Pelvic floor muscle contraction automatic evaluation algorithm for pelvic floor muscle training biofeedback using self-performed ultrasound.

INTRODUCTION: Non-invasive biofeedback of pelvic floor muscle training (PFMT) is required for continuous training in home care. Therefore, we considered self-performed ultrasound (US) in adult women with a handheld US device applied to the bladder. However, US images are difficult to read and require assistance when using US at home. In this study, we aimed to develop an algorithm for the automatic evaluation of pelvic floor muscle (PFM) contraction using self-performed bladder US videos to verify whether it is possible to automatically determine PFM contraction from US videos. METHODS: Women aged ≥ 20 years were recruited from the outpatient Urology and Gynecology departments of a general hospital or through snowball sampling. The researcher supported the participants in their self-performed bladder US and videos were obtained several times during PFMT. The US videos obtained were used to develop an automatic evaluation algorithm. Supervised machine learning was then performed using expert PFM contraction classifications as ground truth data. Time-series features were generated from the x- and y-coordinate values of the bladder area including the bladder base. The final model was evaluated for accuracy, area under the curve (AUC), recall, precision, and F1. The contribution of each feature variable to the classification ability of the model was estimated. RESULTS: The 1144 videos obtained from 56 participants were analyzed. We split the data into training and test sets with 7894 time series features. A light gradient boosting machine model (Light GBM) was selected, and the final model resulted in an accuracy of 0.73, AUC = 0.91, recall = 0.66, precision = 0.73, and F1 = 0.73. Movement of the y-coordinate of the bladder base was shown as the most important. CONCLUSION: This study showed that automated classification of PFM contraction from self-performed US videos is possible with high accuracy.

A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol.

BACKGROUND: Most advanced elderly cancer patients experience fatigue, anorexia, and declining physical function due to cancer cachexia, for which effective interventions have not been established. We performed a phase I study of a new nonpharmacological multimodal intervention called the nutritional and exercise treatment for advanced cancer (NEXTAC) program and reported the excellent feasibility of and compliance with this program in elderly patients with advanced cancer who were at risk for cancer cachexia. We report here the background, hypothesis, and design of the next-step multicenter, randomized phase II study to evaluate the efficacy of the program, the NEXTAC-TWO study. METHODS: Patients with chemo-naïve advanced non-small cell lung cancer or pancreatic cancer, age ≥ 70 years, performance status ≤2, with adequate organ function and without disability according to the modified Katz index will be eligible. In total, 130 participants will be recruited from 15 Japanese institutions and will be randomized into either the intervention group or a control group. Computer-generated random numbers are allocated to each participant. Stratification factors include performance status (0 to 1 vs. 2), site of primary cancer (lung vs. pancreas), stage (III vs. IV), and type of chemotherapy (cytotoxic vs. others). Interventions and assessment will be performed 4 times every 4 ± 2 weeks from the date of randomization. Interventions will consist of nutritional counseling, nutritional supplements (rich in branched-chain amino acids), and a home-based exercise program. The exercise program will include low-intensity daily muscle training and lifestyle education to promote physical activity. The primary endpoint is disability-free survival. It is defined as the period from the date of randomization to the date of developing disability or death due to any cause. This trial also plans to evaluate the improvements in nutritional status, physical condition, quality of life, activities of daily living, overall survival, and safety as secondary endpoints. Enrollment began in August 2017. The study results will demonstrate the efficacy of multimodal interventions for elderly cancer patients and their application for the maintenance of physical and nutritional conditions in patients with cancer cachexia. This work is supported by a grant-in-aid from the Japan Agency for Medical Research and Development. DISCUSSION: This is the first randomized trial to evaluate the efficacy and safety of a multimodal intervention specific for elderly patients with advanced cancer. TRIAL REGISTRATION: Registered at August 23, 2017. Registry number: UMIN000028801 .

Feasibility of early multimodal interventions for elderly patients with advanced pancreatic and non-small-cell lung cancer.

