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AIMS: The recent approval of enzalutamide for metastatic castration-sensitive prostate cancer underscores its growing clinical significance, raising concerns about emerging resistance and limited treatment options. While the reactivation of the androgen receptor (AR) and other genes plays a role in enzalutamide resistance, identifications of novel underlying mechanism with therapeutic potential in enzalutamide-resistant (EnzaR) cells remain largely elusive. METHODS: Drug-resistant prostate cancer cell lines, animal models, and organoids were utilized to examine NUDT21 function by transcriptomic and metabolomic analyses through loss-of-function and gain-of-function assays. Notably, a mono-methylation monoclonal antibody and conditional-knockin transgenic mouse model of NUDT21 were generated for evaluating its function. RESULTS: NUDT21 overexpression acts as a crucial alternative polyadenylation (APA) mediator, supported by its oncogenic role in prostate cancer. PRMT7-mediated mono-methylation of NUDT21 induces a shift in 3'UTR usage, reducing oncogenicity. In contrast, its un-methylation promotes cancer growth and cuproptosis insensitivity in EnzaR cells by exporting toxic copper and suppressing docosahexaenoic acid (DHA) biosynthesis. Crucially, NUDT21 inhibition or DHA supplementation with copper ionophore holds therapeutic promise for EnzaR cells. CONCLUSIONS: The un-methylation of NUDT21-mediated 3'UTR shortening unveils a novel mechanism for enzalutamide resistance, and our findings offer innovative strategies for advancing the treatment of prostate cancer patients experiencing enzalutamide resistance.
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OBJECTIVES: To stratify the severity of cricoarytenoid joint fixation (CAJF) by surgery and understand the role of it played in the bilateral vocal fold immobility (BVFI). The second objective emphasizes on the significance of the preoperative differential diagnosis from neurogenic immobility with medical history and endoscopic findings. METHODS: A retrospective review was conducted of 74 patients between 2005 and 2022. Careful medical history inquiry, and videolaryngoscopy are conducted to recruit the appropriate surgical candidates. All patients underwent arytenoid remobilization (AR) followed by vocal fold medialization with arytenoid adduction (AA) or lateralization with suture lateralization (SL). The severity of CAJF is graded during the operation or inferred based on the period from operation to recurrence. RESULT: A total of 18 patients, aged between 18 and 76 years, were analyzed. Among them, 14 cases were classified as the adducted type with ventilation problems, with three presenting with dyspnea, and 11 requiring artificial airways. Additionally, four patients presented with the abducted type, characterized by aphonia. Meanwhile, two additional cases were considered for comparison but were not included in this cohort of 18 subjects due to incorrect diagnosis and inappropriate management. Using AR procedure, the AA procedure offered three aphonia subjects a voiced sound without airway impairment and the SL procedure decannulated 100% (11/11) of the artificial airways and improved the airway patency in 100% (3/3) of the non-tracheostomized subjects despite the severity of CAJF. The severity of joint ankylosis was distributed as follows: In the aphonia group, there were three subjects with grade I, one subject with grade II, and 0 subjects with grade III. In the ventilation group, there was one subject with grade I, seven subjects with grade II, and six subjects with grade III. In contrast, the two cases used for comparison experienced recurrent dyspnea and failed decannulation because the AR procedure was not performed. The follow-up period was averaged in 58 and 14 months at least. CONCLUSION: From this experience, it is the accurate preoperative diagnosis instead of the severity of CAJF that determines the successful rate in airway patency and voiced phonation if the AR procedure is utilized. Careful medical history inquiry and videolaryngoscopic examination can correctly differentiate the mechanical from neurogenic origin without the help of EMG. Evidence of level: 4.
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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.
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Endoscopía , Posicionamiento del Paciente/métodos , Apnea Obstructiva del Sueño/terapia , Sueño/efectos de los fármacos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
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Apnea Obstructiva del Sueño , Humanos , Preparaciones Farmacéuticas , Sueño , Apnea Obstructiva del Sueño/inducido químicamente , Apnea Obstructiva del Sueño/diagnóstico por imagen , Lengua/diagnóstico por imagen , UltrasonografíaRESUMEN
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.
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Presión de las Vías Aéreas Positiva Contínua/métodos , Rinomanometría/métodos , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/terapia , Adulto , Anciano , Resistencia de las Vías Respiratorias/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polisomnografía/métodos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Apnea Obstructiva del Sueño/diagnóstico , Adulto JovenRESUMEN
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.
