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1.
Artigo em Inglês | MEDLINE | ID: mdl-31673825

RESUMO

PURPOSE: Vactosertib, a novel inhibitor of transforming growth factor-ß type Ι receptor, is under development for the treatment of various cancers. The objective of this study was to characterize the population pharmacokinetics of vactosertib in patients with solid tumors. METHODS: Vactosertib population pharmacokinetics was assessed by nonlinear mixed-effects modelling of plasma concentration-time data obtained from a first-in-human phase 1 trial conducted in patients with advanced solid tumors. The final population pharmacokinetic model was constructed by assessing the effect of covariates on pharmacokinetic parameters including demographic characteristics, laboratory values, hepatic and renal function, and concomitant medications. The robustness of the final model was evaluated using a bootstrap method as well as visual predictive check based on Monte Carlo simulations and goodness-of-fit plots. RESULTS: A total of 559 concentrations from 29 patients were available for pharmacokinetic analysis. A two-compartment linear model with first-order absorption and absorption lag time adequately described the population pharmacokinetics of vactosertib. The estimates of apparent clearance (CL/F) and volume of central compartment (Vc/F) were 31.9 L/h (inter-individual variability, 0.481) and 82.9 L (inter-individual variability, 0.534), respectively. The mixture model accounts for both typical absorption profile in the majority of patients and distinct profile in some patients with uncommon gastrointestinal conditions. Body mass index was significantly associated with Vc/F. CONCLUSIONS: The model developed in this study adequately describes the population pharmacokinetics of vactosertib in patients with advanced solid tumors. The pharmacokinetic characteristics assessed using the model would provide useful quantitative information to assist the future clinical development of vactosertib.

2.
J Plast Surg Hand Surg ; : 1-8, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575315

RESUMO

Current treatment guidelines for biofilm-associated infections (BAI) recommend repeated sharp/surgical debridement followed by treatment with antimicrobial agents until the wound becomes self-sustaining in terms of a positive wound-healing trajectory. However, complete removal of a biofilm is unlikely, and biofilms reform rapidly. We have treated BAI in patients with chronic diabetic ulcers using a meshed skin graft combined with negative pressure wound therapy (NPWT) immediately after surgical debridement, rather than waiting until the development of clean and healthy granulation tissue; the purpose of this exploratory study was to report the clinical results of this treatment strategy. This retrospective study included 75 patients with chronic diabetic ulcers who were treated for BAI by using surgical debridement, simultaneous meshed skin grafts, and NPWT. Healing time along with the percentage of complete wound closure within 12 weeks were evaluated; bacteria isolated from the wounds and their relation to the wound healing rate were investigated. All 75 wounds healed successfully, and the mean time for complete wound healing was 3.5 ± 1.8 weeks. In particular, 76% of wounds healed uneventfully without graft loss. A mean of 3.3 bacterial colonies/wound were isolated; however, no significant difference in wound healing was observed between the monomicrobial and polymicrobial groups. This exploratory study suggests that surgical debridement and simultaneous meshed skin grafts combined with NPWT may be successfully used to combat BAI in patients with chronic diabetic ulcers. We look forward to larger pivotal studies to confirm or refute these initially promising findings.

3.
Acta Otolaryngol ; 139(10): 934-938, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31430217

RESUMO

Background and Objectives: Because the incidence of bilateral facial palsy is extremely low, clinical diagnosis and treatment may be delayed and the possibility of misdiagnosis is high. This systematic review, therefore, evaluated the clinical manifestations of bilateral facial palsy. Methods: The SCOPUS and PubMed databases were searched through 31 August 2018, using the search term 'bilateral facial palsy'. Reference lists of identified studies were also reviewed. Results: A search of titles and abstracts identified 390 studies; after eliminating duplicates and inappropriate studies, 10 studies, involving 75 patients from four countries, were analyzed. The percentage of patients with facial nerve palsy who experienced simultaneous bilateral facial palsy ranged from 0.3% to 2.0%. There were no differences between men and women in all age groups. The causes of bilateral facial palsy differed, and 51% were associated with other cranial nerves. Complete recovery was achieved in 80% of patients and incomplete recovery in 20%. Conclusions: Bilateral facial palsy has various causes. Prognosis for recovery is good.

