Tokyo Medical and Dental University

Background Lung cancer surgery is associated with a high incidence of chronic postsurgical pain (CPSP), which necessitates long‐term analgesic prescriptions. However, while essential for managing pain, these have shown various adverse effects. Current guidelines recommend using peripheral nerve blocks over epidural anaesthesia for perioperative analgesia in minimally invasive thoracic surgery (MITS). However, the impact of perioperative analgesia on chronic analgesic prescriptions remains unclear. Therefore, this study investigated chronic analgesic prescription patterns following MITS in patients with lung cancer who received either perioperative epidural anaesthesia or nerve block. Methods We conducted a retrospective cohort study using data from the Japanese Diagnosis Procedure Combination database. Data were extracted from patients with primary lung cancer who underwent MITS between April 2018 and March 2022. Patients were divided into two groups based on the perioperative analgesia they received: the epidural anaesthesia group and the nerve block group. We compared the proportion of analgesic prescriptions 3–6 months postoperatively between both groups using multivariable logistic regression analysis. Inverse probability of treatment weighting was used to balance the covariates between the two groups. Results Among the 38,719 eligible patients, 4513 (11.6%) were prescribed postoperative analgesics. We found no significant difference in the proportion of analgesic prescriptions between the epidural anaesthesia and nerve block groups (odds ratio, 1.00; 95% confidence interval, 0.99–1.01). Conclusions This nationwide retrospective study suggests that the choice between perioperative epidural anaesthesia or nerve block in patients with lung cancer undergoing MITS does not influence the proportion of postoperative chronic analgesic prescriptions.

Study Design Retrospective study of data abstracted from the diagnosis procedure combination (DPC) database. Objecitives The etiology of cervical fracture dislocation (CFD) remains unknown because of the limited clinical investigations that involve approximately 100 individuals. This study investigated the association of CFD-impaired levels with patient outcomes. Methods This study included 4653 adult patients with a definitive CFD diagnosis from the DPC database. The database consisted of nationwide inpatient data collected from >1000 acute care hospitals in Japan. This DPC database contains information regarding the hospitalization course, such as diagnosis, treatment, medical history, complications, and hospitalization outcomes. We included 866 CFD patients whose impaired levels were specified. We compared the outcomes between the patients whose CFD occurred in the upper cervical levels (“high” group) and the intermediate-low levels (“low” group). This study determined 121 pairs of patients after one-to-one propensity score matching (PSM). The main outcomes included inhospital death, 30-day mortality, and major complications after admission. The secondary outcomes were the length of hospital stay, discharged home rate, and improvement in Barthel index. Results No differences in inhospital death and 30-day mortality were found between the high and low groups, even after adjusting for PSM ( P > 0.05, respectively). Moreover, this analysis revealed that the high group exhibited a higher incidence of respiratory complications than the low group (37.2% vs. 24.8%; P = 0.0256). Conclusions This study revealed no difference in mortality but a significantly higher incidence of respiratory complications with high-level CFD compared to low-level CFD.

Background The guidelines recommend anticoagulation management with uninterrupted warfarin or direct thrombin inhibitors (DTIs) during the atrial fibrillation (AF) ablation periprocedural period. Objectives To clarify the Japanese real‐world latest periprocedural anticoagulation management during AF ablation. Methods This multicenter observational study included 6232 consecutive AF patients (68.7 ± 10.9 years, 4346 men) who underwent periprocedural anticoagulation therapy using direct oral anticoagulants (DOACs) between January 2022 and August 2023. Results The mean CHADS2 and CHA2DS2VASc scores were 1.2 ± 1.1 and 2.3 ± 1.5. Bleeding and thromboembolic events occurred in 79 (1.3%) and eight (0.12%) patients. During the periprocedural period, factor Xa inhibitors (FXaIs) were used in 3063 patients (rivaroxaban in 624, apixaban in 1093, and edoxaban in 1345) and DTIs in 3170 including 2583 in whom DTIs were switched from FXaIs. Both the bleeding (0.85% vs. 1.69%, p = .003) and thromboembolic event rates (0.03% vs. 0.23%, p = .036) were significantly lower in the DTI‐ than FXaI‐group. A multivariate analysis showed periprocedural FXaI use was significantly associated with both bleeding events (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.20–3.08, p = .006) and cardiac tamponade (OR = 2.74, 95% CI = 1.27–5.9, p = .01). The interval between the last DOAC administration and the procedure was significantly shorter in the DTI‐ than FXaI‐group (4.2 ± 4.9 vs. 19.3 ± 10.7 h, p < .01). In the FXaI‐group, the bleeding rate tended to be lower in the minimally interrupted (n = 2105) than uninterrupted group (n = 821) (1.47% vs. 2.56%, p = .06). Two patients in the uninterrupted FXaI‐group required surgical management for cardiac tamponade. Conclusions Our multicenter real‐world data demonstrated that anticoagulation with DTIs was a reasonable periprocedural anticoagulation regimen to reduce periprocedural complications.

