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Abstract Background A percutaneous kidney biopsy (PKB) allows nephrologists to make informed decisions for treating various kidney diseases; however, the risk of bleeding complications should be considered, given the vascularity of the kidney. Many studies have reported risk factors for bleeding events after a PKB. However, while urinary N-acetyl-β-D-glucosaminidase (NAG) is a useful biomarker of kidney disease severity, little is known about whether or not urinary NAG is related to the bleeding risk. Methods Medical records of patients who underwent a PKB at the National Defense Medical College Hospital between October 2018 and October 2023 were retrospectively studied. Hemoglobin (Hb) loss ≥ 1 g/dL was defined as a bleeding event. Results Of the 213 patients, 110 (51.6%) were men, and the median age was 56 years old (interquartile range 40–71). The most frequent diagnosis on a PKB was IgA nephropathy (N = 72; 34.0%). Fifty-four patients (25.3%) experienced Hb loss ≥ 1 g/dL after a PKB, and urinary NAG/Cr levels before the biopsy were able to predict a bleeding event, with an area under the receiver operating characteristic curve of 0.65 (p = 0.005). Using the optimal cutoff value of 35 U/gCr, urinary NAG/Cr was found to be an independent risk factor by multiple logistic regression analysis (odds ratio 3.21, 95% confidence interval 1.42–7.27, p = 0.005). Even after adjusting for previously-reported risk factors, the elevated urinary NAG/Cr ratio remained a statistically significant variable. Compared with the pathological findings, only the severity of multilayered elastic laminae of the small muscular artery was associated with both urinary NAG/Cr levels (p = 0.008) and bleeding events (p = 0.03). Conclusion Urinary NAG successfully predicted not only the severity of kidney disorders but also bleeding events after a PKB. Arteriosclerosis in the kidneys may be the mechanism underlying these increased bleeding events.

Abstract The relationship between blood group and rebleeding in acute lower gastrointestinal bleeding (ALGIB) remains unclear. This study aimed to investigate the association between blood group O and clinical outcomes in patients with ALGIB. The study included 2336 patients with ALGIB whose bleeding source was identified during initial endoscopy (from the CODE BLUE-J Study). The assessed outcomes encompassed rebleeding and other clinical parameters. The rebleeding rates within 30 days in patients with blood group O and those without blood group O were 17.9% and 14.9%, respectively. Similarly, the rates within 1 year were 21.9% for patients with blood group O and 18.2% for those without blood group O. In a multivariate analysis using age, sex, vital signs at presentation, blood test findings, comorbidities, antithrombotic medication, active bleeding, and type of endoscopic treatment as covariates, patients with blood group O exhibited significantly higher risks for rebleeding within 30 days (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.04–1.65; P = 0.024) and 1 year (OR 1.29; 95% CI 1.04–1.61; P = 0.020) compared to those without blood group O. However, the thrombosis and mortality rates did not differ significantly between blood group O and non-O patients. In patients with ALGIB, blood group O has been identified as an independent risk factor for both short- and long-term rebleeding.

Abstract This study investigates the impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest (OHCA) outcomes in Japan, aiming to address a critical research gap. Analyzing data from the All-Japan Utstein registry covering pediatric OHCA cases from 2018 to 2021, the study observed no significant changes in one-month survival, neurological outcomes, or overall performance when comparing the pre-pandemic (2018–2019) and pandemic (2020–2021) periods among 6765 cases. However, a notable reduction in pre-hospital return of spontaneous circulation (ROSC) during the pandemic (15.1–13.1%, p = .020) was identified. Bystander-initiated chest compressions and rescue breaths declined (71.1–65.8%, 22.3–13.0%, respectively; both p

Abstract Background Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. Methods We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them. Results A total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P

Objective: Cerebral vasospasm is an unelucidated complication of subarachnoid hemorrhage. Various treatments exist against cerebral vasospasms however, consensus on the optimal treatment is lacking. We use clazosentan, which is used to prevent cerebral vasospasm, with multidrug combinations. In this study, we aimed to clarify the initial results of using clazosentan in multidrug combinations in the real world. Methods: We retrospectively investigated 54 patients who were treated for subarachnoid hemorrhage and received clazosentan. We compared the results of these patients on the basis of two groups: those with good outcomes (modified Rankin scale score: 0–3) and poor outcomes (4–6) at discharge. Results: Among the patients, poor outcome was observed in 19 patients (35.2 %). Angiographic vasospasms occurred in 10 patients (good outcome [n = 6] vs. poor outcome [n = 4]; p = 0.73), and symptomatic vasospasms occurred in 4 patients (n = 2 vs. n = 2, p = 0.61). The incidence of pleural effusion (28.6 % vs. 73.7 %, p

