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OBJECTIVE: To narrow knowledge gaps in the pathophysiology of idiopathic subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis model with iSGS. STUDY DESIGN: In vivo animal study. SETTING: Academic institution. METHODS: Murine samples/measurements were obtained from mice that underwent chemomechanical injury with a wire brush and bleomycin. Human samples/measurements were obtained from iSGS patients. Anatomic, physiologic, and epithelial molecular data were collected using histology, human peak expiratory flow (PEF) and murine airway conductance, gene expression analysis with quantitative polymerase chain reaction, and protein analysis with quantitative immunohistochemistry. RESULTS: Anatomic patterns of scars at the subglottis and proximal trachea seen in the murine model are similar to iSGS patients. Subglottic stenosis (SGS) mice had a decrease (P = .0194) in airway conductance compared to healthy controls, similar to a decrease (P = .0001) in predilation PEF versus postdilation in iSGS patients. There was decreased epithelial gene expression of E-cadherin (ECAD) (P < 0.01), occludin (OCLN) (P < .01), and cytokeratin-5 (CK5) (P < .05) and protein expression of ECAD (H/M: P < .001), OCLN (H: P < 0.05, M: P < .001), and CK5 (H: P < .001, M: P < .01) in murine SGS and iSGS versus controls. CONCLUSION: The murine SGS model shows anatomic, physiologic, and molecular congruency with human iSGS, making it a reasonable model to investigate iSGS. The molecular similarities in epithelial barrier dysfunction suggest it may best be suited to explore epithelial mechanisms of iSGS and therapies directed at epithelial reconstitution. This model provides a foundation to collect data that will improve understanding of iSGS, and, ultimately, translate into more accurate animal models for future use.
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Laringoestenosis , Laringe , Fibrosis Pulmonar , Humanos , Animales , Ratones , Constricción Patológica , Modelos Animales de Enfermedad , Fibrosis Pulmonar/patología , Laringoestenosis/cirugía , Laringe/patología , FibrosisRESUMEN
OBJECTIVES: To aim of the study was to characterize the molecular profile and functional phenotype of idiopathic subglottic stenosis (iSGS)-scar epithelium. METHODS: Human tracheal biopsies from iSGS scar (n = 6) and matched non-scar (n = 6) regions were analyzed using single-cell RNA sequencing (scRNA-seq). Separate specimens were used for epithelial cell expansion in vitro to assess average growth rate and functional capabilities using transepithelial-electrical resistance (TEER), fluorescein isothiocyanate-dextran flux permeability assay, ciliary coverage, and cilia beating frequency (CBF). Finally, epithelial tight junction protein expression of cultured cells was quantified using immunoblot assay (n = 4) and immunofluorescence (n = 6). RESULTS: scRNA-seq analysis revealed a decrease in goblet, ciliated, and basal epithelial cells in the scar iSGS cohort. Furthermore, mRNA expression of proteins E-cadherin, claudin-3, claudin-10, occludin, TJP1, and TJP2 was also reduced (p < 0.001) in scar epithelium. Functional assays demonstrated a decrease in TEER (paired 95% confidence interval [CI], 195.68-890.83 Ω × cm2 , p < 0.05), an increase in permeability (paired 95% CI, -6116.00 to -1401.99 RFU, p < 0.05), and reduced epithelial coverage (paired 95% CI, 0.1814-1.766, fold change p < 0.05) in iSGS-scar epithelium relative to normal controls. No difference in growth rate (p < 0.05) or CBF was found (paired 95% CI, -2.118 to 3.820 Hz, p > 0.05). Immunoblot assay (paired 95% CI, 0.0367-0.605, p < 0.05) and immunofluorescence (paired 95% CI, 13.748-59.191 mean grey value, p < 0.05) revealed E-cadherin reduction in iSGS-scar epithelium. CONCLUSION: iSGS-scar epithelium has a dysfunctional barrier and reduced structural protein expression. These results are consistent with dysfunctional epithelium seen in other airway pathology. Further studies are warranted to delineate the causality of epithelial dysfunction on the downstream fibroinflammatory cascade in iSGS. LEVEL OF EVIDENCE: NA Laryngoscope, 134:374-381, 2024.