Our brains operate as a complex network of interconnected neurons. To gain a deeper understanding of this network architecture, it is essential to extract simple rules from its intricate structure. This study aimed to compress and simplify the architecture, with a particular focus on interpreting patterns of functional connectivity in 2.5 hr of electrical activity from a vast number of neurons in acutely sliced mouse brains. Here, we combined two distinct methods together: automatic compression and network analysis. Firstly, for automatic compression, we trained an artificial neural network named NNE (neural network embedding). This allowed us to reduce the connectivity to features, be represented only by 13% of the original neuron count. Secondly, to decipher the topology, we concentrated on the variability among the compressed features and compared them with 15 distinct network metrics. Specifically, we introduced new metrics that had not previously existed, termed as indirect-adjacent degree and neighbor hub ratio. Our results conclusively demonstrated that these new metrics could better explain approximately 40%–45% of the features. This finding highlighted the critical role of NNE in facilitating the development of innovative metrics, because some of the features extracted by NNE were not captured by the currently existed network metrics.

Objectives For older adults, spending time out of bed is important for preventing functional decline, but its relationship to mortality is not clear. In this study, we aimed to investigate the association between mortality and time spent out of bed in Japanese older-adult nursing home residents. Design We conducted a cohort study using data from the Long-term Care Information System for Evidence database. Setting and Participants We used data collected between April 2022 and March 2024 from older-adult nursing home residents who required assistance with the activities of daily living. Methods We compared outcome data between residents who spent 6 or more hours per day out of bed (group L) and those who spent less than 6 hours per day out of bed (group S). The outcome was all-cause mortality. Data were analyzed using Kaplan-Meier curves and Cox regression models. Results Data from 185 older-adult nursing home residents (median age: 89 years; 141 women) were analyzed. Group L included 144 residents (77.8% of all participants). Of the 185 participants, 40 died during the observation period. Mortality in group L was significantly lower than in group S (16.7% vs 39.0%, P = .002). Kaplan-Meier curve analysis after the log-rank test revealed a significantly higher mortality in group S than group L. Univariate and multivariate Cox regression analyses with robust (Huber-White) standard errors identified the factor of time spent out of bed (≥6 h) as a significant and independent risk factor for mortality. Conclusion and Implications More time spent out of bed is associated with lower mortality in older-adult nursing home residents who require assistance with the activities of daily living.

Objective To evaluate the correlation between ATP‐binding cassette (ABC) transporter expression and therapeutic efficacy of enfortumab vedotin (EV), an antibody‐drug conjugate targeting Nectin‐4, in urothelial cancer, as only a few studies have been conducted on this topic. Patients and methods This retrospective study included 20 patients with metastatic urothelial carcinoma (mUC), including bladder and upper urinary tract cancers, who were treated with EV at Dokkyo Medical University Hospital between 2022 and 2024. Immunohistochemical staining was performed on formalin‐fixed, paraffin‐embedded tissue samples. Progression‐free survival (PFS) was estimated using the Kaplan–Meier method, and differences between subgroups (e.g., Nectin‐4 and ABC transporter expression) were compared using the log‐rank test. Results Immunohistochemical analysis indicated that tumours with high ABC transporter expression exhibited shorter PFS time and poorer response to EV. Furthermore, a decrease in Nectin‐4 expression and an increase in ABC transporter expression were observed as the disease progressed from non‐muscle‐invasive to muscle‐invasive and metastatic. Patients with Nectin‐4‐positive and ABC transporter‐negative tumours had the longest PFS, underscoring the prognostic significance of these biomarkers. Conclusion To our knowledge, this study is the first to show a correlation between ABC transporter expression and EV efficacy in urothelial carcinoma. Future research should focus on optimizing treatment strategies based on Nectin‐4 and ABC transporter expression to improve outcomes.

