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Objective: To investigate the correlation between hematocrit (HCT) and cardiovascular events in peritoneal dialysis (PD) patients. Methods: Patients undergoing maintenance PD in the PD center of Guizhou Provincial People's Hospital from March 19, 2012 to July 9, 2020 were included. Demographic, baseline clinical and laboratory data of the patients were collected and patients were followed up until April 8, 2022. The primary endpoint was the first occurrence of a cardiovascular event. According to the tertiles of baseline HCT, the patients were divided into group Q1 (HCT≤26.6%), group Q2 (HCT>26.6%-32.4%), and group Q3 (HCT>32.4%). Laboratory indexes and cardiovascular events were compared among the three groups. Kaplan-Meier survival curve, Cox regression analysis and sensitivity analysis were used to analyze the effect of HCT on cardiovascular outcomes. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of HCT for cardiovascular events in PD patients. Results: A total of 860 PD patients were included, including 494 males (57.4%) and 366 females (42.6%), with a mean age of (41.5±15.0) years. There were 287 cases in group Q1, 289 cases in group Q2, and 284 cases in group Q3, respectively. A total of 265 (30.8%) patients experienced first cardiovascular events during the follow-up period. The incidence of cardiovascular events in groups Q1, Q2 and Q3 was 36.2% (104/287), 34.3% (99/289), and 21.8% (62/284), respectively, with a statistically significant difference (P<0.001). The incidence of cardiovascular events decreased with the increase of HCT. Multivariate Cox proportional hazards regression model analysis showed that decreased HCT was a risk factor for cardiovascular events. Compared with group Q3, the risk of cardiovascular events in group Q1 increased by 50.7% (group Q2: HR=1.444, 95%CI: 1.029-2.028, P=0.034; group Q1: HR=1.570, 95%CI: 1.096-2.250, P=0.014). In the sensitivity analysis, using kidney transplantation as the competition event, the risk of cardiovascular events was lower in group Q3 than that in group Q1 (subdistributional HR=1.413, 95%CI: 1.006-1.990, P=0.046). Kaplan-Meier survival curve showed that compared with the other two groups, the cardiovascular events-free survival rate of patients in group Q1 was significantly lower (log-rank χ2=9.722, P=0.008). ROC analysis showed that the area under the curve (AUC) of HCT for predicting cardiovascular events in PD patients was 0.583 (95%CI: 0.542-0.623, P<0.001), with the sensitivity of 40.6% and the specificity of 75.1%. Conclusion: Low-level HCT is associated with an increased risk of the first cardiovascular event in PD patients.
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Doenças Cardiovasculares , Diálise Peritoneal , Humanos , Masculino , Feminino , Estudos Retrospectivos , Doenças Cardiovasculares/etiologia , Adulto , Pessoa de Meia-Idade , Hematócrito , Fatores de Risco , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Endoscopic sinus surgery (ESS) is an effective and safe treatment modality for medically recalcitrant chronic rhinosinusitis (CRS) in the paediatric population, especially in older children or those with nasal polyposis (CRSwNP). We aimed to elucidate the inflammatory pattern and clinical characteristics of CRSwNP related to revision surgery after ESS in a paediatric population. METHODS: We retrospectively enrolled 146 patients with bilateral CRSwNP. Twenty-two patients had recurrent nasal polyps that required revision surgery. The clinical characteristics, computed tomography (CT) features, tissue eosinophil count, and immunoactivity of signature cytokines in the two groups were analysed. RESULTS: Tissue eosinophil infiltration and immunoreactivity of eosinophilic cationic protein and IL-5 in the sinus mucosa were higher in patients that required revision surgery. The revision surgery group was significantly younger and had positive aeroallergen test results, higher total Lund-Mackay scores, and ethmoid/maxillary sinus ratio on CT images than those without revision surgery. A nomogram was developed to predict the probability of the requirement of revision surgery according to the logistic regression analysis results. CONCLUSIONS: We developed a nomogram model using clinical characteristics, tissue eosinophilia, and CT features for the preoperative identification of patients vulnerable to revision surgery in paediatric CRSwNP. This could help clinicians predict the probability of recurrence and perform intensive postoperative adjunct therapy and follow-up.
