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PubMed | Chang Gung University, Chang Gung Memorial Hospital Taoyuan, Chang Gung Memorial Hospital Keelung and National Taiwan University Hospital
Type: | Journal: Frontiers in human neuroscience | Year: 2015

Most neuroimaging research in stroke rehabilitation mainly focuses on the neural mechanisms underlying the natural history of post-stroke recovery. However, connectivity mapping from resting-state fMRI is well suited for different neurological conditions and provides a promising method to explore plastic changes for treatment-induced recovery from stroke. We examined the changes in resting-state functional connectivity (RS-FC) of the ipsilesional primary motor cortex (M1) in 10 post-acute stroke patients before and immediately after 4 weeks of robot-assisted bilateral arm therapy (RBAT). Motor performance, functional use of the affected arm, and daily function improved in all participants. Reduced interhemispheric RS-FC between the ipsilesional and contralesional M1 (M1-M1) and the contralesional-lateralized connections were noted before treatment. In contrast, greater M1-M1 functional connectivity and disturbed resting-state networks were observed after RBAT relative to pre-treatment. Increased changes in M1-M1 RS-FC after RBAT were coupled with better motor and functional improvements. Mediation analysis showed the pre-to-post difference in M1-M1 RS-FC was a significant mediator for the relationship between motor and functional recovery. These results show neuroplastic changes and functional recoveries induced by RBAT in post-acute stroke survivors and suggest that interhemispheric functional connectivity in the motor cortex may be a neurobiological marker for recovery after stroke rehabilitation.


PubMed | Chang Gung University, Changhua Christian Hospital, Chang Gung Medical Foundation, National Taiwan University Hospital and 9 more.
Type: Journal Article | Journal: Liver international : official journal of the International Association for the Study of the Liver | Year: 2016

In Taiwan, patients with chronic hepatitis C virus (HCV) infection are currently treated with pegylated interferon-alpha plus ribavirin, but interferon-based regimens can be poorly tolerated, especially by those with advanced liver disease and the elderly. Sofosbuvir, an oral nucleotide analogue inhibitor of HCV NS5B polymerase, is approved in Europe, the USA and Japan for treating chronic HCV infection. This phase 3b study examined the efficacy and safety of sofosbuvir plus ribavirin in Taiwanese patients with chronic genotype 2 HCV infection compensated cirrhosis.In this multicentre, open-label, phase 3b (NCT02021643) study, 87 patients (n = 43, treatment-naive; n = 44, treatment-experienced) received 12 weeks of treatment with sofosbuvir plus weight-based ribavirin. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were also collected.All 87 patients (100%; 95% confidence interval, 92-100%) achieved SVR12, including the 13 patients with compensated cirrhosis. The most common treatment-emergent adverse events (AEs) were insomnia (16%, 14/87) and upper respiratory tract infection (16%, 14/87). No grade 3 or grade 4 AE was reported. There was one serious AE (biliary colic), which was deemed unrelated to study treatment. Laboratory abnormalities other than ribavirin-related reductions in haemoglobin were uncommon.The results from this phase 3b study demonstrate that 12 weeks of treatment with the interferon-free regimen sofosbuvir plus ribavirin is effective and well tolerated in both treatment-naive and treatment-experienced Taiwanese patients with chronic genotype 2 HCV infection.


PubMed | Chang Gung University, Changhua Christian Hospital, Chang Gung Medical Foundation, Gilead Sciences Inc. and 9 more.
Type: Journal Article | Journal: Journal of gastroenterology and hepatology | Year: 2016

Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients.In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n=42, treatment-nave; n=43, treatment-experienced) with chronic genotype 1 HCV infection (compensated cirrhosis) received 12weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected.The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-nave and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir.Data from this phase 3b study suggest that 12weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.


