High-flow nasal cannulae for respiratory support in adult intensive care patients.

BACKGROUND: High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review. OBJECTIVES: To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches. SELECTION CRITERIA: We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 31 studies (22 parallel-group and nine cross-over designs) with 5136 participants; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; three studies included both comparisons. We found 51 ongoing studies (estimated 12,807 participants), and 19 studies awaiting classification for which we could not ascertain study eligibility information. In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated. HFNC versus standard oxygen therapy HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.45 to 0.86; 15 studies, 3044 participants; low-certainty evidence). HFNC probably makes little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95% CI 0.82 to 1.11; 11 studies, 2673 participants; moderate-certainty evidence). HFNC probably results in little or no difference to cases of pneumonia (RR 0.72, 95% CI 0.48 to 1.09; 4 studies, 1057 participants; moderate-certainty evidence), and we were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95% CI 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). We found low-certainty evidence that HFNC may make little or no difference to the length of ICU stay according to the type of respiratory support used (MD 0.12 days, 95% CI -0.03 to 0.27; 7 studies, 1014 participants). We are uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) within 24 hours of treatment (MD 10.34 mmHg, 95% CI -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). We are uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95% CI -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95% CI -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence). HFNC versus NIV or NIPPV We found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95% CI 0.78 to 1.22; 5 studies, 1758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95% CI 0.64 to 1.31; 5 studies, 1758 participants; low-certainty evidence). We are very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95% CI 0.17 to 1.52; 3 studies, 1750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95% CI 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the length of ICU stay (MD -0.72 days, 95% CI -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO2/FiO2 may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95% CI -71.68 to -44.51; 3 studies, 1086 participants; low-certainty evidence). We are uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95% CI 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma. AUTHORS' CONCLUSIONS: HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, we found no evidence of a difference in effect. However, the evidence was often of low or very low certainty. We found a large number of ongoing studies; including these in future updates could increase the certainty or may alter the direction of these effects.

