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Zhao D.,Zhejiang University | Zhao D.,Capital Medical University | Li Y.,Capital Medical University | Li Y.,University of California at San Diego | And 4 more authors.
Otolaryngology - Head and Neck Surgery (United States) | Year: 2017

Objective This study aims to evaluate the combination of genioglossus (GG) activity and anatomical characteristics in predicting outcomes of velopharyngeal surgery in patients with obstructive sleep apnea (OSA). Study Design Case series with planned data collection. Setting Sleep medical center. Subjects and Methods Forty patients with OSA underwent overnight polysomnography with synchronous genioglossus electromyography (GGEMG) using intraoral electrodes. The upper airway anatomy was evaluated by 3-dimensional computed tomography in patients with OSA. All patients received the same type of velopharyngeal surgery, consisting of revised uvulopalatopharyngoplasty with uvula preservation and concurrent transpalatal advancement pharyngoplasty. We followed up all patients using polysomnography for at least 3 months postoperatively. Results Twenty-five patients (62.50%) were responders, and 15 patients (37.50%) were nonresponders. The decreased apnea-hypopnea index was significantly positively correlated to the sleep onset GGEMG (P =.006) but was negatively correlated to the change in GGEMG (P =.013) and tonic GGEMG (P =.018). Multiple regression analysis revealed that the minimal cross-sectional airway area at the velopharynx (VmCSA) (odds ratio [OR], 1.760; P =.019) and the sleep onset GGEMG (OR, 0.322; P =.043) were significant predictors for surgical outcomes. Combined the two predictors, the area under the ROC curve was 0.901 (OR, 0.789; P =.001) for surgical success, was more valuable than any one predictor. The area under the ROC curve with GGEMG was 0.843, VmCSA was 0.848. Conclusions The combination of sleep onset GGEMG and VmCSA can predict the outcome of velopharyngeal surgery in patients with OSA. © Official journal of the American Academy of Otolaryngology-Head and Neck Surgery Foundation.

PubMed | Capital Medical University, Beijing Tsinghua Chang Gung Hospital and Peking University
Type: Journal Article | Journal: Acta oto-laryngologica | Year: 2016

Variability of GGEMG at sleep onset is associated with apnea severity in OSA patients. At sleep onset, a lower decline in GGEMG might suggest a more severe OSA.The goal of this study was to evaluate genioglossus (GG) activation in the Chinese population at early sleep onset, and clarify the relationship of GG activation and the apnea severity in patients with Obstructive Sleep Apnea (OSA).Thirty-five OSA patients and 10 normal controls underwent overnight polysomnography with synchronous genioglossus electromyography (GGEMG) using intra-oral electrodes. The upper airway (UA) anatomy was evaluated by three-dimensional computer tomography (3D-CT) in all subjects.The average GGEMG and tonic GGEMG were higher in the apnea patients than in the normal controls during wakefulness and early sleep onset period (three breaths) (p<0.01). Eight OSA patients had increased GGEMG at sleep onset and 27 patients had decreased GGEMG values. Between the two groups, there were significant differences in the apnea-hypopnea index (AHI), minimal cross-sectional airway area (mCAS) and minimal lateral airway dimension (mLAT) at velopharynx (p<0.05). The change in GGEMG, phasic GGEMG and tonic GGEMG from awake to sleep showed positive correlations with AHI and negative correlations with velopharynx (mLAT and mCAS) (p<0.05).

PubMed | Beijing University of Technology, Shanghai JiaoTong University, Peking University and Beijing Tsinghua Chang Gung Hospital
Type: Journal Article | Journal: Chinese medical journal | Year: 2016

Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI.Forty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices.Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 666 ng/ml, 22920 1188 ng/ml in the aqueous humor and 884 78 ng/ml, 2556 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups.The corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.

Zhao J.-X.,Chinese PLA General Hospital | Su X.-Y.,Chinese PLA General Hospital | Su X.-Y.,Affiliated Hospital of the Academy of Military Medical science | Zhao Z.,Chinese PLA General Hospital | And 6 more authors.
International Journal of Computer Assisted Radiology and Surgery | Year: 2015

