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Coastal erosion has increasingly become a problem in recent years due to rising sea levels caused by global warming. To prevent further coastal erosion and damage, control structures like seawalls and breakwaters have been installed along vulnerable coastlines. However, it is crucial that these structures are regularly and thoroughly inspected for any abnormalities or deformations. At present, inspections are done manually by visual surveys which are time-consuming and inefficient. There is great potential to optimize this process using drone technology equipped with 3D laser scanners. In this study, we utilized a drone with a green laser scanner to inspect and diagnose control structures along the coast. We conducted surveys to determine the basic performance of this approach and used ICP algorithms to extract any deformations in vanishing wave blocks over two time periods. Our results showed high variability in basic performance due to the influence of waves during the surveys. However, we were still able to detect strain of around 50 cm in a submerged breakwater located 3 meters below the water's surface. Furthermore, an overall settlement of approximately 34 cm was observed in the vanishing wave blocks along with some localized movements. This demonstrates that drones can be successfully implemented for efficient inspection, diagnosis and detection of abnormalities and deformations in coastal structures that are extremely difficult to identify through visual surveys alone. The use of this advanced technology will allow for quicker identification of at-risk structures, enabling timely maintenance and prevention of further coastal erosion. [ABSTRACT FROM AUTHOR]

Pulmonary pleomorphic carcinoma (PC) is a rare non-small-cell lung carcinoma (NSCLC) with a poor prognosis, characterized by tumor necrosis (TN). NETosis is a form of neutrophil-specific cell death, which is morphologically characterized by prominent neutrophil infiltration and cell detritus in the necrotic foci. Seventy-six patients with pulmonary PC who underwent complete resection were enrolled. Tumor necrosis was evaluated using digitally scanned resected specimens. The regions of NETosis were quantified using citrullinated histone H3 (citH3)- and myeloperoxidase-positive regions. We examined the association between the NETosis area and the prognostic outcomes and assessed the correlation between the NETosis area and systemic inflammation. Tumor necrosis was observed in 70 patients (92%). In all the cases, the TN region was accompanied by a citH3-positive region. The patients with high NETosis area (n = 54) had significantly shorter overall survival than those with low NETosis area (n = 16) (p = 0.013). Furthermore, a high NETosis area was an independent poor prognostic factor in the multivariate analyses. Systemic inflammatory markers, including C-reactive protein (CRP), CRP-to-albumin ratio, and neutrophil-to-lymphocyte ratio, were significantly higher in patients with high NETosis area than in those with low NETosis area. Furthermore, the levels of these inflammatory markers were significantly decreased postsurgery. This study shows that in surgically resected pulmonary PC, patients with high NETosis areas have higher systemic inflammation and worse prognosis., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The Phenotypic states of vascular smooth muscle cells (SMCs) are essential to understanding vascular pathophysiology. SMCs in vessels generally express a specific set of contractile proteins, but decreased contractile protein expression, indicating a phenotypic shift, is a hallmark of vascular diseases. Recent studies have suggested the relation of abnormally high wall shear stress (WSS) of approximately 20 Pa with the aortic disease pathogenesis. However, due to the lack of appropriate experimental models to assess SMC phenotypic states, the details of the phenotypic shift under high WSS conditions remain unclear. In this study, we developed a coculture model where vascular endothelial cells (ECs) were cocultured with SMCs expressing calponin 1, a contractile protein involved in the phenotypic shift of SMCs. We investigated the effects of a pathologically high WSS condition on the phenotypic states of SMCs. Increased calponin 1 expression was found upon exposure to 20 Pa WSS compared with a physiological 2 Pa condition, whereas the expression of another contractile protein, α-smooth muscle actin (αSMA) remained unchanged. Furthermore, the inhibition of EC-derived nitric oxide (NO), which is associated with endothelial dysfunction in vascular diseases, resulted in a trend of decreasing αSMA and Calponin 1 expression under 20 Pa WSS conditions compared with 2 Pa. Our findings suggest that EC-derived NO under pathologically high WSS conditions may impact the expression of contractile proteins implicated in aortic pathophysiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Vonoprazan has been known to have a high Helicobacter pylori ( H. pylori ) eradication rate since its launch in 2015. Yet, the risk factors for eradication failure and development of post-eradication gastric cancer (GC) using VPZ regimen remain unclear., Methods: This single-center cohort study included 934 consecutive patients who underwent H. pylori eradication using VPZ between February 2015 and June 2017 and were followed up for five years by the end of 2022. We examined several indicators of systemic immune, inflammatory, and nutritional status at the time of eradication to identify those indicators could predict eradication success, risk of post-eradication GC development, and long-term prognosis., Results: The successful eradication rates were 92.6% (intention-to-treat) and 98.7% (per-protocol). Multivariate analysis showed that only a high peripheral blood neutrophil-to-lymphocyte ratio (NLR) was significantly associated with eradication failure. The 5-year GC incidence rate was 1.67%, and all GCs were stage IA. The mean (standard deviation [SD]) time from eradication to diagnosis was 40.5 (6.1) months. Multivariate analysis showed that high NLR and history of GC and hypertension were significantly associated with GC development. Patients with elevated NLR post-eradication had a higher risk of newly developed GC. Twelve patients died during the study period, and a high NLR was associated with a significantly higher mortality rate., Conclusions: NLR has the potential to be a biomarker that predicts the failure of eradication and development of post-eradication GC. High NLR was also associated with poor long-term prognosis after H. pylori eradication.