ANTECEDENTES: Las cánulas nasales de alto flujo (HFNC) administran flujos elevados de una mezcla humedecida de aire y oxígeno a través de cánulas nasales de gran calibre y pueden ser útiles para proporcionar asistencia respiratoria a los adultos que presentan insuficiencia respiratoria aguda, o que tienen riesgo de presentarla, en la unidad de cuidados intensivos (UCI). Esta es una actualización de una versión anterior de la revisión. OBJETIVOS: Evaluar la eficacia de las HFNC en comparación con la oxigenoterapia estándar, o la ventilación no invasiva (VNI) o la ventilación con presión positiva no invasiva (VPPNI), para la asistencia respiratoria de adultos en la UCI. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en CENTRAL, MEDLINE, Embase, CINAHL, Web of Science y en el Registro Cochrane de covid­19 (17 de abril de 2020), registros de ensayos clínicos (6 de abril de 2020) y se realizaron búsquedas de citas prospectivas y retrospectivas. CRITERIOS DE SELECCIÓN: Se incluyeron los estudios controlados aleatorizados (ECA) con un diseño de grupos paralelos o cruzados que compararon el uso de HFNC versus otro tipo de asistencia respiratoria no invasiva (oxigenoterapia estándar a través de cánulas nasales o mascarilla; o VNI o VPPNI que incluía la presión positiva continua en las vías respiratorias y la presión positiva de dos niveles en las vías respiratorias) en adultos ingresados en la UCI. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los procedimientos metodológicos estándar previstos por la Colaboración Cochrane. RESULTADOS PRINCIPALES: Se incluyeron 31 estudios (22 de grupos paralelos y nueve de diseño cruzado) con 5136 participantes; esta actualización incluyó 20 estudios nuevos. Veintiún estudios compararon la HFNC con la oxigenoterapia estándar, y 13 compararon la HFNC con la VNI o la VPPNI; tres estudios incluyeron ambas comparaciones. Se encontraron 51 estudios en curso (con una estimación de 12 807 participantes) y 19 estudios en espera de clasificación en los que no fue posible determinar la información de elegibilidad del estudio. En 18 estudios el tratamiento se inició después de la extubación. En el resto de los estudios, los participantes no habían recibido de forma previa ventilación mecánica. HFNC versus oxigenoterapia estándar La HFNC podría conducir a un menor fracaso del tratamiento, según lo indicado por el escalamiento a tipos alternativos de oxigenoterapia (razón de riesgos [RR] 0,62; intervalo de confianza [IC] del 95%: 0,45 a 0,86; 15 estudios, 3044 participantes; evidencia de certeza baja). La HFNC probablemente da lugar a poca o ninguna diferencia en la mortalidad cuando se compara con la oxigenoterapia estándar (RR 0,96; IC del 95%: 0,82 a 1,11; 11 estudios, 2673 participantes; evidencia de certeza moderada). La HFNC probablemente da lugar a poca o ninguna diferencia con respecto a los casos de neumonía (RR 0,72; IC del 95%: 0,48 a 1,09; cuatro estudios, 1057 participantes; evidencia de certeza moderada), y no se sabe con certeza su efecto sobre la mucosa nasal ni el traumatismo cutáneo (RR 3,66; IC del 95%: 0,43 a 31,48; dos estudios, 617 participantes; evidencia de certeza muy baja). Se encontró evidencia de certeza baja de que la HFNC podría dar lugar a poca o ninguna diferencia en la duración de la estancia en la UCI según el tipo de asistencia respiratoria utilizada (DM 0,12 días; IC del 95%: ­0,03 a 0,27; siete estudios, 1014 participantes). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en el cociente entre la presión parcial de oxígeno arterial y la fracción de oxígeno inspirado (PaO2/FiO2) en las primeras 24 horas del tratamiento (DM 10,34 mmHg; IC del 95%: ­17,31 a 38; cinco estudios, 600 participantes; evidencia de certeza muy baja). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en la comodidad a corto plazo (DM 0,31; IC del 95%: ­0,60 a 1,22; cuatro estudios, 662 participantes, evidencia de certeza muy baja), o en la comodidad a largo plazo (DM 0,59; IC del 95%: ­2,29 a 3,47; dos estudios, 445 participantes, evidencia de certeza muy baja). HFNC versus VNI o VPPNI No se encontró evidencia de una diferencia entre los grupos en el fracaso del tratamiento cuando se utilizó la HFNC después de la extubación o sin el uso previo de ventilación mecánica (RR 0,98; IC del 95%: 0,78 a 1,22; cinco estudios, 1758 participantes; evidencia de certeza baja), ni en la mortalidad hospitalaria (RR 0,92; IC del 95%: 0,64 a 1,31; cinco estudios, 1758 participantes; evidencia de certeza baja). No hay certeza sobre el efecto del uso de la HFNC en la incidencia de la neumonía (RR 0,51; IC del 95%: 0,17 a 1,52; tres estudios, 1750 participantes; evidencia de certeza muy baja), y la HFNC podría dar lugar a poca o ninguna diferencia en el barotraumatismo (RR 1,15; IC del 95%: 0,42 a 3,14; un estudio, 830 participantes; evidencia de certeza baja). La HFNC podría suponer una diferencia escasa o nula en la duración de la estancia en la UCI (DM ­0,72 días; IC del 95%: ­2,85 a 1,42; dos estudios, 246 participantes; evidencia de certeza baja). El cociente PaO2/FiO2 podría ser menor hasta 24 horas con el uso de la HFNC (DM ­58,10 mmHg; IC del 95%: ­71,68 a ­44,51; tres estudios, 1086 participantes; evidencia de certeza baja). No se sabe si la HFNC mejoró la comodidad a corto plazo cuando se midió mediante puntuaciones de comodidad (DM 1,33; IC del 95%: 0,74 a 1,92; dos estudios, 258 participantes) y respuestas a cuestionarios (RR 1,30; IC del 95%: 1,10 a 1,53; un estudio, 168 participantes); la evidencia para la comodidad a corto plazo fue de certeza muy baja. Ningún estudio informó sobre la mucosa nasal ni el traumatismo cutáneo. CONCLUSIONES DE LOS AUTORES: La HFNC podría dar lugar a un menor fracaso del tratamiento en comparación con la oxigenoterapia estándar, pero probablemente suponga una escasa o nula diferencia en el fracaso del tratamiento en comparación con la VNI o la VPPNI. Para la mayoría de los demás desenlaces de la revisión, no se encontró evidencia de una diferencia en el efecto. Sin embargo, la certeza de la evidencia se consideró baja o muy baja. Se encontró un gran número de estudios en curso; incluirlos en futuras actualizaciones podría aumentar la certeza o podría alterar la dirección de estos efectos.

