RESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory condition affecting the nasal and paranasal sinus mucosa, often accompanied by olfactory dysfunction. Eosinophilic CRS with nasal polyps (ECRSwNP) is a subtype of CRS characterized by eosinophilic infiltration. Animal models for ECRSwNP with olfactory dysfunction are necessary for exploring potential therapeutic strategies. OBJECTIVE: The aim of this study was to establish a mouse model of ECRSwNP combined with olfactory dysfunction in a shorter time frame using intranasal ovalbumin and Aspergillus protease (AP) administration. The efficacy of the model was validated by evaluating sinonasal inflammation, cytokine levels, olfactory function, and neuroinflammation in the olfactory bulb. METHODS: Male BALB/c mice were intranasally administered ovalbumin and AP for 6 and 12 weeks to induce ECRSwNP. The resultant ECRSwNP mouse model underwent histologic assessment, cytokine analysis of nasal lavage fluid, olfactory behavioral tests, and gene expression profiling to identify neuroinflammatory markers within the olfactory bulb. RESULTS: The developed mouse model exhibited substantial eosinophil infiltration, increased levels of inflammatory cytokines in nasal lavage fluid, and confirmed olfactory dysfunction through behavioral assays. Furthermore, olfactory bulb inflammation and reduced mature olfactory sensory neurons were observed in the model. CONCLUSION: This study successfully established a validated mouse model of ECRSwNP with olfactory dysfunction within a remarkably short span of 6 weeks, providing a valuable tool for investigating the pathogenesis and potential therapies for this condition. The model offers an efficient approach for future research in CRS with nasal polyps and olfactory dysfunction.
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Modelos Animales de Enfermedad , Eosinofilia , Pólipos Nasales , Trastornos del Olfato , Rinosinusitis , Animales , Masculino , Ratones , Enfermedad Crónica , Citocinas/metabolismo , Eosinofilia/inmunología , Eosinófilos/inmunología , Eosinófilos/patología , Ratones Endogámicos BALB C , Pólipos Nasales/inmunología , Pólipos Nasales/patología , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/etiología , Trastornos del Olfato/etiología , Trastornos del Olfato/patología , Bulbo Olfatorio/patología , Bulbo Olfatorio/inmunología , Ovalbúmina/inmunología , Rinosinusitis/inmunología , Rinosinusitis/patologíaRESUMEN
PURPOSE: Carotid blowout syndrome (CBS) is a severe complication of radiotherapy in patients with nasopharyngeal carcinoma (NPC). This study is aimed at analyzing risk factors of post-irradiation CBS in patients with NPC. METHODS: We retrospectively analyzed 660 patients with NPC between 2006 and 2019. The patients were divided into those with and without CBS, and their characteristics and outcomes were evaluated. Independent predictors of CBS were determined by multivariate logistic regression analysis. RESULTS: We identified 17 NPC patients with CBS in our study. In multivariate logistic regression analysis, lower body mass index (BMI) (P = 0.018), tumor encasement (P = 0.039), local recurrence (P = 0.006), and skull base osteoradionecrosis (P < 0.001) were independent predictors of CBS, and a predictive equation model was established. Log-rank test revealed that patients with low BMI, tumor encasement of carotid vessels, local recurrence, and skull base osteoradionecrosis all exhibited shorter CBS-free time (all P < 0.001). CONCLUSION: We demonstrated that low BMI, tumor encasement, local recurrence, and skull base osteoradionecrosis were independent predictors for CBS in NPC patients. Physicians can use these factors for the early detection and prevention of CBS.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Osteorradionecrosis , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/complicaciones , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Factores de Riesgo , Neoplasias Nasofaríngeas/radioterapia , Adulto , Osteorradionecrosis/etiología , Osteorradionecrosis/epidemiología , Recurrencia Local de Neoplasia , Anciano , Índice de Masa Corporal , Traumatismos por Radiación/etiología , Traumatismos por Radiación/epidemiología , Modelos LogísticosRESUMEN
BACKGROUND: The clinical features of mitochondrial cardiomyopathy (MCM) are diverse. It can present as hypertrophic cardiomyopathy or dilated cardiomyopathy. The diagnosis of MCM is challenging and usually based on biopsy. CASE PRESENTATION: The 30-year-old man was admitted to hospital due to dyspnea for 1 month and edema of both lower extremities for 1 week. Echocardiography suggested a whole heart enlargement, a whole heart diminished function. Renal impairment and diabetes were observed. Coronary angiography showed single-vessel disease (90% stenosis in the ostium of a small marginal branch). Left ventricular endomyocardial biopsy was performed. CONCLUSION: Myocardial histopathology demonstrated a large number of abnormal mitochondrial accumulation, so the diagnosis was considered as mitochondrial cardiomyopathy.