Summary: The regenerative functions associated with cytokines and growth factors have immense therapeutic potential; however, their poor pharmacokinetics, resulting from structural features, hinder their effectiveness. In this study, we aimed to enhance the pharmacokinetics of growth factors by designing receptor-binding macrocyclic peptides through in vitro mRNA display and grafting them into loops of immunoglobulin’s crystallizable region (Fc). As a model, we developed peptide-grafted Fc proteins with hepatocyte growth factor (HGF) functionality that exhibited a prolonged circulation half-life and could be administered subcutaneously. The Fc-based HGF mimetic alleviated liver fibrosis in a mouse model fed a choline-deficient high-fat diet, which induces hepatic features of non-alcoholic steatohepatitis, including fibrosis, showcasing its potential as a therapeutic intervention. This study provides a basis for developing growth factor and cytokine mimetics with improved pharmacokinetics, expanding their therapeutic applications.

Abstract A young patient diagnosed with advanced colon cancer and liver metastasis was found to have familial adenomatous polyposis (FAP) through comprehensive genomic analysis. Whole-genome array comparative genomic hybridization (aCGH) revealed germline deletions at chromosome 5q22.1-22.2 encompassing the entire APC gene. The patient and her son exhibited mild intellectual disability without developmental delay. This case highlights the need for further exploration of the characteristics associated with whole APC deletions. aCGH is a valuable tool for studying FAP and provides a detailed analysis of large deletions.

Abstract The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P

Subclavian artery aneurysms, occasionally related to connective tissue diseases, including Marfan syndrome, are rare and conventionally managed with surgery or endovascular treatment. However, in some cases, both interventions are challenging because of the inability to reach an aneurysm through a safe route or postoperative adhesion. This report describes the case of a 43-year-old patient with a left subclavian artery aneurysm and Marfan syndrome. In this case, the patient's 5 previous surgeries related to Marfan syndrome made surgery and endovascular treatment difficult. Therefore, an alternative was researched, and we decided to perform a method of percutaneous embolization with coils and N-butyl cyanoacrylate using the direct puncture technique, which succeeded in eliminating the blood flow in the left subclavian artery aneurysm. No severe complications were associated with the procedure. The patient was free from the risk of an aneurysm rupture post-treatment, and the left back pain improved. Follow-up computed tomography 2 years postsurgery revealed the aneurysm being under control without re-enlarging. Our method is considered an effective and safe therapeutic option for cases in which surgical approach and transarterial access routes are limited.

Background and Aims: EUS-guided biliary drainage (EUS-BD) has been performed increasingly worldwide, especially in patients with malignant tumors in which ERCP is difficult, patients with surgically altered GI tracts, and older patients who are at high risk for surgery. EUS-BD requires high-level skills and has limited options for managing adverse events, particularly when stent migration and cholangitis occur. Adverse events, such as persistent bile leakage from the fistula and continuous reflux from the GI tract, are believed to always have a risk of severe exacerbation that could threaten the patient’s life. Methods: We encountered 2 cases of stent migrations and 1 case with repeated cholangitis in patients with malignant tumors among the patients who underwent EUS-BD. The migrated stent was visualized under EUS in 2 patients with stent migration, and an EUS-guided FNA needle was used to puncture the mesh of the stent. The cannulation catheter was directly inserted into the mesh of the stent in 1 case with repeated retrograde cholangitis, while the stent was visualized with an endoscope. Subsequently, a guidewire was inserted through the puncture site, and a second metal stent was deployed between the meshes of the first stent, bridging the GI wall again (Lambda stenting technique). All procedures were performed with the patient under general anesthesia, and the patients safely completed the intervention. Results: Patients’ conditions significantly improved after the second stent insertion, allowing for chemotherapy resumption while maintaining their activities of daily living. The second stent remained in place without any migration, and the stent successfully prevented further cholangitis. Conclusions: The Lambda stenting technique is considered highly effective for managing stent migration and repeated cholangitis, which is a major EUS-BD adverse event. This procedure helps avoid more invasive surgeries when stent migration and cholangitis occur and contributes to expanding EUS-BD applicability.