4.
Invest New Drugs ; 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31300967

RESUMO

Purposes Vactosertib is a new investigational inhibitor of activin receptor-like kinase 5. The objective of this study was to characterize vactosertib pharmacokinetics that are to be applied for subsequent clinical studies. Methods Vactosertib plasma concentration-time data were obtained from a multicenter, dose-escalation, first-in-human phase 1 study conducted in patients with advanced solid tumors. Each patient orally received a fixed dose of vactosertib with the range of 30 mg to 340 mg once daily under fasted condition. Pharmacokinetic analysis was performed using a non-compartmental method. Results Pharmacokinetic data were evaluable in 29 patients. Vactosertib was rapidly absorbed after the first dose with a median time to maximum concentration (tmax) of 1.2 h (interquartile range, 0.8-1.8 h) and quickly eliminated with a median terminal half-life (t1/2) of 3.2 h (2.2-4.2 h) over the dose range studied. Such trend was also observed after repeated doses for five days (median tmax, 1.5 h; median t1/2, 3.0 h). The area under the concentration-time curve within a dosing interval increased in proportion to dose. The median values of apparent clearance and volume of distribution were 29 L/h (21-44 L/h) and 133 L (77-222 L), respectively. The median accumulation ratio after repeated once-daily doses for five days was 0.87 (0.69-1.07). Conclusions Vactosertib pharmacokinetics were dose-proportional within tested dose range with negligible accumulation when administered once daily for five days. Considering the short half-life, it seems necessary to administer vactosertib twice- or thrice-daily to maintain its concentrations above minimum effective level over a dosing interval.

5.
Curr Allergy Asthma Rep ; 19(7): 34, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161431

RESUMO

PURPOSE OF REVIEW: Obesity is a major public health problem associated with various diseases. Improving obesity control and achieving greater patient satisfaction are critical unmet needs. Various otorhinolaryngologic diseases can have negative effects on quality of life or actual health status depending on their type. Over the past decade, the relationship between obesity and otorhinolaryngologic conditions has been investigated. The purpose of this review was to discuss the relationship between obesity and otorhinolaryngological diseases. RECENT FINDINGS: This is a narrative review on the current state of incidence, effects, and associated mechanisms between obesity and otorhinolaryngologic diseases. In various otologic diseases, otitis media (OM) and hearing loss (HL) are associated with obesity. In rhinologic parts, chronic rhinosinusitis (CRS) and obstructive sleep apnea (OSA) were significantly associated with obesity. Most of these diseases are reported to have higher susceptibility and severity as body mass index (BMI) increases. However, the incidence of head and neck cancer (HNC) was inversely associated with obesity, especially central adiposity. The relevance of obesity in laryngopharyngeal reflux disease (LPR) and allergic rhinitis (AR) has yet to be clarified, and this remains controversial. This review provides a comprehensive overview of the current state of incidence, effects, and associated mechanisms between obesity and otorhinolaryngologic diseases. Various otorhinolaryngological diseases are related to obesity. As obesity can be a negative risk factor in these otorhinolaryngologic diseases, early diagnosis and treatment of these diseases in obese patients will be critical.

