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1.
Int J Chron Obstruct Pulmon Dis ; 19: 1547-1559, 2024.
Article in English | MEDLINE | ID: mdl-38979101

ABSTRACT

Purpose: This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women. Participants and Methods: This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (-4 to -1), or high (<-4). AL was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7. The association between the OSTA and AL was assessed using logistic regression analysis. Results: The prevalence of AL was significantly higher in the high OSTA group (15.3%) than in the low OSTA group (3.1%) (p<0.001). In multiple linear regression analysis, the OSTA was independently associated with FEV1/FVC. In logistic regression models adjusted for smoking status, alcohol consumption, current use of medication for diabetes, hyperglycemia, rheumatoid arthritis, second-hand smoke, and ovary removal showed a significantly higher risk of AL (odds ratio: 5.48; 95% confidence interval: 2.90-10.37; p<0.001) in participants with OSTA high risk than in those with OSTA low risk. Conclusion: These results suggest that the OSTA high risk indicates reduced BMD at the femoral neck and presence of AL in Japanese post-menopausal women aged ≥45 years.


Subject(s)
Absorptiometry, Photon , Asian People , Lung , Postmenopause , Spirometry , Humans , Female , Cross-Sectional Studies , Middle Aged , Japan/epidemiology , Aged , Forced Expiratory Volume , Risk Factors , Vital Capacity , Prevalence , Lung/physiopathology , Osteoporosis, Postmenopausal/physiopathology , Osteoporosis, Postmenopausal/ethnology , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/epidemiology , Predictive Value of Tests , Logistic Models , Risk Assessment , Bone Density , Linear Models , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/ethnology , Pulmonary Disease, Chronic Obstructive/epidemiology , Diagnostic Self Evaluation , Odds Ratio , East Asian People
2.
J Biosci Bioeng ; 137(6): 471-479, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38472071

ABSTRACT

Chinese hamster ovary (CHO) cells are widely used as a host for producing recombinant therapeutic proteins due to advantages such as human-like post-translational modification, correct protein folding, higher productivity, and a proven track record in biopharmaceutical development. Much effort has been made to improve the process of recombinant protein production, in terms of its yield and productivity, using conventional CHO cell lines. However, to the best of our knowledge, no attempts have been made to acquire new CHO cell lines from Chinese hamster ovary. In this study, we established and characterized a novel CHO cell line, named CHO-MK, derived from freshly isolated Chinese hamster ovary tissues. Some immortalized cell lines were established via sub-culture derived from primary culture, one of which was selected for further development toward a unique expression system design. After adapting serum-free and suspension culture conditions, the resulting cell line exhibited a considerably shorter doubling time (approximately 10 h) than conventional CHO cell lines (approximately 20 h). Model monoclonal antibody (IgG1)-producing cells were generated, and the IgG1 concentration of fed-batch culture reached approximately 5 g/L on day 8 in a 200-L bioreactor. The cell bank of CHO-MK cells was prepared as a new host and assessed for contamination by adventitious agents, with the results indicating that it was free from any such contaminants, including infectious viruses. Taking these findings together, this study showed the potential of CHO-MK cells with a shorter doubling time/process time and enhanced productivity in biologics manufacturing.


Subject(s)
Antibodies, Monoclonal , Biological Products , Bioreactors , Cricetulus , Recombinant Proteins , CHO Cells , Animals , Recombinant Proteins/metabolism , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics , Cricetinae , Antibodies, Monoclonal/biosynthesis , Biological Products/metabolism , Immunoglobulin G/metabolism , Cell Culture Techniques/methods , Humans , Batch Cell Culture Techniques/methods
3.
J Occup Health ; 66(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38192224

