[Association between the history of falls and being homebound in elderly diabetic patients].

OBJECTIVE: The purpose of this study was to investigate the relationship between a history of falls and being homebound in elderly diabetic patients. METHODS: The subjects were diabetic patients ≥65 years old visiting the outpatient clinic of Ise Red Cross Hospital. Patients were defined as being confined if they went out less than once a day, and their history of falls in the past year was investigated. Adjusted odds ratios for being homebound were calculated using a logistic regression analysis with a dependent variable of being homebound and explanatory variables of a history of falls and adjustment factors (age, sex, duration of diabetes, HbA1c, cardiovascular disease, cognitive and functional decline, depression, living alone, isolation, and diabetes treatment). RESULTS: A total of 564 patients (319 men and 245 women) were included in the study. The numbers of patients with a history of falls and who were homebound were 198 (35.1%) and 88 (15.6%), respectively. The adjusted odds ratio for being homebound to a history of falls was 2.69 (95% confidence interval, 1.31 to 5.52; P=0.007). CONCLUSION: In this study, a history of falls was significantly associated with being homebound. It is important to pay close attention to homebound elderly diabetic patients with a history of falls.

[Multimodal treatment program for elderly diabetic patients with sarcopenia improves the muscle strength and physical function].

OBJECTIVE: To evaluate the effects of a multimodal treatment program on the muscle strength, physical function, and skeletal muscle mass in elderly diabetic patients with sarcopenia. METHODS: Diabetic patients over 65 years old attending the Department of Diabetes and Metabolism, Ise Red Cross Hospital, were included. The diagnosis of sarcopenia was based on the Asian Working Group for Sarcopenia 2019. The measurement of extremity skeletal muscle mass was assessed by the multi-frequency bioelectrical impedance method, muscle strength was assessed by the grip strength, and the physical function was assessed by the 5-time chair stand test. The muscle strength, physical function, extremity skeletal muscle mass, and other parameters were assessed before and after 12 weeks of the multimodal treatment program (optimization of protein intake, resistance training, and patient education on sarcopenia) and then compared. Paired t-tests were used for the statistical analysis. RESULTS: Fourteen patients (3 men and 11 women) were included in the analysis of this study. The mean age was 74.4±4.7 years old. Significant improvements in the grip strength (male, 23.2±5.6 kg to 25.6±5.5 kg, P=0.014; female, 15.5±5.0 kg to 18.9±5.0 kg, P<0.001) and 5-time chair stand test (11.2±2.5 seconds to 8.6±1.7 seconds, P=0.002) were found with the multimodal treatment program. There was also a significant decrease in HbA1c (8.1±0.7% to 7.7±0.9%, P=0.004). However, although an increasing trend in the amount of extremity skeletal muscle mass was noted, there was no significant difference. CONCLUSIONS: A multimodal treatment program for elderly diabetic patients with sarcopenia showed an improvement in the muscle strength and physical function.

Verification of the predictive validity for mortality of the SARC-F questionnaire based on a meta-analysis.

BACKGROUND: Although the association between SARC-F questionnaire positivity and mortality has previously been studied, the results are inconsistent. Testing the predictive validity of the SARC-F questionnaire for clinically relevant outcomes of vital prognoses is important. AIM: The objective of this study was to test the predictive validity of SARC-F by conducting a meta-analysis on the association between SARC-F, a screening tool for sarcopenia, and mortality. METHODS: This meta-analysis used the MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar databases for literature searches. Studies that examined the relationship between SARC-F questionnaire positivity and mortality and reported hazard ratios or odds ratios and 95% confidence intervals were included. A random-effects model was used for statistical analyses, and pooled hazard ratios, pooled odds ratios, and 95% confidence intervals were calculated. RESULTS: Through the literature search, we found five studies (7501 individuals) that met the eligibility criteria for this study. The pooled hazard ratio for SARC-F questionnaire positivity and mortality was 1.87 (95% confidence interval 1.41-2.46; P < 0.001), indicating a significant association. The pooled odds ratio for SARC-F questionnaire positivity and mortality was 1.97 (95% confidence intervals 1.10-3.53; P = 0.02), showing a significant association. CONCLUSIONS: There was a significant association between SARC-F positivity and future mortality, indicating the predictive validity of the SARC-F questionnaire. TRIAL REGISTRATION: Not applicable.