Background: Solid pseudopapillary neoplasm (SPN) is a low-grade malignant tumor that occurs in 60% of all pediatric pancreas tumors. Radical tumor resection is essential; however, spleen preservation is also crucial to prevent overwhelming post-splenectomy infection. In contrast, spleen preservation is not always possible, because left-sided portal hypertension (LSPH) can cause splenic vein stenosis or occlusion induced by pancreatic tumor. We herein report on a pediatric patient of LSPH due to SPN in the pancreatic tail., Case Presentation: A 12-year-old girl was admitted to our hospital with left upper quadrant abdominal pain. A solid mass was palpated in the left costal region. The patient showed slight anemia (Hb: 11.8 g/dL) and elevation of inflammatory reaction (CRP: 5.98 mg/dL) without positive tumor markers. A radiological examination revealed that a 9 cm-sized mass with hemorrhagic necrosis in the pancreatic tail. Splenic venous flow was not detected and collateral draining into the left gastric vein and left renal veins were developed with splenomegaly. LSPH was involved at the time of diagnosis. The tumor was diagnosed with SPN, hence tumor resection with spleen preservation was performed. Six months after surgery, the patient developed a left quadrant abdominal pain that worsened during exercise. There was no improvement of splenic venous flow and splenomegaly. LSPH remained with splenomegaly, which possibly triggered the patient's abdominal pain. The patient underwent splenectomy 9 months after the tumor resection. After the splenectomy, the patient's abdominal pain disappeared without any recurrence 8-year post-surgery., Conclusions: LSPH has not been a major focus in previous SPN pediatric patients, although most symptomatic LSPH patients required splenectomy. Careful post-operative observation for LSPH is important for pediatric SPN patients., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Consent was obtained from the patient and patient’s mother for publication of this case report and accompanying images. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Rationale: Accurate prognostic awareness (PA) and knowledge of the disease are critical for decision-making regarding treatment options, advance care planning, and end-of-life care. However, they have not been investigated in patients with interstitial lung disease (ILD)., Objectives: To determine the prevalence of patients with ILD who have accurate PA and/or knowledge of acute exacerbation. In addition, to determine whether accurate PA is associated with end-of-life medical interventions and quality of dying and death., Methods: Through a nationwide bereavement survey, we examined the prevalence of accurate PA and knowledge of acute exacerbation (AE) in patients with ILD who died in acute general hospitals between January 2018 and February 2020. Patients' PA and knowledge were assessed from the perspective of the bereaved. We also quantified the quality of dying and death from the perspective of the bereaved using three scales, the Good Death Inventory, the Quality of Dying and Death (QODD) questionnaire, and the single-item QODD overall score, and obtained information on end-of-life interventions from the electronic medical record. We examined the associations of accurate PA with end-of-life interventions and quality of dying and death., Results: A total of 296 patients whose caregivers completed questionnaires were analyzed. One hundred sixty-three patients (55.1%, 95% confidence interval [CI] = 49.2-60.8) who died of ILD had accurate PA and 138 (46.9%, 95% CI = 35.9-47.4) recognized that their disease could have AE. Multivariate regression analysis showed that accurate PA was associated with significantly fewer intensive care unit (ICU) deaths (odds ratio = 0.28, 95% CI = 0.10-0.82, P = 0.02). Patients with accurate PA had better quality of dying and death on all the three scales., Conclusions: Approximately half of the patients who died of ILD did not recognize that their disease could lead to death or AE. The lower number of ICU deaths and better quality of dying and death in patients with accurate PA suggest the potential benefits of obtaining accurate PA in patients with ILD.

The authors have identified an error in Table 5 concerning the dissection speed. It is currently listed as follows: S-O group 14.5±9.5 and Control group 25.1±18.9. However, this is incorrect. The correct values should be reversed: S-O group 25.1±18.9 and Control group 14.5±9.5.References:Yoichi Nakatsu, Makoto Furihata, Anna Fujiyama, Arisa Yuzawa, Mako Ushio, Shintaro Yano, Hiroki Okawa, Kumiko Noda, Shinjiro Nishi, Shingo Ogiwara, Tsuneo Kitamura, Naoto Sakamoto, Taro Osada: A Retrospective Study of 290 Patients with Resectable Benign and Malignant Gastric Neoplasms to Compare Postoperative Outcomes of Endoscopic Resection with and without the Internal Traction Method Using a Spring-and-Loop with Clip (S-O Clip). Med Sci Monit, 2024; 30: e945341. DOI: 10.12659/MSM.945341.

We have previously shown that Golgi stacks and recycling endosomes (REs) exist as Golgi/RE units in sea urchin embryos. In this study, we showed that Golgi/RE units were scattered throughout the cytoplasm at early developmental stages but gathered to form a "Golgi ring" surrounding the centric REs at the blastula stage. This change in the cell-wide arrangement of Golgi/RE units coincided with a dramatic change in microtubule organization from a randomly oriented cortical pattern to radial arrays under the apical plasma membrane. A single gigantic Golgi apparatus surrounding centric RE is clearly associated with the center of the radial microtubule arrays. Furthermore, we found that in some animal species belonging to different clades, Golgi stacks lack lateral connections but are likely centralized by microtubule motors. These results suggest that Golgi centralization depends on the organization of the microtubule array in addition to the lateral linking between Golgi stacks.Key words: Golgi stack, recycling endosome, Golgi-ribbon, microtubule, cilium, sea urchin, ascidian.

Purpose: The incidence of esophagogastric junction (EGJ) adenocarcinoma has increased worldwide. As the EGJ is located at the boundary between the thoracic and abdominal cavities, the optimal surgical approach is a subject of debate and estimation of the esophageal invasion length (EIL) is an important factor in its selection., Methods: Data from our in-house database were extracted for consecutive patients with Siewert type I, II and III EGJ adenocarcinoma (EIL ≤ 4 cm), who underwent transhiatal or transthoracic surgical resection between 2010 and 2016. The clinical records of these patients were reviewed and the accuracy of EIL estimation and its discrepancy with the pathological measurement were analyzed., Results: A total of 82 patients were included in the final analysis. We established that EIL was underestimated in 49 of these patients (59.8%). The mean-distance discrepancy between the preoperative and pathological diagnosis of EIL in the underestimation group was 7.0 mm. Multivariate analysis revealed that submucosal cancer spread was an independent risk factor for underestimation (P < 0.01). The mean length of submucosal cancer spread was longer for undifferentiated histologic type EGJ adenocarcinomas. (P < 0.01)., Conclusions: The EIL was underestimated in approximately 60% of EGJ adenocarcinomas requiring surgical treatment. Thus, careful management is necessary, especially for EGJ adenocarcinoma of the undifferentiated histologic type., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate targeting HER2-positive gastric cancer or gastroesophageal junction cancer (GC/GEJC). Although effective, T-DXd has notable toxicities, including interstitial lung disease (ILD). This study evaluated the efficacy, safety, and prognostic factors associated with T-DXd for GC/GEJC., Methods: A retrospective observational study was conducted at our institution by reviewing medical records of patients treated with T-DXd until September 2023. Eligible patients had unresectable advanced or recurrent GC/GEJC, HER2 status of IHC 3 + or IHC 2 + /ISH-positive, and prior treatment with trastuzumab-containing regimen., Results: Among the 101 patients analyzed, the initial T-DXd dose was 6.4 mg/kg in 77 patients and 5.4 mg/kg in 24 patients. The objective response rate was 54.3%, with a median PFS of 5.4 months and a median OS of 11.4 months. The significant prognostic factors for shorter PFS and OS included ECOG PS ≥ 1, presence of primary lesion, and peritoneal metastasis but not the initial T-DXd dose. ILD occurred in 14.9% of patients. Notably, higher T-DXd dose and smaller tumor burden were associated with a higher incidence of ILD., Conclusions: Several factors were associated with prognosis after T-DXd treatment in patients with GC/GEJC. Tumor burden is a potential risk factor for T-DXd-related ILD. Further studies are needed to optimize dosing based on tumor burden and to improve the therapeutic index., (© 2024. The Author(s).)