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Cadherinas , Cicatriz , Humanos , Cadherinas/metabolismo , Cicatriz/metabolismo , Constricción Patológica , Epitelio/metabolismo , Células Epiteliales/metabolismo , PermeabilidadRESUMEN
OBJECTIVE(S): Tracheostomy-associated granulation tissue is a common, recurrent problem occurring secondary to chronic mucosal irritation. Although granulation tissue is composed of predominantly innate immune cells, the phenotype of monocytes and macrophages in tracheostomy-associated granulation tissue is unknown. This study aims to define the myeloid cell population in granulation tissue secondary to tracheostomy. METHODS: Granulation tissue biopsies were obtained from 8 patients with tracheostomy secondary to laryngotracheal stenosis. Cell type analysis was performed by flow cytometry and gene expression was measured by quantitative real-time polymerase chain reaction. These methods and immunohistochemistry were used to define the monocyte/macrophage population in granulation tissue and were compared to tracheal autopsy control specimens. RESULTS: Flow cytometry demonstrated macrophages (CD45+CD11b+) and monocytes (CD45+FSClow SSClow ) represent 23.2 ± 6% of the granulation tissue cell population. The M2 phenotype (CD206) is present in 77 ± 11% of the macrophage population and increased compared to the M1 phenotype (p = 0.012). Classical monocytes (CD45+CD14high CD16low ) were increased in granulation tissue compared to controls (61.2 ± 7% and 30 ± 8.5%, p = 0.038). Eighty-five percent of macrophages expressed pro-inflammatory S100A8/A9 and 36 ± 4% of macrophages co-localized CD169, associated with tissue-resident macrophages. M2 gene expression (Arg1/CD206) was increased in granulation tissue (3.7 ± 0.4, p = 0.035 and 3.5 ± 0.5, p = 0.047) whereas M1 gene expression (CD80/CD86) was similar to controls (p = 0.64, p = 0.3). Immunohistochemistry of granulation tissue demonstrated increased cells co-localizing CD11b and CD206. CONCLUSIONS: M2 macrophages are the dominant macrophage phenotype in tracheostomy-associated granulation tissue. The role of this cell type in promoting ongoing inflammation warrants future investigation to identify potential treatments for granulation tissue secondary to tracheostomy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2346-2356, 2023.
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Macrófagos , Traqueostomía , Humanos , Traqueostomía/efectos adversos , Macrófagos/metabolismo , Monocitos/metabolismo , Fenotipo , Citometría de Flujo/métodos , InflamaciónRESUMEN
OBJECTIVES: Idiopathic subglottic stenosis (iSGS) is characterized by progressive fibrosis and subglottic luminal narrowing. Currently, immune characterization has focused on T-cells; however, macrophages remain largely unexplored. The goals of this study are to characterize the transcriptome of iSGS macrophages and the fibrogenic nature of identifed biomarkers. STUDY DESIGN: Bioinformatics and in vitro. METHODS: Human tracheal biopsies from iSGS scar (n = 4), and matched non-scar (n = 4) regions were analyzed using single-cell RNA-seq (scRNA-seq). Immunofluorescence (IF) was performed on rapidly processed autopsies (RPA) and iSGS tracheal resections (n = 4) to co-localize S100A8/9 and CD11b. Collagen gene/protein expression was assessed in iSGS fibroblasts (n = 4) treated with protein S100A8/9 (1000 ng/ml). Macrophages were subclustered to identify distinct subpopulations. RESULTS: scRNA-seq analysis revealed S100A8/S100A9 (fold change (FC) = 4.1/1.88, p < 0.001) as top differentially expressed genes in iSGS macrophages. IF exhibited increased CD11b+/S100A8/9+ cells in tracheal samples of iSGS versus RPA (26.75% ± 7.08 vs. 0.594% ± 0.974, n = 4, p = 0.029). iSGS fibroblasts treated with S100A8/9 demonstrated increased gene expression of COL1A1 (FC = 2.30 ± 0.45, p = 0.03, n = 4) and COL3A1 (FC = 2.44 ± 0.40, p = 0.03, n = 4). COL1A1 protein assays revealed an increase in the experimental group, albeit not significant, (p = 0.12, n = 4). Finally, macrophage sub clustering revealed one subpopulation as a predominant source of S100A8/S100A9 expression (FC = 7.94/5.47, p < 0.001). CONCLUSIONS: S100A8/9 is a key biomarker in iSGS macrophages. Although S100A8/9 demonstrates profibrotic nature in vitro, the role of S100A8/9+ macrophages in vivo warrants further investigation. LEVEL OF EVIDENCE: NA Laryngoscope, 133:2308-2316, 2023.