ABSTRACT

OBJECTIVES: This study aimed to examine the relationship between physical activity (PA) and locomotive syndrome (LS) among young and middle-aged Japanese workers. METHODS: This cross-sectional study included 335 participants from a company in Kumamoto, Japan. LS was evaluated using the 25-question Geriatric Locomotive Function Scale (GLFS-25); a GLFS-25 score ≥7 was defined as LS. Weekly PA was measured using the International Physical Activity Questionnaire. Work-related PA (time spent sitting, standing, walking, and strenuous work per day) and sedentary breaks were measured using a Work-related Physical Activity Questionnaire. Screen usage (television [TV], smartphones, tablets, and personal computers) during leisure time was recorded. The association between PA and LS was examined using a multivariate logistic regression analysis adjusted for age, sex, body mass index, history of musculoskeletal disorders, cancer, stroke, occupation, employment type, work time, shift system, employment status, and body pain. RESULTS: A total of 149 participants had LS. Fewer sedentary breaks during work (>70-minute intervals, odds ratio [OR] = 2.96; prolonged sitting, OR = 4.12) and longer TV viewing time (≥180 minutes, OR = 3.02) were significantly associated with LS. In contrast, moderate PA (OR = 0.75) was significantly associated with a lower risk of LS. CONCLUSIONS: Fewer sedentary breaks during work and longer TV viewing time could increase the risk of LS in young and middle-aged Japanese workers.


Subject(s)
Locomotion , Pain , Middle Aged , Humans , Aged , Japan/epidemiology , Cross-Sectional Studies , Exercise , Syndrome
4.
Sci Rep ; 13(1): 16997, 2023 10 09.
Article in English | MEDLINE | ID: mdl-37813949

ABSTRACT

Chronic subdural hematoma (CSDH) often causes neurological deterioration and is treated with hematoma evacuation. This study aimed to assess the feasibility of various machine learning models to preoperatively predict the functional outcome of patients with CSDH. Data were retrospectively collected from patients who underwent CSDH surgery at two institutions: one for internal validation and the other for external validation. The poor functional outcome was defined as a modified Rankin scale score of 3-6 upon hospital discharge. The unfavorable outcome was predicted using four machine learning algorithms on an internal held-out cohort (n = 188): logistic regression, support vector machine (SVM), random forest, and light gradient boosting machine. The prediction performance of these models was also validated in an external cohort (n = 99). The area under the curve of the receiver operating characteristic curve (ROC-AUC) of each machine learning-based model was found to be high in both validations (internal: 0.906-0.925, external: 0.833-0.860). In external validation, the SVM model demonstrated the highest ROC-AUC of 0.860 and accuracy of 0.919. This study revealed the potential of machine learning algorithms in predicting unfavorable outcomes at discharge among patients with CSDH undergoing burr hole surgery.


Subject(s)
Hematoma, Subdural, Chronic , Humans , Retrospective Studies , Hematoma, Subdural, Chronic/surgery , Trephining , Machine Learning , Logistic Models
5.
Lung Cancer ; 184: 107349, 2023 10.
Article in English | MEDLINE | ID: mdl-37651927

ABSTRACT

BACKGROUND: Adding bevacizumab to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) prolonged the progression-free survival (PFS), but limited data are available for second-generation EGFR-TKIs. AfaBev-CS is a randomized, phase II trial comparing afatinib plus bevacizumab and afatinib alone as first-line treatment. PATIENTS AND METHODS: Untreated patients with non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations (Del19 or L858R) were enrolled and randomly assigned to receive either afatinib (30 mg) plus bevacizumab (AfaBev group) or afatinib (40 mg) monotherapy (Afa group). The primary endpoint was PFS. The power was >50% under the assumptions of a median PFS of 12 months for the Afa group and hazard ratio (HR) of 0.6 for the AfaBev group. RESULTS: Between August 2017 and September 2019, 100 patients were enrolled. There was no significant difference in PFS between the groups. The median PFS was 16.3 and 16.1 months for the AfaBev and Afa groups, respectively, with an HR of 0.865 (95% confidence interval [CI], 0.539 to 1.388; p = 0.55). In terms of overall survival, there was no significant difference between the groups (HR, 0.84; 95% CI, 0.39 to 1.83; p = 0.67). The overall response rate was 82.6% and 76.6% in the AfaBev and Afa groups, respectively (p = 0.61). Grade ≥ 3 diarrhea, hypertension, acneiform rash, paronychia, and stomatitis were frequently observed in the AfaBev group. CONCLUSIONS: This study failed to show efficacy of AfaBev over Afa for improving PFS in untreated patients with EGFR-mutated NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Afatinib/therapeutic use , Bevacizumab/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , ErbB Receptors/genetics , Mutation
6.
J Cancer Res Clin Oncol ; 149(8): 4933-4938, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36308525