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Cardiomiopatías , Cardiomiopatía Dilatada , Cardiomiopatía Hipertrófica , Masculino , Humanos , Adulto , Cardiomiopatías/diagnóstico , Cardiomiopatías/patología , Miocardio/patología , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Hipertrófica/diagnóstico , BiopsiaRESUMEN
Cardiac shockwave therapy (CSWT) is a noninvasive treatment for patients with refractory angina or myocardial ischemia. This study aims to evaluate the potential beneficial effect and safety of CSWT in patients with severe coronary artery disease (CAD) who have undergone coronary artery bypass grafting (CABG).This was a single-arm prospective cohort study. A total of 30 patients with severe CAD who were not suitable for coronary revascularization and who had undergone CABG were enrolled. All patients received CSWT for nine sessions. Evaluation was performed before and after CSWT, including the Canadian Cardiovascular Society (CCS) classification, New York Heart Association (NYHA) classification, 6-minute walk test (6MWT), Seattle Angina Questionnaire (SAQ) score, nitroglycerin dosage, echocardiography, myocardial perfusion imaging (MPI), and safety parameters. All patients were followed up at both 1 month and 9 months after CSWT.After treatment, CSWT significantly improved CCS classification (P < 0.05), NYHA classification (P < 0.05), nitroglycerin dosage (P < 0.001), and 6MWT (P < 0.05) at 1 month and 9 months after CSWT. SAQ score (P < 0.05) and left ventricular ejection fraction (LVEF; P = 0.037) by echocardiography significantly improved at 1 month after CSWT. Significant decreases in summed stress score (SSS), summed difference score (SDS), ischemic area stress, and ischemic area difference by MPI were observed at 1 month and 9 months after CSWT (P < 0.01). There were no changes in safety parameters before and after CSWT.CSWT may have a beneficial effect on improving myocardial perfusion, clinical symptoms, exertional capacity, and quality of life and is a safe alternative treatment for patients with severe CAD who have undergone CABG.
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Enfermedad de la Arteria Coronaria , Ondas de Choque de Alta Energía , Humanos , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico , Nitroglicerina , Ondas de Choque de Alta Energía/uso terapéutico , Volumen Sistólico , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Función Ventricular Izquierda , Canadá , Puente de Arteria CoronariaRESUMEN
OBJECTIVES: Fungal rhinosinusitis is an inflammatory disease of the nose that may lead to life-threatening complications. This study compared the bacterial and fungal microbiomes between patients with invasive fungal rhinosinusitis (IFRS) and non-IFRS (NIFRS). DESIGN: This was a prospective study including 18 IFRS and NIFRS patients. Fungal and bacterial microbiomes from surgical specimens were sequenced from amplicons of the internal transcribed spacer 1 (ITS1) region and the V3-V4 region of the 16S locus, respectively. Microbiomes were generated using the Illumina MiSeq System 2 x 301 base pair chemistry with a paired-end protocol. SETTING: Tertiary medical centre. RESULTS: Targeted metagenomics identified Aspergillus spp. as the predominant fungus in both IFRS and NIFRS patients. Based on phylum and genera level diversity, and abundance differences, significant differences of operational taxonomic units (OTUs) (Fusobacterium, Prevotella, Pseudomonas, Neisseria and Streptococcus) were more abundant in NIFRS compared with IFRS patients. CONCLUSIONS: This is the first study to analyse bacterial and fungal microbiomes in patients with IFRS and NIFRS via ITS1 and 16S genomics sequencing. Bacterial microbiomes from patients with IFRS demonstrated dysbiosis (alterations in diversity and abundance) compared to those from patients with NIFRS.