BACKGROUND: Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme. METHODS: This was a multicentre prospective single-arm study. We recruited 30 of 46 screened patients aged ≥70 years scheduled to receive first-line chemotherapy for newly diagnosed, advanced pancreatic, or non-small-cell lung cancer. Physical activity was measured using pedometers/accelerometer (Lifecorder® , Suzuken Co., Ltd., Japan). An 8 week educational intervention comprised three exercise and three nutritional sessions. The exercise interventions combined home-based low-intensity resistance training and counselling to promote physical activity. Nutritional interventions included standard nutritional counselling and instruction on how to manage symptoms that interfere with patient's appetite and oral intake. Supplements rich in branched-chain amino acids (Inner Power® , Otsuka Pharmaceutical Co., Ltd., Japan) were provided. The primary endpoint of the study was feasibility, which was defined as the proportion of patients attending ≥4 of six sessions. Secondary endpoints included compliance and safety. RESULTS: The median patient age was 75 years (range, 70-84). Twelve patients (40%) were cachectic at baseline. Twenty-nine patients attended ≥4 of the six planned sessions (96.7%, 95% confidence interval, 83.3 to 99.4). One patient dropped out due to deteriorating health status. The median proportion of days of compliance with supplement consumption and exercise performance were 99% and 91%, respectively. Adverse events possibly related to the NEXTAC programme were observed in five patients and included muscle pain (Grade 1 in two patients), arthralgia (Grade 1 in one patient), dyspnoea on exertion (Grade 1 in one patient), and plantar aponeurositis (Grade 1 in one patient). CONCLUSIONS: The early induction of multimodal interventions showed excellent compliance and safety in elderly patients with newly diagnosed pancreatic and non-small-cell lung cancer receiving concurrent chemotherapy. We are now conducting a randomized phase II study to measure the impact of these interventions on functional prognosis.

Prognostic significance of thymidylate synthase expression in the adjuvant chemotherapy after resection for pulmonary metastases from colorectal cancer.

BACKGROUND: Recent studies have discussed on the prognostic value of thymidylate synthase (TS) assessment in metastases of colorectal cancer (CRC). The aim of this study was to evaluate the prognostic significance of molecular biomarkers including TS expression, after pulmonary metastasectomy followed by 5-fluorouracil-based adjuvant chemotherapy. PATIENTS AND METHODS: A total of 80 patients who underwent metastasectomy for pulmonary recurrence from CRC were included in this study. Tumor sections were stained by immunohistochemistry for TS, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), excision repair cross-complementation group 1 (ERCC1), breast cancer susceptibility gene 1 (BRCA1), vascular endothelial growth factor (VEGF), microvessel density (MVD) assessed by CD34 and p53. RESULTS: Survival after pulmonary metastasectomy was significantly longer in patients treated by adjuvant chemotherapy than those without adjuvant therapy. TS, OPRT, ERCC1, BRCA1 and CD34 expression was significantly associated with better outcome from the use of adjuvant chemotherapy. CONCLUSION: Expression level of TS, OPRT, ERCC1, BRCA1 and MVD in resected colorectal lung metastases may play an important role for predicting outcome after 5-fluorouracil-based adjuvant therapy.

Cardiorenal protective effects of year-long antihypertensive therapy with an angiotensin-converting enzyme inhibitor or a calcium channel blocker in spontaneously hypertensive rats.