Fine motor skills have been suggested to be related to human cognitive abilities. To develop an objective method for evaluating fine motor skills, we applied a flexible tactile sensor based on electrical impedance tomography (EIT) and the contact resistance principle to a cylinder designed to mimic the peg used in the Functional Dexterity Test. Six pinching motions were classified to confirm the feasibility of the prototype system. Two types of classification were performed: classification using reconstructed images and classification using measured voltage vectors. The feasibility of the classification method was evaluated using adult participants, and it was demonstrated that the system can accurately classify various types of pinching motions. The results revealed that utilizing reconstructed images for classification achieved a classification accuracy of 79.4%, while employing measured voltage vectors for classification resulted in a classification accuracy of 91.4%. These findings underscore the potential for developing an automated finger motion analysis system using EIT-based tactile sensor.

Pr-doped scintillators are attracting attention because of their potential applications in medical devices. In this study, we focused on Pr-doped (La, Y)2Si2O7 scintillators to grow single crystals by the micro-pulling-down method and to evaluate their optical and scintillation properties. From the powder XRD results, the crystal structure and the space group were identified to be monoclinic and P21/n, respectively. The results of optical and scintillation characterization show that the luminescence from the Pr3+ 5d1–4f transition increases with increasing Pr3+ concentration. The maximum light yield was also obtained for the sample with the highest Pr3+ concentration. The Pr-doped (La, Y)2Si2O7 single crystal shows promising properties for application in radiation detection.

Abstract Background Adhesion of cancer cells to extracellular matrix laminin through the integrin superfamily reportedly induces drug resistance. Heterodimers of integrin α6 (CD49f) with integrin β1 (CD29) or β4 (CD104) are major functional receptors for laminin. Higher CD49f expression is reportedly associated with a poorer response to induction therapy in childhood B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). Moreover, a xenograft mouse model transplanted with primary BCP‐ALL cells revealed that neutralized antibody against CD49f improved survival after chemotherapy. Aims Considering the poor outcomes in Philadelphia chromosome (Ph)‐positive ALL treated with conventional chemotherapy without tyrosine kinase inhibitors, we sought to investigate an involvement of the laminin adhesion. Methods and results Ph‐positive ALL cell lines expressed the highest levels of CD49f among the BCP‐ALL cell lines with representative translocations, while CD29 and CD104 were ubiquitously expressed in BCP‐ALL cell lines. The association of Ph‐positive ALL with high levels of CD49f gene expression was also confirmed in two databases of childhood ALL cohorts. Ph‐positive ALL cell lines attached to laminin and their laminin‐binding properties were disrupted by blocking antibodies against CD49f and CD29 but not CD104. The cell surface expression of CD49f, but not CD29 and CD104, was downregulated by imatinib treatment in Ph‐positive ALL cell lines, but not in their T315I‐acquired sublines. Consistently, the laminin‐binding properties were disrupted by the imatinib pre‐treatment in the Ph‐positive ALL cell line, but not in its T315I‐acquired subline. Conclusion BCR::ABL1 plays an essential role in the laminin adhesion of Ph‐positive ALL cells through upregulation of CD49f.

Abstract Canine primary lung cancer with metastasis has a poor prognosis with no effective treatment. We previously generated a recombinant measles virus (MV) that lost binding affinity to a principal receptor, SLAM, to eliminate its virulence as a new cancer treatment strategy. The virus, rMV-SLAMblind, targets nectin-4, recently listed as a tumor marker, and exerts antitumor activity against nectin-4-positive canine mammary cancer and urinary bladder transitional cell carcinoma cells. However, the effectivity of rMV-SLAMblind for other types of canine cancers is still unknown. Here we evaluated the antitumor effect of rMV-SLAMblind to canine lung cancer. Nectin-4 is expressed on three canine lung cancer cell lines (CLAC, AZACL1, AZACL2) and rMV-SLAMblind was able to infect these cell lines. CLAC cells showed reduced cell viability after virus infection. In the CLAC xenograft nude mouse model, intratumoral administration of rMV-SLAMblind significantly suppressed tumor growth. In rMV-SLAMblind-treated mice, natural killer cells were activated, and Cxcl10 and Il12a levels were significantly increased in comparison with levels in the control group. In addition, the depletion of NK cells reduced the anti-tumor effect. To understand difference in efficacy among canine lung cancer cell lines, we compared virus growth and gene expression pattern after virus treatment in the three canine lung cancer cell lines; virus growth was highest in CLAC cells compared with the other cell lines and the induction of interferon (IFN)-beta and IFN-stimulated genes was at lower levels in CLAC cells. These results suggested that rMV-SLAMblind exhibits oncolytic effect against some canine lung cancer cells and the cellular response after the virus infection may influence its efficacy.