ABSTRACT

BACKGROUND: Combination therapy with immune checkpoint inhibitors (ICIs) and chemotherapy (ICI + chemotherapy) has become the standard first line treatment for driver oncogene-negative advanced non-small-cell lung cancer (NSCLC). However, it may be more toxic compared to monotherapy, which limits its use. Moreover, the feasibility of the combination therapy in clinical practice remains unknown. METHODS: We conducted a cohort study to determine the implementation rate of ICI + chemotherapy in clinical practice. We retrospectively reviewed clinical data from advanced NSCLC patients who received systemic therapy at 13 institutions between December 2018 and December 2020. RESULTS: After excluding 154 patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene alterations, a total of 919 NSCLC patients were included. Among them, 442 were treated with ICI + chemotherapy (48%), whereas 477 were treated with other therapies (52%). Among these 477 patients, 340 did not receive ICI + chemotherapy because of intolerance (71%); thus, more than one-third of the advanced NSCLC patients do not benefit from the combination therapy due to intolerance. Among the 659 NSCLC patients for whom PD-L1 was < 50% or unknown, only 342 received the ICI + chemotherapy combination (52%) even though it is considered preferable to either therapy alone; the remaining 318 patients were treated with other therapies (48%). Among the 318 patients who did not receive ICI + chemotherapy, 274 were intolerant to it (86%). CONCLUSION: Our results revealed that a substantial proportion of advanced NSCLC patients did not benefit from ICI + chemotherapy due to intolerance. As treatments for NSCLC are moving toward combinations for greater efficacy, their feasibility in clinical practice must be taken into consideration.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Cohort Studies , Retrospective Studies , Oncogenes
7.
J Mot Behav ; 55(1): 31-38, 2023.
Article in English | MEDLINE | ID: mdl-35876130

ABSTRACT

We investigated the generation of anticipatory (APAs) and compensatory postural adjustments (CPAs) in preparation for a step during support surface perturbation. Changes in anticipatory muscle activation in the trunk segment were predominantly in the co-contraction indices from -600 t0 -400 ms to foot-off. Reciprocal indices of the shank muscles were pronounced in the APA intervals. During the CPA intervals, larger reciprocal muscle activities were detected compared to the APA intervals. The results showed subjects co-varied the reciprocal and co-contraction activations in postural muscles to counteract the perturbation and generate mechanical effects sufficient for stepping during the APA and CPA intervals. This study enhances our understanding of the interaction between the APAs and CPAs in balance maintenance.


Subject(s)
Muscle, Skeletal , Postural Balance , Humans , Muscle, Skeletal/physiology , Postural Balance/physiology , Posture/physiology , Leg/physiology , Foot , Electromyography/methods
8.
Gan To Kagaku Ryoho ; 49(7): 775-778, 2022 Jul.
Article in Japanese | MEDLINE | ID: mdl-35851349

ABSTRACT

Weight loss during cancer chemotherapy affects the continuation of treatment; therefore, it is important to maintain and improve nutritional status. Additionally, appropriate fluid and electrolyte replacement is essential for maintaining life. This study included 100 patients who underwent outpatient chemotherapy in April 2021. The degree of dehydration was assessed based on serum osmolality, and the possibility of screening was examined by a hidden dehydration check sheet. Hidden dehydration was noted in 38 patients and dehydration in 6 patients. The incidence of pancreatic cancer was significantly lower than that of lung cancer. In the hidden dehydration check sheet, 51 patients were found to present with high possibility of hidden dehydration and required consultation to a medical professional. The serum osmolality of the results was not significantly different. During outpatient cancer chemotherapy, a certain percentage of patients present with hidden dehydration. To detect dehydration at an early stage, serum osmolality should be actively measured and continuous diet counseling, including confirmation of food and fluid intake, is required.


