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Abstract O6-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme. The roles of this enzyme in immune cells remain unclear. In this study, we explored the roles of MGMT in bone marrow-derived murine macrophages (BMMs) via the use of MGMT knockout (KO) mice. Loss of MGMT altered the response to TLR3 agonists (poly (I:C)), such as dampening the production of TNFα and IL-6. Increased DNA double-strand breaks (DSBs) were observed in MGMT-KO macrophages but did not result in increased cell death. MGMT localized to both nuclei and mitochondria at increasing levels during poly (I:C) stimulation. MGMT deficiency increased the production of mitochondrial reactive oxygen species (mtROS), which was correlated with increased mitophagy. The underlying mechanism involves mediation through activation of the AMPKα pathway. Taken together, our findings reveal the roles of MGMT in macrophages in regulating the response to TLR3, which links DSBs to mtROS and mitophagy via the AMPKα pathway. These roles may have consequences for the inflammatory response and chronic inflammation.

Study Design Retrospective cohort study. Purpose This study aimed to demonstrate the advantages of preservation of the lumbosacral segment (LSS) in adult spinal deformity (ASD) surgery. Overview of Literature Sacroiliac foundation enables sufficient restoration in ASD surgery; however, it could result in poor mobility. Thus, whether LSS provides better activities is still unknown. Methods Among 399 patients who underwent ASD surgery, 62 (≥5 levels fused, >2-year follow-up) underwent fusion from T9–10 to L5 (group L, n=21) or to S2–alar–iliac (group S, n=41). Spinal alignments, Scoliosis Research Society (SRS)-22 scores, performance of activities (clipping toenail, wiping buttock, and wearing socks), proximal and distal junctional failure (PJF+DJF), rod fractures (RFs), and overall revision rates (RRs) were compared between the groups. Results Group L included younger patients and had longer follow-ups when compared with group S. Although the preoperative pelvic incidence and SRS sagittal modifiers were better in group L, postoperative spinal restorations were nonpathological in both groups. Both groups showed similar deformity progression at the 2-year follow-up; however, group L had lower SRS-22 pain scores. Although “wiping buttocks” did not differ between the groups, the performance of “clipping toenails” and “wearing socks” was poorer in group S at 2 years (possible, group S; 40% vs. group L; 85%–90%). The RRs did not differ between the groups; however, the PJF+DJF rate was higher in group L. DJF was not observed in group S, but occurrence of RFs was noted. Conclusions Although poorer SRS-22 pain scores might be related to lumbosacral mobility, sufficient restoration, equivalent deformity progression, and similar RRs with better activity imply that lumbosacral preservation should be considered in younger patients with moderate deformities.

Background/objective: This study aimed to clarify the kinematics of bi-cruciate-retaining (BCR) total knee arthroplasty (TKA) by comparing the mechanical alignment (MA) and functional alignment (FA) methods and to evaluate differences between the two alignment methods. Methods: The in vivo kinematics of 20 MA TKA and 20 FA TKA knees were investigated under fluoroscopy during squatting using a two-to three-dimensional registration technique. Accordingly, knee flexion angle, axial rotational angle, varus–valgus angle, anteroposterior translation of the medial and lateral low contact points of the femoral component relative to the tibial component and kinematic pathway were evaluated. Results: No difference in the knee flexion angle was observed between the MA and FA TKA groups. Femoral external rotation was observed in both groups and no significant difference was observed. Significant varus alignment from extension to early flexion range was observed in the FA TKA group. The posterior translation of the medial side was smaller in the FA TKA group than in the MA TKA group. Conversely, no significant difference in the anteroposterior translation of the lateral side was observed. In the kinematic pathway, a medial pivot motion from 0° to 20° of flexion and a lateral pivot motion beyond 20° of flexion were observed in both groups. Conclusion: During squatting in BCR TKA, the FA TKA group significantly showed varus alignment and smaller posterior translation of the medial side than the MA TKA group from extension to early flexion range.

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.

Abstract Organ fibrosis causes collagen fiber overgrowth and impairs organ function. Cardiac fibrosis after myocardial infarction impairs cardiac function significantly, pulmonary fibrosis reduces gas exchange efficiency, and liver fibrosis disturbs the natural function of the liver. Its development is associated with the differentiation of fibroblasts into myofibroblasts and increased collagen synthesis. Fibrosis has organ specificity, defined by the heterogeneity of fibroblasts. Although this heterogeneity is established during embryonic development, it has not been defined yet. Fibroblastic differentiation of induced pluripotent stem cells (iPSCs) recapitulates the process by which fibroblasts acquire diversity. Here, we differentiated iPSCs into cardiac, hepatic, and dermal fibroblasts and analyzed their properties using single-cell RNA sequencing. We observed characteristic subpopulations with different ratios in each organ-type fibroblast group, which contained both resting and distinct ACTA2+ myofibroblasts. These findings provide crucial information on the ontogeny-based heterogeneity of fibroblasts, leading to the development of therapeutic strategies to control fibrosis.

Abstract Background Long-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on long life expectancy. We experienced a male case of FD under ERT, he was placed on hemodialysis and presented rapidly progressive cognitive function. Case presentation A 51-year-old male patient with FD has been receiving ERT from age of 38 years. Hemodialysis was initiated at the age of 47 years. The patient experienced several attacks of cerebral infarction, and brain images demonstrated wide-spread asymptomatic ischemic lesions. His behavior became problematic at the age of 51 years. He often exhibited restlessness during hemodialysis sessions and failure to communicate effectively. The patient experienced impairment of attention and executive function, topographical disorientation, and amnesia. Consequently, it was necessary for medical staff and family members to monitor his behavior for safe extracorporeal circulation and daily life activities. Annual standardized neuropsychiatric testing revealed worsening of cognitive performance. Conclusions Despite treating with long-term ERT, it is necessary to determine the psychosocial burden derived from the progression of cognitive impairment in patients with FD undergoing hemodialysis.