Effects of Antidiabetic Drugs on Muscle Mass in Type 2 Diabetes Mellitus.

BACKGROUND: When considering the administration of glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or metformin, it is important to understand their weight loss effect as well as the degree of muscle loss caused by each drug in clinical practice. OBJECTIVE: To comparatively examine the effects of GLP-1RAs and oral antidiabetic drugs, including SGLT2 inhibitors and metformin, on muscle mass and body weight in patients with type 2 diabetes via a network meta-analysis of randomized controlled trials. METHODS: We included randomized controlled trials evaluating the effects of antidiabetic drugs on muscle mass and body weight. Mean difference (MD) and 95% confidence intervals (CIs) were calculated using a random-effects network meta-analysis. RESULTS: Of the studies identified, 18 randomized controlled trials (1, 363 subjects) satisfied the eligibility criteria. In all studies, the effects of these drugs on fat-free mass (FFM) were evaluated. Therefore, FFM, which is used as an alternative index of muscle mass, was included in the study. Semaglutide (MD: -1.68, 95% CI: -2.84 to -0.52), dapagliflozin (-0.53, -0.93 to -0.13), and canagliflozin (-0.90, -1.73 to -0.07) showed a significant decrease in FFM compared with the placebo. Metformin did not show a significant decrease in FFM compared with the placebo. When compared with the placebo, semaglutide, dapagliflozin, ipragliflozin, and canagliflozin showed a significant weight loss. CONCLUSION: Although semaglutide, dapaglifrozin, and canagliflozin have a large weight loss effect, it is important to pay attention to muscle loss because a decrease in FFM was observed.

Effects of oral antidiabetic drugs and glucagon-like peptide-1 receptor agonists on left ventricular diastolic function in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis.

The present study aimed to compare the effects of oral antidiabetic drugs (OADs) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on left ventricular diastolic function in patients with type 2 diabetes mellitus using a network meta-analysis of randomized controlled trials (RCTs). Literature searches were conducted on Medline, the Cochrane Controlled Trials Registry, and ClinicalTrials.gov . RCTs that assessed the effects on left ventricular diastolic function of OADs and GLP-1RAs in patients with type 2 diabetes were included. The outcome was the value (E/e') obtained by dividing peak early diastolic transmitral flow velocity (E) by the mitral annular early diastolic velocity (e'). Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated from a random-effects network meta-analysis. Eight RCTs (592 patients) identified in a literature search met the eligibility criteria for this study and were included in the network meta-analysis. Compared with placebo, liraglutide was the only drug that caused a significant improvement in left ventricular diastolic function (SMD, - 0.65; 95% CI, - 1.23 to - 0.08). In addition, when the effects on left ventricular diastolic function were evaluated across drugs, liraglutide alone caused a significant improvement in left ventricular diastolic function compared with OADs (sitagliptin, linagliptin, pioglitazone, rosiglitazone, voglibose, and glimepiride). From the perspective of preventing the onset of heart failure, the administration of liraglutide for type 2 diabetes is promising.

Factors associated with social isolation and being homebound among older patients with diabetes: a cross-sectional study.

OBJECTIVE: We aimed at investigating factors associated with social isolation and being homebound in older patients with diabetes. DESIGN: Cross-sectional study. SETTINGS: Those undergoing outpatient treatments at Ise Red Cross Hospital, Mie Prefecture. PARTICIPANTS: Patients with diabetes aged ≥65 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Social isolation was defined as indulging in less than one interaction per week with individuals other than cohabiting family members. We defined homebound as going outside home less than once a day. To identify factors associated with social isolation and being homebound, we performed logistic regression analysis. The dependent variable was social isolation or homebound and independent variables were basic attributes, glycaemic parameters, complications and treatment details. RESULTS: We analysed 558 cases (320 men and 238 women). Among these, 174 (31.2%) were socially isolated; meanwhile, 87 (15.6%) were homebound. The glycoalbumin/haemoglobin A1c ratio (OR 4.52; 95% CI 1.07 to 19.1; p=0.040) and the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) scores (OR 0.72; 95% CI 0.57 to 0.90; p=0.006) had significant associations with social isolation. TMIG-IC scores (OR 0.78; 95% CI 0.66 to 0.92; p=0.003) and insulin use (OR 4.29; 95% CI 1.14 to 16.1; p=0.031) were associated with being homebound. CONCLUSION: In older patients with diabetes, glycaemic fluctuations and insulin use are associated with social isolation and being homebound, respectively. In addition, a decline in higher level functional capacity is a common factor associated with social isolation and being homebound. Thus, it is important to pay attention to social isolation and being homebound when a decline in higher level functional capacity, increased glycaemic fluctuations and insulin use in older patients with diabetes are observed.