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Microbiota , Humanos , Estudios Prospectivos , Microbiota/genética , Bacterias/genética , Streptococcus , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
This study aims to investigate the mechanism of acacetin in protecting rats from cerebral ischemia-reperfusion injury via the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. Wistar rats were randomized into sham, model, low-and high-dose acacetin, and nimodipine groups, with 10 rats in each group. The rat model of middle cerebral artery occlusion(MCAO) was established with the improved suture method in other groups except the sham group. The neurological deficit score and cerebral infarction volume of each group were evaluated 24 h after modeling. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1ß(IL-1ß), IL-6, tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), supe-roxide dismutase(SOD), and glutathione(GSH). Western blot was employed to determine the expression levels of B-cell lymphonoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and TLR4/NLRP3 signaling pathway-related proteins(TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1ß, and cleaved IL-1ß) in the rat brain tissue. Hematoxylin-eosin(HE) staining was employed to reveal the histopathological changes in the ischemic area. Compared with the sham group, the modeling of MCAO increased the neurological deficit score and cerebral infarction volume, elevated the IL-1ß, IL-6, TNF-α, and MDA levels and lowered the SOD and GSH levels in the brain tissue(P<0.05). Compared with the MCAO model group, low-and high-dose acacetin and nimodipine decreased the neurological deficit score and cerebral infarction volume, lowered the IL-1ß, IL-6, TNF-α, and MDA levels and elevated the SOD and GSH levels in the brain tissue(P<0.05). Compared with the sham group, the model group showed up-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1ß, and cleaved IL-1ß and down-regulated protein level of Bcl-2 in the brain tissue(P<0.05). Compared with the MCAO model group, the acacetin and nimodipine groups showed down-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1ß, and cleaved IL-1ß and up-regulated protein level of Bcl-2 in the brain tissue(P<0.05). In conclusion, acacetin regulates the TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress, thus exerting the protective effect on cerebral ischemia-reperfusion injury in rats.
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FN-kappa B , Daño por Reperfusión , Ratas , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Proteína X Asociada a bcl-2 , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ratas Sprague-Dawley , Caspasa 1/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Nimodipina/farmacología , Interleucina-6 , Ratas Wistar , Transducción de Señal , Infarto de la Arteria Cerebral Media , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/genética , Daño por Reperfusión/prevención & control , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Previous studies proved the efficacy of cardiac shock wave therapy (CSWT) for coronary artery disease (CAD) patients who are not candidate for reperfusion therapy. Randomized control trials are limited. We try to explore the efficacy and safety of CSWT for patients with severe CAD. METHODS: Thirty patients with severe CAD who had obvious ischemia on myocardial perfusion imaging (MPI) were enrolled and randomly assigned to the CSWT group or the control group. They had received optimal medication treatment for at least three months. Nine sessions of shock wave therapy were conducted over 3 months. CSWT group received the real treatment, while the control group received the pseudo-treatment. Clinical symptom, imaging outcomes and safety parameters were compared between two groups. RESULTS: After treatment, regional stress score (P = .023), improvement rate (IR) of ischemic area (IA) stress (P < .001) and IR of IA difference (P < .001) were significantly favor CSWT group. The interaction of summed rest score (P < .001), summed stress score (P = .004), summed difference score (P = .036) were significantly improved in the CSWT group compared to the control group. Seattle angina questionnaire, quality of life (QOL) and the distance of six-minute walking test (6MWT) were improved in both groups without significant difference between them. Hemodynamic parameters were stable during procedure. Myocardial injury markers showed no changes in two groups. CONCLUSIONS: Our study demonstrated CSWT could effectively and safely improve myocardial perfusion in patients with severe CAD. Clinical symptom, QOL and 6MWT were all improved after treatment, but no significant difference between two groups.