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Obstrucción de las Vías Aéreas/terapia , Presión de las Vías Aéreas Positiva Contínua/métodos , Hipnóticos y Sedantes/administración & dosificación , Cirugía Endoscópica por Orificios Naturales/métodos , Apnea Obstructiva del Sueño/terapia , Adulto , Obstrucción de las Vías Aéreas/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Orofaringe/fisiopatología , Hueso Paladar/fisiopatología , Polisomnografía/métodos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/cirugíaAsunto(s)
Laringoplastia , Laringoscopía , Complicaciones Posoperatorias , Edema Pulmonar , Parálisis de los Pliegues Vocales , Pliegues Vocales , Anciano , Atrofia , Diagnóstico Diferencial , Diuréticos , Humanos , Laringoplastia/efectos adversos , Laringoplastia/métodos , Laringoscopía/efectos adversos , Laringoscopía/métodos , Masculino , Terapia por Inhalación de Oxígeno/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/terapia , Edema Pulmonar/diagnóstico , Edema Pulmonar/etiología , Edema Pulmonar/terapia , Ruidos Respiratorios/diagnóstico , Ruidos Respiratorios/etiología , Resultado del Tratamiento , Parálisis de los Pliegues Vocales/diagnóstico , Parálisis de los Pliegues Vocales/etiología , Parálisis de los Pliegues Vocales/fisiopatología , Pliegues Vocales/patología , Pliegues Vocales/cirugíaRESUMEN
Background: The glymphatic system is essential for the maintenance of brain homeostasis. It may be impaired in patients with epilepsy, but its association with neurocognitive function remains unknown. In this study, we aimed to elucidate the association between changes in the glymphatic system and neurocognitive function in individuals diagnosed with frontal lobe epilepsy (FLE). Methods: This retrospective case-control research engaged a group of patients with FLE and age-, sex-, and education-matched healthy volunteers. All participants were subjected to extensive neurocognitive assessments, complemented by structural and diffusion-weighted imaging. The "diffusion tensor imaging analysis along the perivascular space" (DTI-ALPS) index was computed to ascertain differences in glymphatic system function between the groups. Univariate and multivariate analyses were conducted to explore associations between DTI-ALPS, clinical characteristics in patients with FLE, and the neurocognitive test outcomes for both groups. Results: Twenty-five patients [mean age ± standard deviation (SD): 26.28±8.12 years, 10 females] with FLE and 22 healthy control (HC) participants (average age ± SD: 25.86±6.15 years, 11 females) were included. The average ALPS-index in FLE group was significantly lower than that in HC group (1.387±0.127 vs. 1.468±0.114, P=0.026). Further, significant neurocognitive difference was noted in Trail Making Test (TMT), Stroop Color and Word Test (SCWT), Digit Span Test (DST) and similarity test (ST) between the two groups. ALPS-index scores exhibited a negative correlation with disease duration in patients with FLE (r=-0.415, P=0.039), and positive correlations with the Forward Digit Span Test (FDST, r=0.399, P=0.005) and Similarity Test (ST, r=0.395, P=0.006) in both groups. After adjusting for potential confounders, DTI-ALPS maintained a significant independent association with FDST and ST. Conclusions: The findings of the current study suggest a possible association between impairment in glymphatic function and FLE. Furthermore, results indicate that glymphatic dysfunction, as assessed via DTI-ALPS index, appears to be related to neurocognitive decline in FLE.
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Florasulam is widely used for weed control in wheat fields due to its high activity and low dosage. Previous studies on florasulam have focused on soil microbial and residue determination, however, its ecotoxicity to aquatic organisms is unclear. The toxicity of florasulam was evaluated in larvae (120 h) and adult (14 and 28 d) zebrafish. After florasulam (0.1 and 1 µg L-1) exposure, reactive oxygen species levels in larvae and adult zebrafish significantly increased and antioxidant system was activated. Florasulam induced lipid peroxidation in larvae and adult zebrafish. Florasulam did not cause DNA damage to larvae but caused DNA damage to adult zebrafish. Changes in caspase 3/8/9 genes indicated that apoptosis was induced in larvae but inhibited in adult zebrafish. By calculating integrated biomarker response, caspase 3 and malondialdehyde could be used as early warning indicators of florasulam effect on larvae and adult zebrafish, respectively. The higher the exposure concentration, the greater the toxicity of florasulam to larvae and adult zebrafish. Increasing exposure time resulted in higher toxicity to adult zebrafish. Florasulam has different toxicity at larvae and adult zebrafish. In future studies to investigate florasulam toxicity to zebrafish, different zebrafish life stages (larvae and adult) need to be studied.