Subject(s)
Neoplasms , Outpatients , Early Detection of Cancer , Humans , Neoplasms/drug therapy , Osmolar Concentration
9.
J Neuroendovasc Ther ; 16(1): 52-55, 2022.
Article in English | MEDLINE | ID: mdl-37502023

ABSTRACT

Objective: Stent fracture is a risk factor for stroke. It has not been fully elucidated whether stent-in-stent procedures can effectively treat stent fractures. Case Presentation: An 80-year-old man underwent carotid artery stenting (CAS) with an open-cell stent to treat asymptomatic right internal carotid artery (ICA) stenosis. Type III stent fracture occurred during CAS. Six months later, in-stent stenosis progressed on DSA. Repeat CAS with a closed-cell stent was performed. CT showed expansion of the narrowed lumen. The patient remained stroke-free and carotid artery restenosis did not occur for 3 years postoperatively. Conclusion: Repeat CAS with a closed-cell stent is a viable treatment option for stent fracture.

10.
J Biosci Bioeng ; 133(3): 273-280, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34930670

ABSTRACT

Chinese hamster ovary (CHO) cells are widely used for constructing expression systems to produce therapeutic proteins. However, the establishment of high-producer clones remains a laborious and time-consuming process, despite various progresses having been made in cell line development. We previously developed a new strategy for screening high monoclonal antibody (mAb)-producing cells using flow cytometry (FCM). We also reported that p180 and SF3b4 play key roles in active translation on the endoplasmic reticulum, and that the productivity of secreted alkaline phosphatase was enhanced by the overexpression of p180 and SF3b4. Here, we attempted to apply the translational enhancing technology to high mAb-producing cells obtained after high-producer cell sorting. A high mAb-producing CHO clone, L003, which showed an mAb production level of >3 g/L in fed-batch culture, was established from a high mAb-producing cell pool fractionated by FCM. Clones generated by the overexpression of p180 and SF3b4 in L003 cells were evaluated by fed-batch culture. The specific productivity of clones overexpressing these two factors was ∼3.1-fold higher than that of parental L003 cells in the early phase of the culture period. Furthermore, the final mAb concentration was increased to 9.5 g/L during 17 days of fed-batch culture after optimizing the medium and culture process. These results indicate that the overexpression of p180 and SF3b4 would be promising for establishing high-producer cell lines applicable to industrial production.


Subject(s)
Antibodies, Monoclonal , Batch Cell Culture Techniques , Animals , CHO Cells , Cricetinae , Cricetulus , Recombinant Proteins , Technology
11.
Front Hum Neurosci ; 15: 674960, 2021.
Article in English | MEDLINE | ID: mdl-34335209