We used a mathematical approach to investigate the quantitative spatial profile of cancer cells and stroma in lung squamous cell carcinoma tissues and its clinical relevance. The study enrolled 132 patients with 3-5 cm peripheral lung squamous cell carcinoma, resected at the National Cancer Center Hospital East. We utilized machine learning to segment cancer cells and stroma on cytokeratin AE1/3 immunohistochemistry images. Subsequently, a spatial form of Shannon's entropy was employed to precisely quantify the spatial distribution of cancer cells and stroma. This quantification index was defined as the spatial tumor-stroma distribution index (STSDI). The patients were classified as STSDI-low and -high groups for clinicopathological comparison. The STSDI showed no significant association with baseline clinicopathological features, including sex, age, pathological stage, and lymphovascular invasion. However, the STSDI-low group had significantly shorter recurrence-free survival (5-years RFS: 49.5% vs. 76.2%, p < 0.001) and disease-specific survival (5-years DSS: 53.6% vs. 81.5%, p < 0.001) than the STSDI-high group. In contrast, the application of Shannon's entropy without spatial consideration showed no correlation with patient outcomes. Moreover, low STSDI was an independent unfavorable predictor of tumor recurrence and disease-specific death (RFS; HR = 2.668, p < 0.005; DSS; HR = 3.057, p < 0.005), alongside the pathological stage. Further analysis showed a correlation between low STSDI and destructive growth patterns of cancer cells within tumors, potentially explaining the aggressive nature of STSDI-low tumors. In this study, we presented a novel approach for histological analysis of cancer tissues that revealed the prognostic significance of spatial tumor-stroma distribution in lung squamous cell carcinoma., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background and Aims: The prognostic impact of previous-HBV-infection (pHBV) in non-HBV-related hepatocellular carcinoma (non-HBV-related-HCC) and the prevalence, characteristics and significance of recently developed high-sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps., Methods: We retrospectively screened patients with newly diagnosed non-HBV-related-HCC (standard HBsAg-test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non-HBV-related-HCC., Results: A total of 401 non-HBV-related-HCC patients were included (288 with pHBV/113 without pHBV). In non-HBV-related-HCC, pHBV did not affect overall survival (OS). Among non-HBV-related-HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non-HBV-related-HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non-HBV-related-HCC patients with non-B-non-C aetiology and advanced HCC., Conclusions: In non-HBV-related-HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis., (© 2024 John Wiley & Sons Ltd.)

The SCRUM-Japan MONSTAR-SCREEN consortium is a nationwide molecular profiling project employing artificial intelligence-driven multiomics analyses for patients with advanced malignancies, aiming to develop novel therapeutics and diagnostics and deliver effective drugs to patients. Concurrently, studies assessing molecular residual disease-based precision medicine for resectable solid tumors, including CIRCULATE-Japan, are ongoing. The substantial data generated by these platforms are stored within a state-of-the-art supercomputing infrastructure, VAPOR CONE. Since 2015, our project has registered over 24,000 patients as of December 2023. Among 16,144 patients with advanced solid tumors enrolled in MONSTAR-SCREEN projects, 5.0% have participated in matched clinical trials, demonstrating a 29.2% objective response rate and 14.8-month median survival (95% CI, 13.4-16.3) for patients treated in the matched clinical trials. Notably, patients who received matched therapy demonstrated significantly prolonged overall survival compared with those who did not (hazard ratio 0.77; 95% confidence interval, 0.71-0.83). Significance: Our nationwide molecular profiling initiative played pivotal roles in facilitating the enrollment of patients with advanced solid tumors into matched clinical trials and highlighted the substantial survival benefits of patients treated with matched therapy. We aim to facilitate an industry-academia data-sharing infrastructure ecosystem, fostering new drug discovery paradigms and precision medicine., (©2024 The Authors; Published by the American Association for Cancer Research.)

Aim: It is not uncommon to encounter outpatients in the hepatology department with harmful alcohol habits. When treating such chronic liver disease (CLD) patients, an adequate intervention method for harm reduction of alcohol use, such as brief intervention (BI) or BI and nalmefene, should be considered. This study aimed to elucidate the clinical effectiveness of BI for CLD patients affected by harmful alcohol use., Methods: From June 2021 to 2023, 123 Japanese CLD outpatients (hepatitis B virus : hepatitis C virus : alcoholic liver disease : others = 32:18:42:31) with an Alcohol Use Disorders Identification Test (AUDIT) score of ≥8 at the initial interview and a repeat interview with AUDIT 9 months later were enrolled. Clinical features related to patient behavior following the initial AUDIT interview were retrospectively evaluated, and compared between patients without and with BI treatment., Results: For the non-BI and BI groups, baseline AUDIT score (median 10 [interquartile range (IQR) 9-13] vs. 12 [IQR 10-17], p = 0.016) and relative change in AUDIT score (median 0 [IQR -3 to 2] vs. -3 [IQR -7 to 0], p < 0.01) showed significant differences, whereas there was no significant difference between the groups for AUDIT score at the time of the second interview (p = 0.156). Following BI, significant improvements were observed for items 1, 2, 3, 4, 5, 8, and 10 of AUDIT (each p < 0.05)., Conclusion: Patients with an alcohol use disorder as well as those with alcohol dependency who received BI showed a significant decline in AUDIT score, although the score of the follow-up AUDIT indicated continued alcohol use disorder. In addition to BI, medication with nalmefene should be considered, based on individual factors., (© 2024 Japan Society of Hepatology.)

Tubulointerstitial nephritis (TIN) is characterized by inflammation of the renal interstitium with the infiltration of immune cells, mainly consisting of T cells. Recently, patients with TIN with the predominant infiltration of immunoglobulin M (IgM)-positive plasma cells were reported, coined IgMPC-TIN. Here we report the case of a 70-year-old woman diagnosed with Fanconi syndrome and renal tubular acidosis. Renal biopsy revealed IgMPC-TIN. Her renal dysfunction and clinical findings improved after corticosteroid therapy. However, the patient died of progressive liver failure and spontaneous bacterial peritonitis. In laboratory tests, viral hepatitis was excluded, and autoantibodies associated with liver diseases were negative. Generally, IgMPC-TIN is often complicated by primary biliary cholangitis (PBC), whereas her autopsy revealed the local infiltration of IgM-positive plasma cells, obliterative portal venopathy, and nodular regenerative hyperplasia in liver. This case is the first demonstration that IgMPC-TIN is also seen in liver disease with nodular regenerative hyperplasia, although IgMPC-TIN is more common in anti-M2 antibody-positive disease., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Purpose: We investigated whether peripheral pulse synchronization (PPUS) can be an alternate method for electrocardiographic synchronization (ECGS) in measuring myocardial T1 values in cardiac magnetic resonance imaging (CMRI)., Methods: T1 map imaging was performed on 49 patients undergoing CMRI using the 5s (3s) 3s modified Look-Locker inversion recovery (MOLLI) method for both ECGS and PPUS. The short-axis images of basal, mid, and apical segments were obtained. The T1 map images were analyzed using an image processing system, and T1 values were obtained for each cardiac segment. To assess the degree of agreement between T1 values obtained from ECGS and PPUS, the Bland-Altman analysis and the estimating intraclass correlation coefficient (ICC) were performed for the average T1 value of the entire myocardium and T1 values of each cardiac segment. Also, to evaluate whether PPUS imaging is possible in the diastole phase, we measured the length of systole in the electrocardiogram and the length of transmission (R-R') from R in the electrocardiogram to R (R') in the pulse waveform., Results: From the comparison of T1 values, a good agreement of ICC was confirmed between the ECGS and PPUS (whole myocardium: 0.97, apical: 0.93, mid: 0.98, and basal: 0.97). The results of the Bland-Altman analysis also indicated good agreement. Moreover, it was shown that the heart was imaged in the diastole phase even with the default scan parameters of PPUS., Conclusion: Our results indicated that PPUS can be an alternate method for ECGS.