Background In Japan, effective interventions to prevent low nutrition in older people with oral frailty have not been well established. This post‐hoc sub‐group analysis of the Japan‐multimodal intervention trial for the prevention of dementia (J‐MINT) aimed to examine the efficacy of the multidomain intervention in older adults with and without oral frailty. Methods J‐MINT was an 18‐month randomized controlled trial in which participants aged 65‐85 years with mild cognitive impairment were randomized to a multimodal intervention group (physical exercise, nutrition counseling, cognitive training, and vascular risk factor management) and a control group. This study included the participants in J‐MINT who had undergone the intervention program and follow‐up evaluation at least once. Oral frailty was defined as oral frailty (Oral Frailty Index‐8 ≥ 4 points) at baseline assessment. Outcomes were the change from baseline to 18‐month assessment in cognitive function (the composite scores of eight neuropsychological tests), Body Mass Index (BMI), nutritional status (Mini Nutritional Assessment Short‐Form), fat‐free mass, fat mass, food diversity, and appetite (Council on Nutrition Appetite Questionnaire). A mixed model for the repeated measure was used to calculate the mean difference (MD) of outcome between the intervention and control groups. Results Of 531 participants enrolled in J‐MINT, 433 participants were included (mean age: 74.4±4.9; women, 226; intervention group: 215), and 152 participants had oral frailty at baseline assessment. In older adults with oral frailty, although no significant mean difference in cognitive function was observed (MD [95%CI] = 0.099 [‐0.019‐0.217]), significant intervention effect in nutritional status (0.548 [0.034‐1.062]), fat‐free mass (0.842 [0.216‐1.468]), fat mass (‐0.962 [‐1.890–0.038]), food diversity (1.263 [0.374‐2.150]), and appetite (1.315 [0.524‐2.110]) were observed. However, in older adults without oral frailty, there is a significant intervention effect in only food diversity (1.454 [0.808‐2.100]). Conclusion The results of this study suggest the effectiveness of multimodal interventions on nutritional indicators for older adults with oral frailty. Oral frailty may be an effective target for multimodal intervention.

Aim Superiority illusion (SI), a cognitive bias where individuals perceive themselves as better than others, may serve as a psychological mechanism that contributes to well‐being and resilience in older adults. However, the specific neural basis of SI in elderly populations remains underexplored. This study aims to identify brain regions partially associated with SI, exploring its potential role in adaptive psychological processes. Methods This study combined a behavioral task, voxel‐based morphometry (VBM), and resting‐state functional connectivity (rsFC) analyses to investigate the neural substrates of the SI in a cohort of 145 participants, including young (n = 84), middle‐aged (n = 37), and older adults (n = 24). Results Our findings indicated that higher SI scores in older adults were correlated with greater gray matter volume in the right precuneus and stronger rsFC between the right precuneus and the left lateral occipital cortex. However, these correlations were not evident in younger and middle‐aged groups. Conclusion Our findings underscore the importance of the right precuneus and its connectivity in the manifestation of the SI, particularly in older adults, highlighting its potential role in adaptive aging processes.

The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of mRNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we employed tRNASec gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis. This revealed insights into the protective roles of selenoproteins in preserving HSC stemness and B-lineage maturation, despite negligible effects on myeloid cells. Notably, Trsp KO exhibited B lymphocytopenia and reduced HSCs' self-renewal capacity, recapitulating certain aspects of aged phenotypes, along with the upregulation of aging-related genes in both HSCs and pre-B cells. While Trsp KO activated an antioxidant response transcription factor NRF2, we delineated a lineage-dependent phenotype driven by lipid peroxidation, which was exacerbated with aging yet ameliorated by ferroptosis inhibitors such as vitamin E. Interestingly, the myeloid genes were ectopically expressed in pre-B cells of Trsp KO mice, and KO pro-B/pre-B cells displayed differentiation potential toward functional CD11b+ fraction in the transplant model, suggesting that disrupted selenoprotein synthesis induces the potential of B-to-myeloid switch. Given the similarities between the KO model and aged wild-type mice, including ferroptosis vulnerability, impaired HSC self-renewal and B-lineage maturation, and characteristic lineage switch, our findings underscore the critical role of selenoprotein-mediated redox regulation in maintaining balanced hematopoiesis and suggest the preventive potential of selenoproteins against aging-related alterations.

