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Background: There have been few reports of a totally extraperitoneal approach for laparoscopic lateral lymph node dissection (LLND) for patients with metachronous lateral pelvic lymph node metastases following surgery for rectal cancer. Therefore, this study reports the short-term outcomes of LLND via an extraperitoneal approach., Methods: A total of 10 patients underwent LLND through a laparoscopic extraperitoneal approach in our hospital since October 2018. Patients with suspected resectable lateral lymph node recurrence after surgery for rectal cancer on computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography CT (PET-CT) were selected for this procedure., Results: Nine of the 10 cases were completed using this procedure, but one case was converted to an intraperitoneal approach. The median operative time was 231 min, and the median estimated blood loss was 10 ml. There was one case of wound infection, but no other postoperative complications were seen. In one patient, no metastases were found in the retrieved lymph nodes., Conclusion: The short-term outcomes of LLND through a laparoscopic extraperitoneal approach were acceptable. Because this procedure can be performed without violating the peritoneum, it is less invasive than the conventional intraperitoneal approach and is useful for metachronous lateral pelvic lymph node metastases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Tolvaptan, a vasopressin receptor antagonist, has been shown to be effective in the treatment of renal cysts in ADPKD. However, tolvaptan is not indicated for pediatric patients, and reports of its use are rare, making its efficacy and adverse reactions unclear. Herein, we present the case of an 11-year-old girl who had vitiligo from birth. She was diagnosed with West syndrome at 6 months of age and tuberous sclerosis at 2 years of age. At the age of 6 years, an abdominal magnetic resonance imaging (MRI) revealed multiple bilateral renal cysts, and she was diagnosed with ADPKD. Abdominal MRI scans performed at 10 years and 11 years showed rapid renal cyst enlargement, and the renal prognosis was judged to be poor. The patient was treated with tolvaptan to delay cyst exacerbation. There were no apparent adverse events after the initiation of treatment, and the MRI performed 12 months after treatment initiation showed that renal cyst enlargement was suppressed. The results suggest that tolvaptan may be effective in pediatric patients with severe ADPKD who have rapidly enlarging renal cysts, although evaluation of renal cyst enlargement and side effects should be continued., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Purpose: This review investigated the effectiveness of adjuvant therapy combined with constraint-induced movement therapy (CIMT) in improving the paretic upper limb functionality in adults with stroke sequelae during the subacute to chronic rehabilitation phase., Materials and Methods: In this systematic review and meta-analysis of randomized controlled trials (RCT), electronic databases, including PubMed, Web of Science, CINAHL, and MEDLINE, were searched. We included RCTs that investigated the outcomes of adjuvant therapy (i.e. other therapies) added to CIMT compared with CIMT alone. Key trial findings were qualitatively synthesized and analyzed. This meta-analysis examined variables, such as mean scores and standard deviations, using the following outcome measures: Fugl-Meyer Assessment (FMA) upper limb items, Action Research Arm Test (ARAT), Amount of Use (AOU) of Motor Activity Log (MAL), and Quality of Movement (QOM) of MAL., Results: Eighteen eligible RCTs were included in the analysis. Adding CIMT to adjunctive therapy significantly improved FMA compared with CIMT alone (mean difference [MD] 4.02, 95% confidence interval [CI] 2.60-5.44; I 2 = 85%; 15 studies; 330 participants). Similarly, the ARAT and MAL-AOU scores improved significantly., Conclusions: CIMT combined with several adjunctive therapies effectively improved upper limb function.

Background: Distal humerus fracture in the elderly is a challenging fracture for orthopedic surgeons. Non-union is one of the serious complications of distal humerus fracture after surgery. This retrospective multicenter study aimed to estimate the incidence of distal humeral non-union after open reduction and internal fixation, determine factors related to non-union, and compare the postoperative results of cases with non-union to cases with the union., Methods: Among 423 patients diagnosed with distal humeral fracture and who were treated by surgical therapy in 2010-2020 from our database called TRON. Only 190 subjects met the inclusion criteria. We performed a logistic regression analysis with the presence of non-union as the response variable to examine risk factors. We compare the Mayo Elbow Performance Scores of cases with non-union to cases with the union., Results: Non-union occurred after surgery in 15 patients (7.9%). The logistic regression analysis showed that body mass index<20 kg/m 2 and ≥25 kg/m 2 , and ≤3 screws in the articular segment were significant explanatory factors for non-union (odds ratio 10.4 and 47.8, respectively). The Mayo Elbow Performance Scores were significantly worse in patients with non-union., Discussion: Low and high body mass index and three or fewer screws in the articular segment might be risk factors for non-union of distal humerus fracture in the elderly. Non-union is associated with poor clinical outcomes., (© The Author(s) 2022.)

Paired box protein 2 (PAX2) gene variant causes renal coloboma syndrome (MIM#120330). Further, they are associated with focal segmental glomerulosclerosis and characterized by basement membrane changes similar to Alport syndrome.Herein, we report an 8-year-old boy who presented with proteinuria and decreased renal function. His paternal uncle has focal segmental glomerulosclerosis and renal failure, and his paternal grandmother has renal failure and is receiving peritoneal dialysis. Further, his father has stage 2 chronic kidney disease. At 3 years of age, his serum creatinine-estimated glomerular filtration rate was 40-50 mL/min/1.73 m 2 . At 8 years of age, his renal function further decreased and he had proteinuria (urinary protein/Cr 3.39 g/g Cr). Renal histopathology showed oligonephronia and focal segmental glomerulosclerosis. A partial basket-weave pattern, similar to Alport syndrome, was also observed on a transmission electron microscope, and low-vacuum scanning electron microscopy revealed coarse meshwork changes in the glomerular basement membrane. Genetic analysis revealed a PAX2 heterozygous variant (NM&#95;003987.4:c.959C  >  G), a nonsense variant in which the serine at position 320 changes to a stop codon, in our patient and his father. PAX2 is a transcription factor that is important for the podocyte variant. However, podocytes with PAX2 gene variants may cause abnormal basement membrane production and repair, thereby resulting in Alport-like changes., (© 2023. The Author(s).)

Context: Whether continuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) or switching to oral semaglutide is more beneficial for β-cell function is unclear., Objective: To assess the efficacy of switching from DPP-4is to oral semaglutide for β-cell function compared with DPP-4i continuation., Methods: Post hoc analysis of SWITCH-SEMA 2, a multicenter prospective randomized controlled trial on the switch to oral semaglutide vs DPP-4i continuation without dose adjustment for 24 weeks in subjects with type 2 diabetes treated with DPP-4is, was conducted. Changes in markers for glucose metabolism, including homeostatic model assessment (HOMA2) scores and disposition index (DI), were compared between the groups., Results: A total of 146 subjects (semaglutide group, 69; DPP-4i group, 77) were analyzed. In the semaglutide group, glycemic control, liver enzyme deviations, and lipid profiles improved after 24 weeks. Regarding indices for β-cell function, changes in HOMA2-β as well as DI, reflecting the ability of β-cells to compensate for insulin resistance, were significantly higher in the semaglutide group compared with the DPP-4i group (mean change, +10.4 vs +0.6 in HOMA2-β [P = .001] and +0.09 vs 0.0 in DI [P < .001]). Improvement in DI in the semaglutide group was correlated significantly to changes in body mass index (BMI), HbA1c, and fatty liver index reflecting liver steatosis. Multiple linear regression analysis revealed that dose of semaglutide (≥ 7 mg/day), reduction in fatty liver index, and metformin nonuse were independently associated with improvement of DI., Conclusion: Switching to oral semaglutide ameliorated β-cell function compared with DPP-4is, presumably via tissue-to-tissue crosstalk between liver and β-cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Hodgkin lymphoma (HL) and idiopathic multicentric Castleman disease (iMCD) are markedly different conditions. However, in some cases, histological similarities caused by elevated cytokines, including interleukin-6, can lead to a misdiagnosis of HL as Castleman disease (CD). We herein report a patient with HL who had been diagnosed with CD by an expert panel and for whom an additional biopsy was useful for determining the correct diagnosis. Furthermore, we analyzed the positron emission tomography/computed tomography findings at the diagnosis and found that the maximum standardized uptake value was useful for distinguishing HL from iMCD.

