RESUMEN
Objectives/Hypothesis: Compare proteomic profiles of rabbit vocal folds (VFs) injected with micronized cross-linked jellyfish collagen "collagen Type 0" (MX-JC) against two clinical products for injection medialization laryngoplasty (IL). Study Design: Animal model. Methods: Left recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits (N = 6/group). Group 1 received (MX-JC) and adipose-derived stem cells (ADSCs), Group 2, MX-JC alone; Group 3, cross-linked hyaluronic acid; and Group 4, micronized acellular dermis. Animals were sacrificed at 4 and 12 weeks. Proteomic profiling of injected versus noninjected VFs by nano-liquid chromatography, tandem mass spectrometry, and reactome gene ontology analysis was performed. Results: Overall, 37-61 proteins were found to be upregulated and 60-284 downregulated in injected versus non-injected VFs (>1.5 fold, false discovery rate-adjusted p < .05). Over-representation analysis (% of total) revealed top up-regulated pathways at 4 and 12 weeks, respectively: Group 1, keratan sulfate metabolism (46%) and cellular processes (29%); Group 2, extracellular matrix (ECM)/collagen processes (33%) and beta oxidation (39%); Group 3, cellular processes (50%) and energy metabolism (100%); and Group 4, keratan sulfate metabolism (31%) and inflammation (50%). Top downregulated pathways were: Group 1, Inflammation (36%) and glucose/citric acid metabolism (42%); Group 2, cell signaling (38%) and glucose/citric acid metabolism (35%); Group 3, keratan sulfate metabolism (31%) and ECM/collagen processes (48%); and Group 4, glucose/citric acid metabolism (33%) and ECM/collagen processes (43%). Conclusions: MX-JC "collagen Type 0" upregulates pathways related to ECM/collagen formation and downregulates pathways related to inflammation suggesting that it is promising biomaterial for IL. Level of Evidence: NA.
RESUMEN
Objectives: To examine the degree of agreement between MRI and histologically generated volumetric measurements of residual injection laryngoplasty material. Methods: Following left recurrent laryngeal nerve transection, rabbit vocal cords were injected with jellyfish collagen, Cymetra®, or Restylane®. Laryngeal tissue was harvested 4 or 12 weeks post injection followed by MRI imaging and histologic cross-sectioning. Two raters estimated the volume of remaining injection material in specimens within MRI and histologic axial cross sections. Wilcoxon signed rank tests were employed to detect gross differences between inter-rater measurements and between imaging modalities across time. Agreement between rater measurements and imaging (histology and MRI) was assessed using intra-class correlation coefficients. Results: Data was available from 16 rabbits sacrificed at 4 weeks (n = 8) and 12 weeks (n = 8). Inter-rater testing of MRI imaging revealed no significant differences (p > .05) between rater measurements across time points, and excellent agreement (0.93; 95% confidence interval 0.80-0.98) while histologically estimated volumes demonstrated a significant difference at 4 weeks (p < .05) and overall good agreement (0.89; 95% confidence interval 0.59-0.97). Comparison of MRI and histologically estimated volume measurements revealed significant differences at the 4-week time point (p < .05) but not at 12 weeks (p > .05). Overall, there is only moderate agreement between MRI and histology estimates (0.72; 95% confidence interval 0.22-0.90). Conclusions: MRI imaging demonstrates good reliability and similar estimates of volume to histologically estimated measurements of residual injection laryngoplasty material at time points clinically relevant for future injection laryngoplasty experiments. Level of Evidence: NA.
RESUMEN
OBJECTIVES/HYPOTHESIS: Test a new jellyfish collagen biomaterial aimed to increase duration of injection medialization laryngoplasty (IL) against two products in clinical practice. STUDY DESIGN: Animal model. METHODS: Left recurrent laryngeal nerve sectioning and IL were performed in New Zealand White rabbits (N = 6/group). Group 1 received micronized cross-linked jellyfish collagen (MX-JC) and adipose derived stem cells (ADSCs), Group 2, MX-JC alone, Group 3, cross-linked hyaluronic acid (X-HA), and Group 4, micronized acellular dermis (MACD). Animals were sacrificed at 4 and 12 weeks. Major outcomes were MRI tissue volumes and histopathology. RESULTS: After 100 µL IL MRI volumes (means ± STD) at 4 and 12 weeks were: Group 1: 27.2 ± 15.6 and 13.1 ± 5.2 µL, Group 2: 60.8 ± 18 and 27.8 ± 2.47 µL, Group 3: 27.4 ± 12 and 10.6 ± 8 µL, and Group 4: 37.5 ± 11 and 9.85 ± 1 µL. Group 2 volumes were largest and Group 3 were smallest in all comparisons (P < .05). Histologically, low grade inflammatory responses were observed in Group 1, mild histiocytic infiltration in Group 2, widespread muscle fiber loss in Group 3, and plasmocytic infiltration in Group 4. CONCLUSIONS: MX-JC showed the least resorption at 4 and 12 weeks among all groups. T cell inflammatory responses were observed with MX-JC but were reduced by 12 weeks while B cell immune responses, indicative of antibody priming, were predominantly noted with MACD. MX-JC + ADSC showed low grade immunity while the XHA showed greater myocyte loss compared to the other groups. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2452-E2460, 2021.
