An innovative targeted therapy for fluoroscopy-induced chronic radiation dermatitis.

Fluoroscopy-induced chronic radiation dermatitis (FICRD) is a complication of fluoroscopy-guided intervention. Unlike acute radiation dermatitis, FICRD is different as delayed onset and usually appears without preexisting acute dermatitis. Unfortunately, the chronic and progressive pathology of FICRD makes it difficult to treat, and some patients need to receive wide excision and reconstruction surgery. Due to lack of standard treatment, investigating underlying mechanism is needed in order to develop an effective therapy. Herein, the Hippo pathway is specifically identified using an RNA-seq analysis in mild damaged skin specimens of patients with FICRD. Furthermore, specific increase of the Yes-associated protein (YAP1), an effector of the Hippo pathway, in skin region with mild damage plays a protective role for keratinocytes via positively regulating the numerous downstream genes involved in different biological processes. Interestingly, irradiated-keratinocytes inhibit activation of fibroblasts under TGF-ß1 treatment via remote control by an exosome containing YAP1. More importantly, targeting one of YAP1 downstream genes, nuclear receptor subfamily 3 group C member 1 (NR3C1), which encodes glucocorticoid receptor, has revealed its therapeutic potential to treat FICRD by inhibiting fibroblasts activation in vitro and preventing formation of radiation ulcers in a mouse model and in patients with FICRD. Taken together, this translational research demonstrates the critical role of YAP1 in FICRD and identification of a feasible, effective therapy for patients with FICRD. KEY MESSAGES: • YAP1 overexpression in skin specimens of radiation dermatitis from FICRD patient. • Radiation-induced YAP1 expression plays protective roles by promoting DNA damage repair and inhibiting fibrosis via remote control of exosomal YAP1. • YAP1 positively regulates NR3C1 which encodes glucocorticoid receptor expression. • Targeting glucocorticoid receptor by prednisolone has therapeutic potential for FICRD patient.

Submental Ultrasound Is Effective in Predicting Difficult Mask Ventilation but Not in Difficult Laryngoscopy.

The goal of this study was to determine the utility of submental ultrasound parameters in distinguishing difficult airway management from easy airway management. Forty-one adult patients who underwent elective surgery under general anesthesia with endotracheal intubation from March to December 2018 were included. We used submental ultrasound to measure tongue base thickness (TBT) in the midsagittal plane and the distance between lingual arteries (DLA) in the transverse dimension. The primary outcome was difficult laryngoscopy, and the secondary outcome was difficult mask ventilation. Receiver operating characteristic curve analysis and logistic regression revealed no correlation between difficult laryngoscopy and SMUS measurements. Nevertheless, patients with difficult mask ventilation had significantly higher TBT (p = 0.009) and longer DLA (p = 0.010). After adjustment of confounding factors, increased TBT (>69.6 mm) was the sole independent predictor of difficult mask ventilation. The results indicated that SMUS is effective in predicting difficult mask ventilation but not difficult laryngoscopy.

YAP1 overexpression contributes to the development of enzalutamide resistance by induction of cancer stemness and lipid metabolism in prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is a malignant and lethal disease caused by relapse after androgen-deprivation (ADT) therapy. Since enzalutamide is innovated and approved by US FDA as a new treatment option for mCRPC patients, drug resistance for enzalutamide is a critical issue during clinical usage. Although several underlying mechanisms causing enzalutamide resistance were previously identified, most of them revealed that drug resistant cells are still highly addicted to androgen and AR functions. Due to the numerous physical functions of AR in men, innovated AR-independent therapy might alleviate enzalutamide resistance and prevent production of adverse side effects. Here, we have identified that yes-associated protein 1 (YAP1) is overexpressed in enzalutamide-resistant (EnzaR) cells. Furthermore, enzalutamide-induced YAP1 expression is mediated through the function of chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII) at the transcriptional and the post-transcriptional levels. Functional analyses reveal that YAP1 positively regulates numerous genes related to cancer stemness and lipid metabolism and interacts with COUP-TFII to form a transcriptional complex. More importantly, YAP1 inhibitor attenuates the growth and cancer stemness of EnzaR cells in vitro and in vivo. Finally, YAP1, COUP-TFII, and miR-21 are detected in the extracellular vesicles (EVs) isolated from EnzaR cells and sera of patients. In addition, treatment with EnzaR-EVs induces the abilities of cancer stemness, lipid metabolism and enzalutamide resistance in its parental cells. Taken together, these results suggest that YAP1 might be a crucial factor involved in the development of enzalutamide resistance and can be an alternative therapeutic target in prostate cancer.