Yeh C.-H.,Chang Gung Memorial Hospital Keelung | Yeh C.-H.,Chang Gung University | Chen T.-P.,Chang Gung Memorial Hospital Keelung | Wang Y.-C.,Chang Gung Memorial Hospital Keelung | And 2 more authors.
Journal of Thrombosis and Haemostasis | Year: 2013

Background: Considerable evidence suggests that coagulation proteases (tissue factor [TF]/activated factor VII [FVIIa]/FXa/thrombin) and their target protease activated receptors (PAR-1/PAR-2) play important roles in myocardial ischemia-reperfusion (I-R) injury. We hypothesized that localized inhibition of TF/FVIIa on the membrane surfaces of ischemic cells could effectively block coagulation cascade and subsequent PAR-1/PAR-2 cell signaling, thereby protecting the myocardium from I-R injury. Objectives: We recently developed an annexin V-Kunitz inhibitor fusion protein (ANV-6L15) that could specifically bind to anionic phospholipids on the membrane surfaces of apoptotic cells and efficiently inhibit the membrane-anchored TF/FVIIa. In this study, we investigated the cardioprotective effect of ANV-6L15 in a rat cardiac I-R model in comparison with that of hirudin. Methods: Left coronary artery occlusion was maintained for 45 min followed by 4 h of reperfusion in anesthetized Sprague-Dawley rats. One minute before or 2 min after coronary ligation, rats received an intravenous bolus injection of ANV-6L15 (2.5-250 μg kg-1), vehicle, or hirudin via bolus injection and continuous infusion. Results and Conclusions: ANV-6L15 dose-dependently reduced infarct size by up to 87% and decreased plasma levels of cardiac troponin I, tumor necrosis factor-α, and soluble intercellular adhesion molecule-1, by up to 97%, 96%, and 66%, respectively, with little impact on the coagulation parameters. ANV-6L15 also ameliorated hemodynamic derangements, attenuated neutrophil infiltration and reduced Terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic cardiomyocytes. Hirudin was less efficacious even at supraclinical dose. ANV-6L15 confers exceptionally potent cardioprotection and is a promising drug candidate for the prevention of myocardial I-R injury. © 2013 International Society on Thrombosis and Haemostasis.


PubMed | Chang Gung Memorial Hospital Linko Medical Center, Chang Gung University, Chang Gung Memorial Hospital Kaohsiung Medical Center and Chang Gung Memorial Hospital Keelung
Type: Journal Article | Journal: Translational oncology | Year: 2014

Sunitinib has shown benefit in patients with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST). However, its advantages are somewhat diminished because of associated toxicities. Herein, we clarify the efficacy and safety of fractioned dose regimen of sunitinib by a pharmacokinetic and efficacy study.Between 2001 and March 2013, a total of 214 patients with metastatic GIST was treated at Chang Gung Memorial Hospital. Among them, 55 (11.6%) patients who received sunitinib were investigated. One group of patients was administered with standard dose of once-daily sunitinib (standard dose group) and the other group was administered with standard total daily dose of sunitinib in fractioned doses (fractioned dose group).Thirty-two male and 23 female patients with a median age of 55 years received sunitinib. The median duration of sunitinib administration was 9.2 months. The clinical benefit was 65.2%. The mean peak blood level of sunitinib in patients with fractioned doses was significantly lower than that in those with once-daily dose (83.4 vs 50.1 ng/ml, P = .01). The rates of adverse effects of hand-foot syndrome, mucositis, and yellow skin were significantly decreased by fractioned doses of sunitinib. However, the progression-free and overall survival did not differ between patients with different treatment regimens.The fractioned dose regimen of sunitinib appears to be a safe and effective treatment for patients with IM-resistant/intolerant GISTs. Significantly decreased toxicity of this regimen could be explained by significantly lower peak sunitinib blood level. However, the treatment efficacy is not reduced by this regimen.