Asunto(s)
Colágeno/farmacología , Ácido Hialurónico/análogos & derivados , Laringoplastia/métodos , Imagen por Resonancia Magnética/métodos , Parálisis de los Pliegues Vocales/terapia , Dermis Acelular/efectos adversos , Animales , Linfocitos B/inmunología , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/farmacología , Cadáver , Colágeno/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/farmacología , Inmunidad/inmunología , Inflamación/patología , Imagen por Resonancia Magnética/estadística & datos numéricos , Células Madre Mesenquimatosas/patología , Células Plasmáticas/inmunología , Pautas de la Práctica en Medicina , Conejos , Traumatismos del Nervio Laríngeo Recurrente/complicaciones , Traumatismos del Nervio Laríngeo Recurrente/patología , Linfocitos T/patología , Parálisis de los Pliegues Vocales/diagnóstico , Parálisis de los Pliegues Vocales/etiologíaRESUMEN
OBJECTIVE: Recurrent laryngeal nerve injury is a potential complication of cardiothoracic surgery and cause of unilateral vocal fold paralysis (UVFP). Injection laryngoplasty (IL) is an intervention offered to patients with UVFP to alleviate symptoms including dysphagia, dysphonia and weak cough. There is no definitive evidence that IL prevents pneumonia. In this study, we compare rates of pneumonia in patients with UVFP secondary to cardiothoracic surgery who did or did not undergo IL. METHODS: A retrospective chart review identified patients diagnosed with UVFP by an otolaryngologist using flexible laryngoscopy following cardiothoracic surgery from January 1, 2008 to December 31, 2017. Each subject was grouped by IL status and assessed for subsequent pneumonia within 6 months of their diagnosis of UVFP. The association of IL with pneumonia was evaluated using Cox proportional hazards regression. RESULTS: Of 92 patients who met inclusion criteria, 35 (38%) underwent IL and 57 (62%) did not. Twenty patients developed pneumonia, four who had undergone IL and 16 who had not; 12 patients developed aspiration pneumonia including two having undergone IL and 10 who had not. Those who had IL were less likely to develop total pneumonia compared to those who had not (HR = 0.33, P = .045). The protective effect of IL was not as clearly sustained when measuring for aspiration pneumonia, specifically (HR = 0.34; P = .10). DISCUSSION: Injection laryngoplasty may reduce the risk of pneumonia in patients with UVFP secondary to cardiothoracic surgery; however, further research is needed to quantify the potential protective nature of IL in this patient population. LEVEL OF EVIDENCE: 3 (A retrospective cohort study).
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Laringoplastia/efectos adversos , Neumonía/epidemiología , Parálisis de los Pliegues Vocales/terapia , Calidad de la Voz/fisiología , Femenino , Humanos , Inyecciones , Laringoplastia/métodos , Laringoscopía , Masculino , Persona de Mediana Edad , Neumonía/etiología , Complicaciones Posoperatorias , Estudios Retrospectivos , Parálisis de los Pliegues Vocales/complicaciones , Parálisis de los Pliegues Vocales/diagnóstico , Pliegues VocalesRESUMEN
OBJECTIVES/HYPOTHESIS: Design and test a novel biomaterial for injection laryngoplasty aimed to increase the duration of effectiveness of micronized acellular dermis. STUDY DESIGN: Animal model. METHODS: Injection laryngoplasty was performed in three groups (n = 5) of New Zealand White rabbits. Acellular dermis was either used alone as a control (group 1), was combined with undifferentiated stem cells (group 2), or with predifferentiated chondrocytic cells (group 3). Groups 2 and 3 were supplemented with growth factors. Animals were sacrificed 4 and 12 weeks after laryngoplasty and histologic analysis was completed. The major outcome measure was volume of tissue remaining. RESULTS: After 4 weeks, the mean volume of tissue remaining was 341 ± 89 mm3 , 295 ± 102 mm3 , and 133 ± 15 mm3 , for groups 1 to 3, respectively. At the 12-week time point, volumes were 62 ± 62 mm3 , 235 ± 35 mm3 , and 107 ± 99 mm3 . After 12 weeks, there was a significantly higher volume in group 2 compared to group 1 or 3 (P = .01, P = .04). Volumes between week 4 and week 12 were significantly lower in group 1 (P = .02), but not significantly different for groups 2 and 3 (P = .38, P = .74). Histologic evaluation revealed a robust lymphocytic infiltration in all cases as well as morphologic and immunophenotypic features suggestive of chondrogenic differentiation in a single animal. CONCLUSIONS: Micronized acellular dermis combined with stem cells and growth factors showed significantly less resorption 12 weeks after injection laryngoplasty compared to micronized acellular dermis alone. Groups using novel tissue-engineered biomaterial showed a lower resorption rate over time compared with acellular dermis alone. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:160-167, 2018.