Serum expression of Vascular Endothelial-Cadherin, CD44, Human High mobility group B1, Kallikrein 6 proteins in different stages of laryngeal intraepithelial lesions and early glottis cancer.

Background: The study was designed to evaluate the potential validity and utility of selected molecular markers in serum samples from patients with specific stages of laryngeal intraepithelial lesions that could serve as diagnostic tools in differentiation of benign and dysplastic lesions from invasive pathologies. Methods: Prospective study included 80 consecutive patients with vocal fold lesions treated at the single otorhinolaryngology centre. All participants had surgical resection of the lesion. Blood samples were collected from each patient before the surgery. Final diagnosis was confirmed on histopathological examination and included 39 (48.75%) non-dysplastic lesions, eight (10%) low-grade dysplasia, six (7.5%) high-grade dysplasia and 27 (33.75%) invasive cancers. The ELISA procedures were performed according to the manufacturer's instruction. Individual serum concentration of selected proteins was reported in ng/ml: Vascular Endothelial-Cadherin Complex (VE-cad), CD44, Human High mobility group protein B1(HMGB1), Kallikrein 6. Results: The highest mean levels of HMGB1, KLK6 and VE-cad were detected in sera of patients with low-grade dysplasia (81.14, 24.33, 14.17 respectively). Soluble CD44 was the most elevated in patients with non-dysplastic lesions (2.49). The HMGB1, KLK6 and VE-cad serum levels were increasing from non-dysplastic to low-grade dysplasia and followed by the decrease for high-grade dysplasia and invasive cancer, however the differences were not significant (p-values 0.897, 0.354, 0.1 respectively). Patients' serum had the highest CD44 concentration in non-dysplastic and low-grade dysplasia with the following decrease through high-grade dysplasia and invasive cancer. GERD symptomatic patients had higher levels of KLK6 and CD44 than other patients (p-value 0.06 and 0.084 respectively). There were no significant differences of biomarkers levels related to patients' gender (p-value from 0.243 to 1) or smoking status (p-value from 0.22 to 0.706). Conclusions: VE-cad, HMGB1, CD44 and KLK6 did not prove to be reliable biomarkers implicating malignant potential within vocal fold hypertrophic intraepithelial lesions.

Low expression of pRB predicts disease relapse in early glottic cancer treated with transoral laser microsurgery.

OBJECTIVES/HYPOTHESIS: To elucidate the associations among the immunohistochemical expression of tumor markers, clinicopathological variables, and disease-free survival (DFS) in patients with early-stage glottic squamous cell carcinoma (SCC) who underwent transoral laser microsurgery (TLM) as the primary treatment. STUDY DESIGN: Retrospective chart review. METHODS: The records of consecutive patients with Tis-T2N0 glottic SCC who underwent TLM between August 1, 2012 and October 31, 2015 were reviewed. Expression of Bcl-2, pRB, p16INK4A , p53, c-Myc, E-cadherin, and EGFR was examined using tissue microarrays containing tumor specimens through immunohistochemistry. Three-year DFS rates were calculated. RESULTS: A total of 65 consecutive patients were identified, of which 28 were excluded due to insufficient tissue (n = 22) and low biomarker quality (n = 6). Therefore, 37 patients with complete records were included. The included patients were significantly older and had a more advanced type of cordectomy than did the excluded patients (P = .015 and .009, respectively). According to the findings of univariate analysis, age, betel quid chewing, type of cordectomy, BCL-2 expression, and pRB expression significantly predicted 3-year DFS. According to the findings of multivariate analysis, age (adjusted hazard ratio: 0.94, 95% CI: 0.88-1.00), betel quid chewing (adjusted hazard ratio: 5.07, 95% CI: 1.32-19.44), and pRB expression (adjusted hazard ratio: 0.02, 95% CI: 0.00-0.28) were independent predictors of 3-year DFS. CONCLUSIONS: Low pRB expression is a potential biomarker for predicting disease relapse after primary TLM for early-stage glottic SCC and may help to identify high-risk patients who can subsequently undergo intensive management. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:E220-E226, 2019.

Continuous Versus Intermittent Subglottic Secretion Drainage to Prevent Ventilator-Associated Pneumonia: A Systematic Review.