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Laringoestenosis , Humanos , Constricción Patológica , Laringoestenosis/patología , Macrófagos/metabolismo , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismoRESUMEN
OBJECTIVE: Endoscopic surgery has a considerable learning curve due to dissociation of the visual-motor axes, coupled with decreased tactile feedback and mobility. In particular, endoscopic sinus surgery (ESS) lacks objective skill assessment metrics to provide specific feedback to trainees. This study aims to identify summary metrics from eye tracking, endoscope motion, and tool motion to objectively assess surgeons' ESS skill. METHODS: In this cross-sectional study, expert and novice surgeons performed ESS tasks of inserting an endoscope and tool into a cadaveric nose, touching an anatomical landmark, and withdrawing the endoscope and tool out of the nose. Tool and endoscope motion were collected using an electromagnetic tracker, and eye gaze was tracked using an infrared camera. Three expert surgeons provided binary assessments of low/high skill. 20 summary statistics were calculated for eye, tool, and endoscope motion and used in logistic regression models to predict surgical skill. RESULTS: 14 metrics (10 eye gaze, 2 tool motion, and 2 endoscope motion) were significantly different between surgeons with low and high skill. Models to predict skill for 6/9 ESS tasks had an AUC >0.95. A combined model of all tasks (AUC 0.95, PPV 0.93, NPV 0.89) included metrics from eye tracking data and endoscope motion, indicating that these metrics are transferable across tasks. CONCLUSIONS: Eye gaze, endoscope, and tool motion data can provide an objective and accurate measurement of ESS surgical performance. Incorporation of these algorithmic techniques intraoperatively could allow for automated skill assessment for trainees learning endoscopic surgery. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:500-505, 2023.
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Tecnología de Seguimiento Ocular , Cirujanos , Humanos , Estudios Transversales , Endoscopía , Endoscopios , Competencia ClínicaRESUMEN
OBJECTIVE: Tapered low-volume, low-pressure (LVLP) cuffs have been introduced to improve sealing and reduce injury from tracheostomy and endotracheal intubation compared to traditional cylindrical high-volume, low-pressure (HVLP) cuffs. The objective of this study is to develop a swine model of tracheostomy injury and to compare live tissue response following LVLP and HVLP tracheostomy placement. STUDY DESIGN: In vivo animal study. SETTING: Academic institution. METHODS: Swine underwent tracheostomy followed by placement of LVLP and HVLP tracheostomy cuffs at 30 cm H2O. After 24 and 48 hours, tracheal specimens underwent histopathological analysis including cilia, lamina propria and epithelial thickness, and mucosal injury score. RESULTS: In all cuff contact areas, mean epithelial thickness for both tracheostomy cohorts was decreased compared to control epithelium at 24 and 48 hours (P < .01). HVLP proximal epithelium thickness was decreased at 24 and 48 hours relative to LVLP sections (P < .05). Lamina propria thickness in proximal LVLP sections was less than HVLP sections at 24 hours and 48 hours (P < .05). Mucosal injury score at areas of cuff contact was increased in tracheostomy cohorts relative to controls (P < .001), with HVLP injury score greater than LVLP at the proximal cuff (P < .05). CONCLUSION: In a swine model, tracheostomy resulted in increased mucosal injury compared to normal tracheal mucosa. LVLP cuffs resulted in less injury than HVLP cuffs, with reduced mucosal inflammation and improved health of epithelium and lamina propria. The wider proximal LVLP cuff demonstrated improved mucosal health compared to the HVLP cylindrical cuff.
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Intubación Intratraqueal , Traqueostomía , Animales , Diseño de Equipo , Intubación Intratraqueal/métodos , Membrana Mucosa , Porcinos , TráqueaRESUMEN
PURPOSE: The purpose of this study was to compare the safety, efficacy, and efficiency of a Descemet membrane endothelial keratoplasty (DMEK) graft processing device, DescePrep, with a manual dissection technique through the measurement of tissue yield, processing time, and graft viability in nondiabetic and diabetic donor corneas. METHODS: Nondiabetic (n = 20) and diabetic (n = 20) donor corneas were processed using DescePrep, which standardizes the liquid bubble technique. Nondiabetic (n = 20) and diabetic (n = 24) donor corneas were also processed through manual dissection. Corneas were stained, processed, and then evaluated for processing success rate and time. Randomly selected corneas (n = 5, each) were evaluated for cell viability using live/dead staining. RESULTS: One hundred percent of nondiabetic and 95% of diabetic corneas were processed successfully with DescePrep in an average of 3.37 minutes. Ninety percent of nondiabetic and 50% of diabetic corneas were processed successfully with manual dissection in an average of 9.87 minutes. DescePrep had a significantly lower processing time ( P < 0.0001) and significantly higher success rate in comparison with manual dissection. DescePrep grafts had an average cell viability of 91.1% ± 3.3% in nondiabetic and 91.5% ± 2.4% in diabetic corneas. Grafts prepared with manual dissection had an average cell viability of 89.5% ± 5.8% in nondiabetic and 88.1% ± 4.3% in diabetic corneas. CONCLUSIONS: DescePrep provides a more effective and efficient method of cornea preparation in comparison with the current standard, particularly in diabetic corneas, while providing comparable cell viability. Thus, DescePrep offers standardized DMEK processing that produces high-quality grafts at high yields, with the potential to expand access and improve the quality of DMEK graft preparation in a larger pool of donors.