Preparation of the Japanese Version of the Diabetes Caregiver Activity and Support Scale and Verification of Its Reliability and Validity.

PURPOSE: The purpose of the study was to adapt and psychometrically evaluate a Japanese language version of the Diabetes Caregiver Activity and Support Scale (D-CASS-J) to be culturally relevant for people with diabetes living in Japan. METHODS: A Japanese translation of the original version of the D-CASS was prepared, corrected, and back-translated. Family caregivers of patients with diabetes mellitus ages ≥65 years who visited the outpatient diabetes clinic of Ise Red Cross Hospital were included. Cronbach's α coefficients were calculated as an assessment of internal consistency. Exploratory factor analyses were performed to verify construct validity. Hierarchical multiple regression analyses were performed using depression as the dependent variable and D-CASS-J and other variables as explanatory variables. Pearson's correlation coefficients between D-CASS-J scores and the support burden scale scores were calculated to verify criterion-related validity. RESULTS: This analysis included 268 subjects. Cronbach's α coefficient was .86. Factor analyses showed the same single-factor structure as the original version of the D-CASS. Hierarchical multiple regression analyses based on the conceptual model demonstrated construct validity. D-CASS-J scores were significantly correlated with support burden scale scores. CONCLUSIONS: For family caregivers of elderly patients with diabetes in Japan, D-CASS-J can be used as a tool to evaluate difficulties experienced while providing support to patients.

Frequency of Social Isolation and Homeboundness and Their Relationships with High-Level Functional Capacity in Elderly Diabetic Patients.

PURPOSE: To determine the frequency of social isolation (hereinafter, isolation) and homeboundness in elderly diabetic patients and to investigate their relationships with high-level functional capacity. PATIENTS AND METHODS: Subjects were diabetic outpatients aged 65 years and older who were visiting the Japanese Red Cross Ise Hospital. Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) was used to evaluate high-level functional capacity. Isolation was defined as having less than one interaction per week with someone other than co-habiting family members. Homeboundness was defined as leaving the house less than once a day. Multiple regression analysis was performed with the TMIG-IC score as the dependent variable and isolation and homeboundness as independent variables. RESULTS: Four hundred fifty-one patients were included in the analysis. The frequency of isolation and homeboundness affected 37% and 13.3% of men and 28.9% and 20.6% of women, respectively. The adjusted partial regression coefficient of the TMIG-IC scores of isolated, homebound, and isolated+homebound men was -0.94 [95% confidence interval (CI), -1.68 to -0.21; P = 0.012], -0.27 (95% CI, -1.93 to 1.39; P = 0.746), and -4.03 (95% CI, -5.37 to -2.68; P < 0.001) in relation to that of the non-isolated and non-homebound group as reference. In women, the respective coefficients to the reference were -1.33 (95% CI, -2.93 to 0.25; P = 0.099), -0.65 (95% CI, -2.56 to 1.26; P = 0.501), and -3.01 (95% CI, -4.92 to -1.1; P = 0.002), respectively. CONCLUSION: The frequency of isolation was high in both female and male elderly diabetic patients. In men, there was a significant relationship between isolation and decline in high-level functional capacity. In both men and women, there was a significant relationship between isolation+homeboundness and decline in high-level functional capacity.

Preparation, Reliability, and Validity of a Japanese Version of the "Satisfaction of Treatment among Caregivers of Dependent Type 2 Diabetic Patients" Questionnaire.

