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Abstract Texture and color enhancement imaging (TXI) may improve the visibility of gastric tumors and allow their early detection. However, few reports have examined the utility of TXI. Between June 2021 and October 2022, 56 gastric tumors in 51 patients undergoing endoscopic submucosal dissection at Fukuchiyama City Hospital were evaluated preoperatively using conventional white light imaging (WLI), narrow-band imaging (NBI), and TXI modes 1 and 2. The color differences of the tumors and surrounding mucosae were evaluated using the CIE 1976 L*a*b color space, Additionally, the visibility scores were scaled. Of the 56 gastric tumors, 45 were early gastric cancers, and 11 were adenomas. Overall, the color difference in TXI mode 1 was considerably higher compared to WLI (16.36 ± 7.05 vs. 10.84 ± 4.05; p

Second‐generation androgen receptor (AR) signaling inhibitors (ARSIs), such as abiraterone and enzalutamide, prolong the life of patients with castration‐resistant prostate cancer (CRPC). However, patients receiving ARSIs ultimately develop resistance through various complex mechanisms, including AR mutations, constitutively active AR‐splice variants (AR‐Vs), and AR overexpression. Here, we characterized a novel AR pure antagonist, TAS3681, which inhibits AR transcriptional activity and downregulates AR‐full length (AR‐FL) and AR‐Vs. TAS3681 reduced the protein levels of AR‐FL and AR‐Vs including AR‐V7 in enzalutamide‐resistant cells (SAS MDV No. 3‐14), in vitro and in vivo, showing strong antitumor efficacy in an AR‐V7‐positive xenograft model. In AR‐overexpressing VCaP (prostate cancer) cells, conversely to enzalutamide, TAS3681 effectively suppressed cell proliferation and downregulated AR expression. Importantly, TAS3681 blocked the transcriptional activity of various mutant ARs, including mutations F877L/T878A and H875Y/T878A, which confer resistance to enzalutamide, and V716M and H875Y mutations, which confer resistance to darolutamide. Our results demonstrate that TAS3681 suppresses the reactivation of AR signaling, which causes resistance to ARSIs, via a newly identified mechanism of action. Therefore, TAS3681 could be a new therapeutic option for CRPC treatment.

Background: Continuous local antibiotic perfusion (CLAP) is a method for preserving tissue and function against surgical site infections (SSIs) after shoulder surgery. Methods: To describe the application of the novel CLAP technique to 10 patients with SSIs after shoulder surgery that were not controlled with repeated surgical débridement or elderly patients who are insufficient physical resilience for further surgeries. Results: CLAP, consisting of gentamicin, was performed for 2 weeks, after which the infection was well-controlled. The white blood cell count and C-reactive protein level improved rapidly within 1 week of initiating CLAP, after which the patients were switched to oral antibiotics for 3 months. None of the patients experienced any adverse events. Conclusion: CLAP for SSIs after shoulder surgery was successful in preserving implants and grafts. The SSIs were controlled with no adverse events. CLAP may be an important treatment option for SSIs after shoulder surgery.

Abstract Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.

Abstract Background Among the oral antivirals used for treating patients with mild-to-moderate novel coronavirus disease 2019 (COVID-19), nirmatrelvir/ritonavir (NMV/RTV) and ensitrelvir (ESV) are inhibitors of cytochrome P450 (CYP) 3A, and therefore, can cause drug–drug interactions with concomitant medications. Tacrolimus (TAC), a substrate of CYP3A4/5, is administered for a long period to prevent rejection after kidney transplantation. TAC should be discontinued while using NMV/RTV because blood TAC levels significantly increase when these drugs are concomitantly administered. However, the influence of ESV on blood TAC levels has not yet been reported, and the management of TAC doses during the use of ESV remains unclear. Case presentation We experienced three kidney transplant recipients with COVID-19, whose blood trough levels of TAC increased by the concomitant use of NMV/RTV or ESV. In two patients administering NMV/RTV, blood trough levels of TAC increased more than tenfold after combination therapy, whereas in one patient administering ESV, TAC level increased approximately threefold. Conclusions These cases suggest that TAC administration should be discontinued during NMV/RTV treatment to maintain blood TAC levels within the therapeutic range, and a reduced TAC dose is sufficient during ESV treatment.