BACKGROUND: Ventilator-associated pneumonia is associated with high morbidity and mortality in patients receiving mechanical ventilation. Subglottic secretion drainage, which may be performed continuously or intermittently, is believed to be an effective strategy for coping with ventilator-assisted pneumonia. Whether continuous or intermittent subglottic secretion drainage is superior for preventing ventilator-assisted pneumonia remains unknown. METHODS: This study is a comprehensive, systematic meta-analysis of randomized trials comparing continuous and intermittent subglottic secretion drainage in patients receiving mechanical ventilation. Studies in English and Chinese published from January 1970 through November 2015 were identified by searching multiple databases. Summary risk ratios or weighted mean differences with 95% CIs were used to calculate each outcome by means of fixed- or random-effects models. RESULTS: Eight studies enrolling a total of 1071 patients met the inclusion criteria. The summary risk ratio between continuous and intermittent subglottic secretion drainage for incidence of ventilator-assisted pneumonia was 0.83 (95% CI, 0.61-1.13); for time to ventilator-assisted pneumonia occurrence, 2.73 (95% CI, -0.39 to 5.85); for occult blood, 2.34 (95% CI, 0.25-21.88); for duration of mechanical ventilation, -0.89 (95% CI, -2.72 to 0.94); for length of intensive care unit stay, 3.98 (95% CI, -4.44 to 12.41); and for mortality, 0.80 (95% CI, 0.48-1.31). CONCLUSIONS: The results indicate no apparent differences between continuous and intermittent subglottic secretion drainage for the treatment outcomes included in the analysis. Rigorously designed, large-scale randomized controlled trials are warranted to identify the roles of continuous and intermittent subglottic secretion drainage.

Tracheal Tube Design and Ventilator-Associated Pneumonia.

Microaspiration of contaminated oropharyngeal and gastric secretions is the main mechanism for ventilator-associated pneumonia (VAP) in critically ill patients. Improving the performance of tracheal tubes in reducing microaspiration is one potential means to prevent VAP. The aim of this narrative review is to discuss recent findings on the impact of tracheal tube design on VAP prevention. Several randomized controlled studies have reported that subglottic secretion drainage (SSD) is efficient in VAP prevention. Meta-analyses have reported conflicting results regarding the impact of SSD on duration of mechanical ventilation, and one animal study raised concern about SSD-related tracheal lesions. However, this measure appears to be cost-effective. Therefore, SSD should probably be used in all patients with expected duration of mechanical ventilation > 48 h. Three randomized controlled trials have shown that tapered-cuff tracheal tubes are not useful to prevent VAP and should probably not be used in critically ill patients. Further studies are required to confirm the promising effects of continuous control of cuff pressure, polyurethane-cuffed, silver-coated, and low-volume low-pressure tracheal tubes. There is moderate evidence for the use of SSD and strong evidence against the use of tapered-cuff tracheal tubes in critically ill patients for VAP prevention. However, more data on the safety and cost-effectiveness of these measures are needed. Other tracheal tube-related preventive measures require further investigation.

Evaluation of the Safety and Effectiveness of the Rapid Flow Expulsion Maneuver to Clear Subglottic Secretions in Vitro and in Vivo.

BACKGROUND: Clearing subglottic secretions has been proved to reduce ventilator-associated pneumonia. A manual method named the rapid flow expulsion maneuver was developed to clear subglottic secretions. This study evaluates its safety and effectiveness and analyzes the influential factors. METHODS: This study was composed of 2 parts. In an in vitro study, secretions were instilled directly to the area above the cuff in an intubated tracheal model. Secretions were expelled by the rapid flow expulsion maneuver with different volumes and peak flows in 3 tracheal positions (0, 15, and 30°). At each tracheal position, the maneuver was repeated twice, unless secretions above the cuff were <0.5 mL. In an in vivo study, subglottic secretions were suctioned via subglottic secretion drainage and then were cleared by the rapid flow expulsion maneuver. After the initial maneuver, methylene blue (2 mL) was instilled above the cuff, and the maneuver was performed again. The subject's sputum color was then recorded over 24 h. RESULTS: In the in vitro study, no aspiration was observed in the 277 maneuvers completed. Subglottic secretions were visibly expelled in 167 of 277 maneuvers (60.3%), and the median clearance efficiencies of the 3 consecutive maneuvers were 39.6, 6.3, and 0.4%. In the 108 first maneuvers, 93 (86.1%) produced visible secretions. Multiple linear regression models were used to identify predictors of clearance efficiency: tracheal position (P < .001), flow (P = .041), and secretion viscosity (P = .017). In the in vivo study, 77 rapid flow expulsion maneuvers were completed after suctioning via subglottic secretion drainage in 16 subjects, and the maneuvers collected 221.5 mL of secretions. No aspiration was observed over 24 h. CONCLUSIONS: The rapid flow expulsion maneuver was safe and effective to clear subglottic secretions. The first maneuver was the most effective to expel the majority of secretions. Supine position and high peak flow improved the clearance efficiency.