6.
Laryngoscope ; 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31034617

RESUMO

OBJECTIVES: To assess the impact of the American Academy of Sleep Medicine (AASM) 2012Rec criteria on the surgical success rate and polysomnography (PSG) parameters of patients with obstructive sleep apnea (OSA). STUDY DESIGN: A prospective clinical trial. METHODS: A total of 60 patients who performed surgery for treatment of OSA at the sleep breathing disorder center of a tertiary referral university hospital from October 1, 2015, to September 30, 2016, were enrolled. Preoperative and postoperative PSG were performed and scored using AASM 2007Rec and AASM 2012Rec . Surgical success was determined by criteria 1 (postoperative Apnea-Hypopnea Index [AHI] <20% and 50% reduction) and criteria 2 (postoperative AHI <10), and surgical success rates according to AASM 2007Rec and AASM 2012Rec were compared. RESULTS: PSG parameters including AHI, hypopnea index, respiratory effort-related arousals, respiratory disturbance index, and supine AHI scored significantly higher with AASM 2012Rec compared to AASM 2007Rec criteria, both preoperatively and postoperatively (all P < 0.05). Furthermore, when compared to the AASM 2007Rec criteria, AASM 2012Rec resulted in increased proportion of patients with severe OSA (70.0% vs. 95.0%; P < 0.001). For the surgical outcomes, AASM 2012Rec showed significantly lower surgical success rate both in criteria 1 (51.7% vs. 38.3%) and criteria 2 (35.0% vs. 18.3%) compared to the AASM 2007Rec , respectively (P < 0 .05). CONCLUSIONS: This study demonstrated that AASM 2012Rec tends to decrease the success rate of surgical outcome for OSA patients, suggesting that defining success of surgical treatment for OSA could be changed dramatically according to the hypopnea scoring criteria. LEVEL OF EVIDENCE: 4 Laryngoscope, 2019.

7.
Clin J Am Soc Nephrol ; 14(4): 515-522, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30846462

RESUMO

BACKGROUND AND OBJECTIVES: Active smoking is associated with higher risk of various diseases. However, the risk of CKD development in nonsmokers exposed to secondhand smoke is not well elucidated. We aimed to investigate the association between secondhand smoke exposure and the risk of CKD development among never-smokers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 131,196 never-smokers with normal kidney function, who participated in the Korean Genome and Epidemiology Study from 2001 to 2014, were analyzed. The participants were classified into three groups on the basis of frequency of secondhand smoke exposure, assessed with survey questionnaires; no exposure, <3 days per week, and ≥3 days per week. The association between secondhand smoke and CKD, defined as eGFR<60 ml/min per 1.73 m2, was examined in the cross-sectional analysis. In addition, the risk of incident CKD development was analyzed in a longitudinal cohort of 1948 participants without CKD at baseline, which was a subset of the main cohort. RESULTS: The mean age of participants was 53 years, and 75% were women. Prevalent CKD was observed in 231 (1.8%), 64 (1.7%), and 2280 (2.0%) participants in the ≥3 days per week, <3 days per week, and no exposure groups. The odds ratio (OR) of prevalent CKD was significantly higher in the groups exposed to secondhand smoke than the no exposure group (<3 days per week: OR, 1.72; 95% confidence interval [95% CI], 1.30 to 2.27; and ≥3 days per week: OR, 1.44; 95% CI, 1.22 to 1.70). During a mean follow-up of 104 months, CKD occurred in 319 (16%) participants. Multivariable Cox analysis revealed that the risk for CKD development was higher in participants exposed to secondhand smoke than the no exposure group (<3 days per week: hazard ratio, 1.59; 95% CI, 0.96 to 2.65; and ≥3 days per week: hazard ratio, 1.66; 95% CI, 1.03 to 2.67). CONCLUSIONS: Exposure to secondhand smoke was associated with a higher prevalence of CKD as well as development of incident CKD.