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Queratoplastia Endotelial de la Lámina Limitante Posterior , Diabetes Mellitus , Córnea/cirugía , Lámina Limitante Posterior/cirugía , Queratoplastia Endotelial de la Lámina Limitante Posterior/métodos , Endotelio Corneal/trasplante , Humanos , Donantes de Tejidos , Recolección de Tejidos y ÓrganosRESUMEN
OBJECTIVE: Characterize and quantify epithelium in multiple etiologies of laryngotracheal stenosis (LTS) to better understand its role in pathogenesis. STUDY DESIGN: Controlled in vitro cohort study. METHODS: Endoscopic brush biopsy samples of both normal (non-scar) and scar were obtained in four patients with idiopathic subglottic stenosis (iSGS) and four patients with iatrogenic LTS (iLTS). mRNA expression of basal, ciliary, and secretory cell markers were evaluated using quantitative PCR. Cricotracheal resection tissue samples (n = 5 per group) were also collected, analyzed using quantitative immunohistochemistry, and compared with rapid autopsy tracheal samples. RESULTS: Both iSGS and iLTS-scar epithelium had reduced epithelial thickness compared with non-scar control epithelium (P = .0009 and P = .0011, respectively). Basal cell gene and protein expression for cytokeratin 14 was increased in iSGS-scar epithelium compared with iLTS or controls. Immunohistochemical expression of ciliary tubulin alpha 1, but not gene expression, was reduced in both iSGS and iLTS-scar epithelium compared with controls (P = .0184 and P = .0125, respectively). Both iSGS and iLTS-scar had reductions in Mucin 5AC gene expression (P = .0007 and P = .0035, respectively), an epithelial goblet cell marker, with reductions in secretory cells histologically (P < .0001). CONCLUSIONS: Compared with non-scar epithelium, the epithelium within iSGS and iLTS is morphologically abnormal. Although both iSGS and iLTS have reduced epithelial thickness, ciliary cells, and secretory cells, only iSGS had significant increases in pathological basal cell expression. These data suggest that the epithelium in iSGS and iLTS play a common role in the pathogenesis of fibrosis in these two etiologies of laryngotracheal stenosis. SETTING: Tertiary referral center (2017-2020). LEVEL OF EVIDENCE: NA Laryngoscope, 132:2194-2201, 2022.
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Laringoestenosis , Estenosis Traqueal , Cicatriz/patología , Estudios de Cohortes , Constricción Patológica/complicaciones , Humanos , Queratina-14 , Laringoestenosis/cirugía , Mucina 5AC , ARN Mensajero , Estenosis Traqueal/patología , Tubulina (Proteína)RESUMEN
BACKGROUND/AIMS: Laryngotracheal stenosis is a rare but devastating proximal airway fibrosis that restricts a patient's ability to breathe. Treatment is primarily surgical and to date, there has never been a multi-institutional, randomized, prospective, and interventional clinical trial for a medical therapy to treat laryngotracheal stenosis. Therefore, we aimed to obtain patient feedback to guide successful trial design, recruitment, retention, and for identifying potential barriers to study participation. METHODS: Over 1000 members of an international laryngotracheal stenosis online support community (the Living with Idiopathic Subglottic Stenosis Facebook group) were sent two questionnaires for a proposed interventional double-blinded, randomized, placebo-controlled clinical trial. RESULTS: A total of 317 and 558 participants responded to the first and second surveys, respectively. The majority of participants (77%) were willing to consider enrollment, regardless of having a 50% chance of receiving placebo versus treatment (78%). The majority (84%) of participants were willing to travel 200 miles to participate for up to six in-person visits over 50 days. Specific side effects, including anemia/thrombocytopenia (72%) or risk of infection (69.3%) had the greatest impact on clinical trial participation with other side effects (peripheral edema (53%), oral ulcers (51%), and gastrointestinal side effects (41%)) having less impact. CONCLUSION: Patients with laryngotracheal stenosis possess nuanced insight into their disease and treatment options. As a group, they are extremely motivated for better therapies. Future laryngotracheal stenosis clinical trials should focus on providing excellent side effect -related education and utilizing feedback from online advocacy groups to optimize recruitment and retention.
