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Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis.

ABSTRACT: Introduction ?Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. Objective ?To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. Data synthesis ?A systematic review of experimental or observational studies that have evaluated the treatment of laryngotracheal stenoses with the use of topical Mitomycin C was performed. Databases researched: LILACS, PubMed, Embase, Cochrane and Web of Science. Outcomes: resolution (symptom-free time???one year), number of procedures required, and complications resulting from the procedure. A total of 15 studies (involving 387 patients) were selected. Mitomycin C was administered to every patient in 11 studies, and in 4 other studies, the patients were separated into 2 groups, 1 receiving mitomycin C, and the other not. The resolution of the stenosis evaluated in 12 studies in which the patients received mitomycin C was of 69% (95% confidence interval [95%CI]: 61-76%; I 2 ?=?17.3%). A total of 52% of the patients (95%CI: 39-64%, 11 studies; I 2 ?=?64.7%) were submitted to a single endoscopic procedure, and 48% (95%CI: 36-61%, 11 studies; I 2 ?=?64.7%) were submitted to more than 1 procedure. Complications (mediastinal and subcutaneous emphysema, dysphonia, laceration or vocal fold paralysis and acute light obstruction) were reported in 9% of the patients (95%CI: 3-18%, 9 studies; I 2 ?=?79.8%). Conclusions ?The evidence suggests that mitomycin C is an effective and safe option in the endoscopic treatment of laryngotracheal stenosis.

SUBMITTER: Queiroga TLO

PROVIDER: S-EPMC6946955 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis.

Queiroga Thereza L O TLO Cataneo Daniele C DC Martins Regina H G RHG Reis Tarcisio A TA Cataneo Antônio J M AJM

International archives of otorhinolaryngology 20191220 1

Introduction Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. Objective To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. Data synthesis A systematic review of experimental or observational studies that have evaluated the treatment of laryngotracheal stenoses with the use of topical Mitomycin C was performed. Databases res ...[more]

PMID: 31915466

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Project description:Laryngotracheal stenosis is an obstructive respiratory disease that leads to voicing difficulties and dyspnea with potential life-threatening consequences. The majority of incidences are due to iatrogenic etiology from endotracheal tube intubation; however, airway scarring also has idiopathic causes. While recent evidence suggests a microbial contribution to mucosal inflammation, the microbiota associated with different types of stenosis has not been characterized. High-throughput sequencing of the V4 region of the16S rRNA gene was performed to characterize the microbial communities of 61 swab samples from 17 iatrogenic and 10 adult idiopathic stenosis patients. Nonscar swabs from stenosis patients were internal controls, and eight swabs from four patients without stenosis represented external controls. Significant differences in diversity were observed between scar and nonscar samples and among sample sites, with decreased diversity detected in scar samples and the glottis region. Permutational analysis of variance (PERMANOVA) results revealed significant differences in community composition for scar versus nonscar samples, etiology type, sample site, groups (iatrogenic, idiopathic, and internal and external controls), and individual patients. Pairwise Spearman's correlation revealed a strong inverse correlation between Prevotella and Streptococcus among all samples. Finally, bacteria in the family Moraxellaceae were found to be distinctly associated with idiopathic stenosis samples in comparison with external controls. Our findings suggest that specific microbiota and community shifts are present with laryngotracheal stenosis in adults, with members of the family Moraxellaceae, including the known pathogens Moraxella and Acinetobacter, identified in idiopathic scar. Further work is warranted to elucidate the contributing role of bacteria on the pathogenesis of laryngotracheal stenosis.IMPORTANCE The laryngotracheal region resides at the intersection between the heavily studied nasal cavity and lungs; however, examination of the microbiome in chronic inflammatory conditions of the subglottis and trachea remains scarce. To date, studies have focused on the microbiota of the vocal folds, or the glottis, for laryngeal carcinoma, as well as healthy larynges, benign vocal fold lesions, and larynges exposed to smoking and refluxate. In this study, we seek to examine the structure and composition of the microbial community in adult laryngotracheal stenosis of various etiologies. Due to the heterogeneity among the underlying pathogenesis mechanisms and clinical outcomes seen in laryngotracheal stenosis disease, we hypothesized that different microbial profiles will be detected among various stenosis etiology types. Understanding differences in the microbiota for subglottic stenosis subtypes may shed light upon etiology-specific biomarker identification and offer novel insights into management approaches for this debilitating disease.