Nasal Obstruction as a Potential Factor Contributing to Hypoxemia in Obstructive Sleep Apnea.

PURPOSE: This study aimed to evaluate the correlation between nasal resistance and oxygen desaturation to better elucidate the role of nasal obstruction in the pathophysiology of obstructive sleep apnea (OSA). PATIENTS AND METHODS: Eighty-eight OSA patients aged between 22 and 77 years were enrolled in this study. Nasal resistance was measured at pressures of 75, 150, and 300 Pa, with the patients first in the seated position than in the supine position. Relationships between the oximetric variables and nasal resistance in the seated and supine positions were analyzed. RESULTS: From seated to supine position, a statistically significant increase in nasal resistance was observed at pressures of 75 and 150 Pa (p=0.001 and p=0.006, respectively). Significant positive correlations were noted between nasal resistance in the supine position at 75 Pa (SupineNR75) and oximetry variables, including oxygen desaturation index (ODI, p=0.015) and the percentage of total time with oxygen saturation level lower than 90% (T < 90%, p=0.012). However, significant positive correlations existed only in moderate to severe OSA when the study group was further divided into two subgroups (mild vs moderate to severe OSA). Body mass index (ß = 0.476, p<0.001) and SupineNR75 (ß = 0.303, p=0.004) were identified as independent predictors for increased ODI. CONCLUSION: Nasal resistance in the supine position measured at 75 Pa significantly correlated with the severity of oxygen desaturation. Therefore, nasal obstruction may play an important role in the pathophysiology of hypoxemia in OSA patients, especially in patients with moderate to severe OSA.

Effect of back-up head-elevated position during drug-induced sleep endoscopy in obstructive sleep apnea patients.

PURPOSE: This study aimed to evaluate the difference of upper airway collapse between the back-up head-elevated position (a 45° upward inclination) and supine position to better elucidate the role of back-up head-elevated position in reductions of obstructive sleep apnea (OSA) severity. METHODS: From August 2016 to May 2019, 198 patients aged between 18 and 70 years were recruited in this study prospectively. Drug-induced sleep endoscopy (DISE) findings were recorded with the patients first placed in the supine position then into the back-up head-elevated position with a 45° upward inclination. RESULTS: From the supine to back-up head-elevated position, a significant decrease in the severity of collapse was observed in velum anteroposterior collapse and velum concentric collapse (p < 0.001 and p < 0.001, respectively), which was more predominant in patients with mild OSA than in patients with moderate to severe OSA. On the other hand, there was no significant improvement of any other collapse at the level of oropharynx, tongue base, or epiglottis when the position was shifted from the supine into back-up head-elevated position. CONCLUSIONS: The back-up head-elevated position with a 45° upward inclination improved upper airway obstruction during DISE in velum anteroposterior collapse and velum concentric collapse. The proportion of patients with amelioration of upper airway collapse was much higher in patients with mild OSA than in patients with moderate to severe OSA. The back-up head-elevated position may be a reasonable alternative to traditional positional therapy for certain subgroups of patients with OSA.

Dynamic tongue base thickness measured by drug-induced sleep ultrasonography in patients with obstructive sleep apnea.

BACKGROUND/PURPOSE: The aim of this study was to determine the value of drug-induced sleep ultrasonography (DISU) for evaluating tongue base thickness (TBT) from the awake state to drug-induced sleep, to further understand the impact of dynamic changes in TBT in obstructive sleep apnoea (OSA) patients. METHODS: From May 2017 to May 2018, thirty patients with OSA were prospectively recruited. Sleep was induced with propofol via use of a target-controlled infusion (TCI) system. The depth of sedation was monitored by the bispectral (BIS) index with BIS levels ranging from 50 to 70. The dynamic change in the tongue base from the awake state to drug-induced sleep was recorded. The correlation between TBT in the awake state and in drug-induced sleep with OSA severity was analysed. RESULTS: The mean TBT in drug-induced sleep was significantly greater than that in the awake state (66.2 ± 4.8 mm vs 61.6 ± 4.6 mm, P < 0.001). TBT in drug-induced sleep was more correlated with AHI compared to TBT in the awake state (r = 0.50 vs r = 0.40). This study showed that TBT in drug-induced sleep had the largest AUC (Area Under the Curve) in the ROC (Receiver Operating Characteristics) analysis (0.875), providing a cut-off point of 63.20 mm with 95% sensitivity for diagnosis of moderate versus severe OSA. CONCLUSION: Our findings validate the use of DISU in objectively assessing the tongue base collapse in OSA patients. It provides a convenient and non-invasive way to evaluate the upper airway changes in OSA patients in the future.

