Glycaemic control efficacy of switching from dipeptidyl peptidase-4 inhibitors to oral semaglutide in subjects with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 2 study).

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.

Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial.

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.

Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study).

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.

Ulnar Nerve Neuropathy After Surgery for Intraarticular Distal Humerus Fractures: An Analysis of 116 Patients.

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.

A less invasive operative method using a medial cannulated cancellous screw and single plate fixation for the treatment of transcondylar fracture of the humerus in elderly patients in multicenter (TRON group) study.

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.

Clinical comparison of double-plate fixation by the perpendicular plate method versus parallel plate method for distal humeral fracture: a multicenter (TRON group) study.

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.

Effect of tofogliflozin on arterial stiffness in patients with type 2 diabetes: prespecified sub-analysis of the prospective, randomized, open-label, parallel-group comparative UTOPIA trial.

BACKGROUND: Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP). This study evaluated the effects of tofogliflozin on the brachial-ankle pulse wave velocity (baPWV) in patients with type 2 diabetes (T2DM) without a history of apparent cardiovascular disease. METHODS: The using tofogliflozin for possible better intervention against atherosclerosis for type 2 diabetes patients (UTOPIA) trial is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. As one of the prespecified secondary outcomes, changes in baPWV over 104 weeks were evaluated in 154 individuals (80 in the tofogliflozin group and 74 in the conventional treatment group) who completed baPWV measurement at baseline. RESULTS: In a mixed-effects model, the progression in the right, left, and mean baPWV over 104 weeks was significantly attenuated with tofogliflozin compared to that with conventional treatment (- 109.3 [- 184.3, - 34.3] (mean change [95% CI] cm/s, p = 0.005; - 98.3 [- 172.6, - 24.1] cm/s, p = 0.010; - 104.7 [- 177.0, - 32.4] cm/s, p = 0.005, respectively). Similar findings were obtained even after adjusting the mixed-effects models for traditional cardiovascular risk factors, including body mass index (BMI), glycated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, systolic blood pressure (SBP), hypertension, smoking, and/or administration of drugs, including hypoglycemic agents, antihypertensive agents, statins, and anti-platelets, at baseline. The findings of the analysis of covariance (ANCOVA) models, which included the treatment group, baseline baPWV, and traditional cardiovascular risk factors, resembled those generated by the mixed-effects models. CONCLUSIONS: Tofogliflozin significantly inhibited the increased baPWV in patients with T2DM without a history of apparent cardiovascular disease, suggesting that tofogliflozin suppressed the progression of arterial stiffness. Trial Registration UMIN000017607. Registered 18 May 2015. ( https://www.umin.ac.jp/icdr/index.html ).

Investigating particle track topology for range telescopes in particle radiography using convolutional neural networks.

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.

Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation.

The FMS-related tyrosine kinase 3 (FLT3) internal tandem duplication mutations (FLT3-ITD) positive acute myeloid leukemia (AML) is a disease with a dismal outcome. Gilteritinib is a second-generation FLT3 inhibitor with activity against ITD and high affinity toward the FLT3 receptor, thereby showing therapeutic potential for relapsed/refractory FLT3-mutated AML. Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) identical sibling donor was performed in a 38-year-old Japanese male with FLT3-ITD positive AML. Neutrophil engraftment (>0.5 × 109/L) was achieved on day 16, and bone marrow remission was revealed on day 32. The patient's AML relapsed hematologically four months after BMT and was resistant to salvage chemotherapy. Gilteritinib was administered and the patient achieved non-remission but 'stable disease' status according to the response criteria. During administration, liver damage was observed but controllable. The patient received cord blood transplantation (CBT) as the second hematopoietic stem cell transplantation (HSCT) three months after relapse and achieved second remission. There was no evidence of recurrence of AML four months after CBT. This case demonstrates that gilteritinib can control FLT3-ITD positive AML that relapsed early after initial HSCT and can bridge to second HSCT.

Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective, randomized, open-label, parallel-group comparative study.

BACKGROUND: This study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT). METHODS: This prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period. RESULTS: In a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (- 0.132 mm, SE 0.007; - 0.163 mm, SE 0.013; - 0.170 mm, SE 0.020, respectively) and the control group (- 0.140 mm, SE 0.006; - 0.190 mm, SE 0.012; - 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (- 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (- 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (- 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups. CONCLUSIONS/INTERPRETATION: No IMT changes were observed between the tofogliflozin and the conventional treatment groups. However, tofogliflozin is a safe and effective treatment option for managing primary CVD risk factors in this population. Clinical Trial Registration UMIN000017607 ( https://www.umin.ac.jp/icdr/index.html ).

Favourable effect of the sodium-glucose co-transporter-2 inhibitor canagliflozin plus the dipeptidyl peptidase-4 inhibitor teneligliptin in combination on glycaemic fluctuation: An open-label, prospective, randomized, parallel-group comparison trial (the CALMER study).