Consensus on Methodology for Experimental Studies of Nasal Mucosal Injury.

OBJECTIVES: The way wounds heal involves significant complexity, resulting in restoration of functional and anatomical integrity to tissues damaged as a result of trauma (whether mechanical, chemical, or radiation-induced). The authors reviewed the consensus on methodology for experimental studies of nasal mucosal injury. METHODS: The review aims to find where consensus exists amongst different experimental studies in nasal wound healing about the use of animal models. To achieve this, the authors queried the Pubmed, Proquest Central and Google databases for the last 20 years (i.e. 1996-2016). The search terms were: "mucosa injury," "nasal mucosa injury," "injury," "wound healing," "nasal," "nasal wound healing," "experimental," "animal," "model," "rat," "rabbit," "guinea pig," and "mice." These terms were searched for whether they occurred singly or in combination. The search uncovered 18 papers, on the basis of which this review has been prepared. RESULTS: The choice of an appropriate animal model is key in investigating nasal mucosal injury. Suitable animals include rodents such as rats or guinea pigs. There are reports in the literature concerning mechanical injury in rat nasal mucosae without attempts to treat it. Mechanical injury was induced unilaterally by means of an interdental brush. Other techniques involved the use of distilled water or irradiating the tissue to induce trauma. CONCLUSION: In this review, the use of a rat, guinea pig or rabbit model for human nasal mucosal injury is reviewed. Such models are suitable for use in well-designed experimental studies.

Current and Alternative Therapies for Nasal Mucosa Injury: A Review.

Nasal mucosa injury can be caused by trauma, radiotherapy, chronic infection such as sinusitis, and post sinus surgery. The rate of healing and its treatment are important in the recovery of patients especially in post sinus surgery, which introduces new injuries. In this review, the current knowledge in terms of the mechanism underlying nasal wound healing was initially discussed. The currently available treatment options for enhancement of wound healing following sinus surgery were discussed and these had included intravenous antibiotics or steroids, various nasal sprays, and nasal packing. In addition, emerging alternative therapies in nasal mucosa wound healing such as herbal medicine and the advancement of regenerative medicine therapies such as stem cells and their byproducts were also discussed. Despite the various available treatment options for wound healing in nasal mucosa, rigorous strong evidence of their efficacy is gravely warranted in order to recommend them as part of the treatment modality.

Mst1 contributes to nasal epithelium inflammation via augmenting oxidative stress and mitochondrial dysfunction in a manner dependent on Nrf2 inhibition.

Nasal epithelium inflammation plays an important role in transmitting and amplifying damage signals for the lower airway. However, the molecular basis of nasal epithelium inflammation damage has not been fully addressed. Mst1 is reported to modulate inflammation via multiple effects. Thus, the aim of our study is to understand the pathological mechanism underlying Mst1-related nasal epithelium inflammation in vitro. Our result indicated that Mst1 expression was rapidly increased in response to tumor necrosis factor-α (TNF-α) treatment in vitro and this effect was a dose-dependent manner. Interestingly, knockdown of Mst1 via transfecting small interfering RNA markedly reversed cell viability in the presence of TNF-α. Further, we found that Mst1 deficiency reduced cellular oxidative stress and attenuated mitochondrial dysfunction, as evidenced by reversed mitochondrial complex-I activity, decreased mitochondrial permeability transition pore opening rate, and stabilized mitochondrial membrane potential. Besides, we found that Nrf2 expression was increased after deletion of Mst1 whereas silencing of Nrf2 abolished the protective effects of Mst1 deletion on nasal epithelium survival and mitochondrial homeostasis. Moreover, Nrf2 overexpression also protected nasal epithelium against TNF-α-induced inflammation damage. Altogether, our data confirm that the Mst1 activation and Nrf2 downregulation seem to be the potential mechanisms responsible for the inflammation-mediated injury in nasal epithelium via mediating mitochondrial damage and cell oxidative stress.