8.
Eur Arch Otorhinolaryngol ; 276(4): 1011-1016, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30707280

RESUMO

PURPOSE: Patients with Ramsay-Hunt syndrome have a poorer prognosis than patients with Bell's palsy. Factors of metabolic syndrome affecting prognosis were therefore compared between patients with Ramsay-Hunt syndrome and those with Bell's palsy. METHODS: This retrospective study included 106 with Ramsay-Hunt syndrome and 182 with Bell's palsy. Age, sex, body mass index, blood pressure, blood test results, and ENoG results, stratified by House-Brackmann grade, were compared in patients with Ramsay-Hunt syndrome and Bell's palsy. Both groups of patients were treated with steroids and the antiviral agent famciclovir. RESULTS: Age, sex, body mass index, dyslipidemia, triglyceride, diabetes, hypertension, and onset of palsy did not differ in patients with Ramsay-Hunt syndrome and Bell's palsy. Rates of favorable recovery in patients with severe facial palsy and DM were lower in patients with Ramsay-Hunt syndrome than with Bell's palsy and were also lower in low-weight, normal weight, and overweight patients with Ramsay-Hunt syndrome than with Bell's palsy. Rates of favorable recovery in patients with severe facial palsy and normal HDL, as well as in patients with severe facial palsy and < 10% ENoG, were lower in patients with Ramsay-Hunt syndrome than with Bell's palsy. CONCLUSIONS: Among patients with severe facial palsy, along with diabetes and < 10% ENoG, unfavorable recovery rates were significantly higher in those with Ramsay-Hunt syndrome than with Bell's palsy.


Assuntos
Paralisia de Bell , Herpes Zoster da Orelha Externa , Adulto , Fatores Etários , Paralisia de Bell/complicações , Paralisia de Bell/tratamento farmacológico , Pressão Sanguínea , Índice de Massa Corporal , Complicações do Diabetes , Feminino , Herpes Zoster da Orelha Externa/complicações , Herpes Zoster da Orelha Externa/tratamento farmacológico , Humanos , Hipertensão/complicações , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Esteroides/uso terapêutico , Infecção pelo Vírus da Varicela-Zoster/complicações
9.
Nutrients ; 11(2)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717210

RESUMO

Hearing loss (HL) is a major public health problem. Nutritional factors can affect a variety of diseases, such as HL, in humans. Thus far, several studies have evaluated the association between nutrition and hearing. These studies found that the incidence of HL was increased with the lack of single micro-nutrients such as vitamins A, B, C, D and E, and zinc, magnesium, selenium, iron and iodine. Higher carbohydrate, fat, and cholesterol intake, or lower protein intake, by individuals corresponded to poorer hearing status. However, higher consumption of polyunsaturated fatty acids corresponded to better hearing status of studied subjects. In addition to malnutrition, obesity was reported as a risk factor for HL. In studies of the relationship between middle ear infection and nutrition in children, it was reported that lack of vitamins A, C and E, and zinc and iron, resulted in poorer healing status due to vulnerability to infection. These studies indicate that various nutritional factors can affect hearing. Therefore, considering that multifactorial nutritional causes are responsible, in part, for HL, provision of proper guidelines for maintaining a proper nutritional status is expected to prevent some of the causes and burden of HL.


Assuntos
Dieta , Perda Auditiva , Estado Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Otite , Adulto Jovem
10.
Clin Otolaryngol ; 44(3): 305-312, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30672667

RESUMO

OBJECTIVE: Although recurrent facial palsy was first reported in 1871, the aetiology, definitions, classifications, pathogenesis, treatment options and prognosis have not been clearly determined. There have been no systematic reviews and meta-analyses of recurrent Bell's palsy. The purpose of this study was to evaluate the clinical manifestations of recurrent Bell's palsy through a systematic review and meta-analysis. DESIGN: The SCOPUS, PubMed, Cochrane Library and EBSCO databases were searched through 1 May 2018, using the search terms "recurrent Bell's palsy" and "recurrent facial palsy," for studies involving patients with recurrent Bell's palsy. Reference lists of eligible studies were also reviewed. RESULTS: A search of titles and abstracts in these four databases identified 222 studies; of these, 27 studies, involving 1041 patients from 13 countries, were analysed. The mean percentage of patients who experienced recurrence of Bell's palsy ranged from 0.8% to 19.4%. Five studies that included 191 patients were included in the meta-analysis. CONCLUSIONS: Among patients previously affected by Bell's palsy, the mean incidence of recurrent Bell's palsy was 6.5%. Sidedness of recurrent disease, relative to the side of the original disease, had no effect on patient prognosis. Of all patients with Bell's palsy, 66.0% recovered completely, with the recovery rate lower in patients with recurrent than with primary Bell's palsy.