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Eosinofilia , Pólipos Nasais , Rinite , Sinusite , Humanos , Criança , Eosinófilos , Estudos Retrospectivos , Reoperação , Pólipos Nasais/cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Doença Crônica , Tomografia Computadorizada por Raios X , TomografiaRESUMO
BACKGROUND: Sphenoid sinus fungus ball (SSFB) is a rare entity and usually presents with non-specific symptoms. SSFB could potentially lead to serious orbital and intracranial complications. Computed tomography (CT) scan is usually the first imaging test of the diagnostic workup in patients with specific clinical symptoms. This study aimed to compare the clinical characteristics and CT features between SSFB and unilateral (non-fungus ball) chronic sphenoid rhinosinusitis (USRS) and help differentiate between these two most common inflammatory diseases of the sphenoid sinus. METHODS: By retrospective database review, 66 patients with a histopathologic diagnosis of isolated SSFB were recruited for analysis. Fifty-four patients who underwent endoscopic sinus surgery with clinical and histopathological diagnoses of USRS were enrolled as the control group. Clinical characteristics and CT features were evaluated. RESULTS: Headache, rhinorrhoea, nasal obstruction, postnasal dripping, and hyposmia were the most common symptoms in both groups. In the univariate analysis, older age, lower white blood cell counts, irregular surface, bony dehiscence, lateral wall sclerosis, and intralesional hyperdensity (IH) were significant predictors for SSFB. Older age, irregular surface, and IH remained statistically significant in the multivariate analysis. Based on the results of the regression analysis, a nomogram for predicting the probability of SSFB was plotted. CONCLUSIONS: We developed a nomogram model as a novel preoperative diagnostic tool for identifying SSFB according to the predictors both in clinical characteristics and on CT features. This could help the clinicians in predicting the probability of SSFB, to reduce ineffective or delayed treatment and occurrence of complications.
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Sinusite , Seio Esfenoidal , Humanos , Seio Esfenoidal/diagnóstico por imagem , Estudos Retrospectivos , Nomogramas , Sinusite/cirurgia , EndoscopiaRESUMO
BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.
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Distúrbios do Sono por Sonolência Excessiva , Obstrução Nasal , Doenças Nasais , Humanos , Doenças Nasais/complicações , Doenças Nasais/cirurgia , Doenças Nasais/diagnóstico , Qualidade de Vida , Sonolência , Obstrução Nasal/etiologia , Obstrução Nasal/cirurgia , Obstrução Nasal/psicologia , Síndrome , NarizRESUMO
The clinical data of maintenance hemodialysis (MHD) patients from twenty hemodialysis centers in Guizhou province from June to September 2020 were collected by cross-sectional study. The patients were divided into AFD group and non-AFD group according to whether AFD had occurred. LTI was measured by body composition monitor. The results showed that the incidence of AFD in 2 781 MHD patients was 30.0% (835/2 781). Median LTI level was 15.2 (13.2, 17.5) kg/m2. The LTI level in the AFD group was higher than that in the non-AFD group (P < 0.05). According to the tertiles of LTI, low LTI group (LTI ≤ 13.9 kg/m2) had the highest incidence of AFD (35.5%, 334/940), and the high LTI group had the lowest incidence of AFD (26.3%, 241/916), and the difference among the three groups was statistically significant (χ2=20.182,P < 0.001). Multivariate logistic regression analysis showed that low LTI group as the reference, the risk of AFD in moderate LTI group (13.9 kg/m2 < LTI ≤ 16.6 kg/m2) and high LTI group were associated with the 20.0% (OR=0.800, 95% CI 0.650-0.986, P=0.036) and 22.8% (OR=0.772, 95% CI 0.616-0.966, P=0.024) decrease, respectively. These results suggest that low LTI level is independently associated with an increased risk of AFD in MHD patients.
