University Hospital Medical Information Network Research Articles

A Randomized Controlled Trial of Betamethasone on Fatigue in Patients With Advanced Cancer

ContextFatigue is one of the most uncomfortable physical symptoms seen in patients with advanced cancer. Previous studies have reported on the efficacy of corticosteroids from Western countries. ObjectivesTo assess the effectiveness of 4mg betamethasone improving fatigue among Japanese patients with advanced cancer. MethodsA randomized, double-blind, placebo-controlled trial enrolled eligible patients with advanced cancer expected to survive 1–2 months, with an Eastern Cooperative Oncology Group Performance Status of 2–3, and experiencing fatigue according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-15-palliative criteria. Participants received twice-daily oral administration of 2 mg betamethasone (4 mg/d) or placebo for seven days, with fatigue assessed using EORTC QLQ-C15-PAL subscale and numerical rating scale (NRS) score (at baseline and day seven). The trial was registered under the University Hospital Medical Information Network (UMIN)000011913. ResultsAmong the 267 screened patients, 81 were eligible, of which 70 were evaluable (betamethasone, 33; placebo, 37). The mean difference in the EORTC-QLQ-C15-PAL fatigue subscale was −8.2 (95% CIs: −22.3, 0.0; P = 0.178) and in a NRS for fatigue was −1.2 (95% CIs: −2.5, −0.01; P = 0.048), respectively. Emotional function, appetite loss, and global-health were slightly better in the betamethasone group than in the placebo group. ConclusionThe impact of betamethasone 4 mg/d on alleviating fatigue in patients with advanced cancer in the last weeks of life did not reach statistical significance in the EORTC-QLQ-C15-PAL as the primary endpoint, however, it was significant in the NRS, the secondary endpoint.

Inflammation‑based prognostic markers of metastatic pancreatic cancer using real‑world data in Japan: The Tokushukai REAl‑world Data (TREAD) project.

Inflammation-based prognostic markers based on a combination of blood-based parameters, including the modified Glasgow prognostic score (mGPS), have been associated with clinical outcomes in patients with various types of cancer. The present study aimed to evaluate and compare the accuracy of these previously reported markers in patients with metastatic pancreatic cancer receiving first-line chemotherapy. A total of 846 patients were identified between April 2010 and March 2020 as part of a nationwide real-world study from 46 Tokushukai medical group hospitals in Japan. Blood laboratory data collected within 14 days of starting first-line chemotherapy assessed 17 inflammation-based prognostic markers. Information from patients with no missing data was used to compare the accuracy and performance of the inflammation-based prognostic markers. A total of 487 patients were eligible for this supplemental analysis. The 17 inflammation-based markers demonstrated significant prognostic value. Among them, the concordance rate with overall survival (OS) was highest for mGPS. The median OS time of patients with mGPS 0, 1 and 2 was 8.2, 6.0 and 2.9 months, respectively. Compared with mGPS 0, mGPS 1 and 2 showed hazard ratios of 1.39 (95% confidence interval, 1.07-1.81) and 2.63 (2.00-3.45), respectively. The present real-world data analysis showed that various previously reported inflammation-based markers had significant prognostic value in patients with metastatic pancreatic cancer. Among these markers, the mGPS demonstrated the highest level of accuracy. This trial has been registered in the University Hospital Medical Information Network Clinical Trials Registry as UMIN000050590 on April 1, 2023.

Effect of aromatherapy with peppermint essential oil on the gag reflex: a randomized, placebo-controlled, single-blind, crossover study