ABSTRACT

BACKGROUND: Effective training of the backward step response could be beneficial to improve postural stability and prevent falls. Unpredicted perturbation-based balance training (PBT), widely known as compensatory-step training, may enhance the fear of falling and the patterns of postural muscle co-contraction. Contrastingly, PBT with predictable direction or both direction and timing would suppress the fear and the co-contraction patterns during training, but the efficacy of predictable PBT for unpredictable perturbations is still unknown. OBJECTIVE: To compare the adaptation effects of compensatory-step training with and without predictable perturbations on backward stepping against unpredictable perturbations. METHODS: Thirty-three healthy young adults were randomly assigned to one of the following step training groups: Unpredicted, Predicted, and Self-initiated. In training sessions, participants were perturbed to induce a compensatory step with (Predicted group) or without (Unpredicted group) knowledge of the perturbation's direction or while knowing both the direction and timing of the perturbation (Self-initiated group). In test sessions (pre- and post-training), participants were instructed to recover their postural stability in response to an unpredicted perturbation. The margin of stability (MOS), center of mass (COM) shift, and step characteristics were measured during a backward step in both test and training sessions. RESULTS: All three groups showed a significant increase in the step length and velocity in the post-training sessions compared to those in the pre-training sessions. Moreover, in the Unpredicted and Predicted groups, but not in the Self-initiated group, the MOS at step contact was significantly increased following the training session. In addition, the Self-initiated group showed a significant increase in COM shift at 50 ms after slip onset during training compared to the Unpredicted and Predicted groups. CONCLUSION: Unpredicted and predicted PBT improve step characteristics during backward stepping against unpredictable perturbations. Moreover, the unpredictable PBT and PBT with direction-predictable perturbations enhance the feedback postural control reflected as the postural stability at step contact.

12.
World J Clin Cases ; 9(19): 5112-5125, 2021 Jul 06.
Article in English | MEDLINE | ID: mdl-34307562

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) has been suggested as an independent risk factor for nonalcoholic fatty liver disease (NAFLD), and continuous positive airway pressure (CPAP) is the first-line therapy for OSA. AIM: To clarify the efficacy of effective CPAP therapy on NAFLD of OSA patients by serum markers and transient elastography (TE) using FibroScan® (Echosens, Paris, France). METHODS: We prospectively enrolled 123 consecutive patients with OSA who met the indications for CPAP. Liver fibrosis and steatosis were assessed using TE. Before and after 6 mo of CPAP therapy, serum markers and TE were assessed for all patients. The mean usage rate of CPAP therapy for 6 mo was arbitrarily calculated in each patient and expressed as "mean compliance index" (m-CI). RESULTS: In 50 OSA patients with NAFLD, both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly decreased after 6 mo of CPAP therapy. Univariate analysis showed that decreased body weight (BW), decreased body mass index (BMI), decreased AST level, decreased hemoglobin A1c, and high m-CI were significantly related with improved ALT level. In multivariate regression model adjusted for quantities of BW change during 6 mo of CPAP therapy, high m-CI tended to improve ALT level (P = 0.051). All 17 OSA patients with NAFLD, high m-CI and no BMI changes showed significant improvements in AST and ALT levels. Meanwhile, no significant changes in TE data or serum fibrosis markers were seen. CONCLUSION: Some NAFLD could be associated with chronic intermittent hypoxia due to OSA independent of BW changes. In those cases, adequate reoxygenation from effective CPAP therapy may improve NAFLD.

13.
Article in English | MEDLINE | ID: mdl-33776430

ABSTRACT

PURPOSE: This study aimed to reveal the association between airflow limitation (AL) and carotid intima-media thickness (IMT) according to smoking status in Japan. SUBJECTS AND METHODS: This cross-sectional study was performed in 2809 subjects, who underwent a comprehensive health examination with pulmonary function tests and carotid ultrasonographic measurement. AL was defined as forced expiratory volume in 1 s/forced vital capacity of <0.7. The subjects were divided into the following four groups: never smokers without AL, never smokers with AL, former/current smokers without AL, and former/current smokers with AL. Mean IMT, the maximum measurable IMT value in the left and right common carotid arteries (IMT-C max), and mean IMT-C max were measured by carotid ultrasonography. The carotid wall thickness as defined as follows: IMT ≥ 1.1 mm (IMT1.1), IMT-C max ≥ 1.2 mm (IMTc1.2), and IMT-C max > 1.5 mm (IMTc1.5), based on each measured region. The association between AL and the carotid wall thickness according to smoking status was assessed by logistic regression analysis. RESULTS: The mean carotid IMT and mean IMT-C max were significantly higher in never smokers with AL and former/current smokers with or without AL than in never smokers without AL. In logistic regression models adjusted for sex, age, body mass index, hypertension, dyslipidemia, hyperglycemia, physical activity, and alcohol consumption, the risk of carotid wall thickness (IMT1.1 [odds ratio {OR}: 1.55; 95% confidence interval {CI}: 1.07-2.24]; IMTc1.2 [OR: 1.52; 95% CI: 1.03-2.24]; IMTc1.5 [OR: 1.99; 95% CI: 1.15-3.46]) were significantly higher in former/current smokers with AL than in never smokers without AL. CONCLUSION: The present results suggest that greater IMT and risk of carotid wall thickness were associated with AL and smoking experience.