11.
Acta Otolaryngol ; 139(1): 42-47, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30664389

RESUMO

BACKGROUND: Although metabolic syndrome (MetS) has been associated with various diseases, few studies to date have addressed the association between MetS and hearing loss. AIMS/OBJECTIVES: This cross-sectional review of health examination center data sought to determine the association between MetS and hearing disturbance. MATERIAL AND METHODS: This study involved 28,866 subjects. Height, weight, waist circumference, and blood pressure were measured, and basic blood tests and pure-tone audiometry (PTA) were performed. Other factors analyzed included body mass index, hypertension, diabetes mellitus, and hyperlipidemia. RESULTS: Age and gender did not differ between subjects with and without MetS. PTA was slightly higher in subjects with than without MetS, but the difference was not statistically significant (p = .47). The incidence of hearing loss was no higher in subjects who met three of the five diagnostic criteria of MetS than in those who met 0-2 criteria, but was significantly higher in subjects who met four (p = .04) and five (p < .01) criteria. CONCLUSIONS AND SIGNIFICANCE: MetS may be associated with hearing loss, especially in subjects who meet four or five of the diagnostic criteria for MetS.


Assuntos
Perda Auditiva/etiologia , Síndrome Metabólica/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perda Auditiva/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Adulto Jovem
12.
Laryngoscope ; 129(11): 2658-2662, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30623431

RESUMO

OBJECTIVES/HYPOTHESIS: To examine the effect of epiglottis obstruction during drug-induced sleep endoscopy (DISE) on the surgical results of multilevel sleep surgery without epiglottic intervention. STUDY DESIGN: Cross-sectional study. METHODS: This investigation involved patients diagnosed with severe obstructive sleep apnea (OSA) based on preoperative polysomnography (PSG), who underwent DISE followed by multilevel OSA surgery without epiglottic intervention at Kyung Hee Medical Center (Seoul, South Korea) between March 2013 and July 2016. During DISE, obstruction patterns of the upper airway were evaluated using the velum, oropharynx, tongue base, epiglottis classification method. Follow-up PSG was performed 3 months after surgery to determine the success rate of multilevel surgery without epiglottic intervention. A comparison was done between the group with epiglottis obstruction and the group without epiglottis obstruction. RESULTS: Epiglottis obstruction was observed during DISE in 43.7% of patients. After application of exclusion criteria, 54 subjects were included (27 with and 27 without epiglottis obstruction). DISE revealed an association between epiglottis obstruction and tongue base collapse (P = .02). Comparing pre- and postoperative PSG findings, both groups exhibited improvement postoperatively. The success rate was 44.4% in the epiglottis obstruction group and 40.7% in the non-epiglottis obstruction group (P = .80). There was no difference in surgical success rates between the two groups. CONCLUSIONS: The prevalence of epiglottis obstruction requiring epiglottic surgery was lower than what was found during DISE. Sleep surgeons may consider staged epiglottic surgery in patients with epiglottis obstruction. LEVEL OF EVIDENCE: 3b Laryngoscope, 129:2658-2662, 2019.