BackgroundSensitive gag reflexes prevent dental patients from receiving appropriate treatment. Aromatherapy helps patients relax during dental procedures. However, the effect of aromatherapy on the gag reflex caused by the stimulation of the oral cavity is unknown. This study aimed to evaluate whether aromatherapy reduces gag reflexes during oral stimulation.MethodsIn this randomized, placebo-controlled, single-blind, crossover study, the gag reflexes of 24 healthy individuals (12 females and 12 males; mean age: 34.3 ± 9.5 years) were quantified. A standard saliva ejector was slowly guided down the participant’s throat to determine the maximum tolerance of the gag reflex, and the insertion distance was measured to quantify the gag reflex. All individuals participated in an aromatherapy session with peppermint essential oil and a placebo session with distilled water. The gag reflex was quantified before (baseline) and after each session. Another measurement was performed using nitrous oxide/oxygen inhalation as a positive control.ResultsGag reflex values significantly increased after aromatherapy with both peppermint essential oil and placebo compared to baseline values (paired t-test, P < 0.001 and P = 0.014, respectively). The gag reflex value also increased significantly during nitrous oxide/oxygen inhalation (paired t-test, P < 0.001). There was no significant difference in the increase rate of gag reflex values between the positive control and aromatherapy interventions, but it was significantly lower after the placebo intervention (repeated measures analysis of variance, P = 0.003; post-hoc test, P = 0.83 and P = 0.02).ConclusionAromatherapy with peppermint essential oil has the potential for reducing gag reflex during dental procedures.Trial registrationThe study was registered in the University hospital Medical Information Network Clinical Trials Registry under the code UMIN000050616 (approved 17/03/2023).

Evaluating the usefulness of considering the size and morphological type of type B2 vessel area based on Japan Esophageal Society classification in estimating tumor invasion depth in superficial esophageal squamous cell carcinomas: study protocol for a prospective observational study (Japan BEES study)

BackgroundAccurate evaluation of tumor invasion depth is essential to determine the appropriate treatment strategy for patients with superficial esophageal cancer. The pretreatment tumor depth diagnosis currently relies on the magnifying endoscopic classification established by the Japan Esophageal Society (JES). However, the diagnostic accuracy of tumors involving the muscularis mucosa (MM) or those invading the upper third of the submucosal layer (SM1), which correspond to Type B2 vessels in the JES classification, remains insufficient. Previous retrospective studies have reported improved accuracy by considering additional findings, such as the size and macroscopic type of the Type B2 vessel area, in evaluating tumor invasion depth. Therefore, this study aimed to investigate whether incorporating the size and/or macroscopic type of the Type B2 vessel area improves the diagnostic accuracy of preoperative tumor invasion depth prediction based on the JES classification.MethodsThis multicenter prospective observational study will include patients diagnosed with MM/SM1 esophageal squamous cell carcinoma based on the Type B2 vessels of the JES classification. The tumor invasion depth will be evaluated using both the standard JES classification (standard-depth evaluation) and the JES classification with additional findings (hypothetical-depth evaluation) for the same set of patients. Data from both endoscopic depth evaluations will be electronically collected and stored in a cloud-based database before endoscopic resection or esophagectomy. This study’s primary endpoint is accuracy, defined as the proportion of cases in which the preoperative depth diagnosis matched the histological depth diagnosis after resection. Outcomes of standard- and hypothetical-depth evaluation will be compared.DiscussionCollecting reliable prospective data on the JES classification, explicitly concerning the B2 vessel category, has the potential to provide valuable insights. Incorporating additional findings into the in-depth evaluation process may guide clinical decision-making and promote evidence-based medicine practices in managing superficial esophageal cancer.Trial registrationThis trial was registered in the Clinical Trials Registry of the University Hospital Medical Information Network (UMIN-CTR) under the identifier UMIN000051145, registered on 23/5/2023.

MAINTENANCE EFFICACY OF ORAL INDIGO NATURALIS FOR ULCERATIVE COLITIS: A SINGLE-CENTER, OPEN-LABEL, RANDOMIZED, CONTROLLED STUDY