BACKGROUND: The objective of this study was to evaluate the effect of year-long antihypertensive therapy with a calcium channel blocker and an angiotensin-converting enzyme (ACE) inhibitor on cardiac and renal injury. METHODS: Male 15-week-old spontaneously hypertensive rats (SHR) were given either a normal diet and normal drinking water (n = 10), a diet containing 0.05% nitrendipine (n = 10), or drinking water containing 50 mg/L of quinapril (n = 10). After 12 months of antihypertensive treatment, cardiovascular organ injuries were evaluated. RESULTS: Tail-cuff blood pressure (BP) at 12 months was significantly lower in animals receiving nitrendipine or quinapril than in control animals (control, 231 +/- 2 mm Hg; nitrendipine, 194 +/- 3 mm Hg; quinapril, 191 +/- 3 mm Hg; P < .001). Furthermore, aortic thickness was reduced by nitrendipine (-19%, P < .001) or quinapril (-21%, P < .001), and cardiac ventricular weight was significantly reduced by quinapril (-18%, P < .001) but not by nitrendipine (-5%, P = not significant [NS]). Echocardiography at 12 months revealed that midwall fractional shortening was higher in the quinapril group than in the control or the nitrendipine groups (control, 9.3% +/- 0.5%; nitrendipine, 9.8% +/- 0.5%; quinapril, 10.6% +/- 0.6%; P < .05). Left ventricular hydroxyproline levels were lower in the nitrendipine group (-21%, P < .01) and the quinapril group (-36%, P < .001) than in the control animals. In control SHR, creatinine clearance began to decrease and proteinuria began to increase at 6 to 9 months. Quinapril but not nitrendipine attenuated these markers of renal impairment (creatinine clearance at 12 months: control, 4.7 +/- 0.4 mL/min/kg; nitrendipine, 5.0 +/- 0.4 mL/min/kg; quinapril, 6.1 +/- 0.4 mL/min/kg; P < .05). Histologically, the glomerular injury score was lower in the quinapril group than in the control or nitrendipine groups (control, 19 [range, 8 to 30]; nitrendipine, 18 [range, 9 to 32]; quinapril, 7 [range, 3 to 12]; P < .01). CONCLUSIONS: It is suggested that year-long antihypertensive therapy with an angiotensin-converting enzyme (ACE) inhibitor is superior to a calcium channel blocker in terms of cardiorenal protection in SHR.

Localized synovial hypertrophy in the anteromedial compartment of the osteoarthritic knee.

PURPOSE: The purpose of this study was to investigate the clinical and arthroscopic findings of osteoarthritis (OA) of the knee with localized synovial hypertrophy in the anteromedial compartment and the clinical results of arthroscopic partial synovectomy. TYPE OF STUDY: Retrospective case series. METHODS: We treated 19 osteoarthritic knees with localized synovial hypertrophy in 19 patients by arthroscopic partial synovectomy under local anesthesia. All patients had complained of knee pain (mechanical type pain) and catching sensations preoperatively. Preoperative diagnosis based on physical findings and imaging studies was a medial meniscus tear with medial OA in all patients. The mean follow-up was 37 months (range, 28 to 46 months). Clinical results were assessed with the Hospital for Special Surgery (HSS) scoring scale, overall subjective estimation, and patient satisfaction. RESULTS: The catching sensation resolved immediately after surgery in all patients. The mean HSS score improved from 56.8 to 72.4 points (P < .01). Nine patients (47.4%) were rated excellent or good according to the overall subjective estimation, and 11 patients (57.9%) were satisfied with the treatment. Both HSS score and patient satisfaction were higher in patients (10 patients) who complained of intraoperative pain during synovectomy than in those (9 patients) who hardly felt the pain. CONCLUSIONS: Localized synovial hypertrophy in the anteromedial compartment of OA knees occasionally caused symptoms of pain and catching sensations that resembled meniscal symptoms. Arthroscopic partial synovectomy was effective, especially for those who complained of intraoperative pain during synovectomy under local anesthesia. LEVEL OF EVIDENCE: Level IV.

Pain in arthroscopic knee surgery under local anesthesia.

BACKGROUND: We evaluated pain during arthroscopic knee surgery performed under local anesthesia, with respect to various types of lesions and specific procedures used. PATIENTS AND METHODS: Arthroscopic surgery was performed on 63 joints (61 patients), with a median age of 49 years. We asked the patients to describe the pain experienced at each step of the procedure, and to compare the level of pain experienced at the time of injection and during the operation, using a visual analog scale (VAS). RESULTS: Pain experienced at the time of injection of the local anesthetic was more severe than the pain experienced during the surgical procedure. Local anesthesia provided good pain control during partial resection of the meniscus, chondroplasty, and removal of free bodies. Patients sometimes experienced more pain during treatment of the suprapatellar pouch, including the plica and the anterior cruciate ligament. INTERPRETATION: Injection of the local anesthetic was usually the most painful phase of the entire procedure. Patients were generally satisfied with the pain control.