Abstract: Clinically significant cytomegalovirus infection (csCMVi) is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT) and prophylaxis with letermovir is commonly adopted. However, the clinical benefit of letermovir prophylaxis according to graft sources has not been sufficiently elucidated. We retrospectively analyzed 2194 recipients of HSCT who were CMV-seropositive (236 with letermovir prophylaxis and 1958 without prophylaxis against CMV). csCMVi was significantly less frequent in patients with letermovir prophylaxis than in those without (23.7% vs 58.7% at 100 days after HSCT, P < .001) and the same trend was seen when recipients of bone marrow (BM), peripheral blood stem cell (PBSC), or cord blood (CB) transplantation were separately analyzed. In recipients of BM, nonrelapse mortality (NRM) was significantly lower in the letermovir group at 6 months after HSCT (5.0% vs 14.9%, P = .018), and the same trend was observed in recipients of PBSCs (14.7% vs 24.8%, P = .062); however, there was no statistical significance at 1 year (BM, 21.1% vs 30.4%, P = .67; PBSCs, 21.2% vs 30.4%, P = .096). In contrast, NRM was comparable between recipients of CB with and without letermovir prophylaxis throughout the clinical course (6 months, 23.6% vs 24.3%, P =.92; 1 year, 29.3% vs 31.0%, P = .77), which was confirmed by multivariate analyses. In conclusion, the impact of letermovir prophylaxis on NRM and csCMVi should be separately considered according to graft sources., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Aim: To assess whether oral semaglutide provides better glycaemic control, compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) continuation, in people with type 2 diabetes., Materials and Methods: In this multicentre, open-label, prospective, randomized, parallel-group comparison study, participants receiving DPP-4is were either switched to oral semaglutide (3-14 mg/day) or continued on DPP-4is. The primary endpoint was the change in glycated haemoglobin (HbA1c) over 24 weeks. Secondary endpoints included changes in metabolic parameters and biomarkers, along with the occurrence of adverse events. Factors associated with HbA1c improvement were also explored., Results: In total, 174 eligible participants were enrolled; 17 dropped out of the study. Consequently, 82 participants in the DPP-4i group and 75 participants in the semaglutide group completed the study and were included in the analysis. Improvement in HbA1c at week 24 was significantly greater when switching to semaglutide compared with DPP-4i continuation [-0.65 (95% confidence interval: -0.79, -0.51) vs. +0.05 (95% confidence interval: -0.07, 0.16) (p < .001)]. Body weight, lipid profiles and liver enzymes were significantly improved in the semaglutide group than in the DPP-4i continuation group. Multiple linear regression analysis revealed that baseline HbA1c and homeostasis model assessment 2-R were independently associated with HbA1c improvement after switching to semaglutide. Seven participants in the semaglutide group discontinued medication because of gastrointestinal symptoms., Conclusions: Although the potential for gastrointestinal symptoms should be carefully considered, switching from DPP-4is to oral semaglutide may be beneficial for glycaemic control and metabolic abnormalities in people with higher HbA1c and insulin resistance., (© 2023 John Wiley & Sons Ltd.)

Post-transplantation therapy is commonly performed in patients with myeloma and can prolong progression-free survival (PFS). However, whether post-transplantation therapy contributes to achieving and continuing MRD-negativity remains controversial. This retrospective analysis aimed to evaluate the clinical impact of post-transplantation therapy, including tandem autologous stem cell transplantation (ASCT), in myeloma patients. The subjects were 79 patients (median age: 62 years) who received induction therapy, including bortezomib and/or lenalidomide, of whom 58 underwent post-transplantation therapy. At the median follow-up time of 50 months, the 4-year PFS rate was significantly higher in patients who underwent post-transplantation therapy than those who did not (60.6% vs. 28.6%, P = 0.012). Multivariate analysis revealed post-transplantation therapy to be a significant prognostic factor for long PFS. Tandem ASCT followed by consolidation and/or maintenance therapies improved PFS and OS. The minimal residual disease (MRD)-negative rate was significantly higher in patients who underwent post-transplantation therapy than those who did not (50.9% vs. 16.7%, P = 0.006). Post-transplantation therapy contributed to sustained MRD-negativity, which predicted long PFS and overall survival. Patients frequently discontinued post-transplantation therapy due to adverse events within 4 months. In conclusion, post-transplantation therapy improved PFS and contributed to sustained MRD-negativity in myeloma patients., (© 2023. Japanese Society of Hematology.)

Purpose: To identify the incidence and the factors associated with a postoperative ulnar nerve neuropathy in patients who had undergone open reduction and internal fixation for intraarticular distal humerus fractures., Methods: We retrospectively reviewed 116 patients who had undergone surgery between January 2011 and December 2020. Age, sex, BMI, mechanism of injury, open or closed fracture, operation time, tourniquet time, and nerve injury at the final examination were collected from medical charts. We essentially used the paratricipital approach. In cases in which the reduction of intraarticular bone fragments was difficult, olecranon osteotomy was used. Ulnar nerve function was graded according to a modified system of McGowan. We conducted logistic regression analysis to investigate factors of neuropathy using items identified as statistically significant in univariate analysis as explanatory variables., Results: Thirty-four patients (29.3%) had persistent neuropathy at the final follow-up. In the modified McGowan classification, 28 patients had grade 1 and 6 patients had grade 2 neuropathy. Olecranon osteotomy emerged as a distinct explanatory variable for the prophylaxis of ulnar nerve neuropathy in the multivariate analysis (odds ratio, 0.30; 95% confidence interval, 0.12-0.73). Anterior transposition, however, was not a statistically significant factor (odds ratio, 1.91; 95% confidence interval, 0.81-4.56)., Conclusions: Olecranon osteotomy was the only independent factor associated with preventing the occurrence of ulnar nerve neuropathy. Ulnar nerve transposition might not be associated with prevention of ulnar nerve neuropathy., Type of Study/level of Evidence: Prognostic IV., (Copyright © 2023. Published by Elsevier Inc.)