Association Between Breathing Route, Oxygen Desaturation, and Upper Airway Morphology.

OBJECTIVES/HYPOTHESIS: This study aimed to assess the role of capnography in objectively evaluating breathing routes during drug-induced sleep endoscopy (DISE) and further elucidate the relationship between breathing route, obstructive sleep apnea (OSA) severity, and DISE findings. STUDY DESIGN: Prospective observational study. METHODS: Nighty-five patients with established OSA were recruited for this study from May 2017 to May 2019. DISE was performed in the operating room. Sedation was maintained with propofol using a target-controlled infusion system and the depth of sedation was monitored based on the bispectral index. The breathing routes, which included oral breathing, oronasal breathing, and nasal breathing, were detected using capnography. DISE findings were recorded using the VOTE (velum, oropharynx, base of tongue, and epiglottis) classification. RESULTS: Patients with mouth breathing were associated with increased OSA severity, worse oximetric variables, and higher body mass index in comparison with those with other breathing routes. Mouth breathing was associated with a higher degree and higher prevalence of lateral pharyngeal wall collapse and tongue base collapse during DISE. CONCLUSIONS: Mouth breathing was significantly associated with worse oxygen desaturation and increased degree of upper airway collapse. Therefore, patients with mouth breathing during propofol-based intravenous anesthesia should be carefully monitored. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E659-E664, 2021.

The correlation between drug-induced sleep endoscopy findings and severity of obstructive sleep apnea.

OBJECTIVE: This study aimed to assess the relationship between anthropometric data, drug-induced sleep endoscopy (DISE) findings, and severity of obstructive sleep apnea (OSA). METHODS: From August 2016 to August 2017, a total of 147 surgically naïve adult patients with OSA underwent DISE. Factors that were analyzed included anthropometric data and DISE findings. RESULTS: When anthropometric data and DISE findings were analyzed with AHI by univariate analysis, the results showed that Epworth Sleepiness Scale (ESS), body mass index (BMI), neck circumference, concentric collapse of the velum, lateral oropharyngeal collapse, and anterior-posterior collapse of the tongue base were considered potentially independent predictors (p = 0.024, p < 0 .001, p < 0 .001, p < 0.001, p < 0.001, p < 0 .001, respectively, by Spearman correlation). When all important factors were evaluated in a stepwise multiple linear regression analysis, BMI, lateral oropharyngeal collapse, and anterior-posterior collapse of the tongue base were identified as significant predictors for the severity of OSA. The final model was listed as below: AHI score = 2.19 BMI + 7.56 Oropharynx/Lateral degree + 8.23 Tongue base/ Anterior-Posterior degree - 40.59. CONCLUSION: By analyzing anthropometric data and DISE findings with AHI score, the results indicated that BMI, lateral oropharyngeal collapse, and anterior-posterior collapse of the tongue base were important factors associated with the severity of OSA.

Role of drug-induced sleep endoscopy in evaluation of positional vs non-positional OSA.