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Contaminantes Químicos del Agua , Pez Cebra , Animales , Pez Cebra/fisiología , Caspasa 3/metabolismo , Larva , Contaminantes Químicos del Agua/metabolismo , Estrés Oxidativo , Apoptosis , Embrión no MamíferoRESUMEN
Background: Frontal lobe epilepsy (FLE) is the second most common type of focal epilepsy, however, imaging studies of FLE have been far less than Temporal lobe epilepsy (TLE) and the structural findings were not consistent in previous literature. Object: Investigate the changes in cortical thickness in patients with FLE and the alteration of the structural covariance networks (SCNs) of cortical thickness with graph-theory. Method: Thirty patients with FLE (18 males/12 females; 28.33 ± 11.81 years) and 27 demographically matched controls (15 males/12 females; 29.22 ± 9.73 years) were included in this study with high-resolution structural brain MRI scans. The cortical thickness was calculated, and structural covariance network (SCN) of cortical thickness were reconstructed using 68 × 68 matrix and analyzed with graph-theory approach. Result: Cortical thickness was not significantly different between two groups, but path length and node betweenness were significantly increased in patients with FLE, and the regional network alterations were significantly changed in right precentral gyrus and right temporal pole (FDR corrected, p < 0.05). Comparing to HC group, network hubs were decreased and shifted away from frontal lobe. Conclusion: The topological properties of cortical thickness covariance network were significantly altered in patients with FLE, even without obvious surface-based morphological damage. Graph-theory based SCN analysis may provide sensitive neuroanatomical biomarkers for FLE.
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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.
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Antiinflamatorios/uso terapéutico , Fluoroscopía/efectos adversos , Glucocorticoides/uso terapéutico , Prednisolona/uso terapéutico , Radiodermatitis/metabolismo , Animales , Línea Celular , Vía de Señalización Hippo/efectos de los fármacos , Humanos , Queratinocitos/metabolismo , Ratones Endogámicos C57BL , Radiodermatitis/tratamiento farmacológico , Radiodermatitis/genética , Piel/efectos de los fármacos , Piel/metabolismo , Proteínas Señalizadoras YAP/genética , Proteínas Señalizadoras YAP/metabolismoRESUMEN
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 (pâ¯=â¯0.009) and longer DLA (pâ¯=â¯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.
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Manejo de la Vía Aérea , Mentón/diagnóstico por imagen , Intubación Intratraqueal , Laringoscopía , Lengua/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Ultrasonografía , Adulto JovenRESUMEN
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.
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Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Anciano , Índice de Masa Corporal , Endoscopía , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Persona de Mediana Edad , Orofaringe/fisiopatología , Polisomnografía , Propofol/administración & dosificación , Lengua/fisiopatología , Adulto JovenRESUMEN
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.
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Capnografía , Respiración , Sistema Respiratorio/patología , Apnea Obstructiva del Sueño/fisiopatología , Capnografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Polisomnografía , Estudios Prospectivos , Apnea Obstructiva del Sueño/metabolismo , Apnea Obstructiva del Sueño/patologíaRESUMEN
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.
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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.
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Proteínas Adaptadoras Transductoras de Señales/genética , Benzamidas/administración & dosificación , Factor de Transcripción COUP II/genética , MicroARNs/genética , Nitrilos/administración & dosificación , Feniltiohidantoína/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Factores de Transcripción/genética , Anciano , Animales , Benzamidas/efectos adversos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Xenoinjertos , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Persona de Mediana Edad , Células Madre Neoplásicas/efectos de los fármacos , Nitrilos/efectos adversos , Feniltiohidantoína/efectos adversos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Proteínas Señalizadoras YAPRESUMEN
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.
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Endoscopía/métodos , Apnea Obstructiva del Sueño/fisiopatología , Adulto , Estudios Transversales , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Orofaringe/fisiopatología , Polisomnografía , Postura/fisiología , Propofol/administración & dosificación , Sueño , Apnea Obstructiva del Sueño/diagnóstico , Lengua/fisiopatologíaRESUMEN
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.
Asunto(s)
Cefalalgia Histamínica/cirugía , Desnervación/métodos , Manejo del Dolor/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
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.