Background: In the absence of Helicobacter pylori (HP) infection, a characteristic gastric mucus adhesion may appear during the use of vonoprazan. We named this novel characteristic mucus “web-like mucus” (WLM). This study aimed to determine the incidence and risk factors for WLM. Methods: Between January 2017 and January 2022, 5665 patients were enrolled in this study. The patients were divided into a proton-pump inhibitor (PPI)-prescribed group (n = 2000), a vonoprazan-prescribed group (n = 268), and a no-PPI/vonoprazan-prescribed (n = 3397) group, and the presence of WLM was examined. After excluding four patients with autoimmune gastritis, the remaining 264 patients in the vonoprazan group were divided into WLM and non-WLM groups, and their clinical features were analyzed. Results: A total of 55 (21%) patients had WLM, all in the vonoprazan-prescribed group. There were no significant differences in factors such as, sex, age, chronic kidney disease, diabetes mellitus, HP eradication history, smoking, or alcohol consumption between the WLM and non-WLM groups. The median duration from the start of vonoprazan administration to the endoscopic detection of WLM was 2 (1–24) months. Conclusions: WLM appears to be a characteristic feature in patients treated with vonoprazan.

Ankarafantsika National Park (ANP), the last significant remnant of Northwestern Madagascar's tropical dry forests, is facing rapid degradation due to increased incidences of fire. This poses severe threats to biodiversity, local livelihoods, and vital ecosystem services. Our study, conducted on 3,052-ha of ANP's pristine forests, employed advanced remote-sensing techniques to assess fire impacts during the past 37 years. Our aims were to understand historical fire patterns and evaluate forest recovery and susceptibility to repeated fires following initial burns. Using data from multiple Landsat satellite sensors, we constructed a time series of fire events since 1985, which revealed no fire activity before 2014. The Global Ecosystem Dynamics Investigation (GEDI) lidar sensor data were used to observe forest structure in both post-fire areas and undisturbed zones for comparison. We recorded six fire incidents from 2014-2021, during which the fire-affected area exponentially grew. A significant fire incident in October 2021 impacted 1,052 hectares, 59% of which had experienced at least one fire in two-to-four years prior, with 60% experiencing two preceding incidents: one in 2017 and another in 2019. The initial fire drastically reduced plant cover and tree height, with subsequent fires causing minor additional loss. Post-fire recovery was negligible within the initial four years, even in patches without recurrent fires. The likelihood for an initial burn to trigger subsequent fires within a few years was high, leading to larger, more severe fires. We conclude that ANP's dry forests exhibit high vulnerability and low resilience to anthropogenic fires. Prompt preventive measures are essential to halt further fire spread and conserve the park's unique and invaluable biodiversity.

Abstract Background and Aim While short and long attachment caps are available for colonoscopy, it is unclear which type is more appropriate for stigmata of recent hemorrhage (SRH) identification in acute hematochezia. This study aimed to compare the performance of short versus long caps in acute hematochezia diagnoses and outcomes. Methods We selected 6460 patients who underwent colonoscopy with attachment caps from 10 342 acute hematochezia cases in the CODE BLUE‐J study. We performed propensity score matching (PSM) to balance baseline characteristics between short and long cap users. Then, the proportion of definitive or presumptive bleeding etiologies found on the initial colonoscopy and SRH identification rates were compared. We also evaluated rates of blood transfusions, interventional radiology, or surgery, as well as the rate of rebleeding and mortality within 30 days after the initial colonoscopy. Results A total of 3098 patients with acute hematochezia (1549 short cap and 1549 long cap users) were selected for PSM. The rate of colonic diverticular bleeding (CDB) diagnosis was significantly higher in long cap users (P = 0.006). While the two groups had similar rates of the other bleeding etiologies, the frequency of unknown etiologies was significantly lower in long cap users (P