Subject(s)
Carotid Artery Diseases , Pulmonary Disease, Chronic Obstructive , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/epidemiology , Carotid Intima-Media Thickness , Cross-Sectional Studies , Humans , Japan/epidemiology , Risk Factors , Ultrasonography
14.
J Stroke Cerebrovasc Dis ; 30(3): 105539, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33333478

ABSTRACT

BACKGROUND: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a group of systemic disorders characterized by inflammation of blood vessels and eosinophilia. Simultaneous brain and splenic infarcts are extremely rare in patients with EGPA. CASE DESCRIPTION: We report a case of a 61-year-old male with a history of asthma and sinusitis who presented with paresthesia and purpura in the lower extremities. Eosinophilia and positive Myeloperoxidase-anti-neutrophil cytoplasmic antibody were present and the diagnosis of EGPA was confirmed. Multiple bilateral cerebral and cerebellar infarcts and splenic infarction were detected. Although there was evidence of myocarditis, no cardiac thrombus was detected. Immunosuppressive and anticoagulation therapy were provided. The patient was fully recovered. CONCLUSIONS: EGPA can present as splenic infarction and ischemic stroke. Prompt diagnosis and treatment with anticoagulant and immunosuppressive agents may lead to good prognosis.


Subject(s)
Granulomatosis with Polyangiitis/complications , Ischemic Stroke/etiology , Splenic Infarction/etiology , Antibodies, Antineutrophil Cytoplasmic/blood , Anticoagulants/therapeutic use , Biomarkers/blood , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/drug therapy , Male , Middle Aged , Splenic Infarction/diagnostic imaging , Splenic Infarction/drug therapy , Treatment Outcome
15.
J Neuroendovasc Ther ; 15(11): 730-735, 2021.
Article in English | MEDLINE | ID: mdl-37502262

ABSTRACT

Objective: Mechanical thrombectomy is performed on ischemic stroke patients with acute major cerebral artery occlusion within 24 hours of symptom onset. We report a case of delayed mechanical thrombectomy for acute left internal carotid artery occlusion. Case Presentation: A 76-year-old woman suddenly presented with dysarthria and right hemiparesis was admitted to her previous hospital. She was treated by conservative therapy. The next day, she was transferred to our hospital 26 hours after onset with a diagnosis of ischemic stroke due to left carotid artery acute occlusion. Contrast CT revealed left carotid artery occlusion. Arterial fibrillation was detected. Mechanical thrombectomy through the right brachial artery was immediately performed. Complete recanalization was achieved without hemorrhagic complication. Her postoperative course was uneventful. Conclusion: In this case, delayed mechanical thrombectomy for acute major cerebral artery occlusion was safely performed 24 hours after symptom onset.