Abstract BACKGROUND Indigo naturalis (IN) is one of the herbal medicines in Chinese medicine. Recent reports have demonstrated a strong remission induction efficacy of oral IN in induction therapy for ulcerative colitis (UC), but the efficacy of IN in maintenance therapy for UC is unknown. OBJECTIVES We aimed to clarify the maintenance effect of IN. METHODS A single-center, open-label, randomized, controlled trial was conducted from August 2017 to August 2020. Patients with UC who received induction therapy with IN and maintenance therapy with IN for at least 1 year were enrolled. Patients with endoscopically confirmed mucosal healing (Mayo endoscopic subscore 0 or 1) were randomized. Patients were randomized to continue or discontinue IN. The primary endpoint was the remission rate at 52 weeks after discontinuation. Patients who relapsed during the observation period were given additional therapy, and remission rates were examined for patients who received an increased dose of IN or resumed oral therapy. The study was registered in the University Hospital Medical Information Network Center Trials registry, UMIN000028574. RESULTS A total of 20 patients participated in this study, 10 in the IN-continued group and 10 in the IN-discontinued group. The median age was 32.5 years and 33.5 years in the IN-continued group and IN-discontinued group, respectively, and 6 and 5 patients were male. Two patients in the IN-continued group and three patients in the IN-discontinued group were treated with azathioprine. One patient in the IN-continued group and three patients in the IN-discontinued group were treated with anti-tumor necrosis factor therapy. The remission rates at 52 weeks were 90% (9/10) of patients in the IN-continued group and 20% (2/10) in the IN-discontinued group. The remission rate was significantly higher in the IN-continued group (p = 0.0055). Of the 9 patients who relapsed, 7 were treated with increased or resumed oral IN, and all patients were induced remission again. No serious adverse events were observed during the observation period. CONCLUSIONS IN appears to be very effective in maintaining remission; the high efficacy of reintroduction in patients who relapsed after discontinuation of IN suggests that discontinuation of IN in cases of remission may be an option.

Surgeon fatigue in robot-assisted and laparoscopic gastrectomy for gastric cancer: Exploratory prospective observational study ancillary to JCOG1907 randomized controlled trial (JCOG1907A1).

TPS422 Background: Fatigue is being increasingly recognized as an important factor in surgical procedures, because it leads to errors in surgeons' decisions and reduced operating efficiency. In comparison to laparoscopic surgery, robot-assisted surgery is expected to reduce surgeon fatigue due to ergonomic adjustments, comfortable sitting positions, minimal restriction of instrument movement, and stable visualization. The aim of this study is to assess surgeon fatigue and explore the superiority of robot-assisted gastrectomy over laparoscopic gastrectomy in surgeon fatigue. Methods: This study is conducted as a prospective observational study ancillary to a randomized controlled phase III trial investigating the superiority in safety of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-4aN0-3 gastric cancer (JCOG1907: UMIN000039825). The lead surgeon and the first assistant performing surgeries as protocol treatment in JCOG1907 were included. Surgeon fatigue is quantitatively assessed using multiple assessment tools. The primary endpoint is the average NASA-Task Load Index (NASA-TLX) value for the lead surgeons. Secondary endpoints include six individual parameters of NASA-TLX, visual analog scale assessments for fatigue, advanced trail-making tests, and continuous heart rate variability measurements for lead surgeons and first assistants. The primary analysis compares surgeon fatigue between robot-assisted and laparoscopic surgery. Secondary analyses examine the association between surgeon fatigue and various factors, such as surgeon and patient background, and surgical findings, as well as cross-correlations among measures of surgical fatigue. In addition, the association between surgeon fatigue and postoperative complications and its impact on long-term survival outcomes is also evaluated. The sample size is 500 surgical cases, with a planned accrual period of 2 years. This study was initiated in April 2023 and registered at the University Hospital Medical Information Network as UMIN000052120. As of August 2023, 52 cases (10.4% of the planned accrual) have been enrolled in the study. Clinical trial information: UMIN000052120 .

Time-series blood cytokine profiles correlate with treatment responses in triple-negative breast cancer patients.