Subglottic secretion suction for preventing ventilator-associated pneumonia: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Potential benefits of subglottic secretion suction for preventing ventilator-associated pneumonia (VAP) are not fully understood. METHODS: We searched Cochrane Central, PubMed, and EMBASE up to March 2016 to identify randomized controlled trials (RCTs) that compared subglottic secretion suction versus non-subglottic secretion suction in adults with mechanical ventilation. Meta-analysis was conducted using Revman 5.3, trial sequential analysis (TSA) 0.9 and STATA 12.0. The primary outcome was incidence of VAP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the level of evidence. RESULTS: Twenty RCTs (N = 3544) were identified. Subglottic secretion suction was associated with reduction of VAP incidence in four high quality trials (relative risk (RR) 0.54, 95 % confidence interval (CI) 0.40-0.74; p < 0.00001) and in all trials (RR = 0.55, 95 % CI 0.48- 0.63; p < 0.00001). Sensitivity analyses did not show differences in the pooled results. Additionally, the results of the above-mentioned analyses were confirmed in TSA. GRADE level was high. Subglottic secretion suction significantly reduced incidence of early onset VAP, gram-positive or gram-negative bacteria causing VAP, and duration of mechanical ventilation. It delayed the time-to-onset of VAP. However, no significant differences in late onset VAP, intensive care unit (ICU) mortality, hospital mortality, or ICU length of stay were found. CONCLUSIONS: Subglottic secretion suction decreased VAP incidence and duration of mechanical ventilation and delayed VAP onset. However, subglottic secretion suction did not reduce mortality and length of ICU stay. Subglottic secretion suction is recommended for preventing VAP and for reducing ventilation length, especially in the population at high risk of early onset VAP. TRIAL REGISTRATION: A protocol of this meta-analysis has been registered on PROSPERO (registration number: CRD42015015715 ); registered on 5 January 2015.

Audit of UK ventilator care bundles and discussion of subglottic secretion drainage.

AIMS: The UK Department of Health (2012) recommends a ventilator care bundle in the form of a high impact intervention to reduce the incidence of ventilator-associated pneumonia. The aims of this project were to audit compliance with individual components of this care bundle in the UK. DESIGN: The first survey directly addressed compliance with each component of the recommended ventilator care bundle. The second survey was targeted towards the use of subglottic secretion drainage (SSD) and the logistics of implementing it. METHODS: The first survey was distributed electronically to the Nurse Leads of the Critical Care National Network Nurses Forum and then circulated more widely through local networks. This Forum covers England, Wales and Northern Ireland. The second survey was circulated electronically to the Intensive Care Society Linkmen and was UK-wide. RESULTS: The first survey received 112 responses following circulation via 40 Leads. Ninety-nine percent of responses were from nurses, the rest were from doctors. The second survey had 77 responses, 88% from doctors and was circulated via 155 Linkmen. The surveys showed that over 95% of respondents worked in intensive care units that use a ventilator care bundle. Compliance with each component of the bundle was greater than 85% in all units, except for SSD, which was performed in 47-53% of the units. CONCLUSIONS: In this survey, most units comply with most of the nationally recommended ventilator care bundle components with the exception of SSD. Because of a lack of availability of suitable endotracheal tubes, a significant number of patients are being re-intubated to facilitate this therapy. RELEVANCE TO CLINICAL PRACTICE: Compliance with most components of the nationally recommended ventilator care bundle is good. SSD has not been as widely implemented as the other components and patients are undergoing re-intubation to facilitate it.

Evaluation of Analytical Modeling Functions for the Phonation Onset Process.

