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Insulin treatment should be introduced in patients with slowly progressive type 1 diabetes (SPIDDM; definite), according to the revised diagnostic criteria of SPIDDM (2023). In contrast, SPIDDM (probable) patients are in a non-insulin-dependent state; therefore, a more flexible treatment can be considered, although sulfonylurea agents should be avoided. Insulin treatment has been shown to maintain endogenous insulin secretion capacity in SPIDDM (probable); however, this does not mean that all SPIDDM (probable) patients should use insulin from the early phase. Dipeptidyl peptidase-4 inhibitors and biguanides might be the treatment of choice for SPIDDM (probable), but no evidence exists for other hypoglycemic agents. In any case, careful monitoring of the endogenous insulin secretion capacity should be carried out, and if a decrease in insulin secretion capacity is suspected, a change in treatment should be considered to prevent progression to an insulin-dependent state., (© 2024 The Japan Diabetes Society. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Carmine is an aluminium and/or calcium-chelated complex form of carminic acid (CA), which is derived from the Dactylopius coccus extract (cochineal), and is globally used as a red-colourant in foods and cosmetics. Although several allergens in carmine allergies, such as CC38K, have been reported, it remains unknown whether chelation affects the allergenicity of carmine. We report a case of Japanese fish sausage ( Gyoniku Sausage ) anaphylaxis induced by epicutaneous sensitization to carmine contained in eyeshadows. In addition, we report on the effect of chelation on carmine allergy. A 32-year-old woman had experienced itching, wheals, and swelling of her eyelids immediately after applying pink eyeshadows, which contained carmine, on several occasions for 3 years. Two months ago, she developed itching, wheals, and swelling on her whole body, especially her eyelids, and dyspnea immediately after ingesting fried pink fish sausages, which contained cochineal. In skin prick tests (SPTs) with all ingredients ingested in the two episodes of anaphylaxis, only fish sausage was positive. SPT was also positive for carmine. In IgE-immunoblotting using the eyeshadow and fish sausage, the patient serum IgE was bound to three protein bands at approximately 86, 114, and 130 kDa. In addition, IgE-immunoblotting using the carmine showed a broad band at 86-130 kDa, which were consistent with those using the eyeshadow and fish sausage, whereas there is no band using CA. Interestingly, the protein bands using the eyeshadow and carmine were diminished by preincubation in the presence of ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The results indicated that the causative allergens of carmine contained in the eyeshadows could be dechelated by EDTA, reducing its allergenicity. In conclusion, carmine contained in cosmetics can cause epicutaneous sensitisation and consequently can induce food anaphylaxis. To prevent sensitisation in carmine allergy, the effect of chelation on allergenicity of carmine should be considered., Competing Interests: The authors declare that they have no conflicts of interest associated with this manuscript., (Copyright © 2024 Maiko Yamaura et al.)

Background and Aims: To investigate the association between the frequency of intermittent-scanning continuous glucose monitoring (isCGM) and diurnal variation of time in range (TIR), time above range (TAR), and time below range (TBR), we performed a post hoc analysis of the ISCHIA study, a multicenter, prospective, open-label, randomized crossover study of patients with type 1 diabetes mellitus., Method: Data of 93 people who completed the ISCHIA study were used. We calculated scan frequency, TAR, TIR, and TBR of four approximately 6-h intervals: 6:00-11:59 (morning), 12:00-17:59 (afternoon), 18:00-23:59 (evening), and 0:00-5:59 (night). The correlation between scan frequency and diurnal variation of CGM metrics was analyzed using nonparametric Spearman correlation analysis., Results: More frequent scanning was associated with higher TIR in the afternoon (rho = 0.343, P < 0.001), evening (rho = 0.243, P = 0.019), and night (rho = 0.218, P = 0.036); furthermore, it was associated with lower TAR in the afternoon (rho = -0.275, P = 0.008) and TBR in the evening (rho = -0.235, P = 0.024). Concern about the effect of blood glucose fluctuation on social communication affected the number of scans during the day. Concerns about loneliness and hypoglycemia when alone also influenced the number of nighttime scans., Conclusion: Scan frequency is influenced by psychological factors. Afternoon scans were associated with the highest increase in TIR and decrease in TAR. Evening scans were linked to a reduction in TBR., Competing Interests: Conflict of interestNo potential conflicts of interest (COI) as the ISCHIA Study Group relevant to this article were reported. Potential COI concerning all individual investigators were reviewed by the Certified