Introduction: Contrast-enhanced computed tomography (CE-CT) has been gaining attention as an initial investigation in the management of colonic diverticular bleeding (CDB), yet the role of CE-CT other than its diagnostic yield has not been adequately clarified. We aimed to determine whether the use of urgent CE-CT improves identification of stigmata of recent hemorrhage (SRH) in subsequently performed early colonoscopy (≤24 h of arrival) or other clinical outcomes of CDB., Methods: We conducted a randomized, open-label, controlled trial at 23 institutions in Japan. Outpatients with suspected CDB were randomly assigned to undergo either urgent CE-CT followed by early colonoscopy (urgent-CE-CT + early-colonoscopy group) or early colonoscopy alone (early-colonoscopy group). The primary outcome was SRH identification. Secondary outcomes included successful endoscopic hemostasis, early (<30 days) and late (<1 year) rebleeding, length of hospital stay, and transfusion requirements., Results: In total, 240 patients, mostly in a hemodynamically stable condition, were randomized. A contrast extravasation on CE-CT was observed in 20 of 115 patients (17.4%) in the urgent-CE-CT + early-colonoscopy group. SRH was identified in 23 of 115 patients (20.0%) in the urgent-CE-CT + early-colonoscopy group and 21 of 118 patients (17.8%) in the early-colonoscopy group (difference, 2.2; 95% confidence interval [CI], -7.9 to 12.3; p = 0.739). Successful endoscopic hemostasis was achieved in 21 patients in each group (18.3% and 17.8%, respectively) (difference, 0.5; 95% CI, -9.4 to 10.4; p = 1.000). There were also no significant differences between groups in early and late rebleeding, length of hospital stay, and transfusion requirements., Conclusion: The use of urgent CE-CT before early colonoscopy did not improve SRH identification or other clinical outcomes in patients with suspected CDB in a hemodynamically stable condition. The routine use of urgent CE-CT as an initial investigation is not recommended in this population, also considering the low rate of extravasation-positive cases (UMIN registry number, UMIN000026865)., (© 2024 S. Karger AG, Basel.)

Introduction: The most frequently used first-line treatment in patients with advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab. Upon progression after this treatment, the standard of care in many countries is sorafenib, due to the lack of reimbursement for other drugs. Several randomized trials are currently underway to clarify the best second-line therapy in patients with HCC. This real-world study aimed to compare outcomes reached by lenvatinib and sorafenib second-line therapy in this setting., Methods: The overall cohort included 891 patients with HCC from 5 countries treated with atezolizumab plus bevacizumab in first-line setting between October 2018 and April 2022. At the data cut-off (May 2022), 41.5% of patients were continuing a first-line treatment, 5.5% were lost at follow-up, and 53.0% of patients had progressive disease after first-line therapy. 51.5% of patients with progressive disease received a second-line treatment, while 48.5% did not receive any subsequent therapy. Between patients receiving second-line treatment, 11.1% of patients underwent transarterial chemoembolization, 21.0% received sorafenib, 35.4% underwent lenvatinib, and 32.5% were treated with other drugs., Results: Lenvatinib second-line subgroup achieved a median overall survival (mOS) of 18.9 months, significative longer (p = 0.01; hazard ratio [HR]: 2.24) compared to sorafenib subgroup that reached a mOS of 14.3 months. The multivariate analysis highlighted albumin-bilirubin 1 grade (p < 0.01; HR: 5.23) and lenvatinib second-line therapy (p = 0.01; HR: 2.18) as positive prognostic factors for OS. The forest plot highlighted a positive trend in terms of OS in favor of patients treated with lenvatinib second-line regardless of baseline characteristics before first-line therapy., Conclusion: These results suggest that, in patients with HCC progressed to first-line atezolizumab plus bevacizumab, lenvatinib second-line therapy is associated to an improved survival compared to sorafenib., (© 2024 S. Karger AG, Basel.)

Background: Azithromycin has favorable effects on critical respiratory diseases owing to its antimicrobial and anti-inflammatory properties. During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, azithromycin was frequently administered before specific treatments were developed. However, the efficacy of this treatment has not been verified. We retrospectively investigated the effects of its intravenous (IV) administration in patients with severe/critical COVID-19 using the National Administrative Database of Japan during the first wave (February-April 2020)., Methods: Patients were categorized based on whether they received IV azithromycin within three days of hospitalization. An overlap weighting method with estimated propensity scores was used to reduce bias., Results: Among the 830 patients with severe/critical COVID-19, 148 (17.8 %) received azithromycin, and 682 (82.2 %) did not. After adjustment, the use of azithromycin was associated with a shorter duration of intensive care unit (ICU) management (-3.48 days, 95 % confidence interval [CI]: 4.59 to -2.38). However, other endpoints, including mortality rate, duration of mechanical ventilation, and duration of hospital stay, did not suggest any associations. Furthermore, of the 115 ICU patients, 27 (23.5 %) were treated with IV azithromycin and 88 (76.5 %) were not. After adjustment, azithromycin was associated with favorable outcomes, including reduced in-hospital mortality (odds ratio [OR], 0.45, 95 % CI: 0.22 to 0.92), 30-day mortality (OR, 0.46, 95 % CI: 0.22 to 0.94), and a shorter duration of ICU management (-2.94 days, 95 % CI: 5.15 to -0.73)., Conclusion: We verified that IV azithromycin was associated with favorable impact in patients with COVID-19 requiring ICU management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hiroshi Mukae reports a relationship with Pfizer Japan Inc that includes: speaking and lecture fees. Koichi Izumikawa reports a relationship with Pfizer Japan Inc that includes: speaking and lecture fees. Takahiro Takazono reports a relationship with Pfizer Japan Inc that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Exophiala dermatitidis is an emerging black fungus that causes pulmonary infections that may be underestimated by conventional culture methods. We encountered one case that initially appeared to be yeast and was misidentified as Rhodotorula spp. using a commercial identification kit. Thus, genetic identification and clinical background investigations were conducted on 46 strains of Rhodotorula spp. The sequences of the internal transcribed spacer and large-subunit RNA genes (D1/D2 regions) of 43 isolates, excluding two environmental isolates and one difficult-to-culture isolate, were determined and genetically identified. Notably, 22 isolates were identified as E. dermatitidis and misidentified as Rhodotorula spp. using the conventional method. Based on the exclusion criteria, the clinical information of 11 patients was retrospectively reviewed. Five cases (definite) had definite exacerbation of pulmonary infections due to E. dermatitidis, and six cases (possible) had undeniable infections. Of the 11 cases of pulmonary infection suggested to be caused by E. dermatitidis, comorbidities included two cases of chronic pulmonary aspergillosis (CPA), three cases of pulmonary non-tuberculous mycobacterial (NTM) infection and one case of pulmonary nocardiosis, suggesting a trend towards simultaneous detection of chronic pulmonary infections. Steroid and immunosuppressive drug use was observed in five cases, and β-D-glucan elevation was observed in three of five definite cases of pulmonary infections due to E. dermatitidis. The possibility of E. dermatitidis infection should be considered when Rhodotorula spp. are isolated from cultures of airway-derived specimens, and, in addition to CPA and NTM, identification of E. dermatitidis may be important in chronic pulmonary infections., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

The oral mucosa is the first line of defense against pathogenic bacteria and plays a vital role in maintaining tolerance to food antigens and commensal bacteria. We used CD11c reporter mice to visualize dendritic cells (DCs), a key immune cell population, in the oral cavity. We identified differences in DC density in each oral tissue region. Sublingual immune cell clusters (SLICs) extended from the lamina propria to the epithelium, where DCs and T cells resided in close contact with each other and innate lymphoid cells. Targeted in situ photolabeling revealed that the SLICs comprised mostly CD11c+CD11b+ DCs and were enriched for cDC1s and Langerhans cells. Although the frequency of T cell subsets was similar within and outside the SLICs, tissue-resident memory T cells were significantly enriched within the clusters and cluster size increased in response to inflammation. Collectively, we found that SLICs form a unique microenvironment that facilitates T cell-DC interactions in the steady state and during inflammation. Since the oral mucosa is an important target for needle-free vaccination and sublingual immunotherapy to induce tolerogenic responses, the insight into the localized immunoregulation provided in this study may accelerate the development of these approaches.