We previously reported in the study of preventive effects of alogliptin on diabetic atherosclerosis (SPEAD-A) that alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the progression of carotid atherosclerosis in subjects with type 2 diabetes and no history of cardiovascular disease. This extension study of the SPEAD-A trial investigated whether early alogliptin initiation improved long-term cardiovascular outcomes. The SPEAD-A trial randomized 341 subjects with type 2 diabetes to either alogliptin or conventional treatment to investigate the effects of alogliptin on atherosclerosis. All subjects who completed that trial were eligible for this prospective, observational cohort study. The primary endpoint was the first occurrence of a major cardiovascular event, defined as death due to any cause, acute myocardial infarction, or stroke. During the 520-week follow-up period, composite primary outcome events occurred in only a few subjects in each group [8 (5.4%) in the alogliptin group and 9 in the conventional treatment group (5.9%)]. There were no significant differences in the incidence rate of the primary outcome between the two groups. Post hoc Poisson regression analysis showed no significant difference between the two groups in the incidence rate of composite recurrence events for the same outcomes as the primary endpoint. On the other hand, this incidence rate was significantly lower in subjects who received DPP-4 inhibitors before an initial cardiovascular event than in those who did not (5.8 vs. 13.3 per 1000 person-years, respectively, p = 0.04). Early initiation of alogliptin was not associated with a reduced risk of composite cardiovascular disease, which could be attributed to fewer events and/or the addition of DPP-4 inhibitors during the follow-up period., (© 2023. Springer Nature Limited.)

Non-alcoholic fatty liver disease (NAFLD) is an important common comorbidity in individuals with type 2 diabetes (T2DM). Although some glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on NAFLD, the efficacy of once-weekly semaglutide has not been established. This was a subanalysis of the SWITCH-SEMA 1 study, a multicenter, prospective, randomized, parallel-group trial comparing switching from liraglutide or dulaglutide to once-weekly semaglutide in subjects with T2DM (SWITCH) versus continuing current GLP-1RAs (Continue) for 24 weeks. This subanalysis consisted of participants who were suspected to have NAFLD [fatty liver index (FLI) ≥ 30]. In total, 58 participants met the criteria of this subanalysis. There were no statistical differences in baseline characteristics between the SWITCH ( n = 31) and Continue groups ( n = 27). FLI significantly improved during treatment in the SWITCH group (68.6 to 62.7) but not in the Continue group (71.1 to 72.3) ( p < 0.01). The improvement of FLI in the SWITCH group was greater in switching from dulaglutide to semaglutide and significantly correlated with older age ( p = 0.016) and lower baseline FLI ( p < 0.01). The multiple linear regression analysis revealed that the switch from dulaglutide was associated with an improvement in FLI ( p = 0.041). Switching from conventional GLP-1RAs to once-weekly semaglutide might be beneficial for individuals with NAFLD complicated with T2DM.

Introduction: Double-plating methods are popular, with perpendicular and parallel plate methods being widely used surgical method for the rigid fixation of distal humeral fracture (DHF). However, which plate method is better for DHF remains controversial. The aim of this study was to compare patient outcomes including the incidences of complications and reoperation between the two plate methods., Methods: We extracted 383 patients with DHF undergoing surgery between 2011 and 2020 from our multicenter database, which is named TRON. We divided the subjects into two groups: perpendicular plating group (Group A) and parallel plating group (Group B). To adjust for baseline differences between the groups, patients were matched for age, sex, olecranon osteotomy, AO type, and type of injury. We assessed the Mayo Elbow Performance Score (MEPS) at 3 and 6 months and the last follow-up month as the clinical outcome. We investigated the incidences of complications and reoperations in both groups., Results: After matching, each group comprised 50 patients. There was no significant difference between Group A versus Group B in MEPS score at each time point. The incidence of implant removal in Group B was higher than that in Group A (26.5% vs 50%, p = 0.023)., Discussion: Although there were no significant differences in clinical outcomes or complications between the two groups, the incidence of implant removal was higher in Group B than in Group A. In the parallel plate technique, where the plates have to be placed in areas with thin subcutaneous soft tissue, the incidence of implant removal might be high due to the discomfort caused by the implant., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Double plate fixation for transcondylar fracture (TCF) tends to be more invasive to the soft tissue, and often carries a higher risk of postoperative complications, including ulnar nerve neuropathy. This study presents the outcomes of TCF of the distal humerus between patients treated with a single plate and cannulated cancellous screw fixation and patients treated with double plate fixation., Methods: Between 2011 and 2021, 371 cases involving treatment of distal humeral fracture were recorded in our multicenter (named TRON group) database. Patients of ≥ 65 years of age with TCF treated with opeb n reduction and internal fixation were included. Clinical outcomes were assessed by the Mayo elbow performance score, range of motion, and total elbow arc joint. Complications included fracture-related infection (FRI) and ulnar neuropathy., Results: There were significant differences in the average operative time (CCS group vs. Plate group: 119.0 min vs. 186.5 min; p < 0.001) and average tourniquet time (CCS group vs. Plate group: 91.5 min vs. 121.0 min; p < 0.001). FRI occurred as a complication in the Plate group (n = 6). The rates of FRI did not differ to a statistically significant extent (CCS group vs. Plate group: 0% vs. 9.2%; p = 0.477). No patients underwent reoperation. The rate of sensory symptoms in the Plate group was higher than that in the CCS group (CCS group: none [n = 25], numbness [n = 1] vs. Plate group: none [n = 57], numbness [n = 15], sensory depression [n = 2]; p = 0.039)., Discussion: Among patients of ≥ 65 years of age with TCF, the clinical outcomes of patients treated with medial CCS and lateral/posterolateral plate did not differ from those of patients who received double plate fixation, and the former treatment was associated with significantly fewer complications, including ulnar nerve palsy. In addition to double plate fixation, this less invasive method of medial CCS and single plate fixation should be considered as a treatment option for TCF in elderly patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Aim: To investigate whether any reduction in all-cause mortality and cardiovascular disease morbidity was found over the decade in type 2 diabetes on real-world practice., Methods: A prospective observational study was performed by following two independent cohorts recruited in 2004 (n = 3286, Cohort 1) and 2014 (n = 3919, Cohort 2). The primary outcome was a composite of onset of cardiovascular disease and death. Cox proportional hazards analysis was used to explore any difference between Cohort 2 and Cohort 1 for the composite endpoints and cardiovascular disease after adjustment for covariates and accumulation of five risks (smoking, HbA1c, blood pressure, lipids, and albuminuria) outside target ranges., Results: During the 8-year follow-up, 391 (11.9%) and 270 (6.9%) primary outcomes, and 270 (8.2%) and 161 (4.1%) cardiovascular diseases occurred in Cohort 1 and Cohort 2, respectively. Cohort 2 (vs. Cohort 1) exhibited a significant risk reduction for composite endpoints (HR 0.73, 95% CI 0.62 to 0.86) and cardiovascular disease (HR 0.64, 95% CI 0.52 to 0.79), and similarly exhibited a significant reduction independent of the accumulation of the five risks., Conclusions: The significant reduction of Cohort 2 for cardiovascular disease independent of the baseline covariates suggests an integrated effect delivered by the recent treatment advances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Aims/introduction: To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic., Materials and Methods: In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted., Results: The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician-patient interaction and the impossibility of consultation and examination were cited as sources of concern., Conclusions: Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease., Methods: This was a prospective observational 2-year extension study of the "Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)" trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks., Results: The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (- 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (- 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) - 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (- 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (- 100.2 cm/s, 95% CI - 182.8 to - 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups., Conclusions: Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile., (© 2023. The Author(s).)