Project description:ImportanceLaryngotracheal stenosis (LTS) is a fibroproliferative disorder of the glottis, subglottis, and trachea. In models of fibrosis from other organ systems, the CD4+ T-cell response has been shown to regulate extracellular matrix deposition. Specifically, helper T cell 2 (TH2) promotes fibrosis, whereas TH1 and associated cytokines have been shown to be antifibrotic. However, this antifibrotic effect of the TH1 response has not been demonstrated in LTS.ObjectiveTo determine whether the TH1 cytokine interferon-γ inhibits the function of LTS-derived fibroblasts in vitro.Design, setting, and participantsThis in vitro controlled study included 6 patients with iatrogenic LTS undergoing routine surgical subglottic and tracheal dilation at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea. The presence of fibroblasts was confirmed by an immunohistochemical analysis. Laryngotracheal stenosis-derived fibroblasts were treated with interferon-γ and compared with untreated controls (2 sets of untreated, LTS-derived fibroblasts [media did not contain interferon-γ]) and normal airway fibroblasts (fibroblasts isolated from normal trachea). Data were collected from August 2015 through June 2016.InterventionsTreatment with interferon-γ, 10 ng/mL.Main outcomes and measuresCellular proliferation, fibrosis gene expression (using quantitative reverse transcription polymerase chain reaction analysis), soluble collagen, and cellular histologic features were assessed.ResultsAmong the 6 patients (6 women; mean [SD] age, 38.3 [17.2] years), LTS-derived fibroblast proliferation was reduced in patients who received interferon-γ treatment compared with untreated controls on days 3 (mean difference, -6515 cells; 95% CI, -10 630 to -2600 cells) to 6 (mean difference, -47 521 cells; 95% CI, -81 285 to -13 757 cells). Interferon-γ treatment reduced collagen types I and III gene expression by 86% and 68%, respectively, and resulted in lower total collagen production (10.94 vs 14.89 μg/mL). In addition, interferon-γ treatment resulted in a 32% reduction in expression of transforming growth factor β in LTS-derived fibroblasts.Conclusions and relevanceInterferon-γ reduced proliferation, soluble collagen production, and collagen expression in LTS-derived fibroblasts while also reducing the expression of the profibrotic cytokine transforming growth factor β. These findings suggest that therapeutics aimed at increasing interferon-γ and the TH1 response could attenuate LTS.

Project description:BackgroundLumbar spinal stenosis (LSS) is caused by neural compression due to narrowing of the lumbar spinal canal or neural foramen. Surgical intervention is a standard treatment for LSS; however, the steep increase in the surgical rate, post-operative complications, and comparatively low long-term satisfaction are considered to be limitations of this surgical approach. Conversely, acupotomy is a minimally invasive technique that combines the effects of conventional acupuncture with micro-incision, which may offer an alternative to surgery for the treatment of LSS. This review was conducted to investigate and critically review the current evidence on the efficacy and safety of acupotomy for LSS.MethodsEleven databases were searched from their respective inception dates to December 28, 2018. Randomized controlled trials (RCTs) comparing acupotomy and wait-list, sham treatment, or active controls were included. The quality of the included studies was assessed using risk-of-bias tool.ResultsSeven RCTs were included in this review and meta-analysis. The methodological quality of the included studies was generally poor. The acupotomy treatment group was associated with significantly lower visual analogue scale scores (range 0∼10) (5 RCTs; mean difference [MD] -1.55, 95% confidence interval [CIs] -2.60 to -0.50; I = 94%) and higher Japanese Orthopedic Association Score (3 RCTs; MD 4.70, 95% CI 3.73 to 5.68; I = 0%) compared to the active control group. In subgroup analysis based on the type of active controls, acupotomy retained significant benefits over lumbar traction and acupuncture, as well as over lumbar traction, spinal decompression, and acupuncture. Safety data were reported in only 1 study, and no adverse events occurred in either the acupotomy or the acupuncture control group.ConclusionAccording to current evidence, acupotomy might be beneficial for treating LSS. Acupotomy showed consistent superiority over lumbar traction, but the results were mixed in comparisons with other interventions, such as spinal decompression and acupuncture. However, the findings should be interpreted cautiously, given the poor methodological quality of the included studies, and potential small-study effects. Further larger, high-quality, rigorous RCTs should be conducted on this topic and rigorous reporting of acupotomy procedures and safety data should be encouraged.

Project description:BACKGROUND:Proportional modes (proportional assist ventilation, PAV, and neurally adjusted ventilatory assist, NAVA) could improve patient-ventilator interaction and consequently may be efficient as a weaning mode. The purpose of this systematic review is to examine whether proportional modes improved patient-ventilator interaction and whether they had an impact on the weaning success and length of mechanical ventilation, in comparison with PSV. METHODS:We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception through May 13, 2018. We included both parallel-group and crossover randomized studies that examined the efficacy of proportional modes in comparison with PSV in mechanically ventilated adults. The primary outcomes were (1) asynchrony index (AI), (2) weaning failure, and (3) duration of mechanical ventilation. RESULTS:We included 15 studies (four evaluated PAV, ten evaluated NAVA, and one evaluated both modes). Although the use of proportional modes was not associated with a reduction in AI (WMD -?1.43; 95% CI -?3.11 to 0.25; p?=?0.096; PAV-one study, and NAVA-seven studies), the use of proportional modes was associated with a reduction in patients with AI?>?10% (RR 0.15; 95% CI 0.04-0.58; p?=?0.006; PAV-two studies, and NAVA-five studies), compared with PSV. There was a significant heterogeneity among studies for AI, especially with NAVA. Compared with PSV, use of proportional modes was associated with a reduction in weaning failure (RR 0.44; 95% CI 0.26-0.75; p?=?0.003; PAV-three studies) and duration of mechanical ventilation (WMD -?1.78 days; 95% CI -?3.24 to -?0.32; p?=?0.017; PAV-three studies, and NAVA-two studies). Reduced duration of mechanical ventilation was found with PAV but not with NAVA. CONCLUSION:The use of proportional modes was associated with a reduction in the incidence with AI?>?10%, weaning failure and duration of mechanical ventilation, compared with PSV. However, reduced weaning failure and duration of mechanical ventilation were found with only PAV. Due to a significant heterogeneity among studies and an insufficient number of studies, further investigation seems warranted to better understand the impact of proportional modes. Clinical trial registration PROSPERO registration number, CRD42017059791. Registered 20 March 2017.

Dataset Information

Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis.

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Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis.

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