RORA Overexpression Alleviates Nasal Mucosal Injury and Enhances Red Blood Cell Immune Adhesion Function in a Mouse Model of Allergic Rhinitis via Inactivation of the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: In this study, we examined whether RORA (retinoic acid receptor-related orphan receptor alpha) was capable of alleviating the progression of allergic rhinitis (AR). METHODS: In order to elucidate the possible effects of RORA and the regulatory mechanism between RORA and the Wnt/ß-catenin signaling pathway, mouse AR models were established and treated with RORA vector, siRNA against RORA, or the Wnt/ß-catenin pathway inhibitor WIF-1. Subsequently, the serum levels of inflammatory cytokines (IgE, INF-γ, IL-1ß, IL-4, and IL-17), red blood cell (RBC) immune adhesion function, the levels of RORA, ß-catenin, and GSK3ß, as well as the extent of ß-catenin and GSK-3ß phosphorylation were evaluated and measured. RESULTS: The OVA-induced AR mouse model exhibited obvious nasal mucosal injury and inflammatory cell infiltration. RORA overexpression or the inactivation of the Wnt/ß-catenin signaling pathway was uncovered as a way to ameliorate nasal mucosal injury and eosinophil infiltration of the OVA-induced AR mouse model. On the other hand, it reduced the number of eosinophils and mast cells, which also resulted in downregulated expression of IgE, INF-γ, IL-1ß, IL-4, IL-17, ß-catenin, and GSK-3ß. Moreover, this led to a decreased extent of ß-catenin and GSK-3ß phosphorylation, while the rates of C3b receptor rosette and Ic rosette were elevated. CONCLUSION: Taken together, the key findings provided evidence suggesting that the elevated RORA could potentially alleviate nasal mucosal injury and simultaneously enhance RBC immune adhesion function through the inhibition of the Wnt/ß-catenin signaling pathway activation in an OVA-induced AR mouse model. This emphasizes a novel therapeutic target for the treatment of AR.

Conditioned medium from umbilical cord mesenchymal stem cells improves nasal mucosa damage by radiation.

OBJECTIVES: To explore therapeutic effects of conditioned medium from human umbilical cord mesenchymal stem cells (hUC-MSCs) on nasal mucosa radiation damage both in vivo and in vitro. RESULTS: The mucus cilia clearance time (7 and 30 days), degree of mucosal edema (7, 30, 90 and 180 days), cilia coverage (180 days) of concentrated conditioned medium group improved compared with radiotherapy control group. The proliferation and migration abilities of irradiated and non-irradiated nasal epithelial cells significantly increased after culture in bronchial epithelial cell growth medium (BEGM) containing 10% conditioned medium of hUC-MSCs compared to cells cultured in BEGM alone. CONCLUSIONS: Soluble factors secreted by hUC-MSCs may promote nasal epithelial cell proliferation and migration. Intranasal administration of hUC-MSC conditioned medium effectively repairs nasal mucosa radiation damage.

Effects of oral isotretinoin on normal and wounded nasal mucosa: an experimental study.

BACKGROUND: We aimed to investigate the effect of systemic isotretinoin therapy on normal and wounded nasal septal mucosa histopathologically in an experimental rabbit model. METHODS: Circular mucosal defect with a 7 mm diameter was made in the left septum of 12 New Zealand white rabbits. The rabbits were divided into two groups (six rabbits in each group) oral isotretinoin was given with olive oil at the operation day to the first group. The control group was only oil given group. The harvested septum mucosas were divided into four groups (1-wounded-drug given side, 2-unwounded and drug-given side, 3-wounded-control and 4-unwounded-control side). The diameter of the defect, mucosal thickness, epithelial thickness, ciliated cell level, goblet cell level and inflammation were evaluated every week for 4 weeks. RESULTS: At both wounded and normal side, thinning of normal respiratory ciliated epithelium was observed in the postoperative period. In study group at the wounded side; mean mucosal thickness was measured 139.66 µ (± 26.24), and in the control group, mean mucosal thickness was 238.33 µ (± 39.7) at the wounded side. (p < 0.001). The difference between the groups in thickness of normal septal mucosa was also statistically significant (p = 0.016) [190 µ (± 14.6) and 256.66 µ (± 44.66)]. The average cilia level was observed 1.16 in the wounded study group, while the average level was 2.33 in the wounded control group (p = 0.012). Average score measurements of the regenerated mucosa suggested that isotretinoin-given wounded animals have reduced goblet cell recovery, compared to the control both on the regenerated and unwounded mucosas (p = 0.007, p = 0.002, respectively). Inflammation was significantly higher in the wounded isotretinoin group (p = 0.018). CONCLUSION: Oral isotretinoin has negative effects on epithelial and ciliary regeneration, significantly reduces mucosal thickness and goblet cell counts of the normal and regenerated mucosa, causes severe inflammation and significant reactive changes.