Aim: To investigate the effects of switching from liraglutide or dulaglutide to once-weekly semaglutide on glycaemic control and treatment satisfaction in patients with type 2 diabetes., Materials and Methods: In this multicentre, open-labelled, prospective, randomized, parallel-group comparison study, patients treated with liraglutide 0.9-1.8 mg/day (plan A) or dulaglutide 0.75 mg/week (plan B) were either switched to semaglutide or continued current therapy. The primary endpoint was the mean change in glycated haemoglobin over 24 weeks. The secondary endpoints included the changes of Diabetes Treatment Satisfaction Questionnaire scores, body weight and metabolic indices., Results: In total, 110 patients were enrolled, and 10 were excluded; therefore, 37 patients in plan A and 63 patients in plan B completed the study. Glycated haemoglobin levels were significantly reduced in the semaglutide group in both plans [plan A, 7.8% ± 1.0% to 7.8% ± 0.7% (liraglutide) vs. 7.9% ± 0.7% to 7.3% ± 0.7% (semaglutide), p < .01; plan B, 7.8% ± 1.0% to 7.9% ± 1.2% (dulaglutide) vs. 7.8% ± 0.8% to 7.1% ± 0.6% (semaglutide), p < .01]. Semaglutide also improved Diabetes Treatment Satisfaction Questionnaire scores in both groups (plan A, +0.1 vs. +8.3, p < .01; plan B, -1.2 vs. +3.5, p < .01). Switching from dulaglutide yielded greater reductions in body weight and improved metabolic parameters., Conclusions: Once-weekly semaglutide administration improved glycaemic control and treatment satisfaction after switching from liraglutide or dulaglutide. These results highlighted a useful treatment option for patients with metabolic abnormalities despite glucagon-like receptor-1 receptor agonist treatment., (© 2023 John Wiley & Sons Ltd.)

Background: We previously conducted a pilot randomized controlled trial "the MASTER study" and demonstrated that alpha-glucosidase inhibitor miglitol and a dipeptidyl peptidase-4 inhibitor sitagliptin modified postprandial plasma excursions of active glucagon-like peptide-1 (aGLP-1) and active gastric inhibitory polypeptide (aGIP), and miglitol treatment decreased body fat mass in patients with type 2 diabetes (T2D). However, the details regarding the relationships among postprandial plasma aGLP-1 and aGIP excursions, skeletal muscle mass, and body fat mass are unclear., Methods: We conducted a secondary analysis of the relationships among skeletal muscle mass index (SMI), total body fat mass index (TBFMI), and the incremental area under the curves (iAUC) of plasma aGLP-1 and aGIP excursions following mixed meal ingestion at baseline and after 24-week add-on treatment with either miglitol alone, sitagliptin alone, or their combination in T2D patients., Results: SMI was not changed after the 24-week treatment with miglitol and/or sitagliptin. TBFMI was reduced and the rates of aGIP-iAUC change were lowered in the two groups treated with miglitol, although their correlations did not reach statistical significance. We observed a positive correlation between the rates of aGIP-iAUC and TBFMI changes and a negative correlation between the rates of TBFMI and SMI changes in T2D patients treated with sitagliptin alone whose rates of aGIP-iAUC change were elevated., Conclusions: Collectively, although T2D patients treated with miglitol and/or sitagliptin did not show altered SMI after 24-week treatment, the current study suggests that there are possible interrelationships among postprandial plasma aGIP excursion modified by sitagliptin, skeletal muscle mass, and body fat mass.

Objective: This multicentre, phase 2, randomized, controlled study of allogeneic haematopoietic stem cell transplantation (allo-HSCT) recipients compared the immunogenicity of two anti-pneumococcal vaccine regimens: four doses of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) (3+1+1 experimental group), and three doses of PCV13 followed by PPSV23 (3+0+1 group)., Methods: Allo-HSCT recipients without active graft-versus-host disease at enrolment were eligible. The primary endpoint was the IgG response rate (≥0.20 mg/mL) for all eight measured serotypes at 5 months after the PPSV23 booster., Results: Seventy-two recipients were randomized, and seventy recipients who received over one PCV13 dose were analysed. The mean ages were 47.2 years (standard deviation, 14.4) in the 3+1+1 group (n = 35) and 49.0 years (standard deviation, 14.3) in the 3+0+1 group (n = 35). There was no significant difference in the overall IgG response rate at 5 months after the PPSV23 booster between the 3+1+1 and 3+0+1 groups (100% (26/26) vs. 93% (27/29), respectively, relative risk (RR): 1.07; 95% confidence interval (CI): 0.97-1.19). This rate was high immediately before the PPSV23 booster in the 3+1+1 group (100% (26/26) compared with 81% (21/26), respectively, RR: 1.24; 95% CI: 1.03-1.49), but this difference disappeared 1 month after the PPSV23 booster (100% (26/26) vs. 97% (28/29), respectively, RR: 1.04; 95% CI; 0.97-1.11). No serious adverse events leading to study dropout occurred., Discussion: We were not able to determine the efficacy of the experimental arm based on the IgG response rate at 5 months after the PPSV23 booster in allo-HSCT recipients., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aims: This study aimed to evaluate changes in glycemic control and diabetes treatment by age group in Japanese patients with type 2 diabetes., Methods: The study included the results of approximately 40,000 patients/year using cross-sectional and retrospective analyses from 2012 to 2019., Results: There was little change in the glycemic control status in all age groups during the study period. However, by age group, patients aged ≤ 44 years continued to have the highest glycated hemoglobinA1c (HbA1c) values during the study period (7.4 % ± 1.7 % in 2012 and 7.4 % ± 1.5 % in 2019), especially in insulin-treated patients (8.3 % ± 1.9 % in 2012 and 8.4 % ± 1.8 % in 2019). Biguanides and dipeptidyl peptidase-4 inhibitors were widely prescribed. Sulfonylurea and insulin use showed a decreasing trend, but older patients had a higher percentage of prescriptions. Sodium glucose transporter 2 inhibitors were prescribed rapidly, especially in younger patients., Conclusions: There were no obvious changes in glycemic control over time in the study period. The mean HbA1c level was higher in younger patients, which suggested that improvement is required. In older patients, there was a trend toward greater emphasis on management to avoid hypoglycemia. Different treatment strategies based on age showed different drug choices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes., Methods: This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models., Results: During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p = .034) and death (HR 1.64; 95% CI 1.24-2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups., Conclusions: In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has been increasingly recognized as the cause of upper urinary tract infection (UTI) in children. We have been using flomoxef at our department since 2017 as the first-line empiric therapy for children diagnosed with UTIs, and we avoid using carbapenems, which are considered the first-line treatment for ESBL-producing E. coli . However, reports on the use of flomoxef for UTIs are limited, especially for pediatric patients. The presence of vesicoureteral reflux at the onset of pyelonephritis is a concern. Severe vesicoureteral reflux can lead to repeated UTI and future deterioration of renal function, but the indication for voiding urethrography, which closely examines the presence of vesicoureteral reflux complications, is controversial., Methods: We retrospectively reviewed the laboratory findings, treatment, and clinical course of 96 pyelonephritis cases experienced at our department over a 7-year period from April 2014 to March 2021., Results: ESBL-producing E. coli were identified as the cause of pyelonephritis in 51% of cases, and this value was significantly higher (88%) in 2017. No significant differences were found in the febrile period or recurrence rate between the flomoxef-initiated group and other antibiotics groups. We also examined clinical indicators to predict vesicoureteral reflux and found no significant differences in ultrasonographic findings of hydronephrosis., Conclusion: In the present series, 51% of all pyelonephritis cases were found to be caused by ESBL-producing E. coli , with a significant increase in recent years. Flomoxef may be a useful alternative to carbapenem for ESBL-producing E. coli and the initial antibiotic of choice for upper UTIs in children. The indication for voiding cystourethrography should be carefully determined., Competing Interests: The authors declare no conflict of interest., (©2023 Tottori University Medical Press.)