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Composição Corporal , Diálise Renal , Humanos , Estudos Transversais , Diálise Renal/efeitos adversosRESUMO
Polyethylene terephthalate (PET) artificial ligaments offer an unlimited source of ligaments without donor-site-related morbidity and with good mechanical properties for a rapid return to sporting activities. Developing PET artificial ligaments with excellent ligamentisation and ligament-bone healing is still a considerable challenge. This study aimed to investigate the effects of the profiled PET/collagen/calcium phosphate (PET/C/CaP) ligament upon cell growth, ligamentisation and ligament-bone healing in vitro and in vivo. Profiled PET/C/CaP filaments were made by melt-spinning process with 2 % CaP hybrid spinning and collagen coating. Rat mesenchymal stem cells (MSCs) were cultured on the profiled PET/C filaments for cytotoxicity, viability, scanning electron microscopy (SEM) and ligament-related gene expression analysis. MSCs' osteogenic capacity on the profiled PET/CaP filaments was identified by detecting osteogenic gene expression and alizarin red S staining. For in vivo verification, an animal study was performed to evaluate the effect of the profiled PET/C/CaP ligament in a rabbit knee medial collateral ligament reinforcement reconstruction model. The graft ligamentisation and bone formation were investigated by SEM, histology, microcomputed tomography and mechanical tests. The profiled PET/C filaments enhanced MSC proliferation and ligament-related gene expression. Furthermore, they enhanced osteogenic gene expression, alkaline phosphatase activity and mineralisation of MSCs. The in vivo study indicated that the profiled PET/C/CaP ligament enhanced ligamentous matrix remodelling and bone formation. Therefore, their use is an effective strategy for promoting MSCs' ligamentous and osteogenic potential in vitro and enhancing ligamentous matrix remodelling and bone formation in vivo.
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Osteogênese , Polietilenotereftalatos , Animais , Fosfatos de Cálcio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Colágeno/metabolismo , Colágeno/farmacologia , Polietilenotereftalatos/farmacologia , Coelhos , Ratos , Microtomografia por Raio-XRESUMO
BACKGROUND: Whether endoscopic surgery for sellar/parasellar disease causes significant deficits in olfactory function remains unclear. We aimed to systematically review the olfactory outcomes in such settings based on the evidence up to date. METHODS: PubMed, EMBASE, and CENTRAL were searched through February 1, 2021. Included studies were limited to endoscopic surgery for sellar/parasellar disease with follow-up olfactory function measured by standardized olfactory testing methods or subjective assessment. The primary outcome was the change in olfactory function after surgery assessed by standardized olfactory testing methods. The secondary outcome was the change in subjective olfactory function. Random-effects model was used in obtaining combine effects. Study quality was assessed using the Newcastleâ"Ottawa scale. Sensitivity analysis was carried out using the leave-one-out approach, and publication bias was assessed using Egger's test. RESULTS: The results show no significant difference in olfaction assessed by standardized olfactory testing methods at 1-3 months post-surgery (880 patients in 16 studies) or at 6-12 months post-surgery (1320 patients in 16 studies) compared to pre-surgery, whereas a significantly lower subjective olfaction at 3 months was observed. In addition, the lack of significant change in olfaction as assessed by standardized olfactory testing methods was observed regardless of whether patients were treated with or without the nasoseptal flap (NSF) harvesting. Heterogeneity and publication bias were observed, whereas sensitivity analysis showed the meta-analysis results are robust. CONCLUSION: The findings of this updated systematic review and meta-analysis support the conclusion that endoscopic surgery for sellar and parasellar pathology may pose no greater risk of olfactory dysfunction. In addition, the current evidence does not support there is an increased risk of diminished olfaction among patients treated with NSF during surgery.