The Ras homology (Rho) family of GTPases serves various functions, including promotion of cell migration, adhesion, and transcription, through activation of effector molecule targets. One such pair of effectors, the Rho‐associated coiled‐coil kinases (ROCK1 and ROCK2), induce reorganization of actin cytoskeleton and focal adhesion through substrate phosphorylation. Studies on ROCK knockout mice have confirmed that ROCK proteins are essential for embryonic development, but their physiological functions in adult mice remain unknown. In this study, we aimed to examine the roles of ROCK1 and ROCK2 proteins in normal adult mice. Tamoxifen (TAM)‐inducible ROCK1 and ROCK2 single and double knockout mice (ROCK1flox/flox and/or ROCK2flox/flox;Ubc‐CreERT2) were generated and administered a 5‐day course of TAM. No deaths occurred in either of the single knockout strains, whereas all of the ROCK1/ROCK2 double conditional knockout mice (DcKO) had died by Day 11 following the TAM course. DcKO mice exhibited increased lung tissue vascular permeability, thickening of alveolar walls, and a decrease in percutaneous oxygen saturation compared with noninducible ROCK1/ROCK2 double‐floxed control mice. On Day 3 post‐TAM, there was a decrease in phalloidin staining in the lungs in DcKO mice. On Day 5 post‐TAM, immunohistochemical analysis also revealed reduced staining for vascular endothelial (VE)‐cadherin, β‐catenin, and p120‐catenin at cell–cell contact sites in vascular endothelial cells in DcKO mice. Additionally, VE‐cadherin/β‐catenin complexes were decreased in DcKO mice, indicating that ROCK proteins play a crucial role in maintaining lung function by regulating cell–cell adhesion.

BackgroundInflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD.MethodsExperimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs).ResultsOral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides, Allobaculum, and Akkermansia, enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner.ConclusionThese results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD.

Bleomycin (BLM) induces lung injury, leading to inflammation and pulmonary fibrosis. Regulatory T cells (Tregs) maintain self-tolerance and control host immune responses. However, little is known about their involvement in the pathology of pulmonary fibrosis. Here we show that a unique Treg subset expressing trefoil factor family 1 (Tff1) emerges in the BLM-injured lung. These Tff1-expressing Tregs (Tff1-Tregs) were induced by IL-33. Moreover, although Tff1 ablation in Tregs did not change the pathological condition, selective ablation of Tff1-Tregs using an intersectional genetic method promoted pro-inflammatory features of macrophages in the injured lung and exacerbated the fibrosis. Taken together, our study revealed the presence of a unique Treg subset expressing Tff1 in BLM-injured lungs and their critical role in the injured lung to ameliorate fibrosis.

Background/Aims Endoscopic self-expandable metal stent (SEMS) placement is currently the standard technique for treating unresectable malignant distal biliary obstructions (MDBO). Therefore, covered SEMS with longer stent patency and fewer migrations are required. This study aimed to assess the clinical performance of a novel, fully covered SEMS for unresectable MDBO. Methods This was a multicenter single-arm prospective study. The primary outcome was a non-obstruction rate at 6 months. The secondary outcomes were overall survival (OS), recurrent biliary obstruction (RBO), time to RBO (TRBO), technical and clinical success, and adverse events. Results A total of 73 patients were enrolled in this study. The non-obstruction rate at 6 months was 61%. The median OS and TRBO were 233 and 216 days, respectively. The technical and clinical success rates were 100% and 97%, respectively. Furthermore, the rate of occurrence of RBO and adverse events was 49% and 21%, respectively. The length of bile duct stenosis (

Abstract In robot-assisted surgery, in which haptics should be absent, surgeons experience haptics-like sensations as “pseudo-haptic feedback”. As surgeons who routinely perform robot-assisted laparoscopic surgery, we wondered if we could make these “pseudo-haptics” explicit to surgeons. Therefore, we created a simulation model that estimates manipulation forces using only visual images in surgery. This study aimed to achieve vision-based estimations of the magnitude of forces during forceps manipulation of organs. We also attempted to detect over-force, exceeding the threshold of safe manipulation. We created a sensor forceps that can detect precise pressure at the tips with three vectors. Using an endoscopic system that is used in actual surgery, images of the manipulation of excised pig kidneys were recorded with synchronized force data. A force estimation model was then created using deep learning. Effective detection of over-force was achieved if the region of the visual images was restricted by the region of interest around the tips of the forceps. In this paper, we emphasize the importance of limiting the region of interest in vision-based force estimation tasks.

Background: Refractory ascites affects the prognosis and quality of life in patients with liver cirrhosis. Peritoneovenous shunt (PVS) is a treatment procedure of palliative interventional radiology for refractory ascites. Although it is reportedly associated with serious complications (e.g., heart failure, thrombotic disease), the clinical course of PVS has not been thoroughly evaluated. Objectives: To evaluate the relationship between chronological course and complications after PVS for refractory ascites in liver cirrhosis patients. Materials and Methods: This was a retrospective study of 14 patients with refractory ascites associated with decompensated cirrhosis who underwent PVS placement between June 2011 and June 2023. The clinical characteristics, changes in cardiothoracic ratio (CTR), and laboratory data (i.e., brain natriuretic peptide (BNP), D-dimer, platelet) were evaluated. Follow-up CT images in eight patients were also evaluated for ascites and complications. Results: No serious complication associated with the procedure occurred in any case. Transient increases in BNP and D-dimer levels, decreased platelet counts, and the worsening of CTR were observed in the 2 days after PVS; however, they were improved in 7 days in all cases except one. In the follow-up CT, the amount of ascites decreased in all patients, but one patient with a continuous increase in D-dimer 2 and 7 days after PVS had thrombotic disease (renal and splenic infarction). The mean PVS patency was 345.4 days, and the median survival after PVS placement was 474.4 days. Conclusions: PVS placement for refractory ascites is a technically feasible palliative therapy. The combined evaluation of chronological changes in BNP, D-dimer, platelet count and CTR, and follow-up CT images may be useful for the early prediction of the efficacy and complications of PVS.

Abstract This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien–Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54–8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23–8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78–34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83–7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14–16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

Rationale and objectives: To develop and validate a deep learning (DL) model to automatically diagnose muscle-invasive bladder cancer (MIBC) on MRI with Vision Transformer (ViT). Materials and methods: This multicenter retrospective study included patients with BC who reported to two institutions between January 2016 and June 2020 (training dataset) and a third institution between May 2017 and May 2022 (test dataset). The diagnostic model for MIBC and the segmentation model for BC on MRI were developed using the training dataset with 5-fold cross-validation. ViT- and convolutional neural network (CNN)-based diagnostic models were developed and compared for diagnostic performance using the area under the curve (AUC). The performance of the diagnostic model with manual and auto-generated regions of interest (ROImanual and ROIauto, respectively) was validated on the test dataset and compared to that of radiologists (three senior and three junior radiologists) using Vesical Imaging Reporting and Data System scoring. Results: The training and test datasets included 170 and 53 patients, respectively. Mean AUC of the top 10 ViT-based models with 5-fold cross-validation outperformed those of the CNN-based models (0.831 ± 0.003 vs. 0.713 ± 0.007–0.812 ± 0.006, p

Abstract Silicon-based spin qubits offer a potential pathway toward realizing a scalable quantum computer owing to their compatibility with semiconductor manufacturing technologies. Recent experiments in this system have demonstrated crucial technologies, including high-fidelity quantum gates and multiqubit operation. However, the realization of a fault-tolerant quantum computer requires a high-fidelity spin measurement faster than decoherence. To address this challenge, we characterize and optimize the initialization and measurement procedures using the parity-mode Pauli spin blockade technique. Here, we demonstrate a rapid (with a duration of a few μs) and accurate (with >99% fidelity) parity spin measurement in a silicon double quantum dot. These results represent a significant step forward toward implementing measurement-based quantum error correction in silicon.