The aim of this preliminary study was to measure the systolic BP (SBP) and diastolic BP (DBP) and heart rate (HR) of radiological technologists by WD, and evaluate variation among individuals by worktime, day of the week, job, and workplace. Measurements were obtained using a wristwatch-type WD with optical measurement technology that can measure SBP and DBP every 10 minutes and HR every 30 minutes. SBP, DBP, and HR data obtained at baseline and during work time were combined with the hours of work, day of the week, job, and workplace recorded by the participants in 8 consecutive weeks. We calculated the mean, the ratio to baseline and coefficient of variation [CV(%)] for SBP, DBP, and HR. SBP, DBP, and HR values were significantly higher during work hours than at baseline (p&lt;0.03). The ratio to baseline values ranged from 1.02 to 1.26 for SBP and from 1.07 to 1.30 for DBP. The ratio to baseline for SBP and DBP showed CV(%) of approximately 10% according to the day of the week and over the study period. For HR, ratio to baseline ranged from 0.95 to 1.29. The ratio of mean BP to baseline was &gt;1.2 at the time of starting work, middle and after lunch, and at 14:00. The ratio to baseline of SBP were 1.2 or more for irradiation, equipment accuracy control, registration of patient data, dose verification and conference time, and were also working in CT examination room, treatment planning room, linac room, and the office. CV(%) of BP and HR were generally stable for all workplaces. WD measurements of SBP, DBP, and HR were higher during working hours than at baseline and varied by the individuals, work time, job, and workplace. This method may enable evaluation of unconscious workload in individuals., Competing Interests: All authors disclose no conflict of interest., (Copyright: © 2022 Minamimoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims/introduction: Few studies have investigated the renoprotective effect of glucagon-like peptide-1 (GLP-1) receptor in patients with chronic kidney disease (CKD). This study evaluated the effect of dulaglutide 0.75 mg on renal function in Japanese patients with type 2 diabetes and CKD stage 3 to 4., Materials and Methods: Dulaglutide (group A) and non-dulaglutide (group B) were compared using data collected from a computerized diabetes care database. For group B, propensity score weighting based on propensity scores was performed. Evaluation items were a change from baseline in hemoglobin A1c (HbA1c), body weight, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), for 3 years., Results: In total, the data obtained from 255 patients (125 and 130 patients for group A and B, respectively) were analyzed. Propensity score-adjusted patient background characteristics (group A vs B) were age 70.8 vs 69.4 years, body weight 70.2 vs 72.9 kg, body mass index 27.3 vs 28.1 kg/m 2 , HbA1c 8.4 vs 8.5%, eGFR 47.9 vs 47.7 mL/min/1.73 m 2 , and UACR 218 vs 251 mg/gCr. Although there were no statistically significant differences in the change from baseline between groups A and B at most time points in eGFR, a statistically significant eGFR decline in group B was observed in slope analysis for 3 years. This renoprotective effect was marked in patients with macro-albuminuria and/or concomitant SGLT2 inhibitor use., Conclusions: Dulaglutide slowed the eGFR decline in patients with type 2 diabetes and CKD stage 3 to 4., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: We investigated the association between various food groups and obesity in Japanese patients with type 2 diabetes., Methods: 2070 patients with type 2 diabetes who attended 26 diabetes clinics throughout Japan were analyzed and were divided into obese and non-obese groups. Intakes of food groups determined by a food frequency questionnaire were compared. Odds ratios for obesity for quartiles of individual food groups were calculated using a logistic regression model., Results: Non-obese patients consumed a larger variety of food groups than obese patients, with the diets of non-obese individuals closer to the traditional Japanese diet characterized by fish, seaweed, and soybeans/soy products. Among 21 food groups, low vegetable intake and high sweets intake were the most strongly associated with obesity in both men and women. Low intake of both fruits and vegetables and the combination of high intake of sweets and low intake of fruits were associated with obesity., Conclusions: Food groups and their combinations that were strongly associated with obesity in Japanese patients with type 2 diabetes were identified. Our findings also suggested an inverse association between the traditional Japanese diet and obesity.