Triple-negative breast cancer (TNBC) is the most heterogeneous breast cancer subtype. Partly due to its heterogeneity, it is currently challenging to stratify TNBC patients and predict treatment outcomes. In this study, we examined blood cytokine profiles of TNBC patients throughout treatments (pre-treatment, during chemotherapy, pre-surgery, and 1 year after the surgery in a total of 294 samples). We analyzed the obtained cytokine datasets using weighted correlation network analyses, protein-protein interaction analyses, and logistic regression analyses. We identified five cytokines that correlate with good clinical outcomes: interleukin (IL)-1α, TNF-related apoptosis-inducing ligand (TRAIL), Stem Cell Factor (SCF), Chemokine ligand 5 (CCL5 also known as RANTES), and IL-16. The expression of these cytokines was decreased during chemotherapy and then restored after the treatment. Importantly, patients with good clinical outcomes had constitutively high expression of these cytokines during treatments. Protein-protein interaction analyses implicated that these five cytokines promote an immune response. Logistic regression analyses revealed that IL-1α and TRAIL expression levels at pre-treatment could predict treatment outcomes in our cohort. We concluded that time-series cytokine profiles in breast cancer patients may be useful for understanding immune cell activity during treatment and for predicting treatment outcomes, supporting precision medicine. The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index-j.htm ) with the unique trial number UMIN000023162. The association Japan Breast Cancer Research Group trial number is JBCRG-22. The clinical outcome of the JBCRG-22 study was published in Breast Cancer Research and Treatment on 25 March 2021. https://doi.org/10.1007/s10549-021-06184-w .

Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis

BackgroundDisseminated intravascular coagulation (DIC) syndrome is a highly lethal condition characterized by the complication of multiple organ damage. Although the effects of combined antithrombin (AT) and recombinant thrombomodulin (rTM) on DIC syndrome have previously been examined, the results are inconsistent and inconclusive. Therefore, we conducted a systematic review on the combined administration of AT and rTM for the treatment of septic DIC to investigate the superiority of the combination therapy over either AT or rTM monotherapy using a random-effects analysis model.MethodWe searched electronic databases, including Medline, Cochrane Central Register of Controlled Trials, Scopus, and Igaku-Chuo Zasshi (ICHU-SHI) Japanese Central Review of Medicine Web from inception to January 2022. Studies assessing the efficacy of combined AT and rTM were included. The primary outcome was all-cause mortality, and the secondary outcome was occurrence of serious bleeding complications compared to monotherapy. We presented the pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI) depending on reporting results in each primary study.ResultsWe analyzed seven enrolled clinical trials, all of which were observational studies. Combination therapy had a non-significant favorable association with lower 28-day mortality compared to monotherapy (HR 0.67 [0.43–1.05], OR 0.73 [0.45–1.18]). The I2 values were 60% and 72%, respectively, suggesting high heterogeneity.As a secondary outcome, bleeding complications were similar between the two groups (pooled OR 1.11 [0.55–2.23], I2 value 55%).ConclusionsAlthough the findings in this analysis could not confirm a statistically significant effect of AT and rTM combination therapy for septic DIC, it showed a promising effect in terms of improving mortality. The incidence of bleeding was low and clinically feasible. Further research is warranted to draw more conclusive results.Trial registrationThis study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: 000049820).

Comparison of hemostatic ability between spray coagulation and forced coagulation modes in endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for multicenter randomized controlled trial (Spray-G trial)

BackgroundEndoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD.MethodsThis multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study.DiscussionThis trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures.Trial registrationThe trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.

Developing an Educational Program for Ultrasound Hip Screening during Newborn and Infant Home Visits: A Protocol Paper.

Ultrasound hip screening is suitable for the early identification of developmental dysplasia of the hip (DDH). Newborn and infant home visits are good opportunities for hip screening in the community, but studies focusing on nurse-led screenings are lacking. Based on a pre-post design, this study aims to develop and evaluate an ultrasound training program to improve nurses' assessment skills in detecting DDH cases during newborn and infant home visits. Said educational program will include e-learning, hands-on seminars, and clinical training. The primary outcome will be the success rate of imaging standard planes (standardized images for hip assessment) in clinical training. The secondary outcomes will include knowledge test results, objective structured clinical examination scores, time required for imaging, and inter-rater reliability between nurses and physicians. The educational program will address the issue of missed and late detection of DDH cases in resource-limited communities. This study will demonstrate the feasibility of procedures and the effectiveness of the educational program in 2024. The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry before starting the study (no. UMIN000051929, 16 August 2023).