Assuntos
Obstrução das Vias Respiratórias/cirurgia , Endoscopia/efeitos adversos , Epiglote/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Apneia Obstrutiva do Sono/cirurgia , Adulto , Obstrução das Vias Respiratórias/epidemiologia , Obstrução das Vias Respiratórias/etiologia , Estudos Transversais , Endoscopia/métodos , Epiglote/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orofaringe/fisiopatologia , Polissonografia , Complicações Pós-Operatórias/etiologia , Prevalência , Sono/efeitos dos fármacos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Língua/fisiopatologia , Resultado do Tratamento
13.
Artigo em Inglês | MEDLINE | ID: mdl-30518172

RESUMO

Objectives: Aquaporins (AQPs) are integral membrane proteins engaged in the modulation of water homeostasis, but the roles they play in chronic otitis media (COM) have not been well investigated. Accordingly, we undertook document relations between the mRNA expressions of AQPs and COM, and explored the relation between these expressions and otorrhea, which is one of the most common symptoms of COM. Methods: Levels of the mRNAs of AQP 1, 2, 3, 4, 5, 6, 8, and 10 were assayed by real-time polymerase chain reaction in inflammatory tissue samples from 81 patients with COM with or without otorrhea. Relationships between AQP mRNA levels and the presence or absence of otorrhea, the presence or absence of bacteria, hearing threshold levels, types of hearing loss, and clinical manifestations were also evaluated. Results: AQP 1, 2, 3, 4, 5, 6, 8, and 10 mRNAs were expressed in inflammatory tissues obtained from all 81 patients with COM with or without otorrhea. AQP 5 mRNA was most expressed in, followed in descending order by AQP 3, 1, 10, 6, 8, 2, and 4. There were no significant intergroup differences in terms of age, sex, duration of illness, levels of hearing loss in both ears, or incidences of conductive or sensorineural hearing loss. However, AQP 4 (P=0.035) and 6 (P=0.085) mRNA levels were significantly lower in the otorrhea group. In addition, bacteria culture positivity (P=0.014) and the incidence of sensorineural hearing loss (P=0.020) were higher in the otorrhea group. Conclusion: AQP 1, 2, 3, 4, 5, 6, 8, and 10 are involved in the development of COM. Specifically, it shows reductions in AQP 4 and 6 mRNA levels, as observed in the otorrhea group, have an effect on the clinical manifestations of COM.

14.
Artigo em Inglês | MEDLINE | ID: mdl-30545211

RESUMO

Objectives: Factors predictive of the severity of and recovery from Bell's palsy remain unclear. This study evaluated the association between neutrophil to lymphocyte ratio (NLR) and the severity of and recovery from Bell's palsy. Methods: This retrospective study included 51 patients who were hospitalized with Bell's palsy from 2015 to 2017. Degree of paralysis was assessed by House-Brackmann (H-B) grade. Patients with H-B grades 2-4 were classified as having mild to moderate palsy and patients with H-B grade 5 or 6 were classified as having severe palsy. Patients were evaluated for obesity, hypertension and diabetes mellitus, and blood tests were performed to determine NLR and platelet to lymphocyte ratio. Patients were treated with steroids and antiviral agents. H-B grade was assessed 1 week, 1 month, and 3 months after treatment. Results: NLR was significantly higher in patients with severe than with mild to moderate palsy (P=0.048). Recovery time was significantly longer in patients with high NLR than low NLR (P=0.045). Conclusion: Higher NLR in patients with Bell's palsy was associated with longer recovery time. NLR may be prognostic of recovery time in patients with Bell's palsy.

15.
Food Sci Biotechnol ; 27(3): 687-693, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30263794

RESUMO

The impact of heat type, sample type, temperature and time on the heat-induced conversion of gingerols to shogaols in ginger were studied by an UHPLC-ESI-MS/MS. Heat treatments greatly induced the conversion of gingerols to shogaols in ginger. As the temperature increased, the faster conversion of gingerols into shogaols were observed. However, the efficiency of the heat-induced conversion differed greatly with the heat types. Moist heat treatment induced significantly higher quantity of shogaols than dry heat treatment. The moist heat treatment at 120 °C for 360 min induced the highest conversion, reaching to 2991 mg 6-shogaol per kg ginger. In addition, dry-heat induced conversion was affected by the sample type. The dry-heat treatment on dried powder induced significantly higher quantity of shogaols than that on sliced fresh ginger. This represents the first systematic comparative study on the heat and sample types on the heat-induced conversion of gingerols into shogaols in ginger.