Successful Use of Leukocyte Platelet-Rich Fibrin in the Healing of Sinus Membrane Perforation: A Case Report.

PURPOSE: The aim of this case report was to demonstrate the repair of a large sinus membrane perforation related to a sinus floor augmentation procedure, using leukocyte platelet-rich fibrin (L-PRF), for subsequent rehabilitation of a partially edentulous patient. MATERIALS AND METHODS: The patient presented the absence of teeth numbers 18, 17, and 16, associated with insufficient bone height because of the maxillary sinus pneumatization. A maxillary inlay bone graft was proposed, however, during the sinus floor augmentation procedure, a large portion of the sinus membrane was ruptured. To avoid interruption of the surgical procedure, membrane mending was proposed using L-PRF and collagen membranes. RESULTS: After 8 months, 2 external hexagon connection dental implants were placed in the 16 and 17 teeth regions, and a screw-retained implant-supported prosthesis was installed. CONCLUSION: The use of L-PRF associated with collagen membrane was efficient for the sealing of the sinus membrane perforation and enabled bone formation for subsequent implant installation.

Nasal epithelium injury by chlorination products and other stressors predicts persistent sensitization to aeroallergens in young schoolchildren.

BACKGROUND: Allergic sensitization during childhood is a dynamic process with a substantial rate of remission. Factors influencing this process are largely unknown. METHODS: We conducted a two-year prospective study among 121 schoolchildren (mean age, 5.8 years; 64 boys). We measured urea, club cell protein (CC16), ß2-microglobulin and albumin in nasal lavage fluid (NALF) and IgE to cat, pollen or house dust mite (HDM) in nasal mucosa fluid. RESULTS: Odds of persistent sensitization to any aeroallergen increased across baseline ascending tertiles of urea-adjusted ß2-microglobulin or albumin and descending tertiles of albumin- or ß2-microglobulin-adjusted CC16 (P-trend = 0.006, 0.02, 0.044 and 0.006, respectively). Persistent HDM sensitization also increased with baseline descending tertiles of raw or urea-adjusted CC16 (both P-trend = 0.007). Such strong associations were not observed with new-onset or remitted sensitization to any aeroallergen or with raw NALF concentrations of urea, albumin or ß2-microglobulin. At baseline, house cleaning with bleach and chlorinated pool attendance emerged among the strongest and most consistent determinants of NALF biomarkers, being both associated with higher urea and lower CC16 in NALF. CONCLUSION: In young children, a defective nasal epithelium attributable to immaturity or stressors such as chlorination products is predictive of more persistent aeroallergen sensitization.

Anti-adhesive effect of solid mixture of sodium hyaluronate/carboxymethylcellulose in murine nasal cavities.

The purpose of the study was to evaluate the effect of a solid mixture of sodium hyaluronate and carboxymethylcellulose (S-HA/CMC) for the prevention of adhesions after iatrogenic mucosal injury in murine nasal cavities. We introduced iatrogenic adhesions into the bilateral nasal cavities of 20 male Sprague-Dawley rats. S-HA/CMC was applied to the left nasal cavity, while no packing was placed in the right nasal cavity as a control. At 1, 2, and 4 weeks post-procedure, we examined the number of adhesions, the ratio of the longest cross-sectional length of adhesion to septal cartilage length (RAC), and the degree of fibrosis. S-HA/CMC significantly reduced the number of adhesions when compared to the control group in total (p = 0.031), but not at each individual time point. The S-HA/CMC group showed significantly shorter RAC than the control group in total (p = 0.044), but not at each individual time point. The total fibrosis score was less severe in the S-HA/CMC group than in the control group (p < 0.001), with a significant difference between the two groups at the second week (p = 0.001). Therefore, in an animal model, S-HA/CMC can prevent post-injury mucosal adhesions suggesting a potential for clinical applications in endoscopic sinus surgery. Further clinical trials are needed to determine the safety and efficacy of S-HA/CMC as nasal packing after endoscopic sinus surgery.

The effects of the stem cell on ciliary regeneration of injured rabbit sinonasal epithelium.