Abstract Background Acute pancreatitis caused by surgical procedures may occur less frequently in surgeries for aortic aneurysm involving the abdominal branch. However, in such cases, the associated mortality rate increases significantly. There have been few reports on abdominal aortic aneurysm surgery after pancreatoduodenectomy; as such the incidence of postoperative pancreatitis remains unclear. Case presentation Two cases of pararenal artery aortic aneurysm after pancreaticoduodenectomy and endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysm are reported. In the first case, a 74-year-old man was diagnosed with abdominal aortic aneurysm and duodenal cancer 6 years earlier and underwent pancreaticoduodenectomy after EVAR. Subsequently, the abdominal aorta expanded to 58 mm at the level of the renal artery proximal to the EVAR site. Graft replacement was performed through a left thoraco-retroperitoneal incision. However, the patient died from acute pancreatitis, believed to be caused by intraoperative manipulation. Given this initial experience, in the second case, a 77-year-old man had undergone a pancreaticoduodenectomy for a gastrointestinal stromal tumor 17 years earlier and EVAR for an abdominal aortic aneurysm 10 years earlier. The abdominal aorta had expanded to 50 mm immediately below the right renal artery on the proximal side of the EVAR. Subsequently, hematuria was noted, and he was diagnosed with right ureteral cancer. Autologous transplantation of the left kidney and EVAR was performed avoiding manipulation of the area around the pancreas and achieved good results. Combined right renal and ureteral resections were performed 20 days after EVAR. Conclusions While performing aortic surgery after pancreaticoduodenectomy, surgeons should avoid manipulating tissues around the pancreas.

Abstract Objective The objective of this study is to validate the predictive ability of the 2021 European Association of Urology (EAU) risk model compared to that of existing risk models, including the 2019 EAU model and risk scoring tables of the European Organization for Research and Treatment of Cancer, Club Urologico Espanol de Tratamiento Oncologico, and Japanese Nishinihon Uro‐oncology Extensive Collaboration Group. Patients and methods This retrospective multi‐institutional database study included two cohorts—3024 patients receiving intravesical bacillus Calmette–Guerin (BCG) treatment (BCG cohort) and 789 patients not receiving BCG treatment (non‐BCG cohort). The Kaplan–Meier estimate and log‐rank test were used to visualize and compare oncological survival outcomes after transurethral surgery among the risk groups. Harrell's concordance index (C‐index) was used to evaluate the predictive ability of the models. Results We observed a risk shift from the 2019 EAU risk grouping to the 2021 EAU risk grouping in a substantial number of patients. For progression, the C‐index of the 2021 EAU model was significantly higher than that of the 2019 EAU model in both the BCG (0.617 vs. 0.572; P = 0.011) and non‐BCG (0.718 vs. 0.560; P

This study aims to develop a method for estimating the traffic volume at locations and time periods where past data are unavailable. To achieve this, we constructed a model based on seven years of traffic volume observations on 22 main roads in Tokyo. The estimation method comprises two components: a traffic volume fluctuation pattern model that explains pre-clustered patterns and an annual average daily traffic model. Through our analysis, we made three key observations. First, the distance to the city center is a significant explanatory factor for monthly fluctuations, the month number for weekly fluctuations, the day-to-night population ratio for daily fluctuations, and the city center direction angle for hourly fluctuations. These calendar and road geometry variables account for 70–90% of the traffic volume fluctuation. Second, when estimating traffic volume for specific time periods using the traffic volume fluctuation pattern model, we explained approximately 60% of routes where no traffic volume observations were conducted and approximately 80% of routes where observations were made infrequently. Finally, the optimal number of clusters for the traffic volume fluctuation pattern, which maximized the coefficient of determination of the traffic volume model, was 8 for monthly fluctuations, 4 for weekly fluctuations, 6 for daily fluctuations, and 11 for hourly fluctuations. These findings made it possible to estimate traffic volumes on routes where traffic volume observations are not conducted and to interpolate traffic volumes for any given month or date using the results of periodic surveys conducted every few years.

Abstract Chronic metabolic stress paradoxically elicits pro-tumorigenic signals that facilitate cancer stem cell (CSC) development. Therefore, elucidating the metabolic sensing and signaling mechanisms governing cancer cell stemness can provide insights into ameliorating cancer relapse and therapeutic resistance. Here, we provide convincing evidence that chronic metabolic stress triggered by hyaluronan production augments CSC-like traits and chemoresistance by partially impairing nucleotide sugar metabolism, dolichol lipid-linked oligosaccharide (LLO) biosynthesis and N-glycan assembly. Notably, preconditioning with either low-dose tunicamycin or 2-deoxy-D-glucose, which partially interferes with LLO biosynthesis, reproduced the promoting effects of hyaluronan production on CSCs. Multi-omics revealed characteristic changes in N-glycan profiles and Notch signaling activation in cancer cells exposed to mild glycometabolic stress. Restoration of N-glycan assembly with glucosamine and mannose supplementation and Notch signaling blockade attenuated CSC-like properties and further enhanced the therapeutic efficacy of cisplatin. Therefore, our findings uncover a novel mechanism by which tolerable glycometabolic stress boosts cancer cell resilience through altered N-glycosylation and Notch signaling activation.

Abstract Because of their long coherence time and compatibility with industrial foundry processes, electron spin qubits are a promising platform for scalable quantum processors. A full-fledged quantum computer will need quantum error correction, which requires high-fidelity quantum gates. Analyzing and mitigating gate errors are useful to improve gate fidelity. Here, we demonstrate a simple yet reliable calibration procedure for a high-fidelity controlled-rotation gate in an exchange-always-on Silicon quantum processor, allowing operation above the fault-tolerance threshold of quantum error correction. We find that the fidelity of our uncalibrated controlled-rotation gate is limited by coherent errors in the form of controlled phases and present a method to measure and correct these phase errors. We then verify the improvement in our gate fidelities by randomized benchmark and gate-set tomography protocols. Finally, we use our phase correction protocol to implement a virtual, high-fidelity, controlled-phase gate.