Mitochondrial protein import through the outer and inner membranes is key to mitochondrial biogenesis. Recent studies have explored how cells respond when import is impaired by a variety of different insults. Here, we developed a mammalian import blocking system using dihydrofolate reductase fused to the N terminus of the inner membrane protein MIC60. While stabilization of the dihydrofolate reductase domain by methotrexate inhibited endogenous mitochondrial protein import, it neither activated the transcription factor ATF4, nor was affected by ATAD1 expression or by VCP/p97 inhibition. On the other hand, notably, plugging the channel of translocase of the outer membrane) induced YME1L1, an ATP-dependent protease, to eliminate translocase of the inner membrane (TIM23) channel components TIMM17A and TIMM23. The data suggest that unoccupied TIM23 complexes expose a C-terminal degron on TIMM17A to YME1L1 for degradation. Import plugging caused a cell growth defect and loss of YME1L1 exacerbated the growth inhibition, showing the protective effect of YME1L1 activity. YME1L1 seems to play a crucial role in mitochondrial quality control to counteract precursor stalling in the translocase of the outer membrane complex and unoccupied TIM23 channels.

Purpose: This study investigated the effects of femtosecond laser (FL) irradiation on the surface roughness and shear bond strength of high-translucency zirconia (6 mol% yttria-partially stabilized zirconia [6Y-PSZ]) and lithium disilicate (Li2SiO3) glass ceramics. Methods: Fully sintered square-shaped specimens of 6Y-PSZ (7 groups; 20 specimens/group) and Li2SiO3 (8 groups; 20 specimens/group) were surface-treated via sandblasting (50-μm alumina sand or glass beads) or FL irradiation (20- or 40-μm dot or cross-line patterns) or using Monobond Etch & Prime (Ivoclar Vivadent AG; only for Li2SiO3 specimens). The surface roughness (arithmetic average [Sa] and developed interfacial area ratio [Sdr]) and shear bond strength after 24 h and 10,000 thermal cycles were measured and statistically analyzed. Results: The surface roughness of both ceramics significantly increased after 40-μm cross-line FL irradiation. The Sdr also significantly increased after FL irradiation. The 20- and 40-μm cross-line laser-irradiated 6Y-PSZ samples showed the highest shear bond strength after 24 h and 10,000 thermal cycles, respectively. Li2SiO3 glass-ceramic specimens showed the highest shear bond strength after Monobond Etch & Prime treatment for both groups. The 40-μm cross-line laser-irradiated Li2SiO3 glass-ceramic specimens exhibited high shear bond strength after thermal cycling. Conclusions: FL significantly increases the bonding efficacy of 6Y-PSZ and Li2SiO3 glass ceramics. Furthermore, Monobond Etch & Prime is effective for the surface treatment of Li2SiO3 glass ceramics. Therefore, FL can be used to effectively treat the surfaces of dental restorations in clinical settings, facilitating enhanced adhesion between the restoration and the tooth.