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Transtornos do Olfato , Olfato , Humanos , Transtornos do Olfato/etiologia , Resultado do Tratamento , Endoscopia/métodos , Retalhos CirúrgicosRESUMO
PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.
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Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas , Fatores de Crescimento de Fibroblastos/sangue , Peptídeo Natriurético Encefálico/sangue , Proteínas de Neoplasias/sangue , Fragmentos de Peptídeos/sangue , Proteoglicanas/sangue , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Biomarcadores/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Feminino , Humanos , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Patients with obstructive sleep apnea (OSA) have elevated nasopharyngeal resistances due to increased turbulent airflow. The study aims to investigate the effect of oropharyngeal surgery on nasal resistance in patients with various severity levels of OSA. METHODOLOGY: Patients with greater or equal to 5 events hourly on the apnea-hypopnea index (AHI) were enrolled. Patients with retropalatal obstruction underwent uvulopalatopharyngoplasty, while patients with concurrent retrolingual obstruction under- went uvulopalatopharyngoplasty (UPPP) plus tongue base suspension. Before surgery and after surgery, subjective outcomes were assessed using a visual analog scale (VAS), and objective outcomes were assessed using overnight polysomnography and rhinomanometry. The limitation of the study was that UPPP instead of expansion sphincter pharyngoplasty was performed in this study. RESULTS: Sixty-two patients were enrolled, while 30 patients were diagnosed as mild OSA (group Mild) and 32 patients were mo- derate-severe OSA (group MS). The preoperative VAS of nasal obstruction in recumbency during sleep was significantly reduced after surgery in group MS. However, no significant differences between preoperative and postoperative VAS were found in group Mild. The postoperative anterior and posterior total nasal resistances (TNR) in sitting and supine positions were not significantly different from those before surgery in group. In contrast, the postoperative posterior TNR in supine position was 0.292±0.301(Pa/ cm3/s), compared with 0.425±0.343(Pa/cm3/s) preoperatively. CONCLUSIONS: Oropharyngeal surgery improves nasal obstruction during sleep and lowers the supine TNR measured in poste- rior rhinomanometry in patients with moderate-severe OSA. Oropharyngeal surgery is a possible treatment for postural nasal obstruction in patients with moderate-severe OSA.
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Apneia Obstrutiva do Sono , Humanos , Faringe/cirurgia , Polissonografia , Apneia Obstrutiva do Sono/cirurgia , Resultado do Tratamento , ÚvulaRESUMO
AIMS: To study the association between number and positions of mutations with MICs of fluoroquinolone non-susceptible Haemophilus influenzae. METHODS AND RESULTS: More than 40% of 48 H. influenzae isolated from nursing home residents were not susceptible to fluoroquinolone. Amino acid changes in the quinolone resistance determining regions, and correlation with MICs and inhibition zone diameters were analysed. All isolates with reduced susceptibility to fluoroquinolones (MIC ≥0·125 µg ml-1 ) had at least one mutation in gyrA at position 84 and were resistant to nalidixic acid. Compared to isolates with reduced susceptibility, resistant isolates were associated with mutations in gyrA at positions 88 and 134, and in parC at position 88 (P < 0·001). Inhibition zone diameter for nalidixic acid disk ≥23 mm may detect susceptible isolates. CONCLUSIONS: Reduced susceptibility to fluoroquinolones was associated with mutations at position 84 in gyrA. A further increase in fluoroquinolone MIC was associated with mutations in gyrA at positions 88 and 134, and parC at position 88. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to limited resistant H. influenzae strains, prior studies on association between positions of mutations and fluoroquinolone MICs were inconclusive. The comparison of mutations between isolates with susceptibility, reduced susceptibility and high resistance supported the importance of the present study.