Immunocytochemical characteristics of human osteosarcoma cell line HS-Os-1: possible implication in apoptotic resistance against irradiation.

In our previous study, we examined reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy irradiation. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of the hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation. In the succeeding study, we examined radiation-induced ROS formation, oxidative DNA damage, early apoptotic changes, and mitochondrial membrane dysfunction in the human osteosarcoma cell line HS-Os-1. We found that ROS formation and oxidative DNA damage were actually scarcely seen after irradiation of up to 30 Gy in these cells, that mitochondrial membrane potential was preserved, and that apoptotic changes were not demonstrated despite the relatively high-dose irradiation of 30 Gy. In the present study, we examined the immunocytochemical characteristics of the apoptotic-resistance of the HS-Os-1 cell line against irradiation in order to clarify its possible implications regarding radiosensitivity. The results showed that these cells lack P53 and Bax protein expression, and strong peroxidase activity was confirmed in the nuclei of the cells. Moreover, SODII (manganese superoxide dismutase II) protein expression was gradually increased in spite of irradiation of up to 30 Gy. Therefore, it is concluded that HS-Os-1 cells are originally apoptotic-resistant and that the cells possess a strong ability to scavenge for free radicals. To convert these cells to a state of apoptotic-susceptibility, a powerful oxidant such as hydrogen peroxide might exert such an effect in terms of the production of hydroxyl radicals in lysosomes in the cells as shown in our previous studies. The origin of the radioresistance of the human osteosarcoma cell line HS-Os-1 is considered to to be low degree of ROS formation following irradiation, reflecting the strong scavenging ability of these cells for free radicals including hydroxyl radicals.

Cross talk between COX-2 inhibitor and hyaluronic acid in osteoarthritic chondrocytes.

Both hyaluronic acid (HA) and cyclooxygenase-2 (COX-2) inhibitors are used in clinical practice in the treatment of osteoarthritis. There have been no reports regarding cross-talk between HA and COX-2 inhibitors in articular human chondrocytes. The purpose of this study was to investigate whether HA, COX-2 inhibitors or a combination of COX-2 inhibitors and HA have different effects in human articular between lower and highly degenerated chondrocytes. Isolated lower and highly degenerated chondrocytes were divided into 5 groups: ethanol (used as a control for the solvents), HA, COX-2 inhibitors, COX-2 inhibitors plus HA, or no additive. After incubating for 48 h, mitochondrial membrane potential analysis and western blotting of p38 and p44/42 mitogen-activated protein kinase (MAPK) were performed. Glycosaminoglycan, nitric oxide (NO) production and prostaglandin E2 (PGE2) concentrations were assessed. A combination of COX-2 inhibitors and HA resulted in dendritic, proliferating chondrocytes with strong red fluorescence enriched in the mitochondrial membrane, and indicated reduction of apoptosis in chondrocytes. COX-2 inhibitors alone, and a combination of COX-2 inhibitor and HA inhibited the activation of p38 in highly degenerated chondrocytes. A combination of COX-2 inhibitors and HA decreased NO production in highly degenerated chondrocytes. COX-2 inhibitors decreased PGE2 production, however, HA alone had no effect on PGE2 production. The present study demonstrated that COX-2 inhibitors and HA interacted synergistically the MAPK pathway and inhibition of NO production in highly degenerated chondrocytes. Administration of COX-2 inhibitors plus HA could be used as a new alternative way of treating osteoarthritis.

Mechanoreceptors and length of the patellar ligament after Ho-YAG laser treatment: a long-term follow-up in rabbits.

We studied the shortening and the number of mechanoreceptors in the patellar ligament up to 18 months after Ho-YAG irradiation of the ligament's surface in 35 rabbits. The ligaments shortened an average 13% immediately after irradiation. After treatment, we divided the rabbits into a mobilized or immobilized group. At 2 weeks and 12 months after treatment both groups showed no shortening of the ligament, as compared to the intact ligament while that in the mobilized group had elongated at 12 months. Fewer Pacinian and Ruffini corpuscles were found in the irradiated ligaments than in the intact ones at 2 weeks after treatment, but we found no difference between irradiated and intact ligaments at 18 months after treatment.