Introduction: Incretin-based therapies exert antihyperglycaemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent fashion. The first-in-class oral glucagon-like peptide-1 receptor agonist semaglutide has potent effects on glycaemic and weight control, but little evidence has been published for the superiority of semaglutide for glycaemic control in patients after switching from a dipeptidyl peptidase-4 (DPP-4) inhibitor. Therefore, we aim to verify the efficacy of oral semaglutide in patients with T2D being treated with a DPP-4 inhibitor., Methods and Analysis: This study is a multicentre, prospective, randomised, open-label, parallel-group trial. In total, 172 participants with T2D who have been treated with a DPP-4 inhibitor for more than 12 weeks and who have a glycated haemoglobin (HbA1c) level of 7.0%-9.9% will be randomised to continue using their existing DPP-4 inhibitor or switch to oral semaglutide for 24 weeks. Biochemical analyses and physical assessment will be performed, and adverse events will be recorded at baseline and at the end of the study. The primary endpoint will be the effect of oral semaglutide on the change in HbA1c. The secondary endpoints will be the mean changes in body weight, abdominal circumference, systolic and diastolic blood pressure (BP), pulse rate, the relationship between improvement of metabolic parameters including HbA1c and patient background characteristics, side effects and other laboratory parameters., Ethics and Dissemination: This will be the first study to compare the effects of switching from a DPP-4 inhibitor to oral semaglutide on glycaemic control in patients with T2D. The results will be disseminated in peer-reviewed journals and at scientific conferences. Hokkaido University Certified Review Board (CRB no.1180001) has approved the protocol (no. 020-013)., Trial Registration Number: UMIN000045270 in the University Hospital Medical Information Network; jRCT1011210032 in the Japan Registry of Clinical Trials., Competing Interests: Competing interests: AN, TA and HM have received honoraria for lectures and received research funding from some organisations as described further. AN has obtained research support from Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim Co, Kissei Pharmaceutical Co, Ltd and Taisho Pharmaceutical Co, Ltd. AT has received research grants from Astellas Pharma Inc, Takeda Pharmaceutical Co, Ltd, Mitsubishi Tanabe Pharma Co, Chugai Pharmaceutical Co, Ltd, Daiichi Sankyo Co Ltd, Otsuka Pharmaceutical Co, Ltd, Pfizer Inc, Alexion Inc, Ono Pharmaceutical Co, Ltd and Teijin Pharma Ltd; speaking fees from Mitsubishi Tanabe Pharma Co, Chugai Pharmaceutical Co, Ltd, Astellas Pharma Inc, Takeda Pharmaceutical Co, Ltd, Pfizer Inc, AbbVie Inc, Eisai Co Ltd, Daiichi Sankyo Co, Ltd, Bristol-Myers Squibb Co, UCB Japan Co Ltd, Eli Lilly Japan K.K., Novartis Pharma K.K., Eli Lilly Japan K.K., Kyowa Kirin Co, Ltd and Taiho Pharmaceutical Co, Ltd; and fees for consultancies from AstraZeneca plc., Medical & Biological Laboratories Co, Ltd, Pfizer Inc, AbbVie Inc, Ono Pharmaceutical Co Ltd, Novartis Pharma K.K. and Nippon Boehringer Ingelheim Co, Ltd. HM has received honoraria for lectures from Astellas Pharma Inc, Sumitomo Dainippon Pharma Co, Ltd, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co, MSD K.K., Novo Nordisk Pharma Ltd, Kowa Pharmaceutical Co, Ltd, Nippon Boehringer Ingelheim Co, Ono Pharmaceutical Co, Ltd and Sanofi; and has received research funding from Astellas Pharma Inc, Daiichi Sankyo Co, Sumitomo Dainippon Pharma Co, Ltd, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co, Novo Nordisk Pharma, Kowa Pharmaceutical Co, Ltd, Abbott Japan Co, Nippon Boehringer Ingelheim Co, Ono Pharmaceutical Co, Ltd, LifeScan Japan Inc and Taisho Pharmaceutical Co, Ltd. HN, SF, JT, SN, HY, IS, ST, YK, SA, AM, HK and KYC have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We investigated trends in the proportion of diabetes treatment and glycemic control, which may be altered by recent advances in insulin and non-insulin drugs, in Japanese patients with type 2 diabetes., Research Design and Methods: A serial cross-sectional study was performed using a multicenter large-population database from the Japan Diabetes Clinical Data Management study group. Patients with type 2 diabetes who attended clinics belonging to the study group between 2002 and 2018 were included to examine trends in glycated hemoglobin A1c (HbA1c) by treatment group using multivariable non-linear regression model., Results: The proportion of patients with insulin only decreased from 15.0% to 3.6%, patients with insulin+non-insulin drugs increased from 8.1% to 15.1%, patients with non-insulin drugs increased from 50.8% to 67.0%, and those with no drugs decreased from 26.1% to 14.4% from 2002 to 2018, respectively. The HbA1c levels of each group, except for no drugs, continued to decrease until 2014 (unadjusted mean HbA1c (%) from 2002 to 2014: from 7.89 to 7.45 for insulin only, from 8.09 to 7.63 for insulin+non-insulin, and from 7.51 to 6.98 for non-insulin) and remained unchanged thereafter. Among insulin-treated patients, use of human insulin decreased, use of long-acting analog insulin increased, and concomitant use of non-insulin drugs increased (from 35.1% in 2002 to 80.9% in 2018), which included increased use of dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists, and the persistently high use of metformin., Conclusions: During the past two decades, combined use of insulin and non-insulin drugs increased and glycemic control improved and leveled off after 2014 in Japanese patients with type 2 diabetes. Further studies of the trend in association with age and factors related to metabolic syndrome are necessary to investigate strategies aiming at personalized medicine in diabetes care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We aimed to analyze the association between dietary iron intake and obesity assessed by BMI after adjustment for nutrient intake (macronutrients and fiber) and food groups. The study design was cross-sectional. Patients with type-2 diabetes ( n = 1567; 63.1% males; mean age 62.3 ± 11.6 years) were included in the study. To assess diet, consumption of typical food groups was determined by a food frequency questionnaire. Obesity was defined as BMI ≥ 25 kg/m 2 . We performed a binary regression analysis between quartiles of iron intake and obesity by quartiles of age group. A direct linear association was found for the highest quartile of iron intake and obesity in the younger age group of 30 to 54 years (OR = 3.641, 95% CI = 1.020-12.990; p trend = 0.011). Multivariate analysis using food groups as opposed to nutrients revealed a positive trend for obesity in the younger age group after adjusting for lifestyle factors, energy intake and bean and vegetable intake ( p trend = 0.023). In all participants, an inverse association was observed before adjustment by vegetable intake (OR = 0.453, 95% CI = 0.300-0.684; p trend = 0.001). Higher iron intake was associated with obesity independent of macronutrient and fiber intake but only in the youngest quartile of age group examined.

Aims/introduction: Type 2 diabetes mellitus is caused by a relative imbalance between insulin secretion and sensitivity related to the body mass index (BMI). Seven categories of oral antidiabetic drugs (OADs) are available in Japan. It is important to assess the OAD utilization patterns based on patients' BMI levels., Materials and Methods: OAD prescribing patterns from 2002 to 2019 were analyzed using the data collected in the computerized diabetes care database provided by the Japan Diabetes Clinical Data Management Study Group; OAD utilization patterns in 25,751 OAD-treated type 2 diabetes mellitus patients registered in 2019 were analyzed after classifying them into five categories of BMI., Results: Comparing OAD usage between 2002 and 2019, sulfonylureas decreased from 44.5 to 23.2%, and biguanides (BGs) increased from 19.3 to 50.3%. Dipeptidyl peptidase-4 inhibitors (DPP4is) increased to 56.9% in 2019. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) increased to 23.6% in 2019. About 90% of type 2 diabetes mellitus patients had BMI < 30 kg/m 2 . DPP4is were the most used OADs in 2019. When BMI exceeded 30 kg/m 2 , use of BGs and sodium-glucose cotransporter 2 inhibitors increased, and use of sulfonylureas and DPP4is decreased. Although DPP4is were the most used OADs for patients with BMI <30 kg/m 2 , they were the third most prescribed OADs for patients with BMI >35 kg/m 2 after BGs and sodium-glucose cotransporter 2 inhibitors ., Conclusions: DPP4i usage was as high as that of BG in the analysis of Japanese type 2 diabetes mellitus patients with relatively low BMI. This was considered to be a treatment option appropriate for the pathophysiology in Japanese patients., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Proton computed tomography (pCT) and radiography (pRad) are proposed modalities for improved treatment plan accuracy and in situ treatment validation in proton therapy. The pCT system of the Bergen pCT collaboration is able to handle very high particle intensities by means of track reconstruction. However, incorrectly reconstructed and secondary tracks degrade the image quality. We have investigated whether a convolutional neural network (CNN)-based filter is able to improve the image quality., Material and Methods: The CNN was trained by simulation and reconstruction of tens of millions of proton and helium tracks. The CNN filter was then compared to simple energy loss threshold methods using the Area Under the Receiver Operating Characteristics curve (AUROC), and by comparing the image quality and Water Equivalent Path Length (WEPL) error of proton and helium radiographs filtered with the same methods., Results: The CNN method led to a considerable improvement of the AUROC, from 74.3% to 97.5% with protons and from 94.2% to 99.5% with helium. The CNN filtering reduced the WEPL error in the helium radiograph from 1.03 mm to 0.93 mm while no improvement was seen in the CNN filtered pRads., Conclusion: The CNN improved the filtering of proton and helium tracks. Only in the helium radiograph did this lead to improved image quality.