Fructose-induced FGF21 secretion does not activate brown adipose tissue in Japanese young men: randomized cross-over and randomized controlled trials

BackgroundHuman brown adipose tissue (BAT) activity is associated with lower body fatness and favorable glucose metabolism. Previous studies reported that oral fructose loading induces postprandial fibroblast growth factor 21 (FGF21) secretion. FGF21 is a known inducer of adipose tissue thermogenesis; however, the effects of diet-induced FGF21 secretion on BAT thermogenesis remain to be elucidated.MethodsThe effects of both single load and daily consumption of fructose on BAT activity were examined using a randomized cross-over trial and a 2-week randomized controlled trial (RCT), respectively. In the cross-over trial, 15 young men consumed a single dose of fructose solution or water and then consumed the other on a subsequent day. The RCT enrolled 22 young men, and the participants were allocated to a group that consumed fructose and a group that consumed water daily for 2 weeks. BAT activity was analyzed using thermography with cold exposure. Plasma FGF21 level was determined by enzyme-linked immunosorbent assay.ResultsIn the cross-over single-load trial, plasma FGF21 levels were significantly increased at 2 h after oral fructose load (p < 0.01); however, there was no significant difference in BAT activity between the fructose load and drinking water. The 2-week RCT revealed that both plasma FGF21 levels and BAT activity were not significantly increased by daily fructose consumption compared to water. Correlation analyses revealed that BAT activity at the baseline and the final measurements were strongly and positively associated with the RCT (r = 0.869, p < 0.001). Changes in BAT activity were significantly and negatively correlated with changes in plasma glucose levels during the 2-week intervention (r = − 0.497, p = 0.022).ConclusionsOral fructose load induces a temporary increase in circulating FGF21 levels; however, this does not activate BAT thermogenesis in healthy young men. Further studies are needed to elucidate the effect of endogenous FGF21 on physiological function.Trial registrationThis study is registered with the University Hospital Medical Information Network in Japan (number 000051761, registered 1 August 2023, retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000052680).

Real-world clinical evidence of oral semaglutide on metabolic abnormalities in subjects with type 2 diabetes: a multicenter retrospective observational study (the Sapporo-Oral SEMA study).

Oral semaglutide has potent anti-hyperglycemic efficacy in phase III trials. However, the complicated dosing instructions hamper to use this drug; therefore, we evaluated the efficacy and safety of oral semaglutide in subjects with type 2 diabetes in a real-world clinical setting. In this multi-center retrospective observational study, we analyzed subjects with type 2 diabetes newly treated with an oral semaglutide for >6 months at four medical centers located in Sapporo, Japan. The changes in glycated hemoglobin, body weight, and other metabolic parameters were evaluated and any adverse event leading to semaglutide discontinuation were recorded from February 2021 to December 2022. This study was registered with the University Hospital Medical Information Network Center (UMIN000050583). Of 543 subjects who met the inclusion criteria, data for 434 subjects (age 55.5 ± 12.6 years; body mass index 29.6 ± 6.0 kg/m2) were analyzed. After a 6 months of observation period, semaglutide 3 mg, 7 mg, or 14 mg was used by 55 (12.7%), 241 (55.5%), and 138 (31.8%) of subjects, respectively. Both glycated hemoglobin and body weight significantly improved: 7.65 ± 1.11% to 6.88 ± 0.91% (p < 0.001) and 80.2 ± 19.2 kg to 77.6 ± 19.2 kg (p < 0.001), respectively. Efficacy was also confirmed in the subgroup switched from other anti-hyperglycemic agents, including dipeptidyl peptidase-4 inhibitors. In total, 154 subjects had symptomatic gastrointestinal symptoms and 39 (7.2%) were discontinued semaglutide due to the adverse events. None of the participants experienced severe hypoglycemic events. Oral semaglutide in subjects with type 2 diabetes improved glycemic control and body weight in a real-world clinical setting.

Reproductive outcomes of embryo cryopreservation and transfer at the start-up phase of fertility preservation in Japan.