The human voice originates from oscillations of the vocal folds in the larynx. The duration of the voice onset (VO), called the voice onset time (VOT), is currently under investigation as a clinical indicator for correct laryngeal functionality. Different analytical approaches for computing the VOT based on endoscopic imaging were compared to determine the most reliable method to quantify automatically the transient vocal fold oscillations during VO. Transnasal endoscopic imaging in combination with a high-speed camera (8000 fps) was applied to visualize the phonation onset process. Two different definitions of VO interval were investigated. Six analytical functions were tested that approximate the envelope of the filtered or unfiltered glottal area waveform (GAW) during phonation onset. A total of 126 recordings from nine healthy males and 210 recordings from 15 healthy females were evaluated. Three criteria were analyzed to determine the most appropriate computation approach: (1) reliability of the fit function for a correct approximation of VO; (2) consistency represented by the standard deviation of VOT; and (3) accuracy of the approximation of VO. The results suggest the computation of VOT by a fourth-order polynomial approximation in the interval between 32.2 and 67.8% of the saturation amplitude of the filtered GAW.

Subglottic Secretion Drainage and Objective Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVE: Current guidelines recommend endotracheal tubes with subglottic secretion drainage to prevent ventilator-associated pneumonia. Subglottic secretion drainage is associated with fewer ventilator-associated pneumonia diagnoses, but it is unclear to what extent this reflects fewer invasive pneumonias versus fewer false-positive diagnoses due to less secretions and/or less microbial colonization of the oropharynx. We, therefore, undertook a systematic review and meta-analysis of the impact of subglottic secretion drainage on duration of mechanical ventilation, ICU and hospital length of stay, ventilator-associated events, mortality, antibiotic utilization, stridor, and reintubations to better understand the net benefits and limitations of this intervention. DATA SOURCES: We searched Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, and PubMed from inception through February 22, 2015, without language restrictions. STUDY SELECTION: Randomized controlled trials comparing subglottic secretion drainage versus no subglottic secretion drainage in adult patients on mechanical ventilation. DATA EXTRACTION: Eligible trials were abstracted and assessed for risk of bias by two reviewers. DATA SYNTHESIS: We identified 17 eligible trials with a total of 3,369 patients. Subglottic secretion drainage was associated with lower ventilator-associated pneumonia rates (risk ratio, 0.58; 95% CI, 0.51-0.67; I2 = 0%), but there were no significant differences between groups in duration of mechanical ventilation (weighted mean difference, -0.16 d; 95% CI, -0.64 to 0.33; I2 = 0%), ICU length of stay (weighted mean difference, +0.17 d; 95% CI, -0.62 to 0.95; I2 = 0%), hospital length of stay (weighted mean difference, -0.57 d; 95% CI, -2.44 to 1.30; I2 = 0%), ventilator-associated events (risk ratio, 0.97; 95% CI, 0.65-1.43), or mortality (risk ratio, 0.93; 95% CI, 0.84-1.03; I2 = 0%). Two studies observed significantly less antibiotic use with subglottic secretion drainage whereas a third did not. There were no significant differences between groups in stridor or reintubations. CONCLUSIONS: Subglottic secretion drainage is associated with lower ventilator-associated pneumonia rates but does not clearly decrease duration of mechanical ventilation, length of stay, ventilator-associated events, mortality, or antibiotic usage. Further data are required to demonstrate the benefits of subglottic secretion drainage.

Expression and mutational analysis of Cip/Kip family in early glottic cancer.

BACKGROUND: Genetic alteration of cyclin-dependent kinase inhibitors has been associated with carcinogenesis mechanisms in various organs. OBJECTIVE: This study aimed to evaluate the expression and mutational analysis of Cip/Kip family cyclin-dependent kinase inhibitors (p21CIP1/WAF1, p27KIP1 and p57KIP2) in early glottic cancer. METHODS: Expressions of Cip/Kip family and p53 were determined by quantitative reverse transcription polymerase chain reaction and densitometry. For the analysis of p21 inactivation, sequence alteration was assessed using single-strand conformational polymorphism polymerase chain reaction. Additionally, the inactivation mechanism of p27 and p57 were investigated using DNA methylation analysis. RESULTS: Reduced expression of p27 and p57 were detected in all samples, whereas the expression of p21 was incompletely down-regulated in 6 of 11 samples. Additionally, single-strand conformational polymorphism polymerase chain reaction analysis showed the p53 mutation at exon 6. Methylation of p27 and p57 was detected by DNA methylation assay. CONCLUSION: Our results suggest that the Cip/Kip family may have a role as a molecular mechanism of carcinogenesis in early glottic cancer.