Review Board in accordance with the Clinical Trials Act [9]. The COI of the members of the writing group are as follows: YH received lecture fees from Abbott, Eli Lilly, Sanofi, Novo Nordisk, Sumitomo, and Terumo and received a research grant from Sumitomo, Kyowa Kirin, and Medtronic Japan and a donation from Abbott Japan. MM received lecture fees from Abbott, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Orizuru Therapeutics, Sanofi, Sumitomo, and Terumo. SM received lecture fees from Eli Lilly, Kowa, Sumitomo, and Novo Nordisk. JM received lecture fees from Novo Nordisk. AT received lecture fees from Abbott, Eli Lilly, Sanofi, and Terumo. MT received lecture fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sumitomo, and Mitsubishi Tanabe and received subsidies from Cocokara Fine Healthcare, LifeScan, Roche DC, and Super Light Water. TM received a research grant from Medtronic. KH, KK, AS, AK, NK, NS, and AI declare that they have no conflict of interest., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: The primary treatment of patients with advanced ovarian cancer is selected from whether primary debulking surgery or neoadjuvant chemotherapy. We investigated whether pretreatment serum microRNA profiles are useful for selecting patients with advanced high-grade serous ovarian cancer who obtain better outcomes from undergoing primary debulking surgery or neoadjuvant chemotherapy., Methods: Consecutive patients with clinical stage IIIB-IVB and serum microRNA data were selected. Patients who underwent primary debulking surgery or neoadjuvant chemotherapy were subjected to 1:1 propensity score matching before comparing their progression-free survival using Cox modelling. Progression-free probabilities for the selected microRNA profiles were calculated, and the estimated progression-free survival with the recommended primary treatment was determined and compared with the actual progression-free survival of the patients., Results: Of the 108 patients with stage IIIB-IVB disease, the data of 24 who underwent primary debulking surgery or neoadjuvant chemotherapy were compared. Eleven and three microRNAs were independent predictors of progression-free survival in patients who underwent primary debulking surgery and neoadjuvant chemotherapy, respectively. Two microRNAs correlated significantly with complete resection of the tumours in primary debulking surgery. No differences were found between the actual and estimated progression-free survival in the primary debulking surgery and neoadjuvant chemotherapy groups (P > 0.05). The recommended and actual primary treatments were identical in 27 (56.3%) of the 48 patients. The median improved survival times between recommended and actual treatment were 11.7 and 32.6 months for patients with actual primary debulking surgery and neoadjuvant chemotherapy, respectively., Conclusions: Pretreatment microRNA profiles could be used to select subgroups of patients who benefited more from primary debulking surgery or neoadjuvant chemotherapy and might contribute to selecting the optimal primary treatment modality in advanced high-grade serous ovarian cancer patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

One of the resistant mechanisms of EGFR-TKIs is BRAF V600E mutation. Herein, we present the case of a 54-year-old Japanese female who underwent a right middle lobectomy for pathological stage IIB lung adenocarcinoma. One year and nine months after the surgery, she developed multiple intrapulmonary metastases. Osimertinib was administered due to EGFR exon 19 deletion. Although all intrapulmonary metastases had shrunk, the nodule at the superior segment of left lung enlarged after postoperative 4 years. The tumour was resected and BRAF V600E mutation and exon 19 deletion were detected. Three months after treatment with dabrafenib and trametinib instead of osimertinib, the remaining intrapulmonary metastases increased again. The continued growth of the metastatic foci even after EGFR-TKI may indicate an acquired resistance. Thus, a repeat biopsy will aid in confirming the new gene expression. It should have been necessary to administer an additional dose of dabrafenib and trametinib without discontinuing osimertinib., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Selective inhibition of the RGD (Arg-Gly-Asp) integrin αvβ1 has been recently identified as an attractive therapeutic approach for the treatment of liver fibrosis given its function, target expression, and safety profile. Our identification of a non-RGD small molecule lead followed by focused, systematic changes to the core structure utilizing a crystal structure, in silico modeling, and a tractable synthetic approach resulted in the identification of a potent small molecule exhibiting a remarkable affinity for αvβ1 relative to several other integrin isoforms measured. Azabenzimidazolone 25 demonstrated antifibrotic efficacy in an in vivo rat liver fibrosis model and represents a tool compound capable of further exploring the biological consequences of selective αvβ1 inhibition.