Defects in mucosal healing after sinonasal surgery cause infection, scar formation causing obstruction, relapse of the disease within a shorter period and revision surgery. The present study aimed to create a functional ciliated epithelium using a stem cell and stem cell sheet of adipose tissue origin and to show such regeneration ultra-structurally on experimentally injured rabbit nasal epithelium. This was an experimental animal study and basic research. A total of 18 white New Zealand rabbits were divided into three groups. The medial wall of the maxillary sinus of the subjects was peeled off bilaterally. No additional procedure was applied to the subjects in Group 1. In Group 2, adipose tissue-derived mesenchymal stem cell was implanted on the wound edges of the subjects. In Group 3, a stem cell sheet of three layers was laid onto the defect area. All subjects were killed after 3 weeks. The presence of the stem cell stained with bromo-deoxyuridine was assessed with a light microscope, whereas cilia density, ciliated orientation and cilia structure were evaluated with a scanning electron microscope. Ciliary densities in Group 2 and Group 3 were statistically superior compared to the control group (p < 0.001, p = 0.007). Cilia morphology in Group 2 and Group 3 was also better than the control group (p < 0.01, p = 0.048). Ciliary orientation in Group 2 was scored highest (p < 0.01). The ratio of BrDu-stained cells was observed to be 27% in Group 3 and 8% in Group 2. Sub-epithelial recovery was observed to be better in Group 3. Adipose tissue-derived mesenchymal stem cell increased the healing of the injured maxillary sinus mucosa of the rabbits in terms of cilia presence, density and morphology regardless of the implementation technique. Level of evidence NA.

Correlation Between Nasal Epithelial Injury and In Vitro Cytotoxicity Using a Series of Small Molecule Protein Tyrosine Phosphatase 1B Inhibitors Investigated for Reversal of Leptin Resistance in Obesity.

This research provides a cautionary example when evaluating changes in behavioral end points with respect to postulated pharmacologic activity. Various small molecule substrate mimetic protein tyrosine phosphatase 1B (PTP1B) inhibitors were investigated as pharmacologic agents for decreasing food consumption using intranasal (IN) dosing as a means for direct nose-to-brain delivery along the olfactory/trigeminal nerve pathways. Although food consumption was decreased in diet-induced obese (DIO) mice, nasal discharge was observed. Studies were conducted to investigate local effects on the nasal airway and to develop structure-activity relationships. Intranasal administration of PTP1B inhibitors at ≥0.03 mg/d to DIO mice produced dose-dependent injury to various cell types of the nasal epithelia. Protein tyrosine phosphatase 1B inhibitors with calculated log octanol >3.0 were the most toxic. Whereas a pharmacologically inactive analog of a PTP1B inhibitor produced nasal injury, along with decreased food consumption, the marketed IN drug ketorolac produced no lesions at the same dose of 0.3 mg/d and only minor changes at 3 mg/d. Rat skin fibroblast cells were exposed in vitro to PTP1B inhibitors, ketorolac, paraquat, and the detergent sodium dodecylbenzene sulfonate (NDS) followed by measures of cytotoxicity. The most potent PTP1B inhibitors were similar to NDS, whereas ketorolac was the least toxic compound. Cytotoxic potency in vitro was similar to in vivo. In conclusion, PTP1B inhibitors injured nasal epithelium through a mechanism independent of PTP1B inhibition and likely due to nonspecific cytotoxicity such as disruption of the cell membrane. Decreased food consumption in DIO mice was due to toxicity rather than a pharmacologic mode of action.

Schneiderian Membrane Perforation Rate and Increase in Bone Temperature During Maxillary Sinus Floor Elevation by Means of Er: YAG Laser-An Animal Study in Pigs.

PURPOSE: To assess the time of preparation, bone temperature increase, and the Schneiderian membrane perforation rate during maxillary sinus floor elevation. MATERIALS AND METHODS: The research included 30 maxillary sinuses (n = 30) of a pig, divided into 2 groups (n = 15). The lateral bony windows were created using Er:YAG laser (200 mJ, 15 Hz, energy density: 25.48 J/cm) and a diamond bur (control). The membrane was elevated using laser (50 mJ, 50 Hz) and hand instruments. The bone temperature was measured by K-type thermocouple. RESULTS: Significantly lower rates of the Schneiderian membrane perforation were found in the laser group (6.67%) compared with the bur (33%) (P < 0.05). The significant higher increase in temperature (mean 7.6°C) was found in the experimental group as compared with the control group (mean 2°C) (P = 0.0000033). The average time necessary for the laser bony window osteotomy was 10 minutes and 37 seconds, whereas using the bur required middling 5 minutes and 50 seconds (P = 0.000283). CONCLUSION: The application of Er:YAG laser may significantly reduce the risk of iatrogenic perforation of the Schneiderian membrane and does not cause an irreversible thermal damage in a pig model.