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Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/farmacologia , Haemophilus influenzae/efeitos dos fármacos , DNA Girase/genética , DNA Topoisomerase IV/genética , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/genética , Haemophilus influenzae/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Mutação , Casas de Saúde , TaiwanRESUMO
BACKGROUND: Empty nose syndrome (ENS) is a debilitating disorder characterised by paradoxical nasal obstruction after excessive surgical excision of nasal tissues. ENS negatively impacts the quality of life (QOL) and psychological status of patients. This study aimed to determine the associations among disease-specific QOL impairments and the severity of anxiety and depression before and after surgery in ENS patients. METHODS: A total of 68 ENS patients were prospectively recruited and underwent submucosal Medpor implantation. QOL impairments and the severity of anxiety and depression were evaluated using the Sinonasal Outcome Test-25 (SNOT-25), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) 1 day before and 6 months after surgery. RESULTS: The BDI-II and BAI scores were significantly associated with the total score and ear/facial symptoms, psychological dysfunction, sleep dysfunction, and empty nose symptoms domains of the SNOT-25. Surgery improved disease-specific and psychological symptoms. Post-operative changes in the BDI-II score were correlated with changes in the total score and sleep dysfunction and empty nose symptoms domains of the SNOT-25. A SNOT-25 total score of greater than 60, sleep dysfunction domain score of greater than 18, and empty nose symptoms domain score of greater than 14 were good predictors of moderate-to-severe depression. CONCLUSIONS: ENS symptoms are associated with psychological burden and could be good predictors of moderate-to-severe depression. Targeted symptom improvement could reduce the psychological burden.
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Depressão/diagnóstico , Obstrução Nasal/diagnóstico , Obstrução Nasal/psicologia , Procedimentos Cirúrgicos Nasais/efeitos adversos , Ansiedade/diagnóstico , Ansiedade/etiologia , Depressão/etiologia , Humanos , Obstrução Nasal/etiologia , Doenças Nasais/etiologia , Doenças Nasais/cirurgia , Qualidade de Vida , Teste de Desfecho Sinonasal , SíndromeRESUMO
OBJECTIVE: We sought to develop a model to calculate the likelihood of vaginal delivery in nulliparous women undergoing induction at term. STUDY DESIGN: We obtained data from the Consortium on Safe Labor by including nulliparous women with term singleton pregnancies undergoing induction of labor at term. Women with contraindications for vaginal delivery were excluded. A stepwise logistic regression analysis was used to identify the predictors associated with vaginal delivery by considering maternal characteristics and comorbidities and fetal conditions. The receiver operating characteristic curve, with an area under the curve (AUC) was used to assess the accuracy of the model. RESULTS: Of 10,591 nulliparous women who underwent induction of labor, 8,202 (77.4%) women had vaginal delivery. Our model identified maternal age, gestational age at delivery, race, maternal height, prepregnancy weight, gestational weight gain, cervical exam on admission (dilation, effacement, and station), chronic hypertension, gestational diabetes, pregestational diabetes, and abruption as significant predictors for successful vaginal delivery. The overall predictive ability of the final model, as measured by the AUC was 0.759 (95% confidence interval, 0.749-0.770). CONCLUSION: We identified independent risk factors that can be used to predict vaginal delivery among nulliparas undergoing induction at term. Our predictor provides women with additional information when considering induction.