Aim Although perforated peptic ulcer is common in Japan, few large‐scale studies have assessed its management, including surgical procedures and outcomes. This study aimed to survey the characteristics, management, and outcomes of perforated peptic ulcer. Methods A multicenter retrospective descriptive analysis was conducted across seven centers in Japan between 2011 and 2022. Perforated peptic ulcer was defined as gastric or duodenal ulcer perforation, excluding malignant or iatrogenic perforation. Results We enrolled 703 patients with perforated peptic ulcer. The overall in‐hospital mortality rate was 35/703 (5.0%). Conservative treatment was performed as an initial treatment in 217/703 (30.9%) patients, among whom 52 (24.0%) eventually underwent surgery. The median age (interquartile range) of patients who successfully completed the conservative treatment was 60 (46–71) years. A total of 538/703 (76.5%) patients underwent surgery. The gastrectomy percentage increased with the perforation diameter. The anastomotic leakage rate for gastrectomy was high in 10/66 (15.2%) patients. Laparoscopy was performed in 115/538 (21.4%) patients, among whom 23 (20.0%) were converted to open surgery. Patients who underwent laparoscopy had a perforation diameter ≤ 20 mm. The use of laparoscopy varied among facilities, ranging from 1.8% to 61.2%. Conclusion The in‐hospital mortality rate for perforated peptic ulcer in this study was 5.0%, and conservative treatment was safely performed even in elderly patients. As the perforation diameter increased, the rate of gastrectomy tended to rise, and the rate of anastomotic leakage in those patients was high. UMIN Clinical Trials Registry; UMIN000054391.

Purpose: To compare the stress distribution in loaded zirconia resin-bonded fixed dental prostheses (RBFDPs) and periodontal tissue using finite element analysis, considering reduced alveolar bone levels and the number of retainers. Methods: A human skull was micro-CT scanned. Three framework designs were tested: a 2-unit RBFDP using the maxillary left central incisor (#21) as an abutment, another using a canine (#23), and a 3-unit RBFDP using both #21 and #23. The models were categorized based on the distance from the cemento-enamel junction (CEJ) to the alveolar bone: M1 (1 mm), M2 (2 mm), M4 (4 mm), M6 (6 mm), and M8 (8 mm). Results: The shear stresses in the adhesive resin cement were lower in the 2-unit designs than in the 3-unit design in the M4–M8 models. The maximum principal stresses in the framework were smaller in the 2-unit design than in the 3-unit design for all models. The maximum principal strains in the periodontal ligament and trabecular bone in #21 were greater in the 2-units than in the 3-units in the M4–M8 models. Conclusions: This study suggests that cantilever RBFDPs may have a lower risk of framework fracture than 2-retainer RBFDPs, regardless of the reduction in alveolar bone levels. In cases with alveolar bone levels >4 mm below the CEJ, the cantilever RBFDPs had a smaller risk of debonding than the 2-retainer RBFDPs; however, it may increase the damage to periodontal tissue.

Nowadays, consent to use donor bodies for medical education and research is obtained from the body donors and their families before the donation. Recently, the International Federation of Associations of Anatomists (IFAA) published guidelines that could restrict the appearance of cadaveric images in commercial anatomical resources such as textbooks and other educational products. These guidelines state that the donor must expressly consent to using such images for this purpose. Cadaveric photos and drawings made from dissections of cadavers have been used in anatomy textbooks and atlases for hundreds of years. They are invaluable for anatomy students and clinical/surgical practitioners. The IFAA guidelines should not restrict the use of those older books; to do so would infringe the rights of those seeking knowledge from these resources. As the images in such textbooks and atlases are anonymized and are used for teaching and research, and the donors and their families are informed about this before the donation, we believe no additional consent is needed. It is impossible to separate educational from “commercial” usage entirely in any situation, e.g., publications from publishers and the use of cadavers in medical schools. Therefore, our best efforts to avoid unethical use of cadaveric images by following traditional consent processes are still needed so that more people will reap the benefits from them. As senior textbook/atlas authors/editors from over 10 countries, we believe that using cadaveric images in anatomy textbooks is appropriate, and no additional consent should be necessary. Such usage falls within the good faith of professionals using these invaluable gifts.