Background: Atezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II-IIIA non-small cell lung cancer with 1% or more programmed death ligand-1 (PD-L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non-small cell lung cancer. Therefore, our study aimed to compare two PD-L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab., Methods: We retrospectively and prospectively analyzed 98 patients who underwent surgical resection at Kanagawa Cancer Center (Japan). An immunohistochemistry assay was performed for all the cases with both SP263 and 22C3. We statistically analyzed the concordance of PD-L1 expression between SP263 and 22C3 assays., Results: The concordance between the two assays using Cohen's kappa was κ = 0.670 (95% CI: 0.522-0.818) at the 1% cutoff and κ = 0.796 (95% CI: 0.639-0.954) at the 50% cutoff. The Spearman correlation coefficient of 0.874 (p < 0.01) indicated high concordance. PD-L1 expression with 22C3 resulted slightly higher than that with SP263., Conclusions: This study showed a high concordance of PD-L1 expression with the SP263 and 22C3 assays. Further studies examining the therapeutic effects of adjuvant atezolizumab are required., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Objective To examine the impact of lifestyle changes caused by the first emergency declaration issued in 2020 on glycemic control and body weight changes in Japanese individuals with type 1 diabetes mellitus. Methods This study included Japanese individuals with type 1 diabetes mellitus who visited Tokyo Women's Medical University Hospital between January 2019 and September 2020 (n=278). Seasonal changes in glycated hemoglobin (HbA1c) levels and the body mass index (BMI) were compared. A self-administered questionnaire regarding changes in treatment, diet, exercise, sleep, and telecommuting was used to assess lifestyle changes. Results Although HbA1c levels decreased from winter to summer in 2019 and 2020, the annual change was slightly but significantly greater in 2020 than in 2019. Seasonal changes in the BMI between 2019 and 2020 were also significantly different. An increase in the daily insulin dose, overall blood glucose level, diurnal change in blood glucose level, and food intake were significantly associated with increased HbA1c levels. Furthermore, HbA1c levels decreased with increasing moderate physical activity and sleep duration. The change in the BMI increased with increasing insulin dose, overall high blood glucose levels, and food intake. However, an increase in moderate physical activity was associated with a decrease in the BMI. HbA1c levels were significantly lower after the first emergency declaration in individuals with type 1 diabetes mellitus than that before the emergency declaration, even after accounting for seasonal variations. Conclusion Decreased HbA1c levels were associated with a decreased food intake, increased moderate exercise, and increased sleep duration during the state of emergency. The BMI remained relatively unchanged.

Purpose This study aims to evaluate the effects of resin primers containing methyl methacrylate (MMA) and silane agent on the bonding effectiveness of indirect resin composite blocks with three different filler contents.Methods A commercially available computer-aided design/computer-aided manufacturing (CAD/CAM) resin composite block and two experimental resin composite blocks with different filler contents were alumina-blasted and two surface treatments (primer and silane agent) were applied. The resin cement was built up, and the micro-tensile bond strength (μTBS) was measured after 24 hours, 1 month or 3 months of water storage (n = 24 per group). The fracture surfaces after μTBS measurements and resin block/cement interface were observed by scanning electron microscopy (SEM).Results The primer treatment group showed a significantly higher bond strength than the silane group only in F0 (filler content 0 wt%) group (P < 0.001). In the primer group, F0 and F41 (filler content 41 wt%) groups showed significantly higher bond strengths than F82 (filler content 82 wt%) group (P < 0.001). In contrast, in the silane group, F41 group showed significantly higher bond strength than F0 and F82 groups (P < 0.001), and F82 group showed significantly higher bond strength than F0 group (P < 0.001). SEM revealed that the matrix resin was partially destroyed on the fracture surface of the primer group, and an uneven interface surface was observed compared with that of the silane group.Conclusions MMA-containing primers showed higher bonding effectiveness to CAD/CAM resin composite blocks than the silane treatment.