To verify the effectiveness of embryo transfer (ET) using cryopreserved embryo as fertility preservation (FP). This study was a questionnaire survey. The total number of embryo cryopreservation (EC) was investigated between 2014 and 2020. And for patients who underwent ET among study period, details of EC, outcome of ET, number of live births, and mortality were investigated. Of the 150 facilities, 114 responded (76.0%). A total of 1420 EC were performed during the study period; and ET was performed for 417 patients. Breast cancer was the most common primary disease. A total of 199 live births (including prospective) were obtained by ET; 1.7 EC and 2.2 ET were performed per patient, and live birth rate was 21.4% per ET (28.1% on 35-37-year-old patients). The number of EC and ET increased with age. The final birth rate, including pregnancies other than FP, was 51.8%. Ovarian stimulation with aromatase inhibitors was commonly used, although with no effect on live birth rates. Random start stimulation was also common, experienced by 36.3% of breast cancer patients. Reproductive outcomes of ETs following EC as FP are acceptable. This research project was registered in the University Hospital Medical Information Network (UMIN000043664).

The Effects of Adlay Tea Intake on Immune Homeostasis and Vascular Endothelial Function in Healthy Adults: A Randomized, Double-Blind, Parallel-Group Comparative Study.

Excessive immune response and inflammation are associated with an increased risk of various diseases. In particular, excessive myeloperoxidase (MPO) activity in neutrophils causes inflammatory reactions and lifestyle-related diseases. Adlay has a long history of being used as a traditional Chinese medicine. Polyphenols present in adlay seeds are expected to have the effect of suppressing excessive immune and inflammatory responses. Here, we conducted a randomized, double-blind, parallel group, placebo-controlled study was conducted to evaluate the suppressing effects of adlay seeds extract on excessive immune responses. One hundred and twenty adults participated in the study and they were equally divided into an adlay tea intake group and a placebo group. MPO activity was significantly elevated in the placebo group after 8-wk ingestion, while no significant change was observed in the adlay group. Vascular endothelial functions improved in the adlay group, especially in subjects over 40 y old. These results indicate that adlay tea intake may suppress an excessive immune and inflammatory responses, and improve arterial stiffness. Since caffeic acid, p-coumaric acid, and ferulic acid detected in adlay tea are known to inhibit MPO activity, these polyphenols may be the major functional molecules. Collectively, adlay tea is considered to have a preventative effect against lifestyle-related diseases through improving vascular endothelial function by effects to maintain immune homeostasis of the contained polyphenols. This trial was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000032263).

Assessing the Postprandial Glycemic Response to Japonica Rice (Oryza sativa L. cv. Koshihikari) with a Small Amount of Lysolecithin and Canola Oil in Japanese Adult Men: a Double-blind, Placebo-controlled, Crossover Study.

A double-blind, placebo-controlled, crossover trial was performed to analyze the effects of a small amount of lysolecithin and canola oil on blood glucose levels after consuming japonica rice. Overall, 17 Japanese adult men were assigned to consume 150 g of normally cooked japonica rice (placebo group) and 150 g of japonica rice cooked with 18 mg of lysolecithin and 1.8 g of canola oil (treatment group); these lipids were added as emulsified formulation (EMF) for stability and uniformity. Subsequently, blood samples were collected before and 30, 45, 60, 90, and 120 min after consuming test foods. There was no significant difference in blood glucose, insulin, and triglyceride levels between the groups. However, a stratified analysis of 11 subjects with body mass index (BMI) ≥ 22 revealed that blood glucose levels were significantly lower after 30 min in the treatment group than in the placebo group (p = 0.041). Through in vitro digestibility test, the rice sample of the treatment group was observed to release significantly less glucose within 20 min than that in the placebo group rice. These results suggest that the combination of a small amount of lysolecithin and canola oil modulated the increase in postprandial blood glucose levels induced by the intake of cooked japonica rice in adult men with BMI ≥ 22. This clinical trial was registered with the University Hospital Medical Information Network (UMIN) Center, (UMIN000045744; registered on 15/10/2021).

Assessing the Metabolic and Physical Effects of Combined DPP4 and SGLT2 Inhibitor Therapy in Patients with Type-2 Diabetes Mellitus: An Observational Prospective Pilot Study.