The aim of this study was to prepare a Japanese version of the "Satisfaction of Treatment among Caregivers of Dependent Type 2 Diabetic Patients" (STCD2-J) questionnaire, which is used to assess the satisfaction of family caregivers with respect to the treatment for elderly patients with type 2 diabetes mellitus who require support. In addition, the reliability and validity of the STCD2-J questionnaire were analyzed. A Japanese version of the original STCD2 questionnaire was prepared, revised, and back-translated; the back-translated version was sent to the authors of the original version for confirmation. Family caregivers of patients with type 2 diabetes mellitus aged ≥65 years who regularly underwent medical examinations at the diabetes mellitus outpatient clinic of Ise Red Cross Hospital were included. Cronbach's α coefficient was calculated to assess internal consistency. Exploratory factor analyses were performed to assess construct validity, and Pearson's correlation coefficients between STCD2-J score and HbA1c as well as the degree of satisfaction with patients' blood glucose levels, depression, and negative self-assessment of nursing care were calculated to assess criterion-related validity. This study included 208 individuals (55 males and 153 females). Cronbach's α coefficient was 0.88. Factor analyses showed a single-factor structure both with and without rotation. The STCD2-J scores were significantly inversely correlated with HbA1c (r = -0.27, P < 0.001). Significant correlations were observed between the STCD2-J scores and degree of satisfaction with patients' blood glucose levels (r = 0.43, P < 0.001), depression (r = -0.20, P = 0.003), and negative self-assessment of nursing care (r = -0.19, P = 0.004). The reliability and validity of the STCD2-J questionnaire were confirmed. The STCD2-J questionnaire can be used in Japan as a tool to assess the satisfaction of family caregivers with the treatment of elderly patients with type 2 diabetes mellitus requiring support.

Effects of Flash Glucose Monitoring on Dietary Variety, Physical Activity, and Self-Care Behaviors in Patients with Diabetes.

The aim of this study was to evaluate the effects of flash glucose monitoring on dietary variety, physical activity, and self-care behavior in patients with diabetes. This study included outpatients with diabetes using insulin who presented at the Department of Diabetes and Metabolism of the Ise Red Cross Hospital. Before initiating flash glucose monitoring and 12 weeks after its initiation, blood glucose-related parameters were assessed and self-administered questionnaires were completed (Dietary Variety Score (DVS), the International Physical Activity Questionnaire (IPAQ), the Summary of Diabetes Self-Care Activities Measure (SDSCA), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ)) and compared between the two time points. We analyzed 42 patients with type 1 diabetes mellitus and 48 patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus, but not type 1 diabetes mellitus, there was an increase in moderate/high category scores for IPAQ (P < 0.001) and for treatment satisfaction reported via DTSQ. Furthermore, in patients with type 2 diabetes mellitus, the glycemic excursion index improved significantly and HbA1c decreased significantly (from 7.7 (1.2) to 7.4 (0.8), P = 0.025). Results showed that standard deviation and mean amplitude of glycemic excursions significantly decreased in patients with type 1 diabetes mellitus (from 71.2 (20.4) to 66.2 (17.5), P = 0.033 and from 124.6 (31.9) to 108.1 (28.4), P < 0.001, respectively). Flash glucose monitoring is a useful tool to improve physical activity in patients with type 2 diabetes.

[Rapidly Growthing Mediastinal Cystic Teratoma with Suggestive Perforation by Infection in Pregnancy].

The patient was a 34-year-old female and was 32 weeks pregnant. She was admitted to our department because of mediastinal cyst with infection. She complained of chest pain. Chest computed tomography(CT) revealed the rapid growth of anterior mediastinal tumor. The pain increased after 2 days and magnetic resonance imaging (MRI) suggested the rupture of teratoma. After delivery by Caesarean section, we performed abscess drainage, to stabilize the patient's condition and thereafter the resection of mediastinal teratoma with partial resection of right lung was performed. Histological findings showed a mature teratoma.

Activated CD8+ T cell extracellular vesicles prevent tumour progression by targeting of lesional mesenchymal cells.