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Cesárea/estatística & dados numéricos , Trabalho de Parto Induzido/estatística & dados numéricos , Paridade , Adulto , Feminino , Humanos , Trabalho de Parto Induzido/efeitos adversos , Modelos Logísticos , Nomogramas , Gravidez , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Nascimento a Termo , Falha de Tratamento , Estados Unidos , Adulto JovemRESUMO
Objective: To investigate the relationship between intake volume of carbohydrates solution (CHO) and gastric emptying time in termed parturient, thus to optimize fasting time before anesthesia. Methods: This study was a prospective study. From May to July in 2016, a total of 100 termed parturients in Huangyan Hospital of Wenzhou Medical University, were divided into four groups equally by means of random number table: D1 (200 ml), D2 (300 ml), D3 (400 ml) and D4 (500 ml), based on the different intake volume of 12.5% CHO. All the parturients had been fasted preoperatively before the treatment of oral CHO. The cross-sectional area of gastric antrum (CSA) was measured with an ultrasound machine at baseline (T(0)), 3 min (T(1)), 30 min (T(2)), 60 min (T(3)), 90 min (T(4)), 120 min (T(5)) and 150 min (T(6)) after oral CHO, respectively. Gastric emptying in this study is defined as CSA at any time point is equal to or less than that at T(0). Results: Measurement was failed in eight parturients because of poor imaging quality, two each in D1 and D2 group and four in D4 group. The cubic curve was the best model for gastric emptying among several candidate models estimated with SPSS software, with R(2)>0.9 in all groups. Both the cubic curve and Kaplan-Meier curve indicated that gastric emptying time was prolonged as intake volume increased. Gastric emptying times in D1, D2, D3 and D4 were (76.96±17.69), (96.52±20.14), (109.20±14.70) and (122.86±16.17) min respectively, the difference was significant (F=50.471, P<0.001). All parturients in D1, D2 and D3 group had been in the status of gastric emptying 120 min after oral CHO, and all parturients in D4 group had been in the status of gastric emptying either 150 min after oral CHO. Conclusion: Gastric emptying time will be within two hours when 400 ml or less oral CHO is taken by termed parturient, and it will be prolonged as intake volume increases.
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Esvaziamento Gástrico , Carboidratos , Jejum , Estudos Prospectivos , UltrassonografiaRESUMO
This longitudinal study aimed to investigate the associations between the polymorphisms of guanine nucleotide-binding protein subunit ß-3 (GNB3) C825T and metabolic disturbance in bipolar II disorder (BP-II) patients being treated with valproate (VPA). A 100 BP-II patients received a 12-week course of VPA treatment, and their body weight and metabolic indices were measured. At baseline, the GNB3 C825T polymorphisms were associated with the triglyceride level (P=0.032) in BP-II patients. During the VPA treatment course, the polymorphisms were not only associated with body mass index (BMI) and waist circumference (P-values=0.009 and 0.001, respectively), but also with total cholesterol, triglyceride, low-density lipoprotein and leptin levels (P-values=0.004, 0.002, 0.031 and 0.015, respectively). Patients with the TT genotype had a lower BMI, smaller waist circumference, and lower levels of lipids and leptin than those with the CT or CC genotypes undergoing the VPA treatment course.
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Antimaníacos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Dislipidemias/genética , Proteínas Heterotriméricas de Ligação ao GTP/genética , Obesidade/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Ácido Valproico/efeitos adversos , Adulto , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Índice de Massa Corporal , Estudos de Casos e Controles , Dislipidemias/sangue , Dislipidemias/induzido quimicamente , Dislipidemias/diagnóstico , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Leptina/sangue , Lipídeos/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/induzido quimicamente , Obesidade/diagnóstico , Fenótipo , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Circunferência da Cintura , Adulto JovemRESUMO
Screening for drug compounds that exhibit therapeutic properties in the treatment of various diseases remains a challenge even after considerable advancements in biomedical research. Here, we introduce an integrated platform that exploits gene expression compendia generated from drug-treated cell lines and primary tumor tissue to identify therapeutic candidates that can be used in the treatment of acute myeloid leukemia (AML). Our framework combines these data with patient survival information to identify potential candidates that presumably have a significant impact on AML patient survival. We use a drug regulatory score (DRS) to measure the similarity between drug-induced cell line and patient tumor gene expression profiles, and show that these computed scores are highly correlated with in vitro metrics of pharmacological activity. Furthermore, we conducted several in vivo validation experiments of our potential candidate drugs in AML mouse models to demonstrate the accuracy of our in silico predictions.