Key Clinical Message Maintaining a disease‐free status for a long time in cases of renal cell carcinoma with multiple bone metastases and repeated recurrences is challenging. What matters most in the multidisciplinary approach is the treatment strategy. Although this is a case where multidisciplinary treatment resulted in long‐term CR during the TKI era, the treatment strategy is still relevant now that treatment options have increased. Abstract Recent advances in medications, such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs), have improved metastatic renal cell carcinoma (mRCC) outcomes. We report a case of mRCC with bone metastasis that was successfully treated using a multidisciplinary approach. Here, we present a case of a 56‐year‐old man with left renal cancer and large and painful bone metastases at the 11th thoracic vertebrae (Th11). Therefore, a metastasectomy of Th11 was performed. Systemic treatment with TKI, robot‐assisted partial nephrectomy, and metastasectomy were then administered. No recurrence was observed in >2 years. Long‐term disease‐free survival with the TKI‐era multidisciplinary approach in a patient with mRCC remains significant when considering treatment sequences, especially now that drug treatment options—including ICIs—have increased. Treatment strategy and indication and timing of resection of the primary lesion and metastasectomy should be carefully considered in each case.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease, and there has been a rapid increase in cases worldwide. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma and is also associated with an increased risk of cardiovascular disease or exacerbation of other organ diseases, thus posing a significant health problem from both a medical and a socioeconomic perspective. NAFLD is a systemic disease and requires the involvement of numerous medical professionals. Multidisciplinary collaboration, in which different professionals within different specialties come together and work together toward a common goal, supports better patient care by integrating perspectives of multiple experts and facilitating the exchange of opinions. Due to the large number of potential patients, gastroenterologists and hepatologists cannot manage the patients alone, and collaboration between specialists in various fields, including family doctors, dentists, nutritionists, and pharmacists is required for treatment of NAFLD. This review will discuss NAFLD from the perspective of various specialties and introduce multidisciplinary collaboration.

Abstract Background Miyakoshi et al. reported three cases of tethered cord syndrome treated by spine-shortening vertebral osteotomy, which provided relief of the patients’ symptoms with no complications. Although the details of these cases were described in a previous report, the surgical technique was not thoroughly explained. In the present report, we describe the details of our procedure with reference to a fourth case. Case presentation A 47-year-old Asian woman was admitted to our hospital with a 1-year history of worsening leg numbness and urinary dysfunction. Magnetic resonance imaging revealed a low-lying conus medullaris extending to the level of S2 and surrounded by fat tissue at that level. We diagnosed her condition as adult tethered cord syndrome, and spine-shortening vertebral osteotomy was planned. The target level for the osteotomy was L2. Bilateral pedicle screw implants were placed at L1 and L3 using an anterior–posterior image intensifier. In this procedure, it is essential to use monoaxial screws inserted exactly parallel to the rostral endplates of each vertebral body; this ensures appropriate alignment between the L1 caudal endplate and the L2 osteotomy surface. The upper one-third of the lamina of L2 was resected, and the bilateral two-thirds of the pedicle of L2 was removed with a surgical air drill. After exposure of the lateral side of the L1–2 disc, discectomy was performed with a knife and curette. Following complete discectomy of L1–2, the upper vertebral body of L2 was removed with a surgical air drill. After complete removal of the vertebral body, a straight rod was connected to two screws and applied pressure between the screws. Two polyethylene tapes were applied to the L2 lamina and bilateral rods. Conclusion Spine-shortening osteotomy that preserves the caudal one-third of the pedicle and lamina with one-above and one-below instrumentation successfully reduced the spinal cord tension without causing neural damage.

Abstract Objective This study was performed to validate the epidemiology, initial treatment, and clinical practice of lung cancer patients in the Hokushin region, Japan. Methods We retrospectively surveyed data of 5503 newly diagnosed and registered lung cancer patients in 22 principal hospital-based cancer registries in Hokushin region linked with health insurance claims data for registered patients between 2016 and 2017. Results The patients consisted of 3677 (66.8%) men and 1826 (33.2%) women with a mean (range) age of 72.2 (27–103) years). Diagnoses were small cell lung cancer (n = 512, 9.4%), squamous cell carcinoma (n = 1083, 19.7%), and non-squamous non-small cell lung cancer (NSCLC; n = 3906, 70.9%). The population with stage I disease in Toyama prefecture (41.1%) was smaller than in the other three prefectures associated with reduced selection of initial surgical therapy and increased frequencies of stage IV disease (33.2%) and best supportive care (18.6%). Initial chemotherapy for stage IV non-squamous NSCLC consisted of tyrosine kinase inhibitors in 39.3% of cases for EGFR and 4% of cases for ALK-positive non-squamous NSCLC, followed by platinum compounds (25.9%) non-platinum compounds (12.9%), and immune checkpoint inhibitors (10.2%). Carboplatin was the commonly prescribed first-line cytotoxic chemotherapeutic agent (65.4% of patients under 75 years and in 96.7% of patients over 75 years). Conclusion This study revealed real-world data on epidemiological and treatment status in lung cancer in four prefectures in Hokushin region, Japan. Simultaneous analysis of nationwide registry and insurance data could provide valuable insights for the development of lung cancer screening and medical treatment strategies. In addition, the comparative data analysis with other lesions or countries will be useful for evaluating the differences in clinical practice of cancer managements.

Although handheld ultrasound devices (HUDs) are commonplace, their ability to diagnose fecal retention (FR) remains unclear. This prospective observational study examined HUDs’ usefulness in diagnosing FR in patients with constipation in a palliative care setting. Between 10 December 2020 and 30 June 2022, we compared rectal ultrasonographic findings obtained using HUDs with clinical manifestations in 64 males and 70 females (48%, 52%, 68 ± 11 years old) with constipation who had undergone computed tomography (CT). FR was diagnosed using a HUD and compared with CT and digital rectal examination (DRE) results. In total, 42 (31%), 42 (31%), and 41 (31%) patients were diagnosed using HUDs, CT, and DRE, respectively. Thirty-nine (93%) patients in the CT group were also diagnosed with FR using HUDs. A total of 89 of 92 patients with a negative CT diagnosis also had a negative HUD diagnosis. Among the 41 patients in the DRE group, 37 were also diagnosed with FR using HUDs. Among 93 patients with a negative DRE diagnosis, 86 had a negative HUD diagnosis. The sensitivity, specificity, positive predictive value, and negative predictive value of HUDs for CT were 93%, 97%, 93%, and 97%, respectively. Those of HUDs for DRE were 88%, 94%, 86%, and 95%, respectively. The concordance rates for FR diagnosis were 128/134 for CT and HUDs and 123/134 for DRE and HUDs. HUD was useful for diagnosing FR in this setting. HUDs could provide valuable support for appropriate treatment selection. Developing a constipation treatment algorithm based on rectal ultrasonographic findings is warranted in the future.

Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

Abstract Pancreatic cancer primarily arises from microscopic precancerous lesions, such as pancreatic intraepithelial neoplasia (PanIN) and acinar-to-ductal metaplasia (ADM). However, no established method exists for predicting pancreatic precancerous conditions. Endoscopic ultrasonography (EUS) can detect changes in pancreatic parenchymal histology, including fibrosis. This study aimed to elucidate the relationship between pancreatic parenchymal EUS findings and microscopic precancerous lesions. We retrospectively analyzed 114 patients with pancreatobiliary tumors resected between 2010 and 2020 and evaluated the association between pancreatic parenchymal EUS findings and the number of PanIN, ADM, and pancreatic duct gland (PDG). Of the 114 patients, 33 (29.0%), 55 (48.2%), and 26 (22.8%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. Multivariate analyses revealed that abnormal EUS findings were significantly associated with the frequency of PanIN (hyperechoic foci/stranding without lobularity: OR [95% CI] = 2.7 [1.0–7.3], with lobularity: 6.5 [1.9–22.5], P trend = 0.01) and ADM (hyperechoic foci/stranding without lobularity: 3.1 [1.1–8.2], with lobularity: 9.7 [2.6–36.3], P trend = 0.003) but not with PDG (hyperechoic foci/stranding without lobularity: 2.2 [0.8–5.8], with lobularity: 3.2 [1.0–10.2], P trend = 0.12). We observed a trend toward a significantly higher number of precancerous lesions in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. Pancreatic parenchymal EUS findings were associated with the increased frequency of PanIN and ADM. Lobularity may help predict the increased number of precancerous lesions.

Abstract Cross-sectional relationships between nocturia and sleep problems have been well evaluated but the risk association for each incidence is scarcely reported. This analysis included 8076 participants of the Nagahama study in Japan (median age 57, 31.0% male) and associations between nocturia and self-reported, sleep-related problems (poor sleep) were evaluated cross-sectionally. Causal effects on each new-onset case were analyzed longitudinally after 5 years. Three models were applied: univariable analysis, adjustment for basic variables (i.e., demographic and lifestyle variables) and full adjustment for basic and clinical variables. The overall prevalences of poor sleep and nocturia were 18.6% and 15.5%, while poor sleep was positively associated with nocturia (OR = 1.85, p

Meat substitutes production using plant-derived materials is attracting attentions as a solution for sustainable protein supply. We have previously reported the fabrication of soy protein-based fibers by combination of wet spinning and ionic cross-linking of alginate. In this study, we focused on the calcium ion concentration in the coagulant solution and alginate concentration in the spinning solution, which are determinant factors for in the gelation of alginate. The fiber diameter was reduced by increasing calcium ion concentration, probably due to the dehydration from fiber induced by osmotic pressure difference with coagulant solution and the suppression of swelling of fiber by the rapid gelation. The hardness of fibers evaluated by texture analysis increased as the concentrations of alginate and calcium ion increased, while the springiness increased with increasing calcium ion concentration but decreased with alginate concentration. The controlling the structure and texture of fibers by the compositions of spinning and coagulant solutions would improve their applicability to meat substitutes.

IntroductionThe clinical relevance of soluble forms of programmed cell death-1 (sPD-1) and programmed cell death-ligand 1 (sPD-L1) remains unclear. We here investigated the relation between the efficacy of PD-1 blockade and pretreatment plasma levels of sPD-1 and sPD-L1 across a broad range of cancer types.MethodsWe retrospectively analyzed clinical data from 171 patients with advanced solid tumors who received nivolumab or pembrolizumab monotherapy regardless of treatment line. The concentrations of sPD-1 and sPD-L1 were measured with a fully automated immunoassay (HISCL system).ResultsThe study subjects comprised patients with head and neck cancer (n = 50), urothelial cancer (n = 42), renal cell cancer (n = 37), gastric cancer (n = 20), esophageal cancer (n = 10), malignant pleural mesothelioma (n = 6), or microsatellite instability-high tumors (n = 6). High or low levels of sPD-1 or sPD-L1 were not significantly associated with progression-free survival (PFS) or overall survival (OS) for PD-1 blockade in the entire study population. Comparison of treatment outcomes according to combinations of high or low sPD-1 and sPD-L1 levels, however, revealed that patients with low sPD-1 and high sPD-L1 concentrations had a significantly poorer PFS (HR of 1.79 [95% CI, 1.13–2.83], p = 0.01) and a tendency toward poorer OS (HR of 1.70 [95% CI, 0.99–2.91], p = 0.05) compared with all other patients.ConclusionOur findings suggest that the combination of low sPD-1 and high sPD-L1 levels is a potential negative biomarker for PD-1 blockade therapy.

Plant-based meat (PBM) analogues have been developed as a meat substitute in response to the growing demand worldwide. This is partially attributed to changes in human consumption behaviors motivated by the desire for a lifestyle with a smaller environmental impact and the belief that PBMs are healthier than traditional meat. This study conducted a techno-economic assessment (TEA) of PBM production from soy protein using an industrial-scale freeze-alignment technique with an annual production capacity of 100 tons. The calculation result showed that the raw material and labor costs accounted for 32.09 % and 23.53 % of the total production cost, respectively, which resulted in the PBM minimum selling price of 1.18 USD/100 g. Economic indicators showed that the project is an attractive investment opportunity with a positive net present value of 4.05 million USD, discounted payback period of 4.4 years, and an internal rate of return of 29.67 %. By streamlining the production process, which contributed to the reduction in time, labor, raw materials, and energy requirements, the potential for cost reduction and increased project profitability could be realized. This study serves as an initial exploration of the challenges associated with enhancing the efficiency and competitiveness of PBM production in the meat market in the foreseeable future.

Abstract Background Hydrosalpinx and pyosalpinx are rare gynecologic problems during adolescence, especially in girls without a history of sexual activity. They are even rarer in women with Hirschsprung’s disease (HD). We herein report a case of pyosalpinx in an adolescent girl with HD treated by transvaginal ultrasound-guided drainage. Case presentation The present patient was a 12-year-old girl (weight 83 kg; height 159 cm; body mass index 32.8 kg/m2). She had undergone five laparotomies for long-segment HD by 2 years. Her menarche had occurred at 10 years. She was admitted with lower abdominal and anal pain. Computed tomography (CT), magnetic resonance imaging (MRI), and transvaginal ultrasound showed left pyosalpinx and abdominal abscess. Surgical drainage was necessary; however, she had a history of polysurgery and was severely obese, so laparotomy was considered to carry a high risk. Transvaginal ultrasound was deemed more likely to reach the abscess safely. Therefore, she was treated with transvaginal ultrasound-guided drainage by a gynecologist skilled in the procedure. She was discharged home after 52 days. One year and nine months after discharge, there was no reformation of either the abscess or pyosalpinx. Conclusions Adolescent girls with HD are at risk of developing hydrosalpinx. Depending on the defecation status, pyosalpinx may also develop. As a less-invasive surgical treatment, transvaginal ultrasound-guided drainage can avoid laparotomy. Collaboration with a gynecologist is essential for the diagnosis and treatment of this clinical condition. Pediatric surgeons should communicate with gynecologists for such cases beginning around puberty for continuous follow-up.