Fibroblastic tumour stroma comprising mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs) promotes the invasive and metastatic properties of tumour cells. Here we show that activated CD8+ T cell-derived extracellular vesicles (EVs) interrupt fibroblastic stroma-mediated tumour progression. Activated CD8+ T cells from healthy mice transiently release cytotoxic EVs causing marked attenuation of tumour invasion and metastasis by apoptotic depletion of mesenchymal tumour stromal cells. Infiltration of EV-producing CD8+ T cells is observed in neovascular areas with high mesenchymal cell density, and tumour MSC depletion is associated with preferential engulfment of CD8+ T cell EVs in this setting. Thus, CD8+ T cells have the capacity to protect tumour progression by EV-mediated depletion of mesenchymal tumour stromal cells in addition to their conventional direct cytotoxicity against tumour cells.

T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/γcnull mice.

Adoptive cell therapy with lymphocytes that have been genetically engineered to express tumor-reactive T-cell receptors (TCR) is a promising approach for cancer immunotherapy. We have been exploring the development of TCR gene therapy targeting cancer/testis antigens, including melanoma-associated antigen (MAGE) family antigens, that are ideal targets for adoptive T-cell therapy. The efficacy of TCR gene therapy targeting MAGE family antigens, however, has not yet been evaluated in vivo. Here, we demonstrate the in vivo antitumor activity in immunodeficient non-obese diabetic/SCID/γc(null) (NOG) mice of human lymphocytes genetically engineered to express TCR specific for the MAGE-A4 antigen. Polyclonal T cells derived from human peripheral blood mononuclear cells were transduced with the αß TCR genes specific for MAGE-A4, then adoptively transferred into NOG mice inoculated with MAGE-A4 expressing human tumor cell lines. The transferred T cells maintained their effector function in vivo, infiltrated into tumors, and inhibited tumor growth in an antigen-specific manner. The combination of adoptive cell therapy with antigen peptide vaccination enhanced antitumor activity, with improved multifunctionality of the transferred cells. These data suggest that TCR gene therapy with MAGE-A4-specific TCR is a promising strategy to treat patients with MAGE-A4-expressing tumors; in addition, the acquisition of multifunctionality in vivo is an important factor to predict the quality of the T-cell response during adoptive therapy with human lymphocytes.

Biomechanical role of peri-implant cancellous bone architecture.

PURPOSE: The aim of this study was to investigate the biomechanical role of trabecular bone around dental implants in the mandible. MATERIALS AND METHODS: The model in this study was made using micro-computed tomography data taken from a cadaver in whom endosseous implants had been in place for 15 years prior to death. Morphologic analysis and three-dimensional (3D) finite element analysis were performed to calculate the peri-implant loading path of the model in which the trabecular structure was accurately simulated. RESULTS: As seen through multiscale analysis using the homogenization method, the trabecular bone architecture around implants was isotropic for the most part. Also, 3D finite element analysis showed that compressive stresses oblique to the implant axis were transmitted to the lower constrained surface; tensile stresses oblique to the implant axis were transmitted to the upper constrained surface, and they intersected each other with vertical loading. The highest stress in cancellous bone was observed on perpendicular loading, and stress produced in trabeculae decreased approaching horizontal loading. CONCLUSION: Cancellous bone architecture around the implant was generally isotropic. 3D finite element analysis showed that cancellous bone trabeculae around implants dispersed stress by forming load transfer paths. The results suggest that trabecular bone plays a major role in supporting functional pressure exerted via the implant.

Relationship between function of masticatory muscle in mouse and properties of muscle fibers.

Mammals exhibit marked morphological differences in the muscles surrounding the jaw bone due to differences in eating habits. Furthermore, the myofiber properties of the muscles differ with function. Since the muscles in the oral region have various functions such as eating, swallowing, and speech, it is believed that the functional role of each muscle differs. Therefore, to clarify the functional role of each masticatory muscle, the myofiber properties of the adult mouse masticatory muscles were investigated at the transcriptional level. Expression of MyHC-2b with a fast contraction rate and strong force was frequently noted in the temporal and masseter muscles. This suggests that the temporal and masseter muscles are closely involved in rapid antero-posterior masticatory movement, which is characteristic in mice. Furthermore, expression of MyHC-1 with a low contraction rate and weak continuous force was frequently detected in the lateral pterygoid muscle. This suggests that, in contrast to other masticatory muscles, mouse lateral pterygoid muscle is not involved in fast masticatory movement, but is involved in functions requiring continuous force such as retention of jaw position. This study revealed that muscles with different roles function comprehensively during complicated masticatory movement.