[EPISTAXIS DURING NASOTRACHEAL INTUBATION. ATTILA'S SYNDROME.]

BACKGROUND: Nasal bleeding is a common complication during nasotracheal intubation (NTI). This is due to the ana- tomical prerequisites and the hemostatic system failure. Using of various research methods in practice can reduce the frequency of such complications. The purpose of the study is to identify predictors of high probability of epistaxis associated with the NTI and the pecu- liarities of the anatomical mucous membrane structure of the nasal passages, and to assess significance of blood coag- ulationfailures in these cases. MATERIALS AND METHODS: 45 patients (f-25 and m-20), aged 23 to 47 years, with physical status I-IIASA were analyzed. Depending on the degree of surgical trauma manipulation during intubation were formed three groups of patients in whom the NTI was atraumatic, moderately traumatic and overly traumatic. During preoperative period all patients underwent a rhinoscopy. Intubation trauma of the trachea was assessed by visual analogue scale. The results and discussion. The study of the nasal mucosa structure showed that with atraumatic intubation (Group 1; n=9) were dominated by deep type of bedding nonplethoric nonkinking vessels (66.7% ofpatients (n=6)). During mod- erate trauma intubation (Group 2; n=24), superficial and deep vessels were found equally (50% and 50%). In patients with severe trauma during intubation (Group 3; n=13), 100% of the patients, the vessels were located superficially, 75 % were convoluted, plethoric, mucosa contact bleeding. There were no anatomical changes. CONCLUSION: The source of bleeding are superficial, plethoric, kinking vessels of the mucous membrane. Hypocoagu- lation disorders, observed in patients during reconstructive surgeries, exacerbate such bleeding and can lead to fatal complications.

Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.

Transcrestal maxillary sinus augmentation: Summers' versus a piezoelectric technique--an experimental cadaver study.

OBJECTIVES: Sinus floor augmentation using transalveolar techniques is a successful and predictable procedure. The aim of the study was to compare the performance of conventional hand instruments using mallets and osteotomes with that of piezoelectric-hydrodynamic devices for maxillary sinus floor elevation. MATERIAL AND METHODS: In 17 undamaged cadaver heads on randomly allocated sites, Schneiderian membrane elevation was carried out transcrestally using piezosurgery and a hydrodynamic device or by conventional hand instrumentation. After simulation of sinus augmentation by the use of a radiopaque impression material, a post-operative CT scan was carried out and volumes were determined. Statistic significant differences between the two methods were evaluated by nonparametric Mann-Whitney U-test with P < 0.05. RESULTS: A mean graft volume of 0.29 ± 0.18 cm(3) (0.07-0.60 cm(3)) was measured for the Summers' technique compared to 0.39 ± 0.32 cm(3) (0.05-1.04 cm(3)) for the Sinus Physiolift(®) technique. There is no statistically significant difference with regard to trauma to the Schneiderian membrane or augmented volume. CONCLUSIONS: Both techniques generate expedient augmentation volume in the posterior atrophic maxilla. The piezoelectric technique can be recommended as an alternative tool to graft the floor of human maxillary sinuses.

Longitudinal response of membrane thickness and ostium patency following sinus floor elevation: a prospective cohort study.