This study aimed to assess the efficacy of combined administration of dipeptidyl peptide-4 (DPP4) and sodium-glucose cotransporter-2 (SGLT2) inhibitors on metabolic disorders and their preferable and complementary effects. The effectiveness of a 24-week intervention on metabolic parameters (including glucose profile), physical functions (grip strength and calf circumference), and health-related quality of life (HR-QOL) was analyzed using the International Physical Activity Questionnaire and Geriatric Depression Scale 5. A total of 39 patients with type-2 diabetes mellitus (T2DM) treated with the combination of DPP4 and SGLT2 inhibitors were included in this multicenter pilot study. Combination therapy significantly reduced the HbA1c level (median [interquartile range]) after 24 weeks (pretreatment: 7.7% [7.3-8.2] vs. posttreatment: 7.1% [6.6-7.9], P < 0.001). The grip strength significantly increased after 24 weeks (1.7 ± 2.7 kg, P < 0.001), while the mean calf circumference and body mass index significantly decreased. In particular, administration of the SGLT2 inhibitor significantly increased total physical activity in participants aged ≥65 years (P = 0.003), while psychological QOL did not significantly improve. Combination therapy with DPP4 and SGLT2 inhibitors decreased HbA1c levels and improved physical function in patients with T2DM. This study confirmed the effectiveness of combination therapy for metabolic disorders and suggested its beneficial and complementary effects. Therefore, advances in treatment plans to achieve further improvements in glucose profiles using DPP4 and SGLT2 inhibitors are recommended to enhance the QOL of patients with T2DM. Clinical trial number: University Hospital Medical Information Network Center: UMIN000045375.

Effects of intervention by trained care managers on advance care planning engagement among long-term care service users in Japan: a pre- and post-pilot comparative study across multiple institutions.

A majority of Japanese care managers lack medical qualifications, feel uncomfortable discussing future medical choices and believe that it is not their responsibility. As there is a paucity of care manager intervention studies, this study aimed to measure changes in advance care planning engagement among long-term care service users before and after intervention by care managers with communication training. A multi-institutional pre- and post-pilot comparative study. A multi-institutional pre- and post-trial study was performed from August 2022 to January 2023 (trial ID: 000048573). Nine trained care managers communicated with 30 long-term care service users regarding advance care planning, and the pre- and post-trial advance care planning engagement scores were compared. Additionally, the post-trial impact of events score was investigated. All 30 long-term care service users completed the trial. The advance care planning engagement score increased after the trial. The sample size was considered adequate for future trials. Years of experience as a care manager, impact of events score, and having a clinical frailty scale of ⩾5 were significant explanatory variables that affected the objective variable of the difference between pre- and post-trial advance care planning engagement score. This study on the impact of advance care planning communication interventions by trained care managers offers insights into determining appropriate sample sizes and identifying factors influencing future research outcomes. Advance care planning engagement of long-term care service users might change before and after intervention by care managers through advance care planning communication. University Hospital Medical Information (UMIN) Network Trial ID: 000048573.

Oral sodium hyaluronate relieves knee discomfort: A 12‑week double‑blinded, placebo‑controlled study.

Sodium hyaluronate (SH) is a high molecular-weight polysaccharide composed of repeating polymeric disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine. SH is present in every connective tissue and organ, with synovial fluid having the highest concentration of SH in the body. The effectiveness of oral SH on gonarthrosis is known; although, its influence on the knees of healthy individuals is not. However, as severe diseases may require surgery, it is better to take care of healthy knees before the onset of gonarthrosis. Therefore, the present study investigated the functionality of SH on the knee of healthy individuals. The present study was a randomized double-blind, placebo-controlled trial in which healthy adults (mean age: Placebo group, 61.50±1.59; SH group, 58.50±1.81), rated as grade ≤1 based on the Kellgren-Lawrence classification, were administered 111 mg/day SH for 12 weeks. The evaluation of visual analog scales were performed to assess the discomfort in the knees of the participants and were conducted at baseline, and then 6 and 12 weeks after the start of SH ingestion. Additionally, a locomotive syndrome risk test quantifying the mobility of the participants, a one-leg standing time with eyes open test evaluating the strength of the leg muscle as well as the ability to balance by measuring the time to stand on one leg and a blood test (interleukin-10, aspartate aminotransferase, alanine transaminase, γ-glutamyl transferase, lactate dehydrogenase, creatine kinase and C-reactive protein) were performed at baseline and then 12 weeks after the start of SH ingestion. A significant suppression of knee symptoms were demonstrated in the SH group compared with the placebo group in terms of the total visual analog scale scores for pain, stiffness and discomfort for the 31 healthy adult subjects. Significant suppression of symptoms was also demonstrated in the placebo group in terms of discomfort in the knees when descending stairs and pain in the knees after walking for a longer distance or duration than normal. No significant differences between the two groups were demonstrated in the locomotive syndrome risk test, one-leg standing time with eyes open test and the blood test. The results of the present study suggest the possibility that oral SH may help to maintain a healthy condition of the knees. The study protocol was registered with the University Hospital Medical Information Network Clinical Trial Registry in advance (registration no. UMIN000045980, November 4, 2021).