16.
J Am Heart Assoc ; 7(13)2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-29960990

RESUMO

BACKGROUND: Extracellular fluid (ECF) excess is an independent predictor of cardiovascular morbidity in patients undergoing dialysis. This study aimed to investigate the relationship between ECF status, which is affected by renal function, and coronary artery calcification (CAC), which is a marker of cardiovascular disease, in patients with chronic kidney disease (CKD). METHODS AND RESULTS: A total of 1741 patients at all stages of pre-dialysis CKD from the prospective observational cohort of CMERC-HI (Cardiovascular and Metabolic Disease Etiology Research Center-High Risk) were analyzed for the association between ECF status and CAC. ECF status was defined as extracellular water-to-total body water ratio (ECW/TBW) measured using bioelectrical impedance analysis. ECF excess was defined as ECW/TBW ≥0.390 or ≥0.400 depending on its severity. To define CAC, Agatston coronary artery calcium scores were measured. A total coronary artery calcium score of ≥400 was defined as CAC. The CKD stages were defined according to estimated glomerular filtration rate calculated using the CKD Epidemiology Collaboration equation. ECW/TBW and the proportion of ECF excess increased with progressing CKD stages. Multivariable logistic regression analyses showed that ECW/TBW was independently associated with CAC (per 0.01 increase of ECW/TBW, odds ratio 1.168, 95% confidence interval, 1.079-1.264, P<0.001). The adjusted R2 for predicting higher coronary artery calcium scores and CAC significantly improved after ECW/TBW was added to conventional factors. This association was further confirmed by net reclassification and integrated discriminant improvements, sensitivity analysis, and subgroup analysis. CONCLUSIONS: ECF status is independently associated with a high risk of CAC in patients with CKD. STUDY REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02003781.

17.
Auris Nasus Larynx ; 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29934236

RESUMO

OBJECTIVE: Sleep hygiene-related conditions are factors that affect the symptoms experienced by patients with obstructive sleep apnea (OSA). However, very few studies have investigated the association between sleep hygiene and sleep symptoms, especially in patients with mild or moderate OSA. This study evaluated the relationship between factors related to sleep hygiene and clinical symptoms in patients with mild to moderate OSA. METHODS: One hundred and seventy-four patients who visited the Sleep Breathing Disorder Center at a tertiary academic center to evaluate suspected OSA were included. All patients underwent standard polysomnography (PSG) and the Epworth sleepiness scale (ESS) and questionnaires related to daytime and nighttime symptoms and sleep hygiene. Medical records were reviewed for demographic, clinical, and PSG parameters. Correlation analysis between sleep hygiene-related conditions and clinical symptoms in patients with mild to moderate OSA was performed. RESULTS: The correlation analysis between the nine categories of sleep hygiene and the three categories of clinical symptoms showed that, in the case of inadequate temperature and humidity conditions, the three categories of clinical symptoms were more severe (daytime symptoms r=0.382, nighttime symptoms r=0.568, ESS score r=0.321). Drinking alcohol before sleep (daytime symptoms r=0.457, nighttime symptoms r=0.649, ESS score r=0.301) and emotional excitement or arousal (daytime symptoms r=0.378, nighttime symptoms r=0.545, ESS score r=0.341) were correlated with greater severity of each of the clinical symptoms (p<0.05). CONCLUSION: Among the factors of sleep hygiene-related conditions, inadequate temperature and humidity, drinking alcohol before sleep, and emotional excitement or arousal were associated with symptoms of mild to moderate OSA. This study supports the hypothesis that patients with mild to moderate OSA can experience symptom relief if they are trained to correct lifestyle habits to maintain adequate sleep hygiene-related conditions.