Purpose: To establish a new reliable approach for measuring proximal femoral anatomical parameters and determining the optimal entry point of the antegrade intramedullary (IM) nailing. Methods: A new method for measuring the proximal femoral anatomy and locating the optimal entry point for the antegrade nailing was developed using Mimics and 3-Matic softwares (Materialise, Haasrode, Belgium). After verifying the reliability of the measurement method using 15 pairs of the femoral models by the intraclass correlation coefficient, the anatomical parameters of 200 Chinese femurs were measured, and statistical analyses were performed to compare the proximal femoral anatomical parameters between different genders or lateralities and determine the most relevant factors of the optimal entry point. Results: Reliability study showed that both intraobserver reliability and interobserver reliability of the current measurement approach were excellent. After independent samples $$T$$T-test, the proximal femoral anatomical parameters were shown significant difference between genders. Stepwise regression statistical analyses showed that the most relevant factors of the distances between the optimal entry point and the femoral head centre, the femoral neck axis and the tip of the greater trochanter were the 3D femoral neck-shaft angle (Pearson’s $$r = -0.621$$r=-0.621; the model’s $$P < 0.001,\, R^{2}= 0.437$$P<0.001,R2=0.437), the femoral radius (Pearson’s $$r = -0.413$$r=-0.413; the model’s $$P < 0.001,\, R^{2}= 0.254$$P<0.001,R2=0.254) and the femoral length (Pearson’s r = 0.316; the model’s $$P < 0.001,\, R^{2} = 0.154$$P<0.001,R2=0.154), respectively. Conclusions: The current study provided a new and reliable measurement approach to evaluating the anatomical morphology of the proximal femur and revealed the most influential factors on the locations of the simulated optimal entry point for the proximal femoral antegrade IM nailing. Furthermore, this study was useful for establishing methodological basis for future researches and developments of the custom-made IM nailing and affiliated surgical instruments. © 2015, CARS.

PubMed | Chinese Institute of Clinical Medicine, Rishena Technology Development Co., Shandong University, China Japan Friendship Hospital and Beijing Tsinghua Chang Gung Hospital
Type: Journal Article | Journal: Neuromodulation : journal of the International Neuromodulation Society | Year: 2016

Colonic electrical stimulation (CES) may have a therapeutic potential for slow transit constipation (STC). This study aimed to evaluate the effects of implantable CES on gastrointestinal transit and defecation, and explore its mechanisms in a canine STC model.Two pairs of electrodes were implanted in each of the proximal colon and rectosigmoid junction (RSJ). Parameters were individualized according to the symptoms of the stimulated dogs. In the STC model, gastrointestinal transit and defecation were assessed to evaluate the effects of double-site CES, and of double-site CES combined with atropine or N-nitro-L-arginine (L-NNA) in a crossover design.Individualized parameters varied among the animals. The CES significantly shortened gastrointestinal transit time (GITT) and colonic transit time (CTT) compared with sham CES (p = 0.001 and p < 0.001, respectively). Compared with sham CES, the CES also exhibited significantly higher stool frequency and stool consistency score (p = 0.018 and p = 0.001, respectively). Co-treatment with atropine or L-NNA blocked the effects of CES on GITT, CTT, and stool consistency. The stool frequency increased by CES, however, only reduced by co-treatment with L-NNA.This double-site implantable CES can improve the gastrointestinal transit and defecation in a canine STC model, possibly by activating the cholinergic and nitrergic pathways. The CES mode used in this study may be proven feasible in treating STC.

PubMed | Chinese PLA General Hospital, Beijing Tsinghua Chang Gung Hospital, Xinjiang Medical University and Peking Union Medical College
Type: Journal Article | Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons | Year: 2016

The role of autotransplantation in end-stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15-case experience and propose selection criteria for autotransplantation. All patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706g (380-1000g); operative time was 15.5 hours (11.5-20.5 hours); and anhepatic time was 283.8 minutes (180-435min). Postoperative hospital stay was 32.3 days (12-60 days). Postoperative complication Clavien-Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow-up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end-stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.

PubMed | Saint Louis University, Peking Union Medical College, Tianjin Medical University, Beijing Tsinghua Chang Gung Hospital and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Pulse oximetry, which noninvasively detects the blood flow of peripheral tissue, has achieved widespread clinical use. We have noticed that the better the quality of cardiopulmonary resuscitation (CPR), the better the appearance of pulse oximetry plethysmographic waveform (POP). We investigated whether the area under the curve (AUC) and/or the amplitude (Amp) of POP could be used to monitor the quality of CPR.Prospective, randomized controlled study.Animal experimental center in Peking Union Medical Collage Hospital, Beijing, China.Healthy 3-month-old male domestic swine.34 local pigs were enrolled in this study. After 4 minutes of untreated ventricular fibrillation, animals were randomly assigned into two resuscitation groups: a low quality group (with a compression depth of 3cm) and a high quality group (with a depth of 5cm). All treatments between the two groups were identical except for the depth of chest compressions. Hemodynamic parameters [coronary perfusion pressure (CPP), partial pressure of end-tidal carbon dioxide (PETCO2)] as well as AUC and Amp of POP were all collected and analyzed.There were statistical differences between the high quality group and the low quality group in AUC, Amp, CPP and PETCO2 during CPR (P<0.05). AUC, Amp and CPP were positively correlated with PETCO2, respectively (P<0.01). There was no statistical difference between the heart rate calculated according to the POP (FCPR) and the frequency of mechanical CPR at the 3rd minute of CPR. The FCPR was lower than the frequency of mechanical CPR at the 6th and the 9th minute of CPR.Both the AUC and Amp of POP correlated well with CPP and PETCO2 in animal models. The frequency of POP closely matched the CPR heart rate. AUC and Amp of POP might be potential noninvasive quality monitoring markers for CPR.