Objectives: We aimed to determine when a coexisting pseudocyst was likely to complicate the nonsurgical treatment of pancreatolithiasis. Methods: We treated 165 patients with pancreatolithiasis nonsurgically between 1992 and 2020, including 21 with pseudocysts. Twelve patients had a single pseudocyst less than 60 mm in diameter. Pseudocysts in the other nine patients had diameters of at least 60 mm or were multiple. The locations of pseudocysts along the length of the pancreas varied from the area with stone involvement to the pancreatic tail. We compared the outcomes in these groups. Results: We found no significant differences in pain relief, stone clearance, stone recurrence, or the likelihood of adverse events between pseudocyst groups or between patients with vs without pseudocysts. However, 4 of 9 patients with large or multiple pseudocysts required transition to surgical treatment (44%) compared with 13 of 144 patients with pancreatolithiasis and no pseudocyst (9.0%) (P=0.006). Conclusions: Patients with smaller pseudocysts typically underwent nonsurgical stone clearance successfully with few adverse events, similar to findings in patients with pancreatolithiasis and no pseudocysts. Pancreatolithiasis complicated by large or multiple pseudocysts did not cause more adverse events but was more likely to require transition to surgery compared with pancreatolithiasis without pseudocysts. In patients with large or multiple pseudocysts, early transition to surgery should be considered when nonsurgical treatment is ineffective.

Abstract Here, we report a case of mediastinal mesenchymal tumor with a pericytic neoplasm feature that responded to radiation therapy. A 43‐year‐old man visited our hospital with a complaint of esophageal obstruction and chest pain. Chest computed tomography revealed a middle mediastinal tumor and a mesenchymal tumor was diagnosed with a pericytic neoplasm feature by video‐assisted thoracoscopic biopsy. The definitive treatment for soft tissue tumor is surgical resection; however, the mediastinal tumor was unresectable because of esophageal and tracheal invasion. Radiation therapy was administered and there was a partial tumor response and 2 years disease‐free status. With a review of the literature, we discuss the clinical and pathological characteristics of this rare tumor and its treatment.

Abstract Background Management of pelvic node‐positive prostate cancer has been challenging and controversial. We conducted a study to evaluate the outcomes of whole‐pelvic (WP) simultaneous integrated boost (SIB) intensity‐modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT). Methods A total of 67 consecutive patients with cT1c‐4N1M0 prostate cancer were definitively treated by WP SIB‐IMRT. Neoadjuvant ADT (median: 8.3 months) was administered in all cases. WP SIB‐IMRT was designed to simultaneously deliver 78, 66.3, and 58.5 Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes (LNs), and the pelvic LN region, respectively. Adjuvant ADT (median: 24.7 months) was administered in 66 patients. Results The median follow‐up period was 81.6 months (range: 30.5–160.7). Biochemical relapse‐free, overall, and prostate cancer‐specific survival rates at 10 years were 59.8%, 79.6%, and 86.3%, respectively. Loco‐regional recurrence was not observed. Being in International Society of Urological Pathology grade group 5 and having a posttreatment detectable nadir prostate‐specific antigen (PSA) level (≥0.010 ng/ml) were significantly associated with worse prostate cancer‐specific survival and progression of castration resistance. The 10‐year cumulative incidence rates of grade 2 and 3 late toxicities were, respectively, 1.5% and 0% for genitourinary, 0% and 1.5% for gastrointestinal events. No grade 4 acute or late toxicities were observed. Conclusions WP SIB‐IMRT can be safely administered to patients with pelvic node‐positive prostate cancer. Since grade group 5 and detectable nadir PSA levels are risks for castration resistance, we may need to increase the intensity of treatment for such cases.

Abstract Pembrolizumab, an anti‐programmed death 1 monoclonal antibody, has revolutionized the treatment of metastatic urothelial carcinoma. However, the optimal treatment duration for treatment responders has not been established. To address this, we retrospectively assess the treatment outcomes and duration of pembrolizumab for patients whose best response was complete response (CR) or partial response (PR) in a Japanese nationwide cohort of platinum‐refractory metastatic urothelial carcinoma. Of 203 patients whose best response was CR or PR, 83 patients discontinued pembrolizumab before progression. The median pembrolizumab treatment duration was 6.9 months. The 2‐year relapse‐free survival (RFS), treatment‐free survival, and OS rates after discontinuation were 49.0%, 57.4%, and 74.5%, respectively. CR, higher hemoglobin levels, and a better Eastern Cooperative Oncology Group performance status at the time of discontinuation were associated with significantly better RFS. Pembrolizumab was re‐administered to 12 patients. Pembrolizumab re‐challenge resulted in CR, PR, stable disease, and progressive disease in six, three, two, and one patient, respectively. Propensity score‐matched landmark analysis revealed no significant OS difference between patients who continued or discontinued pembrolizumab at 6, 12, and 18 months (p = 0.91, 0.99, and 0.25, respectively). Our findings demonstrated that patients with objective responses had favorable survival outcomes and suggested that pembrolizumab could be discontinued safely in this population. This study should drive further efforts to optimize the treatment duration for pembrolizumab responders.

Abstract Using new castration‐resistant prostate cancer (CRPC) cell lines developed from LNCaP cells as a model for CRPC, we searched for novel biomarkers by analyzing the proteins secreted in culture supernatants. The results showed that the levels of secretory leukocyte protease inhibitor (SLPI) in these cell lines were 4.7–6.7 times higher than those secreted in parental LNCaP. Patients with localized prostate cancer (PC) and who expressed SLPI had a significantly lower prostate‐specific antigen (PSA) progression‐free survival rate than those who did not. Multivariate analysis revealed that SLPI expression was an independent risk factor for PSA recurrence. By contrast, when immunostaining of SLPI was performed on consecutive prostate tissue samples obtained from 11 patients, both in hormone naive (HN) and castration resistant (CR) conditions, only one patient expressed SLPI in the HNPC state; however, four of the 11 patients expressed SLPI in the CRPC state. In addition, two of these four patients were resistant to enzalutamide, and there was a discrepancy between their serum PSA levels and radiographic progression of the disease. These results suggest that SLPI can be a predictor of prognosis in patients with localized PC and disease progression in CRPC patients.