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Laringoestenosis , Estenosis Traqueal , Ensayos Clínicos como Asunto , Constricción Patológica , Humanos , Laringoestenosis/tratamiento farmacológico , Laringoestenosis/cirugía , Estudios Prospectivos , Encuestas y Cuestionarios , Estenosis Traqueal/cirugía , Resultado del TratamientoRESUMEN
STUDY OBJECTIVE: Both simulator practice and intraoperative performance serve to inform surgical trainee training, but the skill transfer from simulation to the intraoperative setting remains unclear. This study evaluates the correlation between trainee performance on virtual reality simulation and (1) overall intraoperative performance during robotic-assisted laparoscopic hysterectomy (RALH) procedures and (2) suturing performance during vaginal cuff closure portion of the case. DESIGN: Retrospective subgroup analysis of randomized controlled trial. SETTING: Academic hospital. PATIENTS: Patients with RALH (N = 29). INTERVENTIONS: Gynecological trainees (N = 21) performed simulation tasks using the da Vinci skills simulator on the day of surgery before performing RALH. Attending surgeons assessed participants' intraoperative performance using Global Evaluative Assessment of Robotic Skills (GEARS). Performance of the vaginal cuff closure step was subsequently assessed using GEARS scoring of anonymized videos. Spearman's correlation was used to quantify the relationship between simulation and intraoperative performances. MEASUREMENTS AND MAIN RESULTS: Trainees achieved a median intraoperative GEARS score of 18.5/30 (interquartile range: 17-22) and a median total simulator score of 84.4/100 (interquartile range: 78.1-87.5). More advanced residents exhibited worse overall simulator performance (median score 86.6/100 compared with 78.8/100, p = .03) and similar intraoperative GEARS scores during overall RALH and vaginal cuff closure compared with less experienced trainees. Total simulation performance score was negatively correlated with GEARS Bimanual Dexterity (ρ = -0.46, p = .02) and Force Sensitivity subscores (ρ = -0.39, p = .05). There was no correlation between total GEARS intraoperative vaginal cuff closure scores and overall simulation performances; however, total Tubes simulation score was correlated with higher GEARS Force Sensitivity subscore (ρ = 0.73, p = .05). CONCLUSIONS: In this study, there was limited correlation between simulation score metrics and trainees' overall intraoperative performance. Furthermore, we identified that GEARS scores could not distinguish between similar trainee skill levels. These findings underscore the need to develop intraoperative assessment tools that can better discriminate different but similar skill levels.
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Laparoscopía , Procedimientos Quirúrgicos Robotizados , Robótica , Realidad Virtual , Competencia Clínica , Simulación por Computador , Femenino , Humanos , Histerectomía , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/educaciónRESUMEN
OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a rare disease, causing life-threatening dyspnea secondary to scarring. Perhaps because it is rarely encountered, there is often a delay in diagnosing iSGS. The objective of this study is to characterize diagnostic delay of iSGS, factors that prolong delay, and its impact on iSGS patients. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review of 124 iSGS patients was performed. Times of symptom onset, presentation to otolaryngologist, diagnosis, imaging, pulmonary function testing (PFTs), surgeries, emergency department (ED) visits, and hospitalizations were recorded and univariate analyses were used to identify risk factors for delay. RESULTS: The median total time to diagnosis from symptom onset was 24.5 months, with time to first presentation of 6.3 months and healthcare delay of 17.8 months. 54.8% of patients were diagnosed with asthma. Earlier presentation to otolaryngologist was associated with shorter healthcare delay and total time to diagnosis (rho = 0.75, rho = 0.99, P < .0001). Earlier CT imaging was correlated to shorter healthcare delay (rho = 0.84, P < .0001) and total time to diagnosis (rho = 0.74, P < .001), while earlier PFTs were correlated to shorter total time to diagnosis alone (rho = 0.71, P = .01). During evaluation, 10.5% (n = 17/124) of patients had ED visits and 13.7% (n = 13/124) patients were hospitalized. Before diagnosis, 7% (9/124) of patients underwent surgeries (including 3% (n = 4) undergoing tracheostomy) and 8% (n = 10) of patients required unplanned urgent endoscopic surgery that may have been avoided with earlier diagnosis. CONCLUSION: iSGS diagnosis is frequently delayed, resulting in additional surgeries (including tracheostomy), ED visits, and hospitalizations. Further, patients' symptoms are commonly attributed to asthma. Earlier otolaryngologist evaluation, PFTs, and CT imaging may expedite iSGS diagnosis. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:413-418, 2022.
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Diagnóstico Tardío , Laringoestenosis/diagnóstico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: The purpose of this study was to evaluate the safety, efficacy, and efficiency of a Descemet membrane endothelial keratoplasty (DMEK) graft preparation device, DescePrep, through measurement of graft viability, yield, and preparation time in both healthy and diabetic (high-risk) donor eyes. METHODS: Twenty nondiabetic and 10 diabetic donor corneas were processed using DescePrep, which standardizes the liquid bubble technique. Corneas were stained with trypan blue and then processed. Cell counts through specular microscopy, optical coherence tomography imaging, and slit-lamp analysis were used for the evaluation of graft separation and viability in 5 nondiabetic corneas. The remaining 25 corneas (15 nondiabetic and 10 diabetic) were evaluated for preparation success rate and processing time. Ten corneas (5 nondiabetic and 5 diabetic) were randomly selected for further evaluation of global cell loss through staining. RESULTS: Ninety-seven percent of corneas (29 of 30) were prepared successfully with DescePrep. The average preparation time was 2.83 ± 1.8 minutes. There was no significant difference in the time of preparation between the nondiabetic and diabetic groups (P = 0.077). The overall average cell death after processing was 7.9% ± 3.7% for all corneas. There was no significant difference in cell viability between diabetic and nondiabetic tissues after DescePrep processing (P = 0.769). CONCLUSIONS: DescePrep is a new DMEK preparation technique that can process both nondiabetic and diabetic donor corneas at high yields in minutes. High-yield preparation of diabetic corneas may offer eye banks access to a larger donor pool, which is important because the demand for DMEK grafts continues to rise worldwide.