Objectives: Intrapulpal calcifications can occur in the dental pulp of patients with diabetes. We focused on the association between ectopic calcifications in the dental pulp and advanced glycation end products (AGEs) in Spontaneously Diabetic Torii (SDT)-fatty rats, an obese type 2 diabetic rat model, to determine the mechanism of calcification with pulp stone in the dental pulp., Materials and Methods: Pathologic calcification in the dental pulp of SDT-fatty rats was observed using electron microscopy and immunohistochemical analysis. Moreover, mechanical analysis of periapical region of molar tooth against occlusal force was performed., Results: In SDT-fatty rats, pathogenic pulpal calcifications occurred during blood glucose elevation after 6 weeks, and granular calcification was observed in the dental pulp after 11 weeks. Pentosidine, a major AGE, and the receptor for AGEs were strongly expressed in the dental pulp of SDT-fatty rats. S100A8, TNF-α, and IL-6 also showed positive response in the dental pulp of the SDT-fatty rat, which indicated pulpal inflammation. Blood flow disorder and hypoxic dental pulp cells were also observed. In silico simulation, strain from occlusal force concentrates on the root apex., Conclusions: Glycation makes blood vessels fragile, and occlusal forces damage the vessels mechanically. These are factors for intrapulpal calcification of diabetes., (© 2023 Wiley Periodicals LLC.)

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, which led to the coronavirus 2019 (COVID-19) pandemic, has promoted the development of novel therapeutic agents and vaccines to combat the global spread of the virus. While the COVID-19 vaccines approved thus far have proven to be effective in clinical settings, there have been reports of autoimmune diseases occurring following vaccination, including autoimmune/inflammatory syndrome induced by adjuvant syndrome. We herein report two cases of type 1 diabetes mellitus that occurred following COVID-19 vaccination and provide a literature review. Both cases received multiple vaccinations as recommended to ensure optimal antibody titers. Moreover, the HLA associated with susceptibility to type 1 diabetes was prototypic in both cases. This indirect evidence suggests that the COVID-19 vaccines may be implicated in the pathogenesis of type 1 diabetes. Further case reports to establish a clearer understanding of a potential association are warranted., Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00695-9., Competing Interests: Conflict of interestNone of the authors have any potential conflicts of interest associated with this case report., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Robotic-assisted thoracoscopic surgery (RATS) is widely performed in thoracic surgery. The open-thoracotomy-view approach (OTVA) is one approach in RATS lung resection. OTVA is a good surgical approach that provides the same field of view as that with open thoracotomy and allows active participation of the assistant. However, the OTVA has certain limitations compared with other approaches, such as difficulty placing a robotic arm in the lower intercostal space, the assistant port is positioned further from the hilum, and CO 2 insufflation is required. We have made some modifications to the OTVA by placing one of the robotic arms in the lower intercostal space, which enhances the operability for the surgeon without the need for CO 2 insufflation. Additionally, by positioning the assistant port between the robotic arms, the assistant is closer to the hilum, and there is no requirement for a closed port owing to the absence of CO 2 insufflation, resulting in improved performance by the assistant. Therefore, for the assistant to perform well, it is necessary to make modifications to the OTVA to widen the typically narrow space between the robotic arms. We performed lung resection using our modified 4-port 3-arm OTVA method in 20 patients from June 2022 to July 2023. Although we have not used our modified OTVA in a large number of cases, we have not observed critical issues to date. In this report, we introduce our modified OTVA as an option in RATS for lung resection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1653/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Aim: The Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus (ISCHIA) study was a randomized, crossover trial that reported the decrease in time below range (TBR) by the use of intermittent-scanning continuous glucose monitoring (isCGM) combined with structured education in adults with type 1 diabetes (T1D) treated by multiple daily injections. The participants were instructed to perform frequent scanning of the isCGM sensor (10 times a day or more) and ingest sugar when impending hypoglycemia is suspected by tracking the sensor glucose levels and the trend arrow. We conducted post-hoc analysis to identify factors affecting difference in TBR (∆TBR), in time in range (∆TIR), and in time above range (∆TAR)., Participants and Methods: Data from 93 participants who completed the ISCHIA study were used. Multiple regression analyses were performed to identify factors affecting CGM metrics., Results: Pearson's correlation analysis showed the negative association between log-transformed scan frequency and with ∆TBR ( r  = - 0.255, P  = 0.015), while there was no significant association of log-transformed scan frequency with ∆TIR ( r  = 0.172, P  = 0.102) and ∆TAR ( r  = 0.032, P  = 0.761), respectively. The log-transformed scan frequency was an independent predictor of ∆TBR (Beta = - 7.712, P  = 0.022), but not of ∆TIR(Beta = 7.203, P  = 0.091) and of ∆TAR (Beta = 0.514, P  = 0.925)., Conclusions: Our findings suggest that more frequent scanning of isCGM may be beneficial to reduce TBR in T1D adults., Competing Interests: Conflict of interestNo potential conflicts of interest (COI) as the ISCHIA Study Group relevant to this article were reported. Potential COI concerning all individual investigators were reviewed by the Certified Review Board in accordance with the Clinical Trials Act [9]. The COI of the members of the writing group are as follows: YH received lecture fee from Abbott, Eli Lilly, Sanofi, Sumitomo and Terumo and received research grant from Sumitomo. AK received lecture fee from Eli Lilly. MM received lecture fee from Abbott, Eli Lilly, Novo Nordisk and Sanofi, and received research grant from Novo Nordisk. SM received lecture fee from Boehringer Ingelheim, Eli Lilly and Novo Nordisk. JM received lecture fee from Terumo. AS received lecture fee from Abbott and Terumo. AT received lecture fee from Abbott, Eli Lilly, Sanofi and Terumo. MT received lecture fee from Abbott, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sumitomo and received subsidies from Cocokara Fine Healthcare, LifeScan, Roche DC and Super Light Water. TM, KH, K Kato, K Koyama, RK, YM, JM, KN, NS and SS declare that they have no conflict of interest., (© The Japan Diabetes Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for 'a definitive diagnosis of SPIDDM': (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement for insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and the presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity <0.6 ng/mL) at the last observed point in time. When a patient fulfills only (1) and (2), but not (3), he/she is diagnosed with 'SPIDDM (probable)' because the diabetes is non-insulin-dependent type., (© 2024 The Japan Diabetes Society (JDS). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Introduction: A 65-year-old man had nonsurgical retreatment using an iodoform and calcium hydroxide paste in a maxillary left canine with persistent apical periodontitis. An apical mineralized barrier (AMB) was observed 3-months postoperatively. Unfortunately, the tooth was extracted due to a cementum tear. This provided an opportunity to analyze the AMB histologically, as there is a lack of previous reports on its microstructure., Methods: After extraction and removal of the granulation tissue from the root surface, the canine was processed, and observed using micro-computed tomography (μCT) and light microscopy. Thereafter, the specimen was resin-embedded specimen was evaluated by scanning electron microscopy, micro-X-ray fluorescence spectroscopy and Raman spectroscopy to understand the mechanism and nature of the AMB formation during apical healing., Results: Nonsurgical retreatment was clinically successful based on the absence of clinical symptoms of apical periodontitis and the radiographic presence of an AMB. The AMB was opaque and could be readily differentiated from dentin under a light microscope. Micro-computed tomography analysis revealed that the AMB had the same mineral density as dentin. Scanning electron microscopy revealed that the AMB had two distinct layers based on the size of the calcified particles. Elemental mapping using micro-X-ray fluorescence spectroscopy showed that the localization of calcium and phosphorus differed between AMB and other areas of biomineralization. Raman spectral mapping revealed that the surface layer of the AMB consisted of collagen, calcium carbonate, and hydroxyapatite., Conclusions: This study explored new analytical methods for elucidating the apical wound-healing process and the nature of the mineralized repair. The findings provided detailed information on the AMB highlighting a bilaminar structure with high calcium components higher on the inside and a brightness similar to cementum not dentin and the presence of hydroxyapatite., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: FreeStyle Libre uses the algorithm to calculate the sensor glucose (SG) levels. The manufacturer announced that they had changed the algorithm from the first generation (Gen. 1) to the third generation (Gen. 3). To assess the difference, we conducted an observational study to analyze the characteristics of the measurements by these two algorithms compared to the capillary blood glucose (BG) levels., Methods: Participants with type 1 diabetes wore two FreeStyle Libre sensors, one on the left arm used with Gen. 3 algorithm, and another on the right arm used in combination with the FreeStyle Libre Reader with Gen. 1 algorithm., Results: Data were collected from 11 participants. The Bland-Altman analysis of the measurements by Gen. 3 algorithm showed bias of 7.4 mg/dl and no proportional bias was observed (r=0.130). In contrast, the Bland-Altman analysis of the measurements by Gen. 1 algorithm showed bias of 4.4 mg/dl and proportional bias was observed (r=0.424). The MARD of Gen. 3 algorithm and Gen. 1 algorithm was 11.9±9.0% and 9.7±8.3%, respectively (P=0.053)., Conclusion: No proportional bias in the measurements by Gen. 3 algorithm was observed, but in those by Gen. 1 algorithm. J. Med. Invest. 71 : 225-231, August, 2024.