When the etiology of pancreatitis cannot be determined despite sufficient investigation, recurrence and progression to chronic pancreatitis often involve genetic mutations. Herein, we describe a case of recurrent pancreatitis with the IVS3+2T>C mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene that progressed to chronic pancreatitis in only 3 years. A 35-year-old man was referred to our hospital, where he was diagnosed with mild pancreatitis and was treated conservatively. However, the patient experienced recurrent episodes of pancreatitis, which progressed to become chronic pancreatitis with a pancreatic calcification 1 year later. After 3 years, the patient developed pancreatic duct stenosis and required a pancreatic duct stent placement. Regarding the cause of chronic pancreatitis, alcohol abuse was ruled out based on history taking. Considering the course of treatment, autoimmune pancreatitis and obstructive pancreatitis, such as pancreatic divisum, were also ruled out. Finally, a germline genetic test was performed to determine the etiology of pancreatitis, which revealed the IVS3+2T>C mutation in SPINK1. This case shows the importance of genetic testing in patients with idiopathic pancreatitis to determine their etiology and is a rare incident that can report the progression of the disease from acute to chronic pancreatitis.

Abstract This study aimed to develop a versatile automatic segmentation model of bladder cancer (BC) on MRI using a convolutional neural network and investigate the robustness of radiomics features automatically extracted from apparent diffusion coefficient (ADC) maps. This two-center retrospective study used multi-vendor MR units and included 170 patients with BC, of whom 140 were assigned to training datasets for the modified U-net model with five-fold cross-validation and 30 to test datasets for assessment of segmentation performance and reproducibility of automatically extracted radiomics features. For model input data, diffusion-weighted images with b = 0 and 1000 s/mm2, ADC maps, and multi-sequence images (b0-b1000-ADC maps) were used. Segmentation accuracy was compared between ours and existing models. The reproducibility of radiomics features on ADC maps was evaluated using intraclass correlation coefficient. The model with multi-sequence images achieved the highest Dice similarity coefficient (DSC) with five-fold cross-validation (mean DSC = 0.83 and 0.79 for the training and validation datasets, respectively). The median (interquartile range) DSC of the test dataset model was 0.81 (0.70–0.88). Radiomics features extracted from manually and automatically segmented BC exhibited good reproducibility. Thus, our U-net model performed highly accurate segmentation of BC, and radiomics features extracted from the automatic segmentation results exhibited high reproducibility.

Background: Radiation or hormonal therapy is considered for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, these therapies have their own complications. To delay the start of these therapies, we investigated the efficacy and safety of Brazilian green propolis for the treatment for BCR after RP. Materials and Methods: This single-center, single-arm open trial included 22 patients who experienced BCR after RP between 2016 and 2019. The patients received nine softgels of Brazilian green propolis (containing 40 mg propolis per capsule) daily for 6 months. The primary outcome was the prostate-specific antigen (PSA) response rate. The secondary outcomes included progression-free time, PSA slope (1/PSA doubling time) response rate, quality of life, and safety profile. Results: The PSA response rate was 0%. The mean PSA slopes before and after baseline were 0.12 month−1 and 0.08 month−1, respectively. Fifteen patients (68%) showed a decreased PSA slope after treatment. There were no negative effects on quality of life or serious adverse events leading to treatment discontinuation. Conclusion: There was no significant anticancer response in patients who received Brazilian green propolis. However, the PSA slope was decreased after propolis administration. Further, Brazilian green propolis may be safely consumed by patients.

Abstract Non-invasive imaging techniques have greatly advanced the assessment of liver fibrosis and steatosis but are not fully evaluated in overweight patients. We evaluated the diagnostic performance of vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE) to assess fibrosis and controlled attenuation parameter (CAP) and MR imaging (MRI)-proton density fat fraction (MRI-PDFF) to assess steatosis in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD). We included 163 biopsy-proven patients with NAFLD who underwent VCTE, MRE/MRI-PDFF, and liver biopsy (years 2014–2020) who were classified according to their body mass index (BMI) as normal (BMI

Abstract Background and Aim Non‐alcoholic fatty liver disease (NAFLD) can progress in non‐obese patients as in obese patients. Reports on long‐term prognosis in non‐obese NAFLD patients are controversial. Therefore, we aimed to examine the long‐term prognosis of non‐obese patients with NAFLD. Methods This single‐center, retrospective cohort study enrolled biopsy‐proven non‐obese and obese NAFLD patients between January 2002 and December 2011 and followed them up until 31 March 2021, for death and clinical events (cardiovascular and liver‐related events and extrahepatic cancers). Results Of the 223 NAFLD patients, 58 (26.0%) were non‐obese. Compared with obese patients, they had a lower fibrosis stage (0.8 ± 0.80 vs 1.2 ± 0.91; P = 0.004), milder lobular inflammation (0.9 ± 0.7 vs 1.1 ± 0.7; P = 0.02), and significantly lower serum creatinine, total bilirubin, ferritin, and type IV collagen 7S and higher high‐density lipoprotein levels. After a median follow‐up of 8.9 years, no significant difference was noted in mortality between the two groups (2 [3.4%] non‐obese vs 5 [3.0%] obese; log‐rank test, P = 0.63). Twelve patients (20.7%) in the non‐obese group and 32 (19.4%) in the obese group had clinical events. Although the obese group had a higher incidence of clinical events during the first 10 years of follow‐up, the non‐obese group had a higher incidence after that (log‐rank test, P = 0.67). The non‐obese group had a high incidence of malignancy (9 [15.5%] non‐obese vs 14 [8.3%] obese; P = 0.13). Conclusion Non‐obese NAFLD does not necessarily have a good prognosis, and some cases have a poor prognosis such as extrahepatic cancers. Further validation is required in the future.

Abstract A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs.

Abstract Background Short bowel syndrome (SBS) is a rare yet costly disease with an incidence rate of 3 per million people. Herein, we report a rare case of eosinophilic gastrointestinal disorders (EGIDs) with SBS after strangulated bowel obstruction. Case presentation A 5-year-old male had a necrotic intestine of 340 cm resected due to strangulated bowel obstruction caused by an intestinal mesenteric hiatal hernia. The length of the residual intestine was 51 cm. Bloody stools appeared 19 days postoperatively. Colonoscopy showed diffuse redness of the colonic mucosa, and pathological findings showed moderate chronic inflammatory cellular infiltration. On blood examination, the eosinophil count was > 30%. EGIDs with short bowel syndrome (SBS) were suspected. Because his symptoms did not improve with initial nutrition therapy, he was transferred to our hospital 5 months after the operation. Prednisolone was administrated at an initial dose of 1.4 mg/kg/day, 6 days after his transfer. Bloody stools disappeared after prednisolone administration. Seven months after discharge, he had no bloody stool recurrence. Conclusion The risk of developing secondary EGIDs in children with SBS should be considered, and postoperative management should include attention to abdominal symptoms and elevated eosinophil counts on blood examination.