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Enfermedades de la Córnea/cirugía , Queratoplastia Endotelial de la Lámina Limitante Posterior/instrumentación , Complicaciones de la Diabetes/cirugía , Eficiencia , Recolección de Tejidos y Órganos/métodos , Anciano , Recuento de Células , Supervivencia Celular/fisiología , Bancos de Ojos/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Microscopía con Lámpara de Hendidura , Factores de Tiempo , Donantes de Tejidos , Resultado del TratamientoRESUMEN
OBJECTIVE: Iatrogenic laryngotracheal stenosis (iLTS) is the pathologic narrowing of the glottis, subglottis, and/or trachea secondary to intubation or tracheostomy related injury. Patients with type 2 diabetes mellitus (T2DM) are more likely to develop iLTS. To date, the metabolomics and phenotypic expression of cell markers in fibroblasts derived from patients with T2DM and iLTS are largely unknown. STUDY DESIGN: Controlled in vitro cohort study. SETTING: Tertiary referral center (2017-2020). METHODS: This in vitro study assessed samples from 6 patients with iLTS who underwent surgery at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea and compared with controls obtained from the trachea of rapid autopsy specimens. Patients with iLTS were subcategorized into those with and without T2DM. Metabolic substrates were identified by mass spectrometry, and cell protein expression was measured by flow cytometry. RESULTS: T2DM iLTS-scar fibroblasts had a metabolically distinct profile and clustered tightly on a Pearson correlation heat map as compared with non-T2DM iLTS-scar fibroblasts. Levels of itaconate were elevated in T2DM iLTS-scar fibroblasts. Flow cytometry demonstrated that T2DM iLTS-scar fibroblasts were associated with higher CD90 expression (Thy-1; mean, 95%) when compared with non-T2DM iLTS-scar (mean, 83.6%; P = .0109) or normal tracheal fibroblasts (mean, 81.1%; P = .0042). CONCLUSIONS: Scar-derived fibroblasts from patients with T2DM and iLTS have a metabolically distinct profile. These fibroblasts are characterized by an increase in itaconate, a metabolite related to immune-induced scar remodeling, and can be identified by elevated expression of CD90 (Thy-1) in vitro.
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Diabetes Mellitus Tipo 2 , Laringoestenosis , Estudios de Cohortes , Constricción Patológica , Diabetes Mellitus Tipo 2/complicaciones , Fibroblastos/patología , Humanos , Enfermedad Iatrogénica , Laringoestenosis/patologíaRESUMEN
Importance: During respiratory disease outbreaks such as the COVID-19 pandemic, aerosol-generating procedures, including tracheostomy, are associated with the risk of viral transmission to health care workers. Objective: To quantify particle aerosolization during tracheostomy surgery and tracheostomy care and to evaluate interventions that minimize the risk of viral particle exposure. Design, Setting, and Participants: This comparative effectiveness study was conducted from August 2020 to January 2021 at a tertiary care academic institution. Aerosol generation was measured in real time with an optical particle counter during simulated (manikin) tracheostomy surgical and clinical conditions, including cough, airway nebulization, open suctioning, and electrocautery. Aerosol sampling was also performed during in vivo swine tracheostomy procedures (n = 4), with or without electrocautery. Fluorescent dye was used to visualize cough spread onto the surgical field during swine tracheostomy. Finally, 6 tracheostomy coverings were compared with no tracheostomy covering to quantify reduction in particle aerosolization. Main Outcomes and Measures: Respirable aerosolized particle concentration. Results: Cough, airway humidification, open suctioning, and electrocautery produced aerosol particles substantially above baseline. Compared with uncovered tracheostomy, decreased aerosolization was found with the use of tracheostomy coverings, including a cotton mask (73.8% [(95% CI, 63.0%-84.5%]; d = 3.8), polyester gaiter 79.5% [95% CI, 68.7%-90.3%]; d = 7.2), humidification mask (82.8% [95% CI, 72.0%-93.7%]; d = 8.6), heat moisture exchanger (HME) (91.0% [95% CI, 80.2%-101.7%]; d = 19.0), and surgical mask (89.9% [95% CI, 79.3%-100.6%]; d = 12.8). Simultaneous use of a surgical mask and HME decreased the particle concentration compared with either the HME (95% CI, 1.6%-12.3%; Cohen d = 1.2) or surgical mask (95% CI, 2.7%-13.2%; d = 1.9) used independently. Procedures performed with electrocautery increased total aerosolized particles by 1500 particles/m3 per 5-second interval (95% CI, 1380-1610 particles/m3 per 5-second interval; d = 1.8). Conclusions and Relevance: The findings of this laboratory and animal comparative effectiveness study indicate that tracheostomy surgery and tracheostomy care are associated with significant aerosol generation, putting health care workers at risk for viral transmission of airborne diseases. Combined HME and surgical mask coverage of the tracheostomy was associated with decreased aerosolization, thereby reducing the risk of viral transmission to health care workers.