Background: In order to provide effective dietary guidance, it is necessary to consider dietary intake, which can change over time. This study analyzed changes in the diet of Japanese patients with type 2 diabetes over a 20-year period., Methods: We compared the results of two dietary surveys that used the food frequency questionnaire format. The first was conducted in 1996 by the Japan Diabetes Complications Study (JDCS) ( n = 1509; males 53.3%), and the second in 2014-2018 by the Japan Diabetes Clinical Data Management Study (JDDM) ( n = 1145; males 65.6%). Both are nationwide representative registries of outpatients with type 2 diabetes in Japan., Results: Over a 20-year period, both men and women with type 2 diabetes had a significant increase in body mass index (BMI). Nonetheless, there was only a small change in energy intake. Conversely, there was a significant increase in fat intake and thus in the fat-to-energy ratio. With regard to food groups, there was a significant increase in meat intake and a decrease in the intake of fish, soybeans/soy products, vegetables, and fruits, with a particularly significant decrease in vegetables., Conclusions: Even in Japan, an industrialized country with a stable socioeconomic environment, there were many significant changes in the dietary intake of patients with type 2 diabetes over the 20-year period.

To investigate the association between dietary energy density (DED) and obesity in people with type 2 diabetes mellitus. Moreover, we compared the strength of the associations of DED with intake of energy and macronutrients in terms of obesity as well as nutritional factors that have long been used for medical nutritional therapy. Cross-sectionally investigated were 1615 outpatients with type 2 diabetes who attended 26 clinics nationwide with diabetes specialists. Odds ratios (ORs) were calculated for the association between obesity and DED, energy, and macronutrients by quintile categories and a 1 SD increment with adjustment for potential confounders. β coefficients were calculated for the association between body mass index (BMI) and each nutritional factor by 1 SD increments in nutritional values. Multi-adjusted OR for obesity between extreme quintiles of DED was 2.99 (95% confidence interval (95% CI): 2.01-3.12). Conversely, the ORs did not differ significantly according to the quintiles of other nutrient factors. Multi-adjusted β coefficient of BMI per 1 SD according to DED was far higher than those of other nutrient factors (β coefficient 0.65, 95% CI: 0.41-0.88). These findings indicated that DED in persons with type 2 diabetes was positively associated with BMI and the prevalence of obesity. DED was also much more potently associated with obesity and BMI than nutritional indicators such as intake of energy or macronutrients.

Aims: To date, no clinical studies have compared once-weekly dipeptidyl peptidase 4 (DPP-4) inhibitors with once-daily DPP-4 inhibitors in terms of glucose variability (GV) and oxidative stress (OS)., Methods: Thirty-six patients with type 2 diabetes mellitus (T2DM) treated with once-daily DPP-4 inhibitors for at least 12 weeks were randomized to either continue once-daily DPP-4 inhibitors or receive omarigliptin, a once-weekly DPP-4 inhibitor, for 24 weeks. The primary end points were changes in the diacron-reactive oxygen metabolite (d-ROMs) test, a marker of OS, and GV using flash glucose monitoring. The secondary end point was changes in the diabetes treatment satisfaction questionnaire (DTSQ) scores., Results: There were no significant group differences in d-ROMs and DTSQ scores after 24 weeks of treatments. However, omarigliptin was superior to once-daily DPP-4 inhibitors in controlling fasting plasma glucose (FPG) and time in range (TIR). Although FPG and TIR were unchanged at 24 weeks after switching to omarigliptin, these parameters increased in the group receiving maintenance therapy with once-daily DPP-4 inhibitors. No statistically significant changes in hemoglobin A1c were observed between the two groups., Conclusions: Our findings suggest that switching from once-daily DPP-4 inhibitors to omarigliptin may be efficacious for maintaining FPG and TIR in T2DM patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Treatment-related quality of life (QOL) is an important aspect of diabetes management. We evaluated the influence of a sodium-glucose cotransporter 2 (SGLT2) inhibitor, tofogliflozin, on treatment-related QOL in Japanese patients with type 2 diabetes mellitus (T2DM)., Methods: This is the prespecified subanalysis study of the "Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)" trial. Treatment-related QOL was evaluated at baseline, week 26, week 52, and week 104 after the initiation of the study using the Diabetes Therapy-Related QOL questionnaire (DTR-QOL). Among the 340 patients in the original UTOPIA study, a total of 252 patients (127, tofogliflozin group; 125, conventional treatment group) who completed the DTR-QOL questionnaire at baseline were the study subjects of the current subanalysis., Results: The tofogliflozin and conventional treatment groups exhibited almost comparable baseline clinical characteristics, while the use of antihypertensive drugs and lipid-lowering agents was significantly lower in the tofogliflozin treatment group than in the conventional treatment group. Tofogliflozin treatment increased the total score of DTR-QOL7 from baseline (P < 0.001), while conventional treatment did not change it. There were statistically significant differences in delta change in the total DTR-QOL7 score and DTR-QOL7 Q4, Q5, Q6, and Q7 scores from the baseline to week 104 between the treatment groups. Delta changes in HbA1c (Spearman's correlation coefficient, ρ =  - 0.30, P < 0.001), fasting blood glucose (ρ =  - 0.16, P = 0.031), BMI (ρ =  - 0.19, P = 0.008), and waist circumference (ρ =  - 0.17, P = 0.024) at week 104 were negatively associated with delta change in the total QOL7 score., Conclusions: Our data indicated that tofogliflozin treatment improved treatment-related QOL compared to conventional treatment in Japanese patients with T2DM, in accordance with the improvement of major cardiovascular risk factors., Trial Registration: UMIN000017607., (© 2021. The Author(s).)