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Antineoplásicos/farmacologia , Expressão Gênica/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Transcriptoma/genética , Animais , Linhagem Celular Tumoral , Descoberta de Drogas/métodos , Células HL-60 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
OBJECTIVES: To estimate the incidence and risk of complications associated with a fetal scalp electrode and to determine whether its application in the setting of operative vaginal delivery was associated with increased neonatal morbidity. DESIGN: Retrospective cohort study. SETTING: Twelve clinical centers with 19 hospitals across nine American Congress of Obstetricians and Gynecologists US districts. POPULATION: Women in the USA. METHODS: We evaluated 171 698 women with singleton deliveries ≥ 23 weeks of gestation in a secondary analysis of the Consortium on Safe Labor study between 2002 and 2008, after excluding conditions that precluded fetal scalp electrode application such as prelabour caesarean delivery. Secondary analysis limited to operative vaginal deliveries ≥ 34 weeks of gestation was also performed. MAIN OUTCOME MEASURES: Incidences and adjusted odds ratios with 95% confidence intervals of neonatal complications were calculated, controlling for maternal characteristics, delivery mode and pregnancy complications. RESULTS: Fetal scalp electrode was used in 37 492 (22%) of deliveries. In non-operative vaginal delivery, fetal scalp electrode was associated with increased risk of injury to scalp due to birth trauma (1.2% versus 0.9%; adjusted odds ratios 1.62; 95% confidence intervals 1.41-1.86) and cephalohaematoma (1.0% versus 0.9%; adjusted odds ratios 1.57; 95% confidence intervals 1.36-1.83). Neonatal complications were not significantly different comparing fetal scalp electrode with vacuum-assisted vaginal delivery and vacuum-assisted vaginal delivery alone or comparing fetal scalp electrode with forceps-assisted vaginal delivery and forceps-assisted vaginal delivery alone. CONCLUSIONS: We found increased neonatal morbidity with fetal scalp electrode though the absolute risk was very low. It is possible that these findings reflect an underlying indication for its use. Our findings support the use of fetal scalp electrodes when clinically indicated. TWEETABLE ABSTRACT: Neonatal risks associated with fetal scalp electrode use were low (injury to scalp 1.2% and cephalohaematoma 1.0%).
Assuntos
Traumatismos do Nascimento/etiologia , Cardiotocografia/instrumentação , Parto Obstétrico/efeitos adversos , Eletrodos/efeitos adversos , Couro Cabeludo/lesões , Adulto , Traumatismos do Nascimento/epidemiologia , Cardiotocografia/efeitos adversos , Parto Obstétrico/métodos , Feminino , Humanos , Incidência , Recém-Nascido , Razão de Chances , Gravidez , Estudos Retrospectivos , Couro Cabeludo/embriologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Hereditary and environmental factors have been related to the occurrence of atopic dermatitis (AD) in early childhood. However, the role of prenatal and early postnatal exposure to air pollutants has not been totally elucidated. OBJECTIVES: To evaluate the association between prenatal air pollutant exposure and occurrence of AD. METHODS: In total 24 200 infant-mother pairs were recruited to participate in the Taiwan Birth Cohort Study in 2005 using multistage stratified sampling. Medical history, including physician-diagnosed AD, was inquired by questionnaire at the infant's age of 6 months. Monthly averages of five criteria air pollutants - NO2 , CO, O3 , SO2 and PM10 - were retrieved from 66 air-quality-monitoring stations, and interpolated to all administrative districts using the kriging method. Exposure data during each of the three gestational trimesters and three months after birth were calculated for each study subject, and odds ratios (ORs) of AD occurrence were calculated by logistic regression. RESULTS: Among the participants, 16 686 mother-infant pairs were qualified for and included in the analysis. Among them, 1206 infants (7·2%) had been diagnosed as having AD before the age of 6 months, and the prevalence was higher in boys (8·3%) than in girls (6·1%). The occurrence of AD was significantly associated with CO exposure during the whole gestational period [adjusted OR (aOR) 1·37, 95% confidence interval (CI) 1·06-1·78] and the first trimester (aOR 1·51, 95% CI 1·16-1·97). We did not observe any significant association among the other air pollutants during either the whole gestational period or any period of the three trimesters and 3 months after birth. CONCLUSIONS: Our study found a relationship between AD occurrence and gestational exposure to CO, where exposure during the first trimester seemed to be the most important.