Yudai Hayashi,* Masao Tsukada,* Daisuke Shinoda, Marina Matsui, Kanichi Iwama, Koichi Kajiwara, Kozai Yasuji Department of Hematology, Tokyo Metropolitan Tama Medical Center, Fuchu City, Tokyo, Japan*These authors contributed equally to this workCorrespondence: Masao Tsukada, Department of Hematology, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashidai, Fuchu City, Tokyo, 183-8524, Japan, Tel +81 42-323-5111, Fax +81 42-312-9175, Email masao_tsukada@tmhp.jpAbstract: Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it occurs. Prolonged use of high-dose steroids can diminish the effectiveness of immune checkpoint inhibitor (ICI) therapy on the primary disease because of T lymphocyte suppression, thus early tapering is necessary. We experienced a rare case of a 79-year-old male who concurrently developed irTCP and multiple myeloma (MM) during treatment with ICIs for lung adenocarcinoma. The patient exhibited severe thrombocytopenia and elevated serum IgA levels. Based on various tests, we diagnosed MM and irTCP. Despite administering the standard bortezomib plus dexamethasone (Bd therapy) treatment for MM, there was no response and the irTCP was steroid-resistant. Consequently, we administered a regimen including daratumumab (DPd therapy) for steroid-resistant irTCP and refractory MM, which resulted in a response. As a result, we were able to avoid prolonged use of high-dose steroids and the patient is stable without exacerbation of lung adenocarcinoma for 1 year and 5 months after the onset of MM. To our knowledge, there are no cases of MM developing during ICI treatment and this is the first case report in which daratumumab was effective for the treatment of irTCP.Keywords: immunotherapy, immune-related adverse event, multiple primary cancer, immune-mediated hematologic toxicity, monoclonal antibody

In this paper, we give a solution formula for the two-phase Stokes equations with and without surface tension and gravity over the whole space with a flat interface. The solution formula has already been considered by Shibata and Shimizu. However, we have reconstructed the formula so that we are able to easily prove resolvent and maximal regularity estimates. The previous work required the assumption of additional conditions on normal components. Here, although we consider normal components, the assumption is weaker than before. The method is based on an $ H^\infty $-calculus which has already been applied for the Stokes problems with various boundary conditions in the half-space.

Objectives: Colorectal perforation is associated with high morbidity and mortality rates after surgery. We investigated various clinical features of patients who underwent emergency surgery for colorectal perforation and explored the risk factors for postoperative complications and hospital mortality. Methods: Data from 147 patients who underwent surgery for colorectal perforation were retrospectively reviewed. We investigated various clinical and operative factors, including inflammation-based prognostic scores (IBPSs), and evaluated the risk factors for postoperative complications and hospital mortality due to colorectal perforation. Results: Among 147 patients, the most frequent postoperative complication was wound infection (32 cases, 21.8%), followed by intra-abdominal abscesses (27 cases, 18.4%) after surgery for colorectal perforation. Time from onset to surgery 2 days (Hazard ratio [HR] = 2.810, p = 0.0383) and prognostic nutritional index (PNI) < 30 (HR = 3.190, p = 0.0488) were identified as risk factors for intra-abdominal abscess, while neutrophil-lymphocyte ratio (NLR) < 6.15 (HR = 5.020, p = 0.0009) was identified as a risk factor for wound infection. Time from onset to surgery 2 days (HR = 7.713, p = 0.0492), severe postoperative complications (Clavien-Dindo grade IIIa) (HR = 10.98, p = 0.0281), and platelet-lymphocyte ratio (PLR) < 144 (HR = 18.84, p = 0.0190) were independent predictive factors for hospital mortality. Conclusions: Time from onset to surgery and IBPSs such as PNI, NLR, and PLR, may be associated with postoperative complications and hospital mortality due to colorectal perforation.

In this paper, we propose a vibration suppression method that takes fuel cutoff into account for an automobile powertrain during rapid acceleration and investigate its effectiveness. An automobile powertrain transmits engine torque to the tires, which causes vibration of the vehicle body during rapid acceleration. The engine is used as an actuator to control this vibration. However, the engine output has a constraint by fuel cut. This degrades the vibration suppression effect of vibration control. In addition, all vehicles will be controlled via controller area networks. The discretization width of control signals and the communications traffic are in the relationship of trade-off. The communications traffic in vehicles will increase in the future. Therefore, we need a control system that can suppress vibration even with coarse discretization widths. In this study, we propose a powertrain vibration control method using an optimal dynamic quantizer as the countermeasure. Optimal dynamic quantizer minimizes the effects on the tracking error (in the control system) due to the quantization. Then, we quantitatively examine the robustness at various quantization widths for the proposed control system. As a result, the optimal dynamic quantizer allows for smoother acceleration while suppressing vibration compared to the case with static quantizers. In conclusion, the performance of the proposed control system is investigated quantitatively.