Subglottic secretion volume and viscosity: effect of systemic volume and oral hydration.

OBJECTIVES: Removal of secretions from the subglottic space, which is the larynx cavity below the glottis that contains the vocal cords, reduces the risk for ventilator associated pneumonia. Relationships between factors associated with subglottic secretion volume and viscosity have not been investigated. Subglottic secretions may have a possible link with systemic volume status and oral cavity hydration. The purpose of this study was to examine the relationships among systemic volume, oral cavity hydration, and subglottic secretion (SS) volume and viscosity in mechanically ventilated adults. DESIGN: Seventy daily oral and SS samples were obtained over a 24-hour collection period from 15 mechanically ventilated adults. Markers of systemic volume and oral cavity hydration and measurements of SS volume and viscosity were collected and analyzed. RESULTS: The daily volume of oral secretions ranged from 0 to 1.0 mL (SD 0.180 mL), and SS ranged from 0 to 15 mL (SD 22.9 mL). BUN/creatinine ratio (marker of systemic volume status) was moderately correlated with oral secretion volume (r = -0.43). Weak correlations were identified between SS volume and oral volume (r = 0.29) and SS viscosity and oral viscosity (r = 0.22). No other linear relationships were identified among the variables. CONCLUSIONS: This study confirmed that SS accumulation occurs, the amount varies widely, and the secretions are highly viscous. SS volume and viscosity were not found to have a very strong relationship with the variables measured. Nevertheless, clinical implications for practice are present. Further research is needed to understand secretion dynamics in ventilated adults to prevent complications and promote positive patient outcomes.

The role of protein p16(INK4a) in glottic laryngeal squamous cell carcinoma.

Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing the common etiological factors. However some differences in pathogenesis and prognosis of HNSCC have been hitherto documented. Laryngeal squamous cell carcinoma (LSCC) is one the most common type of the head and neck cancer. The majority of laryngeal cancers are located in the glottic area. P16 was recently documented to be important prognostic marker in many tumors including HNSCC. The aim of our study was to assess the significance of p16 expression in glottic LSCC. Fifty eight patients after surgical treatment of the glottic LSCC were enrolled in the retrospective study. The p16 expression was immunohistochemically detected and semiquantitatively evaluated in tumor tissue. The results were statistically correlated with clinical and pathological parameters. Protein p16 was expressed in glottic LSCC of 15 patients (25.9 %). Statistically significant higher p16 overexpression was proven in non-smokers in comparison with smokers (75 % versus 18 %; p =0.003). Recurrent cancer was diagnosed in 8 patients (13.8 %), and all these tumors were p16 negative. Our study shows, that p16 expression in glottic LSCC especially in subgroup of non-smokers might be promising prognosticator of better clinical outcome in routine practice. The p16 status did not statistically correlate with cervical lymph node metastases or with grading and staging of cancers, respectively. The preliminary results suggest that p16 overexpression in glottic LSCC may identify patients at low risk of disease recurrence. However, the pathobiology of this tumor as well as predictive role of p16 expression in laryngeal cancer still remains to be better elucidated.

Strategies to prevent ventilation-associated pneumonia: the effect of cuff pressure monitoring techniques and tracheal tube type on aspiration of subglottic secretions: an in-vitro study.