BACKGROUND: The study aimed to evaluate the anatomical differences between positional and non-positional OSA, and to identify the potential predictors for distinguishing between these two types of OSA. METHODS: A cross-sectional study of 230 consecutive patients with OSA undergoing DISE (Drug-induced Sleep Endoscopy) was carried out at a tertiary academic medical center. The factors correlating with positional and non-positional OSA were analyzed, including clinical characteristics, polysomnography data, and DISE findings. RESULTS: Univariate analysis revealed that non-positional dependency was correlated with a higher BMI (p < 0.001), neck circumference (p < 0.001), modified Mallampati score (p = 0.003), AHI (p < 0.001), degree of velum concentric collapse (p = 0.004), degree of oropharyngeal lateral wall collapse (p < 0.001), and degree of tongue base anteroposterior collapse (p = 0.004). Multivariate analysis revealed that oropharyngeal lateral wall collapse (OR = 1.90, p = 0.027) was the only anatomical factor significantly predicted non-positional dependency in OSA patients. AHI (OR = 1.04, p < 0.001), although significant, made only a marginal contribution to the prediction of non-positional dependency. CONCLUSIONS: Oropharyngeal lateral wall collapse was identified as the only anatomical predictor for non-positional dependency in OSA patients. Therefore, further treatment modalities should address the distinct anatomical trait between positional and non-positional OSA.

Role of rhinomanometry in the prediction of therapeutic positive airway pressure for obstructive sleep apnea.

BACKGROUND: This study was conducted to evaluate the relationship between nasal resistance in different posture and optimal positive airway pressure (PAP) level. Other potential factors were also assessed for possible influence on PAP pressure. METHODS: Forty- three patients diagnosed with obstructive sleep apnea (OSA) were prospectively recruited in this study. Nasal resistance was assessed by active anterior rhinomanometry in a seated position and then in a supine position at pressures of 75, 150, and 300 pascal. The factors correlating with PAP pressure were analyzed, including nasal resistance and patients' clinical data. RESULTS: Univariate analysis revealed that PAP pressure was correlated to nasal resistance in the supine position at 75 and 150 pascal (SupineNR75 and SupineNR150) (P = 0.019 and P = 0.004 in Spearman's correlation coefficient analysis), but not correlated to nasal resistance in the seated position at different pressures or in the supine position at 300 pascal. The multiple linear regression analysis revealed that both SupineNR150 and body mass index (BMI) significantly predicted PAP pressure (ß = 0.308, p = 0.044; ß = 0.727, p = 0.006). The final PAP pressure predictive model was: PAP pressure = 0.29 BMI + 2.65 SupineNR150 + 2.11. CONCLUSIONS: Nasal resistance in the supine position measured at 150 pascal may provide valuable information regarding optimal PAP pressure. Rhinomanometry should be included in the treatment algorithm of OSA patients when PAP therapy is considered.

Vidian Neurectomy for Management of Chronic Cluster Headache.

BACKGROUND: Management of chronic cluster headache (CCH) remains a challenging endeavor, and the optimal surgical approach for medically refractory CCH remains controversial. OBJECTIVE: To conduct a preliminary evaluation of the efficacy and safety of vidian neurectomy (VN) in patients with medically refractory CCH. METHODS: Between March 2013 and December 2015, 9 CCH patients, all of whom had failed to respond to conservative therapy, underwent VN with a precise nerve cut and maximal preservation of the sphenopalatine ganglion. Data included demographic variables, cluster headache onset and duration, mean attack frequency, mean attack intensity, and pain disability index measures pre- and through 12-mo postsurgery. RESULTS: Seven of the 9 cases (77.8%) showed immediate improvement. Improvement was delayed by 1 mo in 1 patient, after which the surgical effects of pain relief were maintained throughout the follow-up period. One patient (11.1%) did not improve after surgery. One year after VN, patients' mean attack frequency, mean attack intensity, and pain disability index decreased by 54.5%, 52.9%, and 56.4%, respectively. No patient experienced treatment-related side effects or complications. CONCLUSION: VN is an effective treatment method for CCH patients. Precise Vidian nerve identification and maximal preservation of the sphenopalatine ganglion may achieve good surgical outcomes and dramatically improve quality of life among patients, without significant adverse events.

The predictive value of drug-induced sleep endoscopy for CPAP titration in OSA patients.