Histopathologic examinations of primary central nervous system lymphoma (PCNSL) reveal concentric accumulation of lymphocytes in the perivascular area with fibrosis. However, the nature of this fibrosis in "stiff" PCNSL remains unclear. We have encountered some PCNSLs with hard masses as surgical findings. This study investigated the dense fibrous status and tumor microenvironment of PCNSLs with or without stiffness. We evaluated by silver-impregnation nine PCNSLs with stiffness and 26 PCNSLs without stiffness. Six of the nine stiff PCNSLs showed pathological features of prominent fibrosis characterized by aggregation of reticulin fibers, and collagen accumulations. Alpha-smooth muscle actin (αSMA)-positive spindle cells as a cancer-associated fibroblast, the populations of T lymphocytes, and macrophages were compared between fibrous and control PCNSLs. Fibrous PCNSLs included abundant αSMA-positive cells in both intra- and extra-tumor environments (5/6, 87% and 3/6, 50%, respectively). Conversely, only one out of the seven control PCNSL contained αSMA-positive cells in the intra-tumoral area. Furthermore, the presence of extra-tumoral αSMA-positive cells was associated with infiltration of T lymphocytes and macrophages. In conclusion, recognizing the presence of dense fibrosis in PCNSL can provide insights into the tumor microenvironment. These results may help stratify patients with PCNSL and improve immunotherapies for these patients., (© 2024. The Author(s).)

Purpose: The causes of epidural catheter migration beneath the skin have not been previously investigated. We hypothesized that greater subcutaneous fat thickness might be associated with increased catheter migration beneath the skin., Methods: We conducted a retrospective cross-sectional study of patients who had undergone combined general and epidural anesthesia, selecting individuals who received thoracic and abdominal CT scans within the first 5 postoperative days. Needle depth was defined as the distance from the needle tip to the skin surface when the anesthesiologist determined that the needle tip had reached the epidural space. We measured the length of the epidural catheter from the skin surface to the epidural space (catheter length), and subcutaneous fat thickness (fat thickness) using CT imaging. Migration distance was calculated by subtracting needle depth from catheter length., Results: We analyzed 127 patients (72 males), all undergoing epidural catheter insertion in the left lateral decubitus position via a paramedian approach. The median age of the patients was 71 years. Epidural catheters were postoperatively found to substantially curve beneath the skin. Regression analysis revealed no significant influence of fat thickness on catheter length (regression coefficient 0.10, 95% confidence interval [CI]: - 0.17, 0.38). However, it indicated a positive correlation between fat thickness and needle depth (regression coefficient 0.50, 95% CI: 0.30, 0.70), and a negative correlation between fat thickness and migration distance (regression coefficient - 0.40, 95% CI: - 0.65, - 0.14)., Conclusion: We found a negative correlation between epidural catheter migration beneath the skin and subcutaneous fat thickness. Anesthesiologists should be aware of the possibility of substantial subcutaneous curving of the catheter, especially in patients with scant subcutaneous fat., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

We report a case of an 87 year-old woman who was admitted with jaundice, but had no pain or fever. Contrast-enhanced computed tomography revealed a tumor in the head of the pancreas, which caused distal malignant biliary obstruction. Initial transpupillary drainage by endoscopic retrograde cholangiopancreatography (ERCP) was difficult due to severe biliary stricture caused by the tumor, but cannulation of the pancreatic duct was successful. Pancreatic ductal adenocarcinoma was revealed through cytologic examination of pancreatic juice and the patient underwent percutaneous transhepatic biliary drainage (PTBD). 16 days after the jaundice was resolved, an uncovered Zilver® metallic stent was successfully deployed using a guidewire from the PTBD route, and the patient was discharged with palliative care due to advanced age. However, 54 days after discharge, the patient presented with black vomiting and recurrent jaundice. ERCP revealed an obstructed stent with black debris, and further evaluation revealed a ruptured pseudoaneurysm that branched off the gastroduodenal artery within the metallic biliary stent. Angiography revealed that embolization was successful. The patient recovered and was discharged without further episodes., (© 2024. Japanese Society of Gastroenterology.)

Background: The fecal immunochemical test (FIT) is used for colorectal cancer (CRC) screening. Patients on antithrombotic drugs (ATs) are often screened for CRC, but the effect of ATs on FIT results is controversial., Methods: We divided individuals with FIT-positive results into two groups, patients treated with and without ATs, and retrospectively compared invasive CRC rates, advanced neoplasia detection rates (ANDRs), adenoma detection rates (ADRs), and polyp detection rates (PDRs) between the two groups. We evaluated the factors influencing the FIT positive predictive value (PPV) using propensity matching, adjusting for age, sex, and bowel preparation., Results: We enrolled 2327 individuals (54.9% male; mean age, 66.7  ±  12.7 years). We grouped 463 individuals into the AT user group and 1864 into the nonuser group. Patients in the AT user group were significantly older and more likely to be male. After propensity score matching for age, sex, and Boston bowel preparation scale, the ADR and PDR in the AT user group were significantly lower than those in the nonuser group. Univariate logistic analysis revealed that multiple AT use (odds ratio [OR]: .39, p < 0.001) had the lowest OR for FIT PPV, followed by age- and sex-adjusted factors for the ADR and any AT use (OR: .67, p = 0.0007). No significant factors related to AT use were observed among age-adjusted predictive factors for invasive CRC, but warfarin use was a borderline significant positive predictive factor (OR: 2.23, p = 0.059)., Conclusion: AT use may not affect the PPV for detecting invasive CRC in patients with positive FIT results, but warfarin may have an impact., (© 2023 John Wiley & Sons Australia, Ltd.)

The isotopic compositions of samples returned from Cb-type asteroid Ryugu and Ivuna-type (CI) chondrites are distinct from other carbonaceous chondrites, which has led to the suggestion that Ryugu/CI chondrites formed in a different region of the accretion disk, possibly around the orbits of Uranus and Neptune. We show that, like for Fe, Ryugu and CI chondrites also have indistinguishable Ni isotope anomalies, which differ from those of other carbonaceous chondrites. We propose that this unique Fe and Ni isotopic composition reflects different accretion efficiencies of small FeNi metal grains among the carbonaceous chondrite parent bodies. The CI chondrites incorporated these grains more efficiently, possibly because they formed at the end of the disk's lifetime, when planetesimal formation was also triggered by photoevaporation of the disk. Isotopic variations among carbonaceous chondrites may thus reflect fractionation of distinct dust components from a common reservoir, implying CI chondrites/Ryugu may have formed in the same region of the accretion disk as other carbonaceous chondrites.