16.
Cancer Sci ; 111(10): 3739-3746, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32726470

ABSTRACT

Most clinical trials of non-small-cell lung cancer (NSCLC) exclude patients with poor ECOG performance status (PS). Thus, the efficacy of immune checkpoint inhibitors (ICIs) in patients with poor PS remains unclear. Herein, we used data from a retrospective cohort to assess the potential clinical benefits of ICIs in NSCLC patients with poor PS. Data from NSCLC patients who received ICI monotherapy at 9 institutions between December 2015 and May 2018 were retrospectively analyzed. After excluding 4 patients who lacked PS data, a total of 527 ICI-treated patients, including 79 patients with PS 2 or higher, were used for our analyses. The progression-free survival (PFS) and overall survival (OS) of patients with PS 2 or higher were significantly shorter compared with those of PS 0-1 patients (median PFS, 4.1 vs 2.0 months; P < .001 and median OS, 17.4 vs 4.0 months; P < .001). Among NSCLC patients with programmed cell death protein-ligand 1 (PD-L1) expression of 50% or higher who were treated with pembrolizumab as first-line therapy, the median PFS times of patients with PS 2 and 0-1 were 7.3 and 8.1 months, respectively. There was no significant difference in PFS between patients with PS 2 and 0-1 (P = .321). Although poor PS was significantly associated with worse outcomes in NSCLC patients treated with ICIs, pembrolizumab as a first-line treatment in NSCLC patients expressing high levels of PD-L1 could provide a clinical benefit, even in patients with PS 2.


Subject(s)
B7-H1 Antigen/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/administration & dosage , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , B7-H1 Antigen/antagonists & inhibitors , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Middle Aged , Progression-Free Survival
17.
Res Sports Med ; 28(4): 588-593, 2020.
Article in English | MEDLINE | ID: mdl-32268804

ABSTRACT

We investigated changes in the anticipatory activity of the leg and trunk muscles in preparation for a step during support surface perturbation. Eight healthy subjects performed stepping tasks under three conditions: normal, forward perturbation, and backward perturbation. R and C indices were calculated for the reciprocal and co-activation patterns of muscle pairs within the time intervals typical of anticipatory postural adjustments. When the support surface perturbation occurred, anticipatory muscle activations were predominantly in the C indices in the leg muscles. Significant differences in the maximum displacement of the centre of pressure were seen between conditions (FS vs NS; BS vs FS). The results suggest that activation of the leg muscles rather than the trunk muscles was modified to ensure equilibrium for taking a step in response to support surface perturbation.


Subject(s)
Anticipation, Psychological , Leg/physiology , Muscle, Skeletal/physiology , Postural Balance , Torso/physiology , Adult , Female , Humans , Male , Muscle Contraction , Task Performance and Analysis , Young Adult
18.
Lung Cancer ; 139: 140-145, 2020 01.
Article in English | MEDLINE | ID: mdl-31786476

ABSTRACT

OBJECTIVES: Body mass index (BMI) is reported to be associated with the efficacy of immune checkpoint inhibitors (ICIs) in solid tumors such as melanomas. However, it remains unclear whether such a relationship exists in non-small cell lung cancer (NSCLC) treated with programmed cell death protein 1 (PD-1)/ programmed death-ligand 1(PD-L1) inhibitors. The purpose of this study was to investigate the relationship between BMI and the efficacy of ICI treatment in patients with advanced NSCLC. MATERIALS AND METHODS: The medical records of NSCLC patients who received PD-1/PD-L1 antibody monotherapy at nine institutions between December 2015 and May 2018 were reviewed retrospectively. The effect of BMI was investigated in two cohorts. Cohort 1 included patients with NSCLCs with high PD-L1 expression (≥ 50 %) treated with pembrolizumab as first-line therapy, and cohort 2 included patients with NSCLCs treated with nivolumab/pembrolizumab/atezolizumab as second- or later-line treatment. RESULTS: A total of 513 from nine institutions were analyzed (84 in cohort 1, 429 in cohort 2). Using a BMI cut-off value of 22 kg/m2, which is an ideal BMI in our country (high BMI:22.0 and low BMI:22.0), there was no significant difference in the PFS or OS between the high and low BMI patients in cohort 1. However, in cohort 2, survival was significantly longer in patients with a high versus low BMI (PFS: 3.7 vs. 2.8 months, p = 0.036; OS: 15.4 vs. 13.5 months, p = 0.021). CONCLUSION: BMI was significantly associated with the efficacy of ICIs in patients with NSCLC treated with second- or later-line PD-1/PD-L1 inhibitors in our cohort.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Body Mass Index , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/mortality , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Follow-Up Studies , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
19.
BMC Geriatr ; 19(1): 340, 2019 12 03.
Article in English | MEDLINE | ID: mdl-31795946

