment, death, migration, and differentiation of human umbilical vein endothelial cells (HUVECs) and neovascularization in chicken chorioallantoic membrane (CAM) was examined by MTT assay, BrdU labeling, cell proliferation assay, cell death detection ELISA, transwell assay, tube formation assay, and CAM assay. RESULTS: HC·HA suppressed HUVEC viability more significantly than HA and AM stromal extract, and such suppression was not mediated by CD44. HC·HA also caused HUVECs to become small and rounded, with a decrease in spreading and filamentous actin. Without promoting cell detachment or death, HC·HA dose dependently inhibited proliferation (IC(50), 2.3 µg/mL) and was 100-fold more potent than HA. Migration triggered by VEGF and tube formation was also significantly inhibited by HC·HA. Purified HC·HA did not contain PEDF and TSP-1 but did contain IGFBP-1 and platelet factor 4 while significantly suppressing neovascularization in CAM. CONCLUSIONS: The antiangiogenic activity of HC·HA might explain why AM is developmentally avascular and how AM might exert an antiangiogenic action when transplanted to the ocular surface, and it might indicate a potential therapeutic effect of HC·HA in diseases manifesting pathogenic angiogenesis. Roles of IGFBP-1 and platelet factor 4 in HC·HA antiangiogenic action warrant further investigation.

Efficacy and limitation of sutureless amniotic membrane transplantation for acute toxic epidermal necrolysis.

PURPOSE: The purpose of this case report is to describe the efficacy and limitation of ProKera, a sutureless medical device containing amniotic membrane, for treating acute ocular manifestations of toxic epidermal necrolysis (TEN). METHODS: ProKera was inserted in both eyes at day 10 after onset of ocular symptoms in a 5-year-old boy suffering from acute TEN, manifesting conjunctival inflammation, large conjunctival defects, pseudomembrane formation, and total corneal epithelial defects. RESULTS: At 9-month follow-up, insertion of ProKera resulted in complete reepithelialization, clear corneas, and vision of 20/20 in both eyes. However, because ProKera only covered the cornea and perilimbal conjunctiva, these 2 eyes still showed some conjunctival inflammation several months after discharge from the hospital. Eventually, 1 eye showed mild lid margin keratinization and cicatricial entropion, and both eyes showed trichiasis. CONCLUSIONS: These data suggest that ProKera, when inserted during the acute stage of TEN, may be effective in healing corneal epithelial defects and preventing corneal sequelae. Because of the limited area covered, ProKera may not prevent cicatricial complications in the fornix, tarsus, and eyelid margin as effectively as sutured amniotic membrane transplantation.