Suntogun Nagaizumicho,shizuoka, Japan

rTMS and Robotic Gait Training in Patients With Stroke

This study will include subjects occurring stroke within 3 months. All groups will receive traditional rehabilitation. The subjects will be allocated randomly in three groups which are traditional rehabilitation (Group A), robotic training (Group B), and rTMS (Group C) respectively, with 35 people per group. The group B will be intervened 5 times per week and the group C will receive 10 times rTMS intervention during 4 weeks. At post-intervention and eighth weeks after intervention, basic examination will be executed including basic information, history, Mini-mental State examination, Short -Form 36, Modified Ashworth Scale, Fugl-Meyer assessment, static and dynamic motion examination, ultrasound assessment and examination of cardiorespiratory. Two-way mixed ANOVA will be used to analyze the differences of three groups and times.

A New Spinal Orthosis for Adolescent Idiopathic Scoliosis

Spinal orthosis is an option to treat Adolescent Idiopathic Scoliosis (AIS) and is the most commonly used among conservative treatment. According to Scoliosis Research Society (SRS), orthotic treatment is indicated for AIS patients with curves greater than 25˚ but smaller than 45˚. However, the in-brace correction is hardly maintained and the effectiveness of orthotic treatment is limited, which has been an impetus to develop a more effective method for AIS patients to fulfill the unmet need. In order the orthosis is effective, biomechanical intervention and the patient compliance are two key factors. The purpose of this two-year project is to develop a new spinal orthosis in which an integrated system of electric surface stimulation and heat sensing is imbedded such that the AIS will be effectively treated with the mechanical orthosis plus a nocturnal use of electrical stimulation. In addition to the already stellar device, a totally new concept of spine erectability is proposed to provide evidence that can manifest the unique value of orthotic treatment as opposed to surgery. It is hypothesized that the new spinal orthosis would not only reduce the Cobb angle and apical rotation but also would strengthen the spine erectability in AIS patients. The new device with digital technology provides a new avenue to enable clinicians to communicate wirelessly with the imbedded core system such that they can adjust the electrical stimulation parameters and retrieve the temperature data for further compliance analysis. The smart phone and cloud technology can be effectively applied for both security and convenience. The electrical stimulation technology integrated with the total contact spinal orthosis combines the external correction forces on the spinal skeleton from the passive orthosis with the muscle forces at the lateral trunk from the stimulation process. The electrical stimulation is purposely to tone the muscle in order to replace the external mechanical forces gradually. Ultimately, when being weaned off the orthosis, patients may maintain the correction. With the spinal orthosis, the applied current in stimulation process would be reduced and the skin irritation would too. First year, there will be three tasks. An instrument will be developed for clinicians to assess the applicability of electrical surface stimulation to each AIS patient. System integration of the spinal orthosis with electrical surface stimulation and heat sensing will be accomplished. Clinical study of the effectiveness of passive spinal orthoses on 30 AIS subjects as a control group, where the Cobb angle, apical rotation and spine erectability will be measured before treatment and after. Second year, another 30 AIS patients will be recruited; the applicability of electrical surface stimulation will be assessed; and the new spinal orthosis will be applied to the experiment group. The Cobb angle, apical rotation and spine erectability will be measured before treatment and after for each subject. Independent t test will be carried out for the two groups to test the hypothesis.

A Smart Physical Examination System for the Health Management in Elderly

Aging usually results in a decline of motor function. However, elderly tends to refuse the regular health examination because of travel issues or lack of self-health awareness. Examination unit also has difficulty to intensively track and instantly feedback the health status of elderly due to insufficient manpower. If elderly goes to the hospital only when the health problem is getting worse, his/her health is often irreversible and the cost of medical care would be increased. It is therefore an essential issue for the early detection of functional changes in elderly to prevent the deterioration of the health and function. Currently, the telemedicine cares provided by hospitals are not universal due to the out-of-date legislation and non-successful business model. The wearing and operation issues of the wearable devices used for health management are still a gap affecting the acceptance of elderly. Accordingly, the objective of this project is to develop a handy and easy-to-use smart physical examination system targeted on the unmet need of the elderly. With the use of motion-sensing and big data analysis technology, the non-contact professional and intelligent assessment could simplify the general health checkup procedures to promote the health management and to reduce the manpower cost of health care. Following the principle of commercialization, this project aims at working out the product prototype, finalize the assessment tools/algorithm, and put it into the clinical trials. The project research team comprising the physicians, therapists, hardware and software systems engineering experts, with the early manufacturing involvement from the industry partner. The team members will work closely to solve the clinical, engineering, and market demand issues during the development process. The project will build a platform to deepen the bilateral understanding and research cooperation to solve the aging society problem. The ultimate goal is to realize a commercial product aiming at the silver hair market with functional advantages to meet the unmet needs of health management in elderly.