Prospective Exploratory Phase I Clinical Trial Assessing the Safety of Preoperative Marking for Small Liver Tumors.

Background Small tumors in liver cirrhosis are difficult to distinguish using intraoperative ultrasonography. In addition, preoperative chemotherapy for metastatic liver cancer may diminish tumor size, thus making tumors difficult to identify intraoperatively. To address such difficulties, we devised a method to mark liver tumors preoperatively to facilitate intraoperative identification. This study aimed to investigate the safety of a preoperative liver tumor marking method. Methodology This exploratory prospective clinical trial included patients with liver tumors measuring ≤20 mm requiring resection. Preoperative marking was performed by placing a coil for embolization of blood vessels near the tumor using either the transcatheter or percutaneous approach. The tumor was identified and resected by intraoperative ultrasonography based on the marker. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028608). Results Overall, 19 patients (9 with primary liver cancer and 10 with metastatic tumors) were recruited. The transcatheter and percutaneous methods were used in 13 and 6 patients, respectively. Marking was not possible in two patients in the transcatheter group because the catheter could not be guided to the vicinity of the tumor. There were no marking-related complications. Hepatectomy was performed in all but one patient who was not fit for hepatectomy owing to the development of a metastatic liver tumor. The markers were adequately identified during hepatectomy. Additionally, there were no difficulties in the surgical procedure or postoperative complications. Conclusions Preoperative marking with embolization coils can be performed safely for intraoperative identification of liver nodules.

Potential Long-Term Benefit of Home Systolic Blood Pressure Below 125 mm Hg for Cardiovascular Risk Reduction: The J-HOP Study Extended.

The long-term benefit of achieving the Japanese Society of Hypertension home systolic blood pressure (SBP) target of <125 mm Hg has not been fully evaluated. This study investigated the long-term risk of cardiovascular disease events in individuals with home SBP <125 versus 125 to <135 or ≥135 mm Hg who participated in the J-HOP study (Japan Morning Surge-Home Blood Pressure). The J-HOP study enrolled outpatients with ≥1 cardiovascular risk factor between 2005 and 2012, with follow-up until March 2015 and extended follow-up from December 2017 to May 2018. Cardiovascular disease events (stroke, coronary artery disease, congestive heart failure, and aortic dissection) were compared between home SBP subgroups. During mean 5.9 years of follow-up in 4231 participants (mean age, 65 years), cardiovascular events included stroke (n=89), coronary artery disease (n=116), congestive heart failure (n=37), and aortic dissection (n=8). The adjusted 10-year risk of total cardiovascular disease was slightly higher, and stroke risk was significantly higher when baseline home SBP was ≥135 versus <125 mm Hg (adjusted hazard ratio, 1.39 [95% CI, 0.97-2.00] for overall cardiovascular disease and 2.68 [95% CI, 1.34-5.38] for stroke; this was largely due to between-group differences in the first 5 years of follow-up, which were maintained over the subsequent 5 years). Findings were similar in the subgroup of high-risk patients (those with diabetes or stroke history). These data highlight the potential long-term benefit of strict home SBP control and validate this as an appropriate Japanese Society of Hypertension guideline target although confirmation in larger populations is needed. URL: https://www.umin.ac.jp/ctr/; University Hospital Medical Information Network Clinical Trials Registry; Unique identifier: UMIN000000894 (Japan Morning Surge-Home Blood Pressure study).