BACKGROUND: Ventilation-associated pneumonia (VAP) is the commonest nosocomial infection in intensive care. Implementation of a VAP prevention care bundle is a proven method to reduce its incidence. The UK care bundle recommends maintenance of the tracheal tube cuff pressure at 20 to 30  cmH2O with 4-hourly pressure checks and use of tracheal tubes with subglottic aspiration ports in patients admitted for more than 72  h. OBJECTIVE: To evaluate the effects of tracheal tube type and cuff pressure monitoring technique on leakage of subglottic secretions past the tracheal tube cuff. DESIGN: Bench-top study. SETTING: Laboratory. INTERVENTIONS: A model adult trachea with simulated subglottic secretions was intubated with a tracheal tube with the cuff inflated to 25  cmH2O. Experiments were conducted using a Portex Profile Soft Seal tracheal tube with three cuff pressure monitoring strategies and using a Portex SACETT tracheal tube with intermittent cuff pressure checks. OUTCOME MEASURES: Rate of simulated secretion leakage past the tracheal tube cuff. RESULTS: Mean ±â€ŠSD leakage of fluid past the Profile Soft Seal tracheal tube cuff was 2.25 ±â€Š1.49  ml  min⁻¹ with no monitoring of cuff pressure, 2.98 ±â€Š1.63  ml  min⁻¹ with intermittent cuff pressure monitoring and 3.83 ±â€Š2.17  ml  min⁻¹ with continuous cuff pressure monitoring (P <0.001). Using a SACETT tracheal tube with a subglottic aspiration port and aspirating the simulated secretions prior to intermittent cuff pressure checks reduced the leakage rate to 0.50 ±â€Š0.48  ml  min⁻¹ (P <0.001). CONCLUSION: Subglottic secretions leaked past the tracheal tube cuff with all tube types and cuff pressure monitoring strategies in this model. Significantly higher rates were observed with continuous cuff pressure monitoring and significantly lower rates were observed when using a tracheal tube with a subglottic aspiration port. Further evaluation of medical device performance is needed in order to design more effective VAP prevention strategies.

Supraglottic laryngeal tumor microenvironmental factors facilitate STAT3 dependent pro-tumorigenic switch in tumor associated macrophages to render utmost immune evasion.

Content of tumor microenvironment (TME) is varied greatly among different types of laryngeal tumors, namely, supraglottic, glottic and subglottic tumors. These three different TMEs shape infiltrating monocytes/macrophages toward M2 genotypes in variable degrees. Results obtained from in vitro studies demonstrated extent of expression of M2 phenotypic features on macrophages was maximum after their exposure to supraglottic laryngeal tumor cell lysates (SLTCL) than glottic or subglottic lysates. Moreover, M2 macrophages generated under influence of SLTCL show less nitric oxide production, greater IL-10: IL-12 ratio and poor antigen presentation. Co-culture of such M2 macrophages with T cells from healthy donors resulted decreased activation of T cells and T cell mediated tumor cell cytotoxicity, than, glottic or subglottic. SLTCL mediated macrophage polarization is STAT3 dependent and might be one of the major factors for severe immune paralysis leading to poor prognosis of supraglottic laryngeal tumor bearer following standard treatment.

Polymorphisms in HIF-1 alpha affect presence of lymph node metastasis and can influence tumor size in squamous-cell carcinoma of the glottic larynx

BACKGROUND: HIF-1alpha plays a key role in the development and progression of cancer. Its polymorphic variants C1772T and G1790A have been associated with greater susceptibility to cancer and increased tumor progression. METHODS: We determined the distribution of these polymorphisms among 121 patients with glottic cancer and 154 healthy volunteers by PCR-RFLP. We also analyzed the relationship between the presence of these polymorphisms and various clinicopathologic variables. RESULTS: Advanced tumors (T3-T4) were associated with the TT variant (p = 0.036), which was present in 75 % of T4 tumors (p = 0.008). Among patients with nodal metastasis (N+), 41.7 and 22 % were carrying the TT and GA variants, respectively, compared with 9.4 and 2 % of the patients with no metastasis (N0), (p = 0.006 and p = 0.032). CONCLUSIONS: The presence of the TT and GA variants were associated with lymph node metastasis, while the presence of the TT variant can be associated with larger tumor size (AU)

Subglottic secretion drainage for preventing ventilator-associated pneumonia: an updated meta-analysis of randomized controlled trials.