Robotic Versus Conventional or Endoscopic Nipple Sparing Mastectomy for Breast Cancer

Nipple-sparing mastectomy (NSM), which preserved the nipple areolar complex (NAC) and skin flap during mastectomy, was increasingly performed in breast cancer patients due to better cosmetic outcome, higher patient satisfaction, and maintained oncologic safety. Minimal invasive surgery had become the main stream of operations, and new surgical innovations of NSM, like endoscopic nipple sparing mastectomy (E-NSM) or robotic nipple sparing mastectomy (R-NSM), were emerging and applied in the surgical treatment of breast cancer. E-NSM, which is performed through small axillary and/or peri-areolar incisions, was reported to be associated with small inconspicuous incision and good cosmetic outcome. Conventional E-NSM was performed with two separate incisions over axilla and peri-areolar regions. E-NSM with areolar incision, just like NSM with areolar related incision (NAC ischemia/necrosis rate: range 7%-81.8%), was associated with increased NAC ischemia/necrosis (reported ranged: 9.1-19%). New technique modifications of E-NSM were emerging focusing on single axillary incision NSM, which spare the peri-areolar incision and thereby decrease the compromise of bloody supply from mastectomy skin flap, was reported to have low NAC necrosis rate (0%). However, the 2-dimensional endoscopic in-line camera produces an inconsistent optical window around the curvature of the breast skin flap, and the internal mobility was limited and the dissection angles were inadequate with traditional endoscopic rigid tips instruments through single access. Due to the limitations of endoscopy instruments and technique difficulty, neither conventional E-NSM nor single access E-NSM was widespread used in breast cancer R-NSM, which introduce da Vinci surgical platform through a small extramammary axillary or lateral chest wound to perform NSM, had been applied in the surgical treatment of early breast cancer or risk reducing mastectomy. R-NSM, which incorporated 3- dimensional (3D) imaging system and flexibility of robotic arm and instruments, was reported to have the potential to overcome the technique difficulty of E-NSM. The preliminary results of R-NSM from current literature reported series and ours were safe, and associated with good cosmetic outcome and high patients' satisfaction. However, evidence comparing R-NSM to conventional NSM (CNSM) or E-NSM was lacking. In this study, the authors aim to investigate and analyze the clinical and aesthetic outcomes as well as the cost effectiveness of R-NSM through a longitudinal cohort study design whereby a retrospective review will be carried out for patients undergoing R-NSM, E-NSM or C-NSM. Multi-centers pooled data analysis would be performed for comparisons of R-NSM compared with C-NSM or E-NSM.

Robotic Versus Conventional or Endoscopic Nipple Sparing Mastectomy in the Management of Breast Cancer-Prospective Study

Nipple-sparing mastectomy (NSM), which preserved the nipple areolar complex (NAC) and skin flap during mastectomy, was increasingly performed in breast cancer patients due to better cosmetic outcome, higher patient satisfaction, and maintained oncologic safety. Minimal invasive surgery had become the main stream of operations, and new surgical innovations of NSM, like endoscopic nipple sparing mastectomy (E-NSM) or robotic nipple sparing mastectomy (R-NSM), were emerging and applied in the surgical treatment of breast cancer. E-NSM, which is performed through small axillary and/or peri-areolar incisions, was reported to be associated with small inconspicuous incision and good cosmetic outcome. Conventional E-NSM was performed with two separate incisions over axilla and peri-areolar regions. E-NSM with areolar incision, just like NSM with areolar related incision (NAC ischemia/necrosis rate: range 7%-81.8%), was associated with increased NAC ischemia/necrosis (reported ranged: 9.1-19%). New technique modifications of E-NSM were emerging focusing on single axillary incision NSM, which spare the peri-areolar incision and thereby decrease the compromise of bloody supply from mastectomy skin flap, was reported to have low NAC necrosis rate (0%). However, the 2-dimensional endoscopic in-line camera produces an inconsistent optical window around the curvature of the breast skin flap, and the internal mobility was limited and the dissection angles were inadequate with traditional endoscopic rigid tips instruments through single access. Due to the limitations of endoscopy instruments and technique difficulty, neither conventional E-NSM nor single access E-NSM was widespread used in breast cancer R-NSM, which introduce da Vinci surgical platform through a small extra-mammary axillary or lateral chest wound to perform NSM, had been applied in the surgical treatment of early breast cancer or risk reducing mastectomy. R-NSM, which incorporated 3-dimensional (3D) imaging system and flexibility of robotic arm and instruments, was reported to have the potential to overcome the technique difficulty of E-NSM. The preliminary results of R-NSM from current reported series and ours were safe, and associated with good cosmetic outcome and high patients' satisfaction. However, evidence comparing R-NSM to conventional NSM (C-NSM) or E-NSM was lacking. In this study, the authors aim to investigate and analyze the clinical and aesthetic outcomes as well as the cost effectiveness of R-NSM through a prospective cohort of patients undergoing R-NSM, E-NSM or C-NSM.

Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC

Cabozantinib and Lanreotide as Treatment for Gastroenteropancreatic Neuroendocrine Tumors

This is an Open-Label Phase I/II Study of daily cabozantinib plus lanreotide every 4 w eeks to treat advanced G1-2 gastroentero-pancreatic neuroendocrine tumor (GEP-NET) patients who failed to one line or more than one line of small molecule kinase inhibitor or well-differentiated (W-D) G3 GEP-NET who failed to one line of small molecule kinase inhibitor or chemotherapy. The primary objective of the study is to determine the maximal tolerated dose (MTD) of cabozantinib of this combinational regimen in the phase I study and the progression free survival in the phase II study. The secondary objectives are the objective response rate, overall survival, toxicities and biomarker analysis of this regimen. Eligible patients will receive a combination of oral cabozantinib 40-60 mg/day and lanreotide 120mg deep subcutaneous injection (SC) in day 1 every 4 weeks. Four weeks is a cycle. The patients will continue to receive this regimen till disease progression, intolerable adverse events (after dose modification), death, or withdrawal by patients' or principle investigator's decision.

JNJ-90301900 (NBTXR3) Activated by Radiotherapy With or Without Cetuximab in LA-HNSCC

Participants will undergo a screening assessment over a period of less than or equal to (<=) 28 days to determine eligibility. Eligible participants will be treated by the Investigator's choice of RT alone or RT in combination with cetuximab. Following the Investigator's choice, participants will be randomized in a 1:1 ratio: - Arm A: JNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab - Arm B: Investigator's choice of RT alone or RT in combination with cetuximab All participants (Arm A and Arm B) will receive 70 Gy in 35 fractions over a 7 week period. An EOT visit will be performed 4 weeks after the completion of RT. Follow-up visits will start at 12 weeks post-RT completion, and will continue every 12 weeks for 2 years, and then every 24 weeks thereafter until death; the participant is determined to be lost to follow up; withdrawal of consent; or the end of the study, whichever occurs first. Participants who have received further anti-cancer therapy for the study disease and/or have had disease progression/recurrence will be followed only for survival information

Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors

Part D allocation for 1 cohort will be randomized.

Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) for Patients With Hepatitis C Virus Infection

Hepatitis C virus (HCV) infection is a global health problem and it is estimated that about 71 million people are HCV carriers worldwide. Based one the excellent efficacy and safety, interferon (IFN)-free direct-acting antiviral agents (DAAs) have become the standard of care (SOC) for the care of HCV. Currently, about 10 different DAA regimens have been approved by FDA and EMA for the treatment of HCV, the sustained virologic response (SVR) rates are generally more than 95% by these treatment. Despite the efficacy and safety are excellent in patients receiving DAAs for HCV, about 1%-5% of these patients fail to successfully clear virus by DAA treatment. Retreating patients who fail to respond to DAAs with more potent DAAs would be of paramount importance for treating physicians and patients. Even since 2017, an estimated of 110,000 to 120,000 viremic patients in Taiwan have received governmental reimbursement with DAA treatment. Based on a recent report from National Hepatitis C Program (NHCP) office, about 2% of subjects in Taiwan have virologic failures to DAA treatment, which implies that about 2,200 to 2,400 HCV-infected patients remain viremic with the currently approved first-line DAA therapies. Furthermore, the majority of them have been treated with HCV non-structural 5A (NS5A)-based DAA regimens. Sofosbuvir/velpatasvir/voxilaprevir, a pangenotypic DAA regimen, serves as a rescue therapy for HCV patients who do not respond to first-line DAA treatment. The phase 3 POLARIS-1 trial which retreated HCV patients who failed to respond to NS5A-containing DAAs with SOF/VEL/VOX for 12 weeks revealed that the SVR12 rate was 96%. Among patients without cirrhosis and with compensated cirrhosis, the SVR12 rates were 99% and 93%, respectively. In addition, the phase 3 POLARIS-4 trial which retreated HCV genotype 1a and 3 patients who failed to respond to non-NS5A-containing DAAs with SOF/VEL/VOC for 12 weeks in HCV revealed that the SVR12 rates were 98% and 94%, respectively. Because all patients enrolled in the POLARIS-1 and POLARIS-4 trials who failed to prior genotype-specific DAA regimens, data regarding the effectiveness and safety of SOF/VEL/VOX for patients who failed to prior pangenotypic DAA regimens remain elusive. Two small-scale real-world studies assessing the performance of SOF/VEL/VOX for 12 weeks in patients who failed to pangenotypic SOF/VEL or glecaprevir/pibrentasvir (GLE/PIB) revealed that SVR12 rates were 100% and 94%. Nonetheless, two real-world studies in Western countries showed that the SVR12 rates of SOF/VEL/VOX for 12 weeks ranged from 95%-96% for HCV patients who failed to prior DAA therapies. Based on the approval of governmental reimbursement of SOF/VEL/VOX retreatment for HCV genotype 1-6 patients who fail to prior NS5A-containing DAA regimens and HCV genotype 1a and 3 patients who fail to prior non-NS5A-containing DAA regimen on September 1, 2021 in Taiwan, the investigators aim to conduct a multicenter observational study to assess the real-world effectiveness and safety of SOF/VEL/VOX for 12 weeks in these patients to provide a powerful evidence to optimize the clinical practice in Taiwan.