Objectives: Cardiovascular disease remains the most common cause of death in patients with type 2 diabetes mellitus. Because periodontitis is a risk factor of cardiovascular disease, identification of risk factors of periodontitis is valuable to control periodontitis effectively. The purpose of this study was to examine the association of education and household income with periodontal status in patients with type 2 diabetes mellitus., Methods: Participants were 2,436 patients (59.8% male, aged 29-93 years) with type 2 diabetes mellitus from 27 medical clinics. Participants' medical records and information about education, household income, general health status, and health behaviors were collected. Periodontal status was assessed in a nearby dental office. Multiple linear regression analyses and ordered logistic regression analyses were conducted to examine the association of periodontal parameters with education and household income after adjusting for age, sex, general health status, and health behaviors., Results: Multiple linear regression analysis showed that mean probing pocket depth was not significantly associated with education and household income. Ordered logistic regression analyses showed statistically significant odds ratios (ORs) of junior high school (reference: university) for the tertiles of the percentage of sites with bleeding on probing (OR: 1.42; 95% confidence interval [CI]: 1.11-1.81), percentage of mobile teeth (OR: 1.58; 95% CI: 1.24-2.03), and number of teeth present (OR: 0.51; 95% CI: 0.39-0.65), and statistically significant odds ratios of high school (reference: university) for the tertiles of the percentage of mobile teeth (OR: 1.27; 95% CI: 1.06-1.51) and number of teeth present (OR: 0.74; 95% CI: 0.62-0.88), but not household income., Conclusions: These results suggest that low education is one of the important predictors of poor periodontal status in patients with type 2 diabetes mellitus. It is important to provide targeted interventions including periodontal education in junior high school., (© 2020 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Aims/introduction: To identify the effect of combination therapy with a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter 2 inhibitor compared with switching from a dipeptidyl peptidase-4 inhibitor to a sodium-glucose cotransporter 2 inhibitor on improving the glucose variability in patients with or without impaired endogenous insulin secretion., Materials and Methods: A secondary analysis regarding the relationship between endogenous insulin secretion and the change in mean amplitude of glycemic excursions (ΔMAGE) was carried out in a multicenter, prospective, randomized, parallel-group comparison trial that enrolled patients with type 2 diabetes who had been taking teneligliptin and were treated by switching to canagliflozin (SWITCH) or adding canagliflozin (COMB). Participants were categorized into the following four subgroups: SWITCH or COMB and high or low fasting C-peptide (CPR) divided at baseline by the median., Results: ΔMAGE in the COMB group was greatly improved independent of a high or low CPR (-29.2 ± 28.3 vs -20.0 ± 24.6, respectively; P = 0.60). However, ΔMAGE was not ameliorated in the low CPR SWITCH group, and the ΔMAGE was significantly smaller than that in the high CPR COMB group (P < 0.01)., Conclusions: COMB would be a better protocol rather than switching teneligliptin to canagliflozin to improve daily glucose variability in patients with impaired endogenous insulin secretion., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims/introduction: We recently reported the beneficial effect of the combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor on daily glycemic variability in patients with type 2 diabetes mellitus. Additional favorable effects of combination therapy were explored in this secondary analysis., Materials and Methods: The CALMER study was a multicenter, open-label, prospective, randomized, parallel-group comparison trial for type 2 diabetes mellitus involving continuous glucose monitoring under meal tolerance tests. Patients were randomly assigned to switch from teneligliptin to canagliflozin (SWITCH group) or to add canagliflozin to teneligliptin (COMB group). The continuous glucose monitoring metrics, including time in target range, were investigated., Results: All 99 participants (mean age 62.3 years; mean glycated hemoglobin 7.4%) completed the trial. The time in target range was increased in the COMB group (71.2-82.7%, P < 0.001). The extent of the reduction in time above target range was significantly larger in the COMB group compared with the SWITCH group (-14.8% vs -7.5%, P < 0.01). Area under the curve values for glucose at 120 min after all meal tolerance tests were significantly decreased in the COMB group compared with the SWITCH group (P < 0.05)., Conclusions: Sodium-glucose cotransporter 2 inhibitor combined with dipeptidyl peptidase-4 inhibitor improved the quality of glycemic variability and reduced postprandial hyperglycemia compared with each monotherapy., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Introduction: Changes in albuminuria or estimated glomerular filtration rate (eGFR) can be used as a surrogate endpoint of end-stage kidney disease (ESKD) in people with type 2 diabetes. We investigated whether the combined changes in albuminuria and eGFR are more strongly associated with future risk of ESKD., Research Design and Methods: Using data from a multicenter observational cohort study of people with type 2 diabetes, we evaluated the association of percentage change in urine albumin to creatinine ratio (UACR) and/or annual change in eGFR over 2 years with subsequent ESKD risk., Results: Among 1417 patients with repeated albuminuria and eGFR over 2 years, 129 (9.1%) developed ESKD. Patients with >30% UACR decline had lower ESKD risk (HR 0.47; 95% CI 0.29 to 0.77), whereas those with >30% UACR increase had higher ESKD risk (HR 2.31; 95% CI 1.52 to 3.51), compared with those with minor UACR change. Patients with greater eGFR decline had an increased ESKD risk than those with minor eGFR change (a decline of <2.5 mL/min/1.73 m 2 /year): HR 4.19 (95% CI 1.87 to 9.38) and 2.89 (95% CI 1.32 to 6.33) for those with a decline of >5 and 2.5-5 mL/min/1.73 m 2 /year, respectively. When the combined changes in UACR and eGFR were used, the highest ESKD risk (HR 5.60; 95% CI 2.08 to 15.09) was observed among patients with >30% UACR increase and an eGFR decline of >5 mL/min/1.73 m 2 /year compared with those with a minor change in UACR and eGFR., Conclusions: Combined changes in albuminuria and eGFR over 2 years were strongly associated with future risk of kidney failure in patients with type 2 diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Glucagon-like peptide (GLP)-1 receptor agonists exert potent hypoglycemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent manner. Once-weekly subcutaneous administration of the GLP-1 receptor agonist semaglutide has beneficial effects on glycemic and body weight control, but it is currently unclear if semaglutide provides superior glycemic control compared to conventional GLP-1 receptor agonists in the Japanese population. We aim to compare the effects of once-weekly subcutaneous semaglutide with those of liraglutide or dulaglutide administration in Japanese patients with T2D., Methods: This study is a multicenter, prospective, randomized, open-label, blinded-endpoint, parallel-group trial. In total, 100 participants with T2D who have been treated with liraglutide (0.9-1.8 mg/day in plan A) or dulaglutide (0.75 mg/week in plan B) for more than 12 weeks and have a glycated hemoglobin (HbA1c) level of 6.0-9.9% and a body mass index (BMI) of ≥ 22 kg/m 2 will be randomized to either continue using their existing GLP-1 receptor agonist or switch to subcutaneous semaglutide once weekly for 24 weeks. Biochemical analysis, physical assessment, and a quality-of-life questionnaire (DTSQ) will be completed at baseline and at the end of the study. The primary endpoint is the effect of semaglutide on the change in HbA1c. The secondary endpoints are the mean changes in total DTSQ score, body mass, abdominal circumference, systolic and diastolic blood pressure, pulse rate, factors associated with improvement in HbA1c and secondary endpoints, side effects, and other laboratory parameters., Planned Outcomes: The results of the study will provide useful information regarding the effects of switching to semaglutide from other GLP-1 receptor agonists on glycemic control in patients with T2D., Ethics and Dissemination: The Hokkaido University Certified Review Board (CRB no. 1180001) has approved the protocol (no. 018-005). The results will be disseminated in peer-reviewed journals and at scientific conferences., Trial Registration: UMIN000042369 in the University Hospital Medical Information Network (UMIN); jRCT1011200008 in the Japan Registry of Clinical Trials (jRCT); pre-results.

Radiation therapy using protons and heavier ions is a fast-growing therapeutic option for cancer patients. A clinical system for particle imaging in particle therapy would enable online patient position verification, estimation of the dose deposition through range monitoring and a reduction of uncertainties in the calculation of the relative stopping power of the patient. Several prototype imaging modalities offer radiography and computed tomography using protons and heavy ions. A Digital Tracking Calorimeter (DTC), currently under development, has been proposed as one such detector. In the DTC 43 longitudinal layers of laterally stacked ALPIDE CMOS monolithic active pixel sensor chips are able to reconstruct a large number of simultaneously recorded proton tracks. In this study, we explored the capability of the DTC for helium imaging which offers favorable spatial resolution over proton imaging. Helium ions exhibit a larger cross section for inelastic nuclear interactions, increasing the number of produced secondaries in the imaged object and in the detector itself. To that end, a filtering process able to remove a large fraction of the secondaries was identified, and the track reconstruction process was adapted for helium ions. By filtering on the energy loss along the tracks, on the incoming angle and on the particle ranges, 97.5% of the secondaries were removed. After passing through 16 cm water, 50.0% of the primary helium ions survived; after the proposed filtering 42.4% of the primaries remained; finally after subsequent image reconstruction 31% of the primaries remained. Helium track reconstruction leads to more track matching errors compared to protons due to the increased available focus strength of the helium beam. In a head phantom radiograph, the Water Equivalent Path Length error envelope was 1.0 mm for helium and 1.1 mm for protons. This accuracy is expected to be sufficient for helium imaging for pre-treatment verification purposes.