PubMed | Chinese Institute of Clinical Medicine, Rishena Technology Development Co., Shandong University, China Japan Friendship Hospital and Beijing Tsinghua Chang Gung Hospital
Type: Journal Article | Journal: International journal of colorectal disease | Year: 2016

This study aimed to compare the effects of colonic electrical stimulation (CES) on gastrointestinal transit time (GITT), energy consumption, stool frequency, stool consistency, and food intake using different individual parameter patterns and stimulation sites.Eight beagle dogs underwent surgery and CES. First, CES was conducted to determine the individual parameters with different pulse configurations, based on symptoms. Second, influences on energy consumption and GITT were compared between CES sessions with different pulse configurations. Third, GITT, stool frequency, stool consistency, and food intake were compared to assess the effects of CES at different stimulation sites.The individual parameters varied greatly among the dogs. In proximal colon electrical stimulation (PCES) and rectosigmoid colon electrical stimulation (RCES), energy consumption was lower with the constant pulse width mode than with the constant pulse amplitude mode (p=0.012 and p=0.018, respectively). There was no statistical difference between the two pulse configurations in GITT assessment. The PCES, RCES, and sequential CES sessions significantly accelerated GITT compared to sham stimulation. There was no statistical difference in GITT between PCES, RCES, and sequential CES sessions. Compared to sham CES session, RCES and sequential CES sessions exhibited significant higher stool frequency (p<0.001 and p=0.001, respectively), and PCES and RCES sessions inhibited food intake (p=0.003 and p=0.002, respectively).Constant pulse width mode is an appropriate pulse configuration for individual CES. At different stimulation sites, CES may exert different effects on stool frequency and food intake. This study provides an experimental basis for the clinical application of CES.

Chen R.,Peking Union Medical College | Wang H.,Beijing Tsinghua Chang Gung Hospital | Shi J.,Hoffmann-La Roche | Hu P.,Peking Union Medical College
International Journal of Clinical Pharmacology and Therapeutics | Year: 2016

Purpose: CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to evaluate the appropriate and precise time points for phenotyping after single-dose and multiple-dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. Methods: This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRS) from AUC∞ after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. Results: In the single-dose part of the study, statistically significant correlations were found between MRDM/DX from AUC∞ and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple-dose part, statistically significant correlations were found between MRDM/DX from AUC0-12hon day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. Conclusion: MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6. © 2016 Dustri-Verlag Dr. K. Feistle.

PubMed | University of Manchester, Hoffmann-La Roche, Beijing Tsinghua Chang Gung Hospital and Peking Union Medical College
Type: | Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences | Year: 2016

Determining metabolic ratio from single-point plasma is potentially a good phenotyping method of CYP2D6 to reduce the required time interval and increase the reliability of data. It is difficult to conduct large sample size clinical trials to evaluate this phenotyping method for multiple plasma points. A physiologically based pharmacokinetic (PBPK) model can be developed to do simulations based on the large virtual Chinese population and evaluate single-point plasma phenotyping method of CYP2D6.Pharmacokinetic data of dextromethorphan (DM) and its metabolite dextrorphan (DX) after oral administration were used for model development. The SimCYP model incorporating Chinese demographic, physiological, and enzyme data was used to simulate DM and DX pharmacokinetics in different phenotype groups.The ratios of the simulated to the observed mean AUC and Cmax of DM were 1.01 and 0.81 for extensive metabolizers (EMs), 0.90 and 0.81 for intermediate metabolizers (IMs), and 1.12 and 0.84 for poor metabolizers (PMs). The ratios of the simulated to the observed mean AUC and Cmax of DX were 1.12 and 0.89 for EMs, 0.66 and 0.62 for IMs. All ratios were within the predefined criterion of 0.5-2. The simulations of DM and DX pharmacokinetic profiles in 1000 virtual Chinese subjects with reported frequencies of different phenotypes indicated that statistically significant correlations were found between metabolic ratio of DM to DX (MRDM/DX) from AUC and from single-point plasma from 1 to 30h (all p-values <0.001).MRDM/DX from single-point plasma from 1 to 30h after the administration of 30mg controlled-release DM could predict the MRDM/DX from AUC well and could be used as the phenotyping method of CYP2D6 for EMs, IMs, and PMs.

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