18.
Acta Otolaryngol ; 138(8): 701-707, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29607712

RESUMO

OBJECTIVE: This study analyzed the associations between measured levels of aquaporin (AQP) mRNAs and clinical manifestations in patients with various types of otitis media (OM). METHODS: AQP1, 2, 3, 4, 5, 6, 8, and 10 mRNA levels were assayed by real-time PCR from 57 patients with chronic otitis media (COM), 24 patients with cholesteatomatous otitis media (choleOM), and 82 patients with otitis media with effusion (OME). The relationships of these mRNA levels with the presence of bacteria, the type of hearing loss, and clinical manifestations of OM types were evaluated. RESULTS: All eight AQP mRNAs were expressed in inflammatory tissue, chole matrix, and effusion fluid obtained from all 163 patients with OM. The levels in OME of AQP2, 4, 6, and 10 mRNA; and the levels in choleOM of AQP1, 3, 4, and 10 mRNA were elevated significantly compared to the corresponding levels in COM (p < .05). The expression level of AQP8 mRNA did not differ among OM types. Among samples positive for bacterial culture, AQP1 mRNA was significantly higher in OME than in COM and choleOM, AQP5 mRNA was significantly lower in OME than in COM and choleOM, and AQP10 mRNA was significantly higher in OME and choleOM than in COM (p < .05). CONCLUSIONS: The levels of expression of AQP mRNA are associated with the pathophysiology of OM.


Assuntos
Aquaporinas/metabolismo , Otite Média/metabolismo , Adolescente , Adulto , Idoso , Criança , Feminino , Perda Auditiva/etiologia , Perda Auditiva/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Otite Média/complicações , Otite Média/microbiologia , RNA Mensageiro/metabolismo , Adulto Jovem
19.
Cancer Med ; 7(5): 1766-1773, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29577681

RESUMO

Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of chronic myeloid leukemia in chronic phase (CP-CML). Here, using the data from a Phase 3 study conducted in patients with newly diagnosed CP-CML, the dose-efficacy as well as dose-safety relationship analyses were performed to determine a safe and effective initial dosage regimen of radotinib. A significant positive association was detected between the starting dose of radotinib adjusted for body weight (Dose/BW) and the probability of dose-limiting toxicity (≥grade 3 hematologic and nonhematologic toxicity) (P = 0.003). In contrast, a significant inverse association was discovered between Dose/BW and the probability of major molecular response (BCR-ABL1/ABL1 ≤ 0.1%) when controlled for sex (P = 0.033). Moreover, frequent dose interruptions and reductions secondary to radotinib toxicities occurred in the Phase 3 study, resulting in nearly half (44%) of patients receiving a reduced dose at a 12-month follow-up. In conclusion, the results of this study demonstrate the need for initial radotinib dose attenuation to improve the long-term efficacy and safety of radotinib. Hence, the authors suggest a new upfront radotinib dose of 400 mg once daily be tested in patients with newly diagnosed CP-CML.

20.
Molecules ; 23(4)2018 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-29565818

RESUMO

Otitis media (OM) is a group of inflammatory diseases of the middle ear (ME), regardless of cause or pathological mechanism. Among the molecular biological studies assessing the pathology of OM are investigations into the expression of C-type lectin receptors (CLR) in the ME and Eustachian tube (ET). To date, nine studies have evaluated CLR expression in the ME and ET. The expression of individual CLRs in mammalian ME and ET varies by species and model of OM. Assessments have shown that the patterns of CLR expression in the ME and ET vary; that CLR expression may vary by type of OM; and that the distribution and levels of expression of CLRs may depend on the presence or absence of inflammation, with variations even within the same species and same tissue. Infection of the ME and ET with various pathogens is a common cause of all types of OM, with host responses to pathogens mediated initially by the innate immune system. CLRs are important factors in the innate immune system because they act as both adhesion molecules and as pathogen recognition receptors. The expression of CLRs in OM tissues suggests that CLRs are associated with the pathogenesis of various types of OM.


Assuntos
Orelha Média/metabolismo , Tuba Auditiva/metabolismo , Lectinas Tipo C/metabolismo , Otite Média/metabolismo , Animais , Humanos
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