Objectives: In the present study, we aimed to clarify the mechanisms by which periodontal pathogens, particularly Prevotella intermedia , induce severe neutrophilic inflammation. In addition, we aimed to test the efficacy of macrolides, which has not been resolved in the neutrophilic inflammation induced by P. intermedia . Methods: NCl-H292 human airway epithelial cells were pre-incubated with clarithromycin for 2 h before incubation with P. intermedia supernatants. Then, C-X-C motif chemokine ligand 8 ( CXCL8 ) transcription and interleukin (IL)-8 production were measured. To elucidate the signaling pathway, mitogen-activated protein kinase inhibitors were added to the cell culture, and the cells were subjected to Western blotting. Results: P. intermedia supernatants promoted CXCL8 transcription and IL-8 production, and the reactions were significantly suppressed by clarithromycin pretreatment. Only trametinib, the selective mitogen-activated extracellular signal-regulated kinase inhibitor, downregulated CXCL8 transcription and IL-8 production. Furthermore, Western blotting revealed that stimulation with P. intermedia supernatants specifically induces extracellular signal-regulated kinases (ERK) 1/2 phosphorylation, which is suppressed by clarithromycin pretreatment. Notably, the interference analysis revealed that ERK3 might be dispensable for IL-8 production under the stimulation of P. intermedia supernatants. Conclusions: Our results provide new insight into the mechanism underlying P. intermedia -induced production of IL-8 from human airway epithelial cells. Furthermore, macrolides might have therapeutic potential in regulating periodontal pathogen-induced neutrophilic inflammation in the lungs.

Background and Aim: Endoscopic resection (ER) is widely performed to treat early colorectal cancer. However, additional surgery for pathological T1 colorectal cancer (pT1CRC) after ER is controversial because of the imprecise prediction of lymph node metastasis (LNM). Recently, several patients of pT1CRC with lymphoid follicular replacement (LFR) without LNM have been reported. This study aimed to investigate the clinicopathological features and risk of LNM in patients with pT1CRC with LFR., Methods: We retrospectively analyzed patients who underwent ER or surgical resection and were diagnosed with pT1CRC between January 2010 and December 2020. We defined pT1CRC with LFR as the replacement of a part of the lymphoid follicular component within the submucosal area by adenocarcinoma, with no invasion into other submucosal areas., Results: Among the 600 eligible patients, the incidence rate of pT1CRC with LFR was 6.7% (40/600). Patients with pT1CRC with LFR represented 14.3% (37/258) of the endoscopically treated patients and 0.9% (3/342) of the surgically treated patients. For patients with pT1CRC with LFR, 80.0% (32/40) had flat and depressed lesions, and 35.0% (14/40) had submucosal invasion depth ≥1000 μm. Patients with pT1CRC with LFR had negative lymphovascular invasion, differentiated type, and budding grade 1. In the median follow-up of 61 months, patients with pT1CRC with LFR had no LNM., Conclusions: The presence of LFR in pT1CRC may be associated with a low risk of LNM. In patients with pT1CRC with LFR, follow-up without additional surgery is possible even if the submucosal invasion depth is ≥1000 μm., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: It is still unclear whether body mass index (BMI) affects bleeding and cardiovascular events in patients requiring oral anticoagulants (OAC) for atrial fibrillation (AF) and antiplatelet agents after percutaneous coronary intervention (PCI) for coronary artery disease (CAD). The aim of this study was to evaluate the relationship between BMI and clinical events in patients who underwent PCI under OAC therapy for AF., Method: This was a multicenter, observational cohort study conducted at 15 institutions in Japan. AF patients who underwent PCI with drug-eluting stents for CAD were retrospectively and prospectively included. Patients were divided into the Group 1 (BMI <21.3 kg/m2) and the Group 2 (BMI ≥21.3 kg/m2) according to the first-quartile value of BMI. The primary endpoint was net adverse clinical events (NACE), a composite of major adverse cardiovascular events (MACE) and major bleeding events within one year after index PCI procedure., Results: In the 720 patients, 180 patients (25.0%) had BMI value <21.3 kg/m2. While the rates of NACE and MACE were significantly higher in the Group 1 than the counterpart (21.1% vs. 11.9%, p = 0.003 and 17.2% vs. 8.9%, p = 0.004), that of major bleeding did not differ significantly between the 2 groups (5.6% vs. 4.3%, p = 0.54). The cumulative rate of NACE and MACE was significantly higher in the Group 1 than the Group 2 (both log-rank p = 0.002), although that of major bleeding events was equivalent between the 2 groups (log-rank p = 0.41). In multivariable Cox regression analyses, while BMI value <21.3 kg/m2 was not associated with major bleeding events, that cut-off value was an independent predictor for increased NACE and MACE., Conclusions: Among the patients undergoing PCI for CAD and requiring OAC for AF, BMI value was a useful indicator to predict major adverse clinical events., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yamazaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The complement system plays an important role in biological defense as an effector to eliminate microorganisms that invade an organism and it is composed of more than 50 proteins, most of which are produced in the liver. Of these proteins, the mRNA expression of C3 and Cfb is known to be positively regulated by the nuclear receptor HNF4α. To investigate whether HNF4α regulates the complement system, we analyzed the hepatic expression of genes involved in the complement activation pathway and membrane attack complex (MAC) formation within the complement system using liver-specific Hnf4a-null mice (Hnf4a ΔHep mice) and tamoxifen-induced liver-specific Hnf4a-null mice (Hnf4a f/f;AlbERT2cre mice). We found that hepatic expression of many complement genes including C8a, C8b, C8g, and C9 that are involved in formation of the MAC was markedly decreased in Hnf4a ΔHep mice and Hnf4a f/f;AlbERT2cre mice. Furthermore, expression of C8A, C8B, and C8G was also decreased in human hepatoma cell lines in which the expression of HNF4α was suppressed, and expression of C8G and C9 was induced in a human immortalized hepatocyte cell line with forced expression of HNF4α. Transactivation of C8g and C9 was dependent on HNF4α expression of HNF4α binding sites, indicating that C8g and C9 are novel target genes of HNF4α. The results suggest that hepatic HNF4α plays an important role in regulation of the complement system, mainly MAC formation., (© 2024. The Society for In Vitro Biology.)