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Aerosoles , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Cuerpo Médico de Hospitales , Traqueostomía/efectos adversos , Virión , Animales , COVID-19/prevención & control , COVID-19/transmisión , Investigación sobre la Eficacia Comparativa , Electrocoagulación/efectos adversos , Calor , Humanos , Humedad , Maniquíes , Máscaras , Factores de Riesgo , SARS-CoV-2 , Porcinos , Traqueostomía/instrumentaciónRESUMEN
AIM: To identify instrument holding archetypes used by experienced surgeons in order to develop a universal language and set of validated techniques that can be utilized in manual small incision cataract surgery (MSICS) curricula. METHODS: Experienced cataract surgeons performed five MSICS steps (scleral incision, scleral tunnel, side port, corneal tunnel, and capsulorhexis) in a wet lab to record surgeon hand positions. Images and videos were taken during each step to identify validated hand position archetypes. RESULTS: For each MSICS step, one or two major archetypes and key modifying variables were observed, including tripod for scleral incision, tripod-thumb bottom for scleral tunnel, underhand-index to thumb grip for side port, index-contact tripod for corneal entry, and tripod-forceps for capsulorhexis. Key differences were noted in thumb placement and number of fingers supporting the instrument, and modifying variables included index finger curvature and amount of flexion. CONCLUSION: Identification of optimal hand positions and development of a formal nomenclature has the potential to help trainees adopt hand positions in an informed manner, influence instrument design, and improve surgical outcomes.
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OBJECTIVE: Subglottic stenosis (SGS) is a known complication of granulomatosis with polyangiitis (GPA). We investigated the impact of medical and surgical interventions on the surgical dilation interval and characterized patients with glottic involvement. STUDY DESIGN: A retrospective chart review of patients with GPA-associated SGS was performed from 2010 to 2019. SETTING: Tertiary academic medical center. METHODS: The impact of medical and surgical interventions on dilation interval was assessed. The prevalence of glottic involvement was assessed, and clinical characteristics and outcomes were compared with patients without glottic involvement. RESULTS: A total of 39 patients with GPA-associated SGS were analyzed. Dilation intervals in patients receiving leflunomide (n = 4; median, 484 days; 95% CI, 405-1099) were greater than in those not receiving leflunomide (median, 155 days; 95% CI, 48-305; P = .033). The surgical technique used did not affect dilation interval. Patients with glottic involvement (n = 13) had a greater incidence of dysphonia (13/13 vs 15/26 [58%], P = .007) and a shorter dilation interval with involvement (median, 91 days; interquartile range, 70-277) versus without involvement (median, 377 days; interquartile range, 175-1148; hazard ratio, 3.38; 95% CI, 2.26-5.05; P < .001). Of 13 patients, 8 (62%) did not have glottic involvement on first presentation. CONCLUSION: Although GPA is classically thought to affect the subglottis, it also involves the glottis in a subset of patients. These patients have greater complaints of dysphonia and require more frequent surgery. Systemic therapy may increase dilation intervals. In this preliminary study, patients taking leflunomide demonstrated an improvement, highlighting the need for further study of immunosuppression regimens in the treatment of GPA-associated SGS.
Asunto(s)
Dilatación , Granulomatosis con Poliangitis/complicaciones , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Laringoestenosis/cirugía , Adulto , Femenino , Granulomatosis con Poliangitis/tratamiento farmacológico , Granulomatosis con Poliangitis/cirugía , Humanos , Laringoestenosis/etiología , Masculino , Estudios Retrospectivos , Factores de TiempoRESUMEN
PURPOSE: Middle ear disease is increasingly being managed via transcanal endoscopic ear surgery (TEES). A limitation of TEES is that it restricts the surgeon to single-handed dissection. One solution to this would be an endoscope holder to facilitate two-handed dissection. Current endoscope holders are stationary, and can cause potential damage from endoscope contact with the ossicles or ear canal if unintended head motion occurs from inadequate anesthetic. A dynamic device that could detect and react to patient motion would mitigate these concerns, but currently there is little formal characterization of the frequency, velocity and acceleration of unintended patient head motion during otologic procedures performed under general anesthesia. The present study aims to characterize intraoperative patient head motion kinematics during cases utilizing TEES. MATERIALS AND METHODS: This is a prospective study of adults undergoing otologic procedures performed with general anesthesia and without paralysis. Head motion was characterized using a nine-axis inertial measurement unit (IMU), (LPMS-B2, Life Performance Research) mounted to each patient's forehead for the procedure duration. RESULTS: Data was collected across 10 cases; 50% of patients were female and mean age was 50 ± 14 years. There was observed patient head motion in 40% of cases with maximum linear acceleration of 0.75 m/s2 and angular velocity of 12.50 degrees/s. CONCLUSIONS: Patient movement during otologic procedures was commonly observed, demonstrating the need for a dynamic holder to allow two-handed TEES. Results from this study are the first objective characterization of patient head motion kinematics during otologic procedures performed under general anesthesia.