Assuntos
Poluição do Ar/efeitos adversos , Dermatite Atópica/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Prevalência , Características de Residência/estatística & dados numéricos , Distribuição por Sexo , Taiwan/epidemiologiaRESUMO
BACKGROUND: Malignancy is known to be associated with an increased mortality rate in patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, risk factors contributing to the poor prognosis of patients with SJS/TEN with malignancies remain undefined. OBJECTIVES: To explore the potential involvement of malignancy and its related factors contributing to the poor outcome of SJS/TEN, in a retrospective study. METHODS: In total 517 patients with SJS/TEN were enrolled. Forty-seven who sustained various types of malignancies were analysed for numerous malignancy-related factors, including cancer types, clinical stages and chemotherapies given or not before the onset of SJS/TEN. RESULTS: We found that the mortality rate of patients with SJS/TEN with malignancies was higher than that of patients without malignancies (32%, 15/47 vs. 8·5%, 40/470, respectively) (P < 0·001). The use of phenytoin was significantly higher in the malignancy group. The presence of hepatocellular carcinoma (80%, four of five; P < 0·001; odds ratio 43) and colorectal cancer (67%, two of three; P = 0·022; odds ratio 21·5) significantly increased the death rate of patients with SJS/TEN, whereas lung cancer and urothelial carcinoma did not. Patients who had received ongoing or recent chemotherapy showed higher mortality than those without chemotherapy (P = 0·022; odds ratio 4·95). Furthermore, among the 47 patients with SJS/TEN with malignancies, lower serum albumin, haemoglobin and platelet count were detected in the deceased patients than in the surviving patients before the onset of SJS/TEN. CONCLUSIONS: Our results suggest that several factors related to malignancies, such as specific cancer types, chemotherapy and malnutrition, may contribute to poor prognosis in patients with malignancies developing SJS/TEN.
Assuntos
Neoplasias/mortalidade , Síndrome de Stevens-Johnson/mortalidade , Antibacterianos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticonvulsivantes/efeitos adversos , Antineoplásicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sepse/mortalidade , Síndrome de Stevens-Johnson/complicações , Taiwan/epidemiologiaRESUMO
OBJECTIVE: Previous studies examining the association between genetic variations in prostaglandin pathway and risk of head and neck cancer (HNC) have only included polymorphisms in the PTGS2 (COX2) gene. This study investigated the association between genetic polymorphisms of six prostaglandin pathway genes (PGDS, PTGDS, PTGES, PTGIS, PTGS1 and PTGS2), and risk of HNC. METHODS: Interviews regarding the consumption of alcohol, betel quid, and cigarette were conducted with 222 HNC cases and 214 controls. Genotyping was performed for 48 tag and functional single-nucleotide polymorphisms (SNPs). RESULTS: Two tag SNPs of PTGIS showed a significant association with HNC risk [rs522962: log-additive odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.01-1.99 and dominant OR = 1.58, 95% CI: 1.02-2.47; rs6125671: log-additive OR = 1.49, 95% CI: 1.08-2.05 and dominant OR = 1.96, 95% CI: 1.16-3.32]. In addition, a region in PTGIS tagged by rs927068 and rs6019902 was significantly associated with risk of HNC (global P = 0.007). Finally, several SNPs interacted with betel quid and cigarette to influence the risk of HNC. CONCLUSIONS: Genetic variations in prostaglandin pathway genes are associated with risk of HNC and may modify the relationship between use of betel quid or cigarette and development of HNC.