Gremlin 1 (GREM1) is an antagonist of bone morphogenetic protein (BMP). GREM1 is expressed in the stromal cells of various carcinomas and promotes tumor progression by suppressing BMP signaling. We designed this study to establish an evaluation strategy for GREM1 expression, focusing on the tumor stroma, and to examine its clinicopathological significance in gastric cancer (GC) progression. We employed RNA in situ hybridization (ISH) to evaluate the prognostic value of GREM1 expression in a cohort of 104 surgically resected GC cases and assessed ISH scores according to previous reports. GREM1 expression was observed in tumor stromal cells, including fibroblasts. We defined GREM1-positive cells as those expressing ISH score ≥ 3 and quantified the number of GREM1-positive cells using image analysis software. We examined the relationship between the number of GREM1-positive cells in the tumor stroma and clinicopathological features. The number of GREM1-positive cells per tumor stroma ranged from 0 to 714.7 cells/mm 2 (median, 1.65 cells/mm 2 ). We divided the 104 GC cases into GREM1-High and GREM1-Low expression groups based on the abovementioned median value. GREM1-High expression group was significantly associated with a more advanced pT grade, pN grade, lymphatic invasion, and venous invasion. Kaplan-Meier analysis showed significantly poorer survival in the GREM1-High expression group than in the GREM1-Low expression group. These results indicated that GREM1 expression in GC is localized in tumor stromal cells, and that high GREM1 expression in the tumor stroma could be a poor prognostic factor., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Overall assessment of KEYNOTE-164 study, KEYNOTE-158 study and CheckMate 142 study demonstrated the clinical benefits of immune checkpoint inhibitors(ICIs)among patients with mismatch repair deficient(dMMR)/high microsatellite instability(MSI-H)cancer. As a result, ICIs have been approved for treatment of MSI-H solid tumor regardless of the tumor type. However, the frequency of real-world diagnosed dMMR gastrointestinal cancer were rarely reported. Therefore, the results of immunohistochemical staining for DNA mismatch repair proteins was investigated. 175 samples of gastrointestinal cancers were examined between November 2019 and June 2023. Clinical and pathological characteristics were obtained from clinical and histopathological records. In real world populations with high proportion of elderly people, the frequency of diagnosed dMMR gastrointestinal cancer may be high compared with previous reports. Furthermore, based on the deficient pattern of mismatch repair protein and age, most cases classified as dMMR may be sporadic. Right side tumors and female may increase the likelihood of dMMR colorectal cancer. The current results justified immunohistochemical staining for DNA mismatch repair proteins, strongly involved in the appropriate patient selection for ICIs therapy, should be conducted for elderly patients newly diagnosed as gastrointestinal cancer. We believe that further clinical cancer immunology research, and then challenging insight targeting dMMR gastrointestinal cancer will result in future development of novel immunotherapy combination strategies well tolerated even in elderly patients.

Background: While guidelines recommend immune checkpoint inhibitor (ICI) rechallenge as second-line therapy for unresectable hepatocellular carcinoma (HCC), data supporting this remain limited, particularly regarding a standard regimen for first- and second-line treatments. Tremelimumab/durvalumab was recently approved but data on ICI rechallenge are lacking., Objectives: The purpose of this study was to evaluate the early efficacy and safety of tremelimumab/durvalumab for HCC as an ICI rechallenge following initial ICI therapy with atezolizumab/bevacizumab., Patients and Methods: This multicenter retrospective study included patients with HCC who underwent treatment with tremelimumab/durvalumab, with relevant available clinical information. We evaluated the safety and efficacy of tremelimumab/durvalumab as ICI rechallenge following initial treatment with atezolizumab/bevacizumab. We analyzed the outcomes in patients who underwent tremelimumab/durvalumab as an ICI rechallenge and those who received tremelimumab/durvalumab as their initial ICI therapy RESULT: A total of 45 patients treated with tremelimumab/durvalumab were included, with 55.6% (25/45) undergoing ICI rechallenge. The objective-response and disease-control rates in patients who underwent ICI rechallenge were 14.3% (3/21) and 47.6% (10/21), respectively, similar to those in patients initially treated with tremelimumab/durvalumab. All patients (n = 3) who experienced the best response to progressive disease (PD) with initial atezolizumab/bevacizumab experienced PD during ICI rechallenge. The incidence rates of adverse events were similar between patient groups treated with tremelimumab/durvalumab as ICI rechallenge and initial ICI. Among patients experiencing immune-related adverse events (irAEs) with atezolizumab/bevacizumab, 75% (3/4) encountered similar irAEs during ICI rechallenge., Conclusion: Early safety and efficacy profiles of durvalumab/tremelimumab as ICI rechallenge are satisfactory., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Researchers have attempted to identify the factors involved in lymph node recurrence in cT1-2N0 tongue squamous cell carcinoma (SCC). However, studies combining histopathological and clinicopathological information in prediction models are limited. We aimed to develop a highly accurate lymph node recurrence prediction model for clinical stage T1-2, N0 (cT1-2N0) tongue SCC by integrating histopathological artificial intelligence (AI) with clinicopathological information. A dataset from 148 patients with cT1-2N0 tongue SCC was divided into training and test sets. The prediction models were constructed using AI-extracted information from whole slide images (WSIs), human-assessed clinicopathological information, and both combined. Weakly supervised learning and machine learning algorithms were used for WSIs and clinicopathological information, respectively. The combination model utilised both algorithms. Highly predictive patches from the model were analysed for histopathological features. In the test set, the areas under the receiver operating characteristic (ROC) curve for the model using WSI, clinicopathological information, and both combined were 0.826, 0.835, and 0.991, respectively. The highest area under the ROC curve was achieved with the model combining WSI and clinicopathological factors. Histopathological feature analysis showed that highly predicted patches extracted from recurrence cases exhibited significantly more tumour cells, inflammatory cells, and muscle content compared with non-recurrence cases. Moreover, patches with mixed inflammatory cells, tumour cells, and muscle were significantly more prevalent in recurrence versus non-recurrence cases. The model integrating AI-extracted histopathological and human-assessed clinicopathological information demonstrated high accuracy in predicting lymph node recurrence in patients with cT1-2N0 tongue SCC., (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Objectives: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD., Methods: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured., Results: CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044)., Discussion: The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.

Purpose: The purpose of the study was to evaluate the efficacy and safety of pre-emptive transcatheter arterial embolization (P-TAE) of aortic side branches to prevent type II endoleak in patients with abdominal aortic aneurysm after endovascular abdominal aneurysm repair (EVAR)., Materials and Methods: This multicenter, prospective, single-arm trial enrolled 100 patients with abdominal aortic aneurysm from nine hospitals between 2018 and 2021. There were 85 men and 15 women, with a mean age of 79.6 ± 6.0 (standard deviation) years (range: 65-97 years). P-TAE was attempted for patent aortic side branches, including the inferior mesenteric artery, lumbar arteries, and other branches. The primary endpoint was late type II endoleak incidence at 6 months post-repair. Secondary endpoints included changes in aneurysmal sac diameter at 6- and 12 months, complications, re-intervention, and aneurysm-related mortality. Aneurysm sac changes at 6- and 12 months was compared between the late and no-late type II endoleak groups., Results: Coil embolization was successful in 80.9% (321/397) of patent aortic side branches, including 86.3% of the inferior mesenteric arteries, 80.3% of lumbar arteries, and 55.6% of other branches without severe adverse events. Late type II endoleak incidence at 6 months was 8.9% (8/90; 95% confidence interval: 3.9-16.8%). Aneurysm sac shrinkage > 5 mm was observed in 41.1% (37/90) and 55.3% (47/85) of the patients at 6- and 12-months post-EVAR, respectively. Patients with late type II endoleak had less aneurysm sac shrinkage than those without type II endoleak at 12 months (-0.2 mm vs. -6.0 mm; P = 0.040). No patients required re-intervention for type II endoleak, and no aneurysm-related mortalities occurred., Conclusion: P-TAE is safe and effective in preventing type II endoleak, leading to early sac shrinkage at 12 months following EVAR., Competing Interests: Declaration of competing interests The authors declare no actual or potential conflict of interest related to this study., (Copyright © 2024 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