PURPOSE: The aim of this study was to identify possible upper airway obstructions causing a higher continuous positive airway pressure (CPAP) titration level, utilizing drug-induced sleep endoscopy (DISE). METHODS: A total of 76 patients with obstructive sleep apnea (OSA) underwent CPAP titration and DISE. DISE findings were recorded using the VOTE classification system. Polysomnographic (PSG) data, anthropometric variables, and patterns of airway collapse during DISE were analyzed with CPAP titration levels. RESULTS: A significant association was found between the CPAP titration level and BMI, oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and neck circumference (NC) (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively, by Spearman correlation). Patients with concentric collapse of the velum or lateral oropharyngeal collapse were associated with a significantly higher CPAP titration level (P < 0.001 and P = 0.043, respectively, by nonparametric Mann-Whitney U test; P < 0.001 and P = 0.004, respectively, by Spearman correlation). No significant association was found between the CPAP titration level and any other collapse at the tongue base or epiglottis. CONCLUSIONS: By analyzing PSG data, anthropometric variables, and DISE results with CPAP titration levels, we can better understand possible mechanisms resulting in a higher CPAP titration level. We believe that the role of DISE can be expanded as a tool to identify the possible anatomical structures that may be corrected by oral appliance therapy or surgical intervention to improve CPAP compliance.

KTP laser assisted endoscopic tissue fibrin glue biocauterization for congenital pyriform sinus fistula in children.

OBJECTIVE: This study aims to assess the efficacy of a novel endoscopic management for congenital pyriform sinus fistula (CPSF) using potassium titanyl phosphate (KTP) laser assisted endoscopic tissue fibrin glue biocauterization in children. METHOD: From 2010 to 2014, a total of 5 children with recurrent or acute suppurative thyroiditis or neck abscess secondary to CPSF were enrolled retrospectively in this study. RESULTS: Mean age at the first time of endoscopic biocauterization was 6.2 ± 0.7 (5-7) years. The barium swallow study detected a fistula in four cases. Endoscopy identified an internal opening at the pyriform sinus in all cases with four on the left side and one on the right side. All patients underwent KTP laser assisted endoscopic tissue fibrin glue biocauterization as treatment for CPSF. Only one case required the second endoscopic procedure due to fluctuation of symptoms. Post-endoscopic follow-up duration of these patients was 24.6 ± 11.6 (7-36) months. Neither complications nor recurrences were noted during follow-up in all patients. CONCLUSIONS: For children presenting with repeated acute suppurative thyroiditis or neck infections, clinicians should highly suspect the possibility of CPSF. Endoscopy should be performed not only to confirm the diagnosis but also could be served as an initial treatment modality of biocauterization by KTP laser and tissue fibrin glue, which was demonstrated as a less invasive, safe, and effective method in children.

Test battery of cranial nerves VII and VIII for assessing herpes zoster oticus.

OBJECTIVE: This study adopted a test battery of cranial nerves (CNs) VII and VIII comprising a facial nerve function test, audiometry, a caloric test, and ocular and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP, respectively) tests to assess the function of CNs VII and VIII comprehensively so as to predict facial nerve recovery in patients with herpes zoster oticus (HZO). STUDY DESIGN: Case series with chart review. SETTING: University hospital. METHODS: A total of 20 patients with HZO underwent a test battery of CNs VII and VIII. Registering the unaffected nerve bundles in the internal auditory canal was based on the number of normal results in the test battery of CNs VII and VIII. Fair facial nerve recovery is defined as the improvement of facial paresis to facial nerve grades I to II/VI. RESULTS: In 20 patients with HZO, 6, 7, 3, and 4 patients had 0, 1, 2, and 3 unaffected nerve bundles, respectively. A significantly positive correlation was identified between the number of unaffected nerve bundles and fair facial nerve recovery. Similarly, a statistically significant predictor of fair facial nerve recovery was noted for unaffected nerve bundles (odds ratio, 15.42) but not for grading of the facial nerve (odds ratio, 0.49). CONCLUSION: Grading of the facial nerve alone fails to predict the outcome of facial paresis in patients with HZO mainly because it overlooks the involvement of CN VIII. Alternatively, a combined test battery of CNs VII and VIII may serve as a strong predictor for facial nerve recovery.

Giant cell tumour of a temporomandibular joint presenting as a parotid mass: case report and analysis of the 19 cases in the literature.

Giant cell tumour (GCT) in the parotid region is a rare lesion whose origin can be divided into three compartments: giant cell tumour of the salivary gland (GCT-SG), giant cell tumour of the bone (GCT-bone) and giant cell tumour of the soft tissue (GCT-ST). A low risk of malignancy has been observed, in which all of them were GCT-SG. We present a case of GCT in the parotid region and review the features of GCT in origin, immunohistochemical characteristics, treatment of choice and disease outcome.