BACKGROUND: Subglottic secretion drainage (SSD) has been shown to be associated with a lower incidence of ventilator-associated pneumonia (VAP) in a previous meta-analysis. However, a number of randomized controlled trials (RCTs) have been published since then, and so we aimed to conduct an updated meta-analysis. METHODS: A systematic literature search of Pubmed, Embase, and Cochrane Central Register of Controlled Trials was conducted using specific search terms. Eligible studies were RCTs that compared SSD with standard endotracheal tube care in mechanically ventilated adult patients. RESULTS: Ten RCTs with 2,213 patients were identified. SSD significantly reduced incidence of VAP (relative risk [RR] = 0.56, 95% confidence interval [CI]: 0.45-0.69, p < 0.00001) and early-onset VAP (RR = 0.23, 95% CI: 0.13-0.43, p < 0.00001), shortened ventilation duration by 1.55 days (95% CI: -2.40 to -0.71 days, p = 0.0003), and prolonged time to VAP by 3.90 days (95% CI: 2.56-5.24 days). Subgroup analyses suggested a significant reduction in incidence of VAP when stratified by intermittent (RR = 0.49, 95% CI: 0.34-0.71, p = 0.0001) and continuous SSD (RR = 0.61, 95% CI: 0.46-0.79, p = 0.0003). No significant differences were observed regarding incidence of late-onset VAP, overall mortality, or length of intensive care unit or hospital stay. CONCLUSIONS: This updated meta-analysis confirmed that SSD was beneficial in preventing VAP. Furthermore, the effect of SSD on late-onset VAP, comparison between intermittent and continuous SSD, and safety of SSD in mechanically ventilated patients should be evaluated in future RCTs. LEVEL OF EVIDENCE: I, meta-analysis.

Effectiveness and safety of the Levitan FPS Scope™ for tracheal intubation under general anesthesia with a simulated difficult airway.

PURPOSE: Studies show that the Levitan FPS (first pass success) Scope™ (LFS) is analogous to a bougie in simulated difficult airways with comparable tracheal intubation success rates. In this study, the efficacy and safety of tracheal intubation with the LFS was compared with that of the Macintosh laryngoscope utilizing manual in-line stabilization (MILS) to simulate difficult airways. METHODS: Ninety-four subjects successfully completed the trial. Manual in-line stabilization of the cervical spine was applied and the initial laryngoscopy was performed using either the Macintosh or the LFS in conjunction with the Macintosh. Following the initial grading, a second laryngoscopy was repeated using the second randomized technique. Cormack-Lehane grades, percentage of glottic opening (POGO) scores, time to intubate, number of intubation attempts, and the use of alternate techniques were recorded. The anesthesiologist rated the subjective difficulty in using each technique with a numeric rating scale and a visual rating scale. RESULTS: There was no significant difference in the primary outcome "good laryngoscopic views" (Cormack-Lehane grade 1 and 2) compared with "poor laryngoscopic views" (Cormack-Lehane grade 3 and 4) between the LFS and the Macintosh. There were higher POGO scores with the LFS compared with the Macintosh (80% vs 20%, respectively; P < 0.0001), but this did not translate to easier intubations, as documented by the need for an alternate intubation technique or time to intubate (< 30 and < 60 sec, respectively). The incidence of mucosal trauma, sore throat, and hemodynamic responses did not differ significantly between the two techniques. CONCLUSION: The LFS in conjunction with the Macintosh laryngoscope does not improve the efficacy or safety of tracheal intubation in a simulated difficult airway.

Ki-67 expression predicts radiotherapy failure in early glottic cancer.

BACKGROUND: Early-stage laryngeal squamous cell carcinoma is managed with radiotherapy or endoscopic surgery. Although cure rates are high, radiation failures often require total laryngectomy for salvage. Biomarkers that can predict tumour radioresistance may be useful in modifying the treatment approach for individual patients. METHODS: Retrospective patient chart review yielded 75 patients with T1-T2 glottic squamous cell carcinoma treated with radiation therapy at the London Health Sciences Centre. Pretreatment tumour biopsies were immunostained for B-cell lymphoma 2 (Bcl-2), Ki-67, and epidermal growth factor receptor (EGFR) to correlate biomarker expression with disease-free survival (DFS). RESULTS: Ki-67 expression was strongly associated with recurrence following radiation and independently predicted poor DFS (hazard ratio 4.86, 95% CI 1.58-15.00; p  =  .006). EGFR and Bcl-2 were not associated with a risk of recurrence. CONCLUSIONS: Ki-67 expression identified a subset of patients with increased risk of local recurrence after radiation therapy. Ki-67 expression can potentially guide improved personalized treatments for patients with early-stage glottic squamous cell carcinomas.