This multicentre, prospective, randomized, open-label, blinded-endpoint, parallel-group, short-term (4-5 weeks) controlled trial was conducted to investigate the superiority of the effect of reducing mean amplitude of glycaemic excursions (MAGE) during meal tolerance tests (MTTs) for the combination of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter-2 (SGLT2) inhibitor compared with SGLT2 inhibitor monotherapy. Ninety-nine patients with type 2 diabetes who were taking teneligliptin (20 mg/d) were randomized to one of the following two groups: those who switched to 100 mg/d of canagliflozin (SWITCH group) or those who added 100 mg/d of canagliflozin (COMB group). MAGE in the COMB group was significantly decreased compared with that in the SWITCH group (COMB 117.5 ± 39.8 to 92.2 ± 28.0 mg/dL vs SWITCH 110.7 ± 29.8 to 104.2 ± 27.6 mg/dL; P<0.01). Mean blood glucose decreased significantly during MTTs in both groups, although the extent of the reduction was significantly greater in the COMB group (COMB 142.3 ± 28.7 to 119.5 ± 25.1 mg/dL vs SWITCH 146.4 ± 25.5 to 135.5 ± 22.4 mg/dL; P < 0.01). SGLT2 inhibitor combined with DPP-4 inhibitor therapy strongly reduced glycaemic fluctuation compared with SGLT2 inhibitor monotherapy.

Concurrent immunoglobulin G-lambda type multiple myeloma and mixed cellularity classical Hodgkin lymphoma: A case report.

A 66-year-old man with a swollen right inguinal lymph node (LN) had pain on the lower side of the back. Computed tomography revealed bone disease in the back and swollen right inguinal LNs. Laboratory studies showed anemia and serum immunoglobulin G-lambda (IgG-λ) type monoclonal protein. The bone marrow contained 39.6% plasma cells. He was diagnosed with IgG-λ type multiple myeloma (MM). However, the pathological findings of the right inguinal LN were mixed cellular classical Hodgkin lymphoma (HL). The administration of melphalan, prednisone, and bortezomib (MPB) was started for MM; however, swelling in the right inguinal LN increased. After three cycles of MPB, the administration of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was started for HL. However, HL was refractory to ABVD. Pancytopenia subsequently progressed and rapid swelling occurred in his LNs. He died 7 months after diagnosis. Multiple myeloma was diagnosed, based on the typical symptoms, although the pathological findings of the LN indicated a diagnosis of HL. We analyzed the molecular relationship between MM and HL cells using a direct sequencing method. The sequencing results demonstrated that the variable-diversity-joining (VDJ) region of the IgH gene was identified with 94.4% of IGLV3-32*01 in the bone marrow sample at diagnosis. Furthermore, clonotypic IgH sequence was identified in CD30-positive cells from the LN. These results suggested that the clonal HL cells were derived from the same source as the clonal MM cells and demonstrated that MM and HL in this patient may have originated from the same B cell progenitor.

The bridge treatment selected at the decision for transplantation did not affect the outcomes in patients with MDS.

The optimal treatment for use as a bridge to allogeneic hematopoietic stem cell transplantation at the decision for transplantation has not been established in patients with myelodysplastic syndrome (MDS). We retrospectively evaluated the clinical outcomes after the decision for transplantation in our patients with MDS or acute myeloid leukemia (AML) secondary to MDS, aged more than 15 years, who underwent transplantation between 2007 and 2012. A total of 124 patients were included. We classified patients into two groups according to the bridge treatment selected at the decision for transplantation: Group 1, supportive care (n = 79), immunosuppressive therapy (n = 7), low-dose chemotherapy (n = 12); Group 2, AML-type induction chemotherapy (ICT: n = 22), azacitidine (Aza: n = 4). The rate of blasts in the bone marrow significantly influenced the treatment selection at the time of decision. There was no significant difference between the two groups in the rate of overall survival (OS) from the decision (73.1% vs 80.4% at 1 year) or from transplantation (59.0% vs 59.2% at 1 year). A significant difference was not observed even after patients were stratified according to either the rate of blasts in the bone marrow at the time of decision or the propensity score. In conclusion, the bridge treatment selected at the decision for transplantation did not affect the outcomes of transplantation in patients with MDS. However, this analysis did not include patients who could not undergo transplantation after the decision, and thus a prospective study is warranted. Copyright © 2015 John Wiley & Sons, Ltd.

A new analytical method for characterizing nonlinear visual processes with stimuli of arbitrary distribution: Theory and applications.

Characterization of the functional relationship between sensory inputs and neuronal or observers' perceptual responses is one of the fundamental goals of systems neuroscience and psychophysics. Conventional methods, such as reverse correlation and spike-triggered data analyses are limited in their ability to resolve complex and inherently nonlinear neuronal/perceptual processes because these methods require input stimuli to be Gaussian with a zero mean. Recent studies have shown that analyses based on a generalized linear model (GLM) do not require such specific input characteristics and have advantages over conventional methods. GLM, however, relies on iterative optimization algorithms and its calculation costs become very expensive when estimating the nonlinear parameters of a large-scale system using large volumes of data. In this paper, we introduce a new analytical method for identifying a nonlinear system without relying on iterative calculations and yet also not requiring any specific stimulus distribution. We demonstrate the results of numerical simulations, showing that our noniterative method is as accurate as GLM in estimating nonlinear parameters in many cases and outperforms conventional, spike-triggered data analyses. As an example of the application of our method to actual psychophysical data, we investigated how different spatiotemporal frequency channels interact in assessments of motion direction. The nonlinear interaction estimated by our method was consistent with findings from previous vision studies and supports the validity of our method for nonlinear system identification.