Chuang T.-Y.,Taipei Medical University | Ho W.-P.,Taipei Medical University | Chen C.-H.,Chang Gung Memorial Hospital Keelung | Lee C.-H.,Taipei Medical University | And 2 more authors.
American Journal of Sports Medicine | Year: 2012

Background: In a single arthroscopic surgery for rotator cuff tears with a stiff shoulder, closed manipulation with or without arthroscopic capsular release has been combined with the repair. Few studies have reported functional results after this surgery, and a clinical comparison has not been reported. Purpose: To compare functional outcomes with and without capsular release in arthroscopic treatment of rotator cuff tears with a stiff shoulder. Study Design: Cohort study; Level of evidence, 3. Methods: Among patients who underwent arthroscopic rotator cuff repairs with a concomitant stiff shoulder, 34 patients were treated with either manipulation and arthroscopic capsular release (group A; n = 18) or manipulation without capsular release (group B; n = 16). Preoperative mean passive forward flexion was 118° in group A and 117° in group B, whereas external rotation at the side was 28° and 29°, respectively. All patients were evaluated at a minimum 2-year follow-up in terms of visual analog scale for pain, muscle power, range of motion, Constant score, modified American Shoulder and Elbow Surgeons (ASES) shoulder evaluation form, and modified University of alifornia at Los Angeles (UCLA) scores. Results: The mean modified ASES score was 90.3 for group A and 87.7 for group B (P = .086). The mean UCLA scores were 34.3 and 33.0, respectively (P = .247). The 2 groups showed a significant difference in forward flexion and external rotation postoperatively, as group B recovered more slowly. There was no difference in the mean visual analog scale for pain at the last follow-up, but a 13° difference in forward flexion (P<001) and a 10° difference in external rotation (P =.001) were seen. Conclusion: Overall satisfactory results could be achieved by either method, whereas rapid recovery and improvement of range of motion could be achieved by using a single arthroscopic repair and concomitant release for patients with rotator cuff tears with stiff shoulder. © 2012 The Author(s).


Wang L.-J.,Chang Gung Memorial Hospital Keelung | Wang L.-J.,Chang Gung University | Ree S.-C.,Chang Gung Memorial Hospital Keelung | Chu C.-L.,Chang Gung Memorial Hospital at Linkou | And 2 more authors.
Psychiatria Danubina | Year: 2011

Zolpidem is a non-benzodiazepine property which binds selectively to the α 1-GABA A receptors, and has been widely prescribed to patients suffering from insomnia. We report two cases of zolpidem dependence with withdrawal seizure in the Asian population. The first case is a 43-year-old woman who took zolpidem up to the dosage of 200 to 400 mg per night. The second case is a 35-year-old woman who even began to take zolpidem every 15 to 30 minutes to get euphoric and relaxed, and she gradually increased the dosage to 400 to 500mg per day. After abrupt discontinuation of zolpidem, both cases immediately developed anxiety, global insomnia, restlessness, and tonic seizure. The purpose of this case report is to suggest that clinicians should pay close attention to the potential of zolpidem tolerance, abuse and dependence. The possibility of withdrawal seizure cannot be excluded especially at high doses. © Medicinska naklada.


Lo T.-S.,Chang Gung Memorial Hospital Keelung | Bt Karim N.,Chang Gung Memorial Hospital Keelung | Cortes E.F.,Chang Gung Memorial Hospital Keelung | Wu P.-Y.,Chang Gung Memorial Hospital Keelung | And 2 more authors.
International urogynecology journal | Year: 2015