Abstract Endoscopic papillectomy for early ampullary tumors is considered a minimally invasive and useful alternative to pancreatoduodenectomy; however, its indications remain unclear. This study aimed to clarify the advantages of endoscopic papillectomy by investigating the clinical outcomes of patients who underwent endoscopic papillectomy or pancreatoduodenectomy for early ampullary tumors. Patients diagnosed with early ampullary tumors (adenoma, Tis, T1a) who underwent endoscopic papillectomy or pancreatoduodenectomy between June 2008 and October 2019 were included, and their clinical outcomes were analyzed. Seventy-four patients (34 patients with adenomas and 40 patients with adenocarcinomas) were divided into two groups, namely endoscopic papillectomy (n = 43) and pancreatoduodenectomy (n = 31). The estimated 5-year overall survival rate of all early ampullary tumors was 92%. Complete resection rate was significantly lower for endoscopic papillectomy patients versus pancreatoduodenectomy patients (48.8% vs. 100%; p

A coherent quantum link between distant quantum processors is desirable for scaling up of quantum computation. Noiri et al. demonstrate a strategy to link distant quantum processors in silicon, by implementing a shuttling-based two-qubit gate between spin qubits in a Si/SiGe triple quantum dot.

Introduction Paragangliomas (PGLs) are frequently reported around the abdominal aorta; however, are extremely rare near the urachus. Case presentation A 78‐year‐old woman was referred to the urology department of our hospital for further examination and treatment of a 1.2‐cm tumor in the lower abdominal wall, a tumor excision was then performed. On immunohistochemical staining, the tumor and supporting cells were positive for chromogranin A and the S 100 protein, respectively, and were diagnosed as PGL. The PGL was thought to be derived from chromaffin cells that migrated to the wall of the urachus during embryonic life and remained even after the wall regressed. Conclusion We report a case of PGL near the urachus that can be explained by the distribution of the sympathetic network around the midline of the lower abdominal wall during embryonic development. Therefore, PGL should be considered in the differential diagnosis of periurachal tumors.

Abstract The incidence of nonalcoholic fatty liver disease (NAFLD) has recently increased and is related to obesity and the associated surge in type 2 diabetes mellitus (T2DM) and metabolic syndromes. This trial follows up on our previous work and forms part of the ToPiND study. We aimed to combine tofogliflozin and pioglitazone treatment for hepatic steatosis in patients with NAFLD and T2DM. In this open‐label, prospective, single‐center, randomized clinical trial, patients with NAFLD with T2DM and a hepatic fat fraction of ≥10% were assessed based on magnetic resonance imaging proton density fat fraction. Eligible patients received either 20 mg tofogliflozin or 15–30 mg pioglitazone orally, once daily for 24 weeks, followed by combination therapy with both medicines for an additional 24 weeks. The effects on diabetes mellitus and hepatic steatosis were examined at baseline and after the completion of monotherapy and combination therapy. Thirty‐two eligible patients received the combination therapy of tofogliflozin and pioglitazone. The combination therapy showed additional improvement in glycated hemoglobin compared with each monotherapy group and showed improvement in steatosis, hepatic stiffness, and alanine aminotransferase levels compared with the tofogliflozin monotherapy group. Pioglitazone monotherapy–mediated increase in body weight decreased following concomitant use of tofogliflozin. The combination therapy resulted in lower triglyceride, higher high‐density lipoprotein cholesterol, higher adiponectin, and higher ketone body levels. Conclusion: In addition to the additive effects of tofogliflozin and pioglitazone in patients with T2DM and NAFLD, combination therapy was suggested to reduce weight gain and induce cardioprotective effect. Further studies with more patients are needed to investigate the combination therapy of various drugs.

Abstract The risk factors for non-alcoholic fatty liver disease (NAFLD) progression are not completely known. Porphyromonas gingivalis infection is a risk factor for systemic diseases. We investigated the association of P. gingivalis infection with the risk of non-alcoholic steatohepatitis progression. Here, hematological tests, periodontal examination, and saliva collection were performed for 164 patients with NAFLD. P. gingivalis was identified in saliva using polymerase chain reaction. Hepatic steatosis and stiffness were evaluated using vibration-controlled transient elastography (VCTE) and magnetic resonance imaging. In patients with NAFLD, P. gingivalis positivity (P. gingivalis ratio ≥ 0.01%) in saliva correlated with liver stiffness determined using magnetic resonance elastography (MRE; p 10 periodontal pockets with depths ≥ 4 mm had significantly increased hepatic stiffness on both VCTE and MRE.

Abstract Background Owing to the aging population, fragility fractures of the pelvis are occurring more frequently. Fixation of the fracture and stabilization of the pelvic ring usually provide good clinical results. A case of distal sacral nerve roots severed by a fragility fracture of the sacrum is presented. Case presentation A 62-year-old Japanese woman with schizophrenia with low back pain, gait disorder, dysuria, and fecal incontinence presented to an emergency department, and plain X-rays showed no findings. She also complained of dysuria, and neurogenic bladder and cystitis were diagnosed. One month later, she was admitted to a psychiatric hospital for exacerbation of schizophrenia. In hospital, she had a urethral catheter inserted and spent 3 months in bed. She was referred to our orthopedic department because a gait disorder was discovered after her mental condition improved and she was permitted to walk. On examination, she could not walk and had decreased sensation from the buttocks to both posterior thighs and around the anus and perineum. Manual muscle testing of her lower limbs showed mild weakness of about 4 in bilateral flexor hallucis longus and gastrocnemius, and bilateral Achilles tendon reflexes were lost. Her anal sphincter did not contract, and urinary retention continued after urethral catheter removal. Imaging examinations showed an H-shaped sacral fracture consisting of a transverse fracture with displacement of the third sacral vertebra and vertical fractures of the bilateral sacral wings, with severe stenosis of the spinal canal at the site of the transverse fracture. The patient was diagnosed as having bladder and rectal dysfunction due to a displaced, unstable sacral fracture. First to third sacral laminectomy and alar–iliac fixation using percutaneous pedicle screws and sacral alar–iliac screws were then performed. The bilateral distal sacral nerve roots (S3, S4, S5) were completely severed at the second to third sacral levels, but bilateral second sacral nerve roots were not compressed from the bifurcation to the sacral foramen. Postoperatively, bladder and rectal dysfunction remained, but the low back pain was alleviated. Two weeks postoperatively, she could walk with a walker and was discharged. Three months after the operation, bone fusion of the fracture was observed. Conclusions In cases of bladder–rectal dysfunction with low back pain, the possibility of sacral fracture should be considered, and computed tomography, magnetic resonance imaging, and X-ray examinations should be performed. Even sacral fractures without displacement require attention because they can cause serious injury in the event of a nerve root being severed if not diagnosed early and given appropriate treatment.