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Enfermedad de la Arteria Coronaria , Tratamiento con Ondas de Choque Extracorpóreas , Ondas de Choque de Alta Energía , Imagen de Perfusión Miocárdica , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Ondas de Choque de Alta Energía/efectos adversos , Humanos , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: Clopidogrel is a widely-used antiplatelet and acts as an adenosine diphosphate receptor inhibitor. Neutropenia is a rare but serious adverse effect of clopidogrel. It is unknown whether this adverse effect has any association with impaired kidney function. CASE PRESENTATION: An 80-year-old male with chronic kidney disease was diagnosed with non-ST elevation myocardial infarction and underwent percutaneous coronary intervention. During hospitalization, the patient was diagnosed with contrast-induced nephropathy, treated symptomatically, and discharged with a back-to-baseline creatinine level. Two weeks later, the patient presented to the emergency department with fever and chills. Complete blood count showed leukopenia (0.84 × 103/mm3) and severe neutropenia (0.13 × 103/mm3). Blood cultures were positive for Pseudomonas aeruginosa. Clopidogrel was stopped immediately and switched into ticagrelor. Imipenem and granulocyte colony-stimulating factor were administered to the patient. The patient's white blood cell and absolute neutrophil count were within the normal range after four days of treatment. The patient was discharged after a 10-day hospitalization, and his complete blood counts were normal during further follow-ups. CONCLUSIONS: Clopidogrel was the most likely primary cause of neutropenia in our case. The incidence of clopidogrel-induced neutropenia is low and the exact mechanism is not fully explained. We provide suggestions on the management of clopidogrel-associated neutropenia, and summarize all five cases of clopidogrel-induced neutropenia in patients with impaired kidney function.
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Clopidogrel/efectos adversos , Enfermedad de la Arteria Coronaria/terapia , Neutropenia/inducido químicamente , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Anciano de 80 o más Años , Clopidogrel/administración & dosificación , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Sustitución de Medicamentos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Imipenem/uso terapéutico , Masculino , Neutropenia/sangre , Neutropenia/diagnóstico , Neutropenia/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Insuficiencia Renal Crónica/diagnóstico , Factores de Riesgo , Ticagrelor/administración & dosificación , Resultado del TratamientoRESUMEN
PURPOSE: Radiotherapy for nasopharyngeal carcinoma (NPC) may induce cerebrovascular diseases including ischemic stroke and transient ischemic attack (TIA), which can cause severe disability. However, information on the incidence and predictors of cerebrovascular diseases is scarce. This study aimed to estimate the incidence of cerebrovascular diseases following NPC, and attempts to ascertain the predictors of cerebrovascular diseases to facilitate early prevention. METHODS: We performed a retrospective cohort study on 655 NPC patients who received radiotherapy between 2006 and 2018 in a medical center. This study analyzed the incidence, clinical and imaging presentation of patients with cerebrovascular diseases. Cox proportional hazard model was used to identify risk factors associated with cerebrovascular diseases following radiotherapy. RESULTS: There were 14 patients who developed an ischemic stroke, and 3 patients developed a TIA after a mean follow-up of 5.8 years. Most ischemic events were from large-artery atherosclerosis (76.5%), and the most common symptom of ischemic stroke was unilateral limb weakness (57.1%). The cumulative incidence of ischemic stroke or TIA 15 years after radiotherapy was 9.1% (95% confidence interval [CI] = 4.7-17.2%). Multivariate Cox regression identified vertebral artery stenosis (HR: 18.341; 95% CI = 3.907-86.100; P < 0.001), atrial fibrillation (HR: 13.314; 95% CI = 1.306-135.764; P = 0.029), and hypertension (HR: 7.511; 95% CI = 1.472-38.320; P = 0.015) as independent predictors of ischemic stroke or TIA. CONCLUSION: Our study found that NPC patients with vertebral artery stenosis, atrial fibrillation, or hypertension carry a higher risk for ischemic stroke or TIA. Regular assessment of vertebral artery after radiotherapy was suggested.