OBJECTIVES: To investigate the influence of sinus floor elevation (SFE) on sinus physiology, including Schneiderian membrane thickness (MT) and ostium patency, using cone beam computed tomography (CBCT). MATERIALS AND METHODS: Based on pre-established selection criteria, 53 patients in combination with 53 sinuses were referred for SFE with a lateral approach using deproteinized bone mineral. CBCT was performed prior to, immediately after surgery and before staged implant placement. The Schneiderian MT of the elevated region, ostium patency, and other clinical data was evaluated. RESULTS: The two-stage sinus augmentation technique was applied in 33 males and 20 females. Four membrane perforations were observed during the surgical procedure. The Schneiderian membrane exhibited significant swelling immediately after augmentation (P < 0.0001), but this difference disappeared after a mean healing period of 7.51 months. The corresponding changes were also observed for ostium patency with a tendency of transient obstruction after surgery. Sinuses with flat mucosal thickening or pseudocysts did not present a liability of perforation compared to the normal cases, and the augmentation procedure was not likely to deteriorate the pathology of mucosal thickening or pseudocysts. CONCLUSIONS: The results show that SFE with a lateral approach has no significant influence on MT and ostium patency after the healing period except for postoperative transient swelling and obstruction. Thickened membranes and antral pseudocysts in a small size might not be contraindications to SFE from the standpoint of the surgical impact on the Schneiderian membrane.

The Significance of Rhinologic Evaluation and Pretreatment for Patients Undergoing Two-Jaw Surgery Through Nasotracheal Intubation.

The aim of this study is to determine whether rhinologic preoperative evaluation and pretreatments reduce intranasal trauma and decrease postoperative complications, such as nasal obstruction and epistaxis, in patients undergoing 2-jaw surgery with nasotracheal intubation. This study included 360 patients with malocclusion (Class III) who underwent 2-jaw surgery under general anesthesia via nasotracheal intubation in our hospital from January to December 2013 and categorized into 3 groups. Nasotracheal intubation was performed according to the nasal cavity the patient was able to breathe comfortably (Group I). The site of nasotracheal intubation was decided by 1 rhinologic specialist who evaluated preoperative dental computed tomography (Group II). The site of nasotracheal intubation was decided upon nasal endoscopic findings, dental computed tomography evaluation, and rhinologic pretreatment (Group III).Group II and Group III showed less damage to the nasal mucosa compared with the nasal status of Group I. Upon comparing Group II and Group III, Group III showed better overall status of the nasal mucosa compared with Group II. Visual analogue scale scores for nasal obstruction were pretty similar for all groups on the first postoperative day. In Group III, the nasal mucosa, however, was improved to that of preoperative status on the third postoperative day.In conclusion, it may be useful to pre-evaluate the mucosal and anatomical status of the nasal cavity to select patients requiring rhinologic pretreatment and decide the site for nasotracheal intubation to minimize complications arising from nasotracheal intubation.

Incidence, Risk Factors, and Complications of Schneiderian Membrane Perforation in Sinus Lift Surgery: A Meta-Analysis.

OBJECTIVES: To evaluate the incidence of Schneiderian membrane perforation occurring during sinus lift surgery, and to investigate possible risk factors and associated complications. MATERIALS AND METHODS: A systematic search for papers published between 1975 and 2015 was performed in MEDLINE, EMBASE, Scopus, Web of Science, Trip, Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials, and ProQuest Dissertations & Theses. The quality assessment of each study was performed using the GRADE system. All extracted data were synthesized using either fixed or random effect models as indicated. RESULTS: Out of 1652 sinus lift surgeries reported in 12 studies, 388 membrane perforations occurred. The weighted incidence rate of perforation was 23.5% ranging from 3.6% to 41.8%. Both reduced membrane thickness and sinus septa increased the risk of perforation. The difference in the weighted implant survival rates between perforated and nonperforated side was not significant (P = 0.24). The use of piezoelectric instrumentation appears to reduce the perforation risk. CONCLUSIONS: With an incidence ratio of 1:4, membrane perforation is a common surgical complication during sinus lift surgery. We should keep in mind that appropriately handled and treated membrane perforation tends to show comparable implant survival when compared with intact membrane.

[The possibility of using соformulated intranasal drugs after surgical correction of nasal breathing].

One of the major causes of chronic nasal obstruction is the nasal septum deformation and increase of the lower nasal turbinates. The number of septoplasty--operations ranges from 14% to 44,2% of all ENT-operations. The results of surgery are swelling of the tissues and damaged ciliar epithelium, that leads to the inparament of the mucociliar transport. In the postoperati e period the nasal cavity should be cleaned. Drugs, that are used, should reduce swelling, improve regeneration and should not supress ciliar activity. The results of supervisory, non-interventional study have shown, that application of Nasiс after septoplasty and submucose vasotomy of inferior nasal turbinates increases reparative process and leads to more rapid recovery of respiratory function of nasal cavity.