OBJECTIVE: The aim of this study was to assess the incidence of de novo stress urinary incontinence (SUI) and sonographic features of implanted transvaginal mesh in continent women treated with Elevate(™) anterior/apical [single-incision mesh (SIM-A)] or Perigee(™) [transvaginal mesh with sacrospinous fixation (TVM + SSF)] in extensive pelvic organ reconstruction surgery.METHODS: This prospective observational study was done from May 2010 to January 2013. Patients were recruited from two tertiary centers, and the Elevate(™) and Perigee(™) systems were compared. Patients who had overt or occult SUI, previous prolapse or mesh insertion were excluded.RESULT: Fifty-seven patients in the SIM-A group and sixty-one in the TVM + SSF group were analysed. All completed a minimum of 1-year follow-up. Groups were demographically and statistically similar. There was a significantly high incidence of de novo SUI postoperatively in the SIM-A group. The objective and subjective cure rate of pelvic organ prolapse (POP) were comparable between groups, with incidence of mesh erosion in the SIM-A group and three in the TVM + SSF group. Sonographic evaluation showed significant increase in mesh length in the SIM-A group.CONCLUSION: Elevate(™) a offered lower incidence of mesh erosion and comparable results on anatomical POP correction; however, incidence of de novo SUI was high. There is an apparent lengthening of implanted Elevate® mesh sonographically.


PubMed | Chang Gung Memorial Hospital Keelung
Type: Comparative Study | Journal: International urogynecology journal | Year: 2015

The aim of this study was to assess the incidence of de novo stress urinary incontinence (SUI) and sonographic features of implanted transvaginal mesh in continent women treated with Elevate() anterior/apical [single-incision mesh (SIM-A)] or Perigee() [transvaginal mesh with sacrospinous fixation (TVM + SSF)] in extensive pelvic organ reconstruction surgery.This prospective observational study was done from May 2010 to January 2013. Patients were recruited from two tertiary centers, and the Elevate() and Perigee() systems were compared. Patients who had overt or occult SUI, previous prolapse or mesh insertion were excluded.Fifty-seven patients in the SIM-A group and sixty-one in the TVM + SSF group were analysed. All completed a minimum of 1-year follow-up. Groups were demographically and statistically similar. There was a significantly high incidence of de novo SUI postoperatively in the SIM-A group. The objective and subjective cure rate of pelvic organ prolapse (POP) were comparable between groups, with incidence of mesh erosion in the SIM-A group and three in the TVM + SSF group. Sonographic evaluation showed significant increase in mesh length in the SIM-A group.Elevate() a offered lower incidence of mesh erosion and comparable results on anatomical POP correction; however, incidence of de novo SUI was high. There is an apparent lengthening of implanted Elevate mesh sonographically.


PubMed | Chang Gung Memorial Hospital Keelung
Type: Journal Article | Journal: International urogynecology journal | Year: 2015

The aim of this study was to look for possible predictors preoperatively for the development of de novo stress urinary incontinence (SUI) in urodynamically continent women who underwent pelvic reconstructive surgery (PRS).Medical records of 637 continent women who underwent PRS for severe prolapse from January 2005 to December 2013 in our institutions were included in this study. We excluded women who had urodynamic stress incontinence (UDI) either occult or overt, detrusor overactivity, neurogenic bladder-voiding dysfunction, and previous anti-incontinent surgery. Primary outcome measure was the development of de novo SUI at 6 months to 1 year post operation.Of women in this study, 11 % developed postoperative de novo SUI at 6 months to 1 year of follow-up. Women older than 66 years were 2.86 times [95 % confidence interval (CI) 1.01-2.53, p=0.14], diabetes mellitus (DM) 2.18 times (95 % CI 1.63-4.21, p=0.002), certain type of transvaginal mesh procedure 3.5 times (95 % CI, p<0.001), maximum urethral closure pressure (MUCP)<60 mmH20 4.65 times (95 % CI, 2.87-8.64, p<0.001), and functional urethral length (FUL)<2 cm 3.48 times (95 % CI, 2.13-5.83, p<0.001) at greater risk of developing de novo SUI.Continent women with advanced pelvic organ prolapse (POP)>66 years, with DM or low MUCP and FUL values during preoperative urodynamic evaluation have higher risk of developing de novo SUI; therefore, we suggest counselling such women for concomitant PRS and anti-incontinent surgery.

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