International travel is a risk factor for acquiring sexually transmitted infections (STIs) owing to factors such as increased sexual opportunities, a sense of freedom, and the allure of the sex industry. We investigated the incidence of travel-associated STIs in Japan using data from the Japan Registry for Infectious Diseases from Abroad (J-RIDA) reported by 17 participating medical institutions between October 2017 and December 2022. Data were collected on the patients' age, sex, nationality, chief complaint, whether they had visited a travel clinic before travel, travel history, and final diagnosis. Of 4545 cases of travel-associated illness reported, 52 (1.1%) were STIs. Most patients with STIs were male (81%) with a median age of 31 years. HIV (17%), genital herpes (13%), syphilis (13%), and gonorrhea (12%) were the most frequently reported STIs. Only one patient had visited a travel clinic before travel. Promoting awareness and vaccination is crucial for preventing travel-associated STIs., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

BACKGROUND The spring-and-loop with clip (S-O clip) consists of a spring and a nylon loop located on one side of the claws of the clip, and is used in gastric endoscopic submucosal dissection (ESD) to allow countertraction. This retrospective study included 290 patients with early gastric neoplasms (eGNs) and aimed to compare postoperative outcomes of ESD with and without the use of the S-O clip. MATERIAL AND METHODS We retrospectively reviewed the data of 347 patients with eGN who underwent ESD, with or without an S-O clip, at our institution between April 1, 2017 and March 31, 2023. Overall, 290 patients were analyzed after excluding ineligible participants. The control group (n=149; adenoma: 1, carcinoma: 148) underwent ESD without an S-O clip between April 2017 and March 2020, while the S-O group (n=141; adenoma: 4, carcinoma: 137) used the clip between April 2020 and March 2023. Primary outcomes included procedure time, en bloc resection rate, and complete resection rate. Subgroup analysis for examined procedure time concerning endoscopist expertise, submucosal fibrosis, and neoplasm locations. RESULTS The S-O group had a shorter procedure time (44.4±23.9 vs 61.1±40.9 min, P<0.001) and a higher complete resection rate (97.9% vs 92.6%, P<0.05) than the control group. Subgroup analysis revealed that the S-O clip significantly reduced procedure time for trainees compared to the control group (40.8±18.3 vs 61.1±35.6 min, P<0.05). CONCLUSIONS The scheduled use of S-O clips in gastric ESD is effective in improving procedural time and complete resection rates, benefiting endoscopists across all experience levels.

Crystallization in Earth's deep magma ocean could have caused trace element fractionation in the lower mantle that might be inherited to the isotopic compositions of the present-day mantle. However, the trace element partitioning has been experimentally investigated only up to the uppermost lower-mantle pressures. Here, we determined the bridgmanite/melt partition coefficients D of La, Nd, Sm, Lu, and Hf from 24 to 115 gigapascals, covering the wide pressure range of the lower mantle. Results demonstrate substantial reductions in D Lu and D Hf from >1 to ≪1 with increasing pressure to 91 gigapascals. We also found D Lu / D Hf > 1 and D Sm / D Nd < 1 under deep lower-mantle conditions, evolving melts toward low Lu/Hf and high Sm/Nd ratios by crystallizing bridgmanite. If residual melts form a dense hidden reservoir in the lowermost mantle, the complementary accessible mantle has the Hf and Nd isotopic compositions matching the observed terrestrial mantle array that deviates from the bulk silicate Earth reference.

Introduction: This case report presents the successful detection of an EGFR exon 19 deletion using virtual bronchoscopic navigation (VBN) and endobronchial ultrasound with guide sheath (EBUS-GS) brushing, integrated with highly sensitive next-generation sequencing (NGS), even in challenging biopsy scenarios. The growing prevalence of driver gene alterations in non-small cell lung cancer necessitates effective bronchoscopic technology and reliable multiplex gene NGS panels. However, data regarding the optimal bronchoscopic techniques when using highly sensitive NGS panels are limited. Herein, we report a case utilizing VBN-guided EBUS-GS brushing as an exploratory approach to address this challenge., Case Presentation: A 71-year-old man was evaluated for a band-like lesion near the left pleura during spinal cord infarction. Transbronchial specimens were obtained from lesions invisible on conventional chest radiography and X-ray fluoroscopy using VBN and EBUS-GS brushing. Cytological brushing specimens revealed lung adenocarcinoma, and highly sensitive NGS identified an EGFR exon 19 deletion. He was diagnosed with stage IB disease and underwent radical radiotherapy owing to his fragile condition. If recurrence occurs, the patient will be treated with an EGFR inhibitor., Conclusion: VBN-guided EBUS-GS brushing, a minimally invasive approach, combined with highly sensitive NGS has the potential to provide accurate molecular diagnoses to more patients with lung cancer, thereby offering opportunities for personalized treatment. Our findings warrant further investigation to determine optimal bronchoscopic technologies for obtaining tumor specimens., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background and Objective: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model., Methods: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected., Results: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2., Conclusion: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered., (© 2024 Asian Pacific Society of Respirology.)

Tumor budding in the cancer stroma has been reported to be a prognostic factor in non-small cell lung cancer. Micronest in cancer stroma (MICS) is often observed as a formation that is larger and more conspicuous than budding, but its clinicopathologic significance is unclear. In this study, we aimed to examine the clinicopathological significance of MICS in lung squamous cell carcinoma (LSqCC). A total of 198 consecutive patients with pathologically diagnosed LSqCC (anyT N0-1M0) were enrolled in this study. MICS were defined as those that met the following criteria: (1) consisting of 5-200 tumor cells or less than 200 μm in diameter and (2) more than 200 μm away from the adjacent main lesion. The prognostic impact of the presence or absence of MICS and the characteristics of MICS-forming cancer cells were evaluated by immunohistochemistry (IHC). MICS was observed in 57 patients (28.8%), and overall survival (OS) and recurrence-free survival (RFS) were significantly shorter in the MICS-positive group (OS: 44.4% vs. 84.4%, p < 0.001; RFS: 30.0% vs. 82.6%, p < 0.001). Univariate and multivariate analyses revealed that the presence of MICS was an independent poor prognostic factor for OS (hazard ratio [HR] 3.54, p < 0.001) and RFS (HR 4.99, p < 0.001). Immunohistochemistry showed that the expression levels of the cell-cell adhesion molecule E-cadherin and hypoxia-induced protein GLUT-1 were significantly decreased in cancer cells forming MICS lesions compared to the tumor component excluding MICS within the same tumor (non-MICS lesions). Our data show that MICS is a distinct morphological feature with important biological and prognostic significance., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to the present study., (Copyright © 2024 Elsevier Inc. All rights reserved.)