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Fibrilación Atrial , Hipertensión , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Neoplasias Nasofaríngeas , Accidente Cerebrovascular , Insuficiencia Vertebrobasilar , Fibrilación Atrial/complicaciones , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/etiología , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/radioterapia , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Insuficiencia Vertebrobasilar/complicaciones , Insuficiencia Vertebrobasilar/etiologíaRESUMEN
PURPOSE: Previous cancers can be observed in patients with nasopharyngeal carcinoma (NPC). However, whether prior cancer diagnosis affects survival outcomes remains unknown. This study aimed to explore the impact of prior cancer on the survival of patients with NPC. METHODS: We retrospectively collected data from 666 NPC patients between 2006 and 2018. The patients in this study were divided into those without prior cancer, with prior head and neck cancer, and prior non-head and neck cancer. The demographic data and survival of these groups were then analyzed. The independent prognostic factors for NPC were determined using multivariate Cox regression analysis. RESULTS: We identified 25 NPC patients with prior cancer in our case series, most of whom had a history of colorectal cancer. Patients with a history of cancer were older than those without a history of cancer (p = 0.001). In the subgroup analysis stratified by the timing of prior cancer, NPC patients with prior non-head and neck cancer within 24, 36, 60, and 120 months showed worse survival than patients without prior cancer (all p < 0.05). When stratified by cancer stage, stage III NPC patients with prior non-head and neck cancer showed worse survival than patients without prior cancer (p < 0.001). Prior cancer and diabetes can predict worse survival in patients with stage III NPC. CONCLUSION: This study demonstrated that prior cancer and diabetes are independent prognostic factors in patients with stage III NPC.
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Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
A novel DEK-AFF2 fusion has been recently identified in four cases of basaloid to nonkeratinizing squamous cell carcinoma (SCC) in the sinonasal tract and middle ear with high-grade morphology. The exceptional response to immune checkpoint inhibitor in the first reported case highlights the potential clinical importance of identifying tumors with DEK-AFF2 fusions. We herein reported the first series of seven cases of DEK-AFF2 fusion-associated sinonasal SCC with deceptively bland morphology, including four cases of low-grade papillary Schneiderian carcinoma, which is a recently described tumor type with unknown molecular underpinnings. The DEK gene rearrangement was confirmed by DEK break-apart fluorescence in situ hybridization and DEK-AFF2 fusion transcripts were detected by reverse transcription polymerase chain reaction. In contrast to the previously reported DEK-AFF2 fusion-positive high-grade carcinomas, these tumors had a monotonous and bland morphology and were all initially diagnosed as sinonasal papilloma (SP) of various types, with or without dysplasia or carcinoma in situ. The tumor was characterized by mixed exophytic and inverted patterns, broad papillary fronds, acantholytic change, cellular monotony, dense neutrophilic infiltrates, and peripheral palisading. All tumors were diffusely positive for p40 or p63 and negative for NUT and p16. Molecular drivers associated with SP, including EGFR and KRAS mutations and both high and low-risk human papillomavirus infection, were negative in all cases. Although there was no overt stromal invasion or desmoplastic reaction in the initial specimens, these tumors tended to progress locoregionally through a prolonged clinical course and occasionally develop lymph node metastases, high-grade transformation, or extensively local destruction eventually leading to death. These justify more aggressive clinical management. Therefore, we propose the new terminology "DEK-AFF2 fusion-associated papillary SCC of the sinonasal tract" to better describe this clinicopathologically and molecularly distinct entity.
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Carcinoma Papilar/genética , Proteínas Cromosómicas no Histona/genética , Neoplasias Nasofaríngeas/genética , Proteínas Nucleares/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Oncogénicas/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Adulto , Anciano , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patología , Proteínas Cromosómicas no Histona/metabolismo , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Proteínas Nucleares/metabolismo , Proteínas Oncogénicas/metabolismo , Proteínas de Fusión Oncogénica/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
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
Doxorubicin, as a first line chemotherapeutic agent, its usage is limited owing to cardiotoxicity. Necroptosis is a new form of programmed cell death, and recent investigations indicated that necroptosis is vitally involved in serious cardiac pathological conditions. Dexrazoxane is the only cardiac protective drug approved by FDA for anthracycline. We aimed to explore whether and how dexrazoxane regulates doxorubicin-induced cardiomyocyte necroptosis. First, doxorubicin could cause heart failure and reduce cardiomyocyte viability by promoting cell apoptosis and necroptosis in vivo and in vitro. Second, necroptosis plays an important role in doxorubicin induced cardiomyocyte injury, which could be inhibited by Nec-1. Third, dexrazoxane increased cell viability and protect heart function by decreasing both cardiomyocyte apoptosis and necroptosis after doxorubicin treatment. Forth, dexrazoxane attenuated doxorubicin-induced inflammation and necroptosis by the inhibition of p38MAPK/NF-κB pathways. These results indicated that dexrazoxane ameliorates cardiotoxicity and protects heart function by attenuating both apoptosis and necroptosis in doxorubicin induced cardiomyocyte injury.