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the efficacy of dance in the experienced older dancers compared to the inexperienced older adults. We explored the effect of dance on the composition of muscle groups and multi-muscle synergies stabilizing the center of pressure (COP) displacement in preparation to take a step during support surface translation. METHODS: Eight dance experienced elderly participants were asked to take a step in response to support surface perturbations. Uncontrolled manifold analysis was used to identify muscle modes (M-modes) as factors in the muscle activation space. Variance components in the M-mode space and indices of M-mode synergy stabilizing COP displacement were computed. RESULTS: The reciprocal M-modes were observed more frequently in the dance group than in the control group prior to the step initiation. Dance led to higher indices of multi-muscle synergies and earlier anticipatory synergy adjustments during preparation for making a step in response to the support surface translations. CONCLUSIONS: Dance appeared to be associated with adjustments in both the composition of M-modes and M-mode co-variation patterns resulting in stronger synergies stabilizing COP coordinate in older adults. The results reported here could have clinical relevance when offering a dance approach to balance training for impaired individuals.


Subject(s)
Dancing/physiology , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Postural Balance/physiology , Age Factors , Aged , Case-Control Studies , Cross-Sectional Studies , Electromyography , Female , Humans , Male , Middle Aged
20.
Int J Chron Obstruct Pulmon Dis ; 14: 2355-2363, 2019.
Article in English | MEDLINE | ID: mdl-31695355

ABSTRACT

Introduction: This study aimed to assess the association between airflow limitation (AL) severity and reduced bone mineral density (BMD) in Japanese men. Subjects and methods: This cross-sectional study included 290 subjects aged over 40 years (mean age 72.0, SD 11.6), who underwent a comprehensive health examination, including spirometry and measurement of BMD at the left femoral neck using dual-energy X-ray absorptiometry (DXA), between 2016 and 2017 at Japanese Red Cross Kumamoto Health Care Center. AL was defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of <0.7. Reversibility tests were not performed in this study. The criteria used for the AL staging were developed according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines. The subjects were divided into the following three groups: a control group (normal pulmonary function), GOLD Stage I group (mild AL), and GOLD Stage II-IV group (moderate-to-very severe AL). BMD was classified based on the young adult mean (YAM) as normal (88.6% ≦ YAM [-1 SD ≦]), osteopenia (70% -2.5 SD]), or osteoporosis (YAM ≦ 70% [≦ -2.5 SD]). Reduced BMD was defined as osteopenia, osteoporosis, or medication used for osteoporosis. Logistic regression analysis was used to assess the association between AL severity and the reduced BMD. Results: The prevalence of reduced BMD in subjects with moderate-to-severe AL (76.2%) was significantly higher than in those without AL (47.9%) (p=0.030). In logistic regression models adjusted for age, body mass index, pack-years, physical activity, and alcohol drinking, the risk of reduced BMD (odds ratio: 3.87; 95% confidence interval: 1.20-12.49; p=0.024) was significantly higher in subjects with moderate-to-severe AL than in those with normal pulmonary function. Conclusion: Present results suggest that reduced BMD is associated with AL severity in Japanese men.


Subject(s)
Bone Density , Bone Diseases, Metabolic/complications , Bone Diseases, Metabolic/physiopathology , Osteoporosis/complications , Osteoporosis/physiopathology , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Ventilation , Aged , Aged, 80 and over , Cross-Sectional Studies , Forced Expiratory Volume , Humans , Japan , Male , Middle Aged , Severity of Illness Index , Vital Capacity
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