Background Concentrated Growth Factor (CGF) is a biomaterial with regenerative potential, enriched with platelets, leukocytes, growth factors, and fibrin, but it degrades within 2–3 weeks. Albumin extends CGF stability, while silver nanoparticles (SNPs) improve its mechanical and antibacterial properties. This in vitro and ex vivo study investigates the impact of albumin (Alb-CGF) and albumin with SNPs (Alb-CGF-SNP) on CGF’s mechanical properties, degradation rate, and cellular bioactivity. Methods Blood samples were collected from 15 healthy volunteers who met specific inclusion criteria, with the sample size determined using GPower software for power calculation. Three groups were prepared: control CGF, experimental Alb-CGF, and Alb-CGF-SNP. Membranes were produced using a Medifuge MF200 centrifuge and activated plasma albumin gel (APAG) device following standard settings. In experimental groups, the superficial 2.5 ml of plasma layer was heated at 75°C for 10 minutes before combining with the buffy coat layer of CGF. Mechanical properties were tested using a texture analyzer, degradation rates were measured by weight loss percentage, and cellular bioactivity was evaluated with a Sysmex hematology analyzer. Data analysis was conducted using GraphPad Prism 8.0. Group differences were assessed via one-way ANOVA and Welch ANOVA, with Tukey’s HSD test for post hoc paired group comparisons. Results The control (CGF) showed the highest mechanical properties, with Ultimate Tensile Strength (UTS) (95.6 kPa), Modulus of Toughness (55.55 kJ/m³), and Young’s Modulus (75.73 kPa; P = .00). No significant differences were observed in the strain at break across groups ( P > 0.90). Alb-CGF-SNP displayed superior degradation resistance, with 45.2% weight loss at day 60 versus 84.2% in CGF ( P = .00). CGF had the highest WBC and platelet levels, with amounts of 2.25 and 3.11-fold ( P = .00). Conclusion CGF offers high tensile strength and cellular content, though its rapid degradation limits long-term applications. In contrast, Alb-CGF and Alb-CGF-SNP provide extended degradation resistance, making them effective as barrier membranes. Despite lower elasticity restricting suturing uses, their similar plasticity supports use as fillers or for tissue phenotype alteration, especially when minimizing degradation is vital. Future research on growth factor release, antibacterial efficacy, and in vivo applications is crucial for validation.

Periodontitis is a globally prevalent chronic inflammatory disease caused by dysbiosis of the oral microbiome. However, it remains unclear whether the bacterial communities of periodontitis and its precursor, gingivitis, transition to a state resembling healthy sites with no history of periodontitis following periodontal treatment or persist in a state prone to recurrence. Therefore, in this study, we performed metatranscriptomic analysis on subgingival plaque samples from the anterior teeth in healthy, gingivitis, and periodontitis sites before and after non-surgical treatment in 28 patients. To minimize inter-individual variability, all samples were collected from the same oral cavity in each patient. We revealed a new bacteriological characteristic of periodontitis, where periodontal pathogens emerge within the bacterial network alongside excessive and skewed interactions among bacterial taxa, such as those in the Streptococcus and Actinomyces genera. Furthermore, these imbalances were found improvable through non-surgical treatment. By comparing groups in which periodontitis resolved and those in which it did not, specific bacterial taxa, such as Neisseria elongata and Rothia aeria, were suggested to play a role in the periodontitis healing process, while the increase in functional genes encoding glycine dehydrogenase β-subunit and cleaved adhesin domain was implicated in inhibiting the healing process. However, even in clinically resolved gingivitis or periodontitis, the bacterial networks did not fully revert to the state observed in healthy sites. This was due to the persistence of periodontal pathogens, absent in the networks of healthy sites. As a result, continuous maintenance and monitoring are considered important to achieve sustained periodontal health.

Background Data on the first-line treatment options for patients with Pneumocystis pneumonia (PCP) without human immunodeficiency virus (HIV) infection are limited. Therefore, we evaluated the outcome of pentamidine compared to trimethoprim-sulfamethoxazole (TMP-SMX) in non-HIV patients with PCP. Methods We used data from the Japanese Diagnosis Procedure Combination Inpatient Database. We included non-HIV PCP patients who initially received TMP-SMX or pentamidine between July 2010 and March 2022. We categorized eligible patients into TMP-SMX and pentamidine groups and performed a propensity score overlap weighting analysis to compare in-hospital mortality between the groups. Results Among 5,870 eligible patients, 5,456 and 414 received TMP-SMX and pentamidine, respectively. Pentamidine treatment was associated with a higher in-hospital mortality than TMP-SMX treatment in the propensity score overlap weighting analysis (23.6% vs. 40.1%; risk difference, 16.5%; 95% confidence interval, 10.8-22.2%; p<0.001). Conclusions Based on these findings, pentamidine may not be as effective as TMP-SMX for treating PCP in non-HIV patients.