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Apoptosis/efectos de los fármacos , Dexrazoxano/farmacología , Doxorrubicina/efectos adversos , Miocitos Cardíacos/efectos de los fármacos , Necroptosis/efectos de los fármacos , Animales , Células Cultivadas , Dexrazoxano/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones Endogámicos C57BL , Relación Estructura-ActividadRESUMEN
Background Thiostrepton, a natural antibiotic, has recently been shown to be a potential anticancer drug for certain cancers, but its study in nasopharyngeal carcinoma (NPC) is still limited. The aims of this study were to investigate the anticancer effect of thiostrepton on NPC cells and to explore its underlying mechanism. Methods The effects of thiostrepton on the proliferation, migration, and invasion of NPC cells were investigated by a WST-1 assay, wound healing assay, and cell invasion assay, respectively. Microarrays were conducted and further analyzed by Ingenuity Pathways Analysis (IPA) to determine the molecular mechanism by which thiostrepton affects NPC cells. Results Our results showed that thiostrepton reduced NPC cell viability in a dose-dependent manner. Thiostrepton inhibited the migration and invasion of NPC cells in wound healing and cell invasion assays. The microarray data analyzed by IPA indicated the top 5 ingenuity canonical pathways, which were unfolded protein response, NRF2-mediated oxidative stress response, retinoate biosynthesis I, choline biosynthesis III, and pancreatic adenocarcinoma signaling. Conclusion Thiostrepton effectively suppressed NPC cell proliferation, migration, and invasion, likely by several mechanisms. Thiostrepton may be a potential therapeutic agent for treating NPC in the future.
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Antibacterianos/farmacología , Antineoplásicos/farmacología , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Tioestreptona/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genéticaRESUMEN
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.
Asunto(s)
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 study aimed to determine the efficacy of multilevel surgery (hyoid myotomy and suspension with uvulopalatopharyngoplasty) and continuous positive airway pressure (CPAP) for the treatment of moderate to severe obstructive sleep apnea syndrome (OSAS) and to clarify whether our surgical protocol could be as effective as CPAP. METHODS: We conducted a case series study comparing the effects of multilevel surgery and CPAP in the same subjects to minimize the influence of confounding factors. Fifteen subjects were enrolled with a pretreatment apnea-hypopnea index (AHI) ≥ 15. RESULTS: Both CPAP and multilevel surgery could improve the AHI and oxygen desaturation index (ODI). The median AHI for baseline, CPAP and surgery were 38.9, 1.2 and 12.6, respectively (p < 0.001). The medina ODI for baseline, CPAP and surgery were 34.8, 0.9 and 7.2, respectively (p < 0.001). However, the results indicated CPAP as the more efficacious treatment modality compared with multilevel surgery. Moreover, CPAP not only decreased N1 sleep but also had beneficial effects on blood pressure control, whereas multilevel surgery did not have any significant difference. CONCLUSION: CPAP is efficacious in improving OSAS severity, oxygen desaturation, sleep stage, and blood pressure control; while hyoid myotomy and suspension with uvulopalatopharyngoplasty are only efficacious in improving OSAS severity and oxygen desaturation. This study suggested that CPAP is the first choice when considering treatment of OSAS, especially in patients with hypertension or other cardiovascular diseases.
Asunto(s)
Miotomía , Apnea Obstructiva del Sueño , Presión de las Vías Aéreas Positiva Contínua , Humanos , Polisomnografía , Apnea Obstructiva del Sueño/cirugía , Úvula/cirugíaRESUMEN
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.