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Enfermedades del Oído/cirugía , Oído Medio/cirugía , Endoscopía/métodos , Cabeza/fisiología , Movimiento/fisiología , Procedimientos Quirúrgicos Otológicos/métodos , Adulto , Anestesia General , Conducto Auditivo Externo , Osículos del Oído , Endoscopía/efectos adversos , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Otológicos/efectos adversos , Estudios ProspectivosRESUMEN
PURPOSE: Middle ear disease is increasingly being managed via transcanal endoscopic ear surgery (TEES). A limitation of TEES is that it restricts the surgeon to single-handed dissection. One solution to this would be an endoscope holder to facilitate two-handed dissection. Current endoscope holders are stationary, and can cause potential damage from endoscope contact with the ossicles or ear canal if unintended head motion occurs from inadequate anesthetic. A dynamic device that could detect and react to patient motion would mitigate these concerns, but currently there is little formal characterization of the frequency, velocity and acceleration of unintended patient head motion during otologic procedures performed under general anesthesia. The present study aims to characterize intraoperative patient head motion kinematics during cases utilizing TEES. MATERIALS AND METHODS: This is a prospective study of adults undergoing otologic procedures performed with general anesthesia and without paralysis. Head motion was characterized using a nine-axis inertial measurement unit (IMU), (LPMS-B2, Life Performance Research) mounted to each patient's forehead for the procedure duration. RESULTS: Data was collected across 10 cases; 50% of patients were female and mean age was 50 ± 14 years. There was observed patient head motion in 40% of cases with maximum linear acceleration of 0.75 m/s2 and angular velocity of 12.50 degrees/s. CONCLUSIONS: Patient movement during otologic procedures was commonly observed, demonstrating the need for a dynamic holder to allow two-handed TEES. Results from this study are the first objective characterization of patient head motion kinematics during otologic procedures performed under general anesthesia.
Asunto(s)
Endoscopía/métodos , Cabeza/fisiología , Movimiento (Física) , Movimiento/fisiología , Procedimientos Quirúrgicos Otológicos/métodos , Adulto , Anestesia General , Fenómenos Biomecánicos , Oído Medio/cirugía , Endoscopía/efectos adversos , Femenino , Humanos , Periodo Intraoperatorio , Enfermedades del Laberinto/cirugía , Persona de Mediana Edad , Procedimientos Quirúrgicos Otológicos/efectos adversosRESUMEN
PURPOSE: Venous malformations (VMs) are low-flow vascular anomalies that are commonly treated with image-guided percutaneous sclerotherapy. Although many VMs can be safely accessed and treated using ultrasonography and fluoroscopy, some lesions may be better treated with magnetic resonance imaging (MRI)-guided sclerotherapy. The aim of this study is to evaluate the feasibility, efficiency, and outcomes of MRI-guided sclerotherapy of VMs using a 3T MRI system. METHODS: Six patients with VMs in the neck (n = 2), chest (n = 1), and extremities (n = 3) underwent sclerotherapy with 3T MRI guidance. Feasibility was assessed by calculating the technical success rate and procedural efficiency. Efficiency was evaluated by using planning, targeting, intervention, and total procedure times. Outcomes were assessed by measuring VM volumes before and after sclerotherapy, patient-reported pain scores, and occurrence of complications. RESULTS: Technical success was achieved in all 6 procedures. There was a non-significant 30% decrease in mean VM volume after the procedure (P = .350). The procedure resulted in a decrease in mean pain score (on an 11-point scale) of 2.6 points (P = .003). After the procedure, 4 patients reported complete pain resolution, 1 reported partial pain resolution, and 1 reported no change in pain. Procedural efficiency was consistent with similar sclerotherapy procedures performed at our institution. There were no major or minor complications. CONCLUSION: 3T MRI guidance is feasible for percutaneous sclerotherapy of VMs, with promising initial technical success rates, procedural efficiency, and therapeutic outcomes without complications.