Myelodysplastic syndrome with myelofibrosis in which azacitidine therapy was effective and cord blood transplantation was carried out.

Myelodysplastic syndrome with myelofibrosis (MDS-F) is a disease with a poor prognosis, and patients with this condition are at an increased risk of engraftment failures after allogeneic hematopoietic stem cell transplantation (SCT). Azacitidine (AZA) is effective in high-risk MDS patients. However, the effects of AZA on MDS-F have not been elucidated. AZA was administered to a 62-year-old male with MDS-F for 7 days at a dose of 75 mg/m2. Hematological improvements were observed after only 1 course of treatment. No suitable donor was found through the Japan Marrow Donor Program; therefore, the patient underwent umbilical cord blood transplant (UCBT). Neutrophil engraftment was observed on day 21 after the transplant procedure. He developed acute graft versus host disease (GVHD) of the skin (stage 3/grade II), but it could be controlled using prednisolone. Chronic GVHD was not observed and he was discharged in good general condition on day 68. While treatment prior to allogeneic SCT of MDS-F has not been established, in the present case, the hematological improvement brought about by AZA likely contributed to the patient's positive response to UCBT.

Additional Nucleophile-Free FeCl3-Catalyzed Green Deprotection of 2,4-Dimethoxyphenylmethyl-Protected Alcohols and Carboxylic Acids.

The deprotection of the methoxyphenylmethyl (MPM) ether and ester derivatives can be generally achieved by the combinatorial use of a catalytic Lewis acid and stoichiometric nucleophile. The deprotections of 2,4-dimethoxyphenylmethyl (DMPM)-protected alcohols and carboxylic acids were found to be effectively catalyzed by iron(III) chloride without any additional nucleophile to form the deprotected mother alcohols and carboxylic acids in excellent yields. Since the present deprotection proceeds via the self-assembling mechanism of the 2,4-DMPM protective group itself to give the hardly-soluble resorcinarene derivative as a precipitate, the rigorous purification process by silica-gel column chromatography was unnecessary and the sufficiently-pure alcohols and carboxylic acids were easily obtained in satisfactory yields after simple filtration.

Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation.

A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III-IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.

Donor lymphocyte infusion for the treatment of relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation.

Because the efficacy of donor lymphocyte infusion (DLI) for acute myeloid leukemia (AML) relapse after allogeneic hematopoietic stem cell transplantation (HSCT) remains uncertain, especially in the Asian population, a nationwide registry study was retrospectively performed by the Adult AML Working Group of the Japan Society for Hematopoietic Cell Transplantation to identify the factors affecting the patient survival after DLI. Among 143 adult AML patients who received DLI for the treatment of first hematological relapse after HSCT, the overall survival rates at 1 year, 2 years, and 5 years were 32% ± 4%, 17% ± 3%, and 7% ± 3%, respectively. Complete remission (CR) at the time of DLI, which was obtained in 8% of the patients, was the strongest predictive factor for survival after DLI. Therefore, long-term survival after DLI was achieved almost exclusively in patients who successfully achieved a CR before DLI, indicating the limited efficacy of DLI in a minority of patients.

Clinical impact of albuminuria and glomerular filtration rate on renal and cardiovascular events, and all-cause mortality in Japanese patients with type 2 diabetes.

BACKGROUND: The number of patients suffering from diabetic nephropathy resulting in end-stage kidney disease is increasing worldwide. In clinical settings, there are limited data regarding the impact of the urinary albumin-to-creatinine ratio (UACR) and reduced estimated glomerular filtration rate (eGFR) on renal and cardiovascular outcomes and all-cause mortality. METHODS: We performed a historical cohort study of 4328 Japanese participants with type 2 diabetes from 10 centers. Risks for renal events (requirement for dialysis or transplantation, or half reduction in eGFR), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), and all-cause mortality were assessed according to UACR and eGFR levels. RESULTS: During follow-up (median 7.0 years, interquartile range 3.0-8.0 years), 419 renal events, 605 cardiovascular events and 236 deaths occurred. The UACR levels increased the risk and the adjusted hazard ratios for these three events. In addition to the effects of UACR levels, eGFR stages significantly increased the adjusted hazard ratios for renal events and all-cause mortality, especially in patients with macroalbuminuria. Diabetic nephropathy score, based on the prognostic factors, well predicted incidence rates per 1000 patient/year for each event. CONCLUSIONS: Increased UACR levels were closely related to the increase in risks for renal, cardiovascular events and all-cause mortality in Japanese patients with type 2 diabetes, whereas the association between high levels of UACR and reduced eGFR was a strong predictor for renal events.

Low and high body mass index and lower numbers of screws in the articular segment are risk factors for non-union of distal humeral fractures in the elderly: A multi-center retrospective study (TRON study).

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/m2 and ≥25 kg/m2, 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.