Background and Objective: Rescue Helicobacter pylori eradication can be challenging. Rifabutin (RBT) demonstrates high activity against Helicobacter pylori and is incorporated into various rescue eradication regimens. This exploratory study was performed to evaluate the efficacy and safety of a rescue regimen comprising RBT, metronidazole (MNZ), and vonoprazan (VPZ). Methods: This prospective, single-center, single-arm, interventional study was performed in Japan. Eligible patients were those who underwent failed primary eradication treatment (7-day treatment with three drugs: VPZ or a proton pump inhibitor [PPI], amoxicillin [AMPC], and clarithromycin) and secondary eradication treatment (7-day treatment with three drugs: VPZ or a PPI, AMPC, and MNZ) and those who were unable to receive first- and second-line therapy because of penicillin allergy. Twenty Helicobacter pylori-positive patients were treated with RBT (150 mg twice daily), MNZ (250 mg twice daily), and VPZ (20 mg twice daily) for 10 days (RBT-MNZ-VPZ therapy). Eradication success was evaluated using the urea breath test. Drug susceptibility test results were available in 16 patients. This study is registered in the Japan Registry of Clinical Trials (jRCT031220504). Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of RBT-MNZ-VPZ therapy were 70% (90% confidence interval [CI]: 49.2%–86.0%) and 72.2% (95% CI: 50.2%–88.4%), respectively. In the MNZ-susceptible subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were 100% (90% CI: 68.8%–100%) and 100% (90% CI: 65.2%–100%). In the MNZ-resistant subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were both 62.5% (90% CI: 28.9%–88.9%). All infections were RBT-susceptible. Conclusions: These findings suggest that RBT-MNZ-VPZ therapy may be a promising rescue regimen, especially in MNZ- and RBT-susceptible infections or patients with penicillin allergy.

Abstract Recent clinical evidence has suggested that interatrial septal (IAS) adiposity contributes to atrial fibrillation (AF). The present study aimed to confirm the usefulness of transesophageal echocardiography (TEE) to estimate IAS adiposity in patients with AF. The histological IAS analysis based on autopsy samples sought to clarify characteristics that underlie the contribution of IAS adiposity to AF. The imaging study analyzed the TEE results in patients with AF (n = 184) in comparison with transthoracic echocardiography (TTE) and computed tomography (CT) results. The autopsy study histologically analyzed IAS in subjects with (n = 5) and without (n = 5) history of AF. In the imaging study, the ratio of interatrial septum adipose tissue (IAS-AT) volume per epicardial adipose tissue (EpAT) volume was greater in patients with persistent AF compared (PerAF) to those with paroxysmal AF (PAF). Multivariable analysis revealed that both TEE-assessed IAS thickness and TTE-assessed left atrial dimension were predicted by CT-assessed IAS-AT volume. In the autopsy study, the histologically-assessed IAS section thickness was greater in the AF group than that in the non-AF group and was positively correlated with the IAS-AT area percentage. In addition, the size of adipocytes in IAS-AT was smaller, compared to EpAT and subcutaneous adipose tissue (SAT). IAS-AT infiltrated into the IAS myocardium, as if adipose tissue split the myocardium (designated as myocardial splitting by IAS-AT). The number of island-like myocardium pieces as a result of myocardial splitting by IAS-AT was greater in the AF group than in the non-AF group and was positively correlated with the IAS-AT area percentage. The present imaging study confirmed the usefulness of TEE to estimate IAS adiposity in patients with AF without radiation exposure. The autopsy study suggested that the myocardial splitting by IAS-AT may contribute to atrial cardiomyopathy leading to AF.

Oxaliplatin is a key drug for colorectal cancer and causes peripheral neuropathy. Oxaliplatin-induced laryngopharyngeal dysesthesia is an acute peripheral neuropathy similar to a hypersensitivity reaction. Hypersensitivity reactions to oxaliplatin do not require immediate discontinuation, but re-challenge and desensitization therapy can be very burdensome for patients. We encountered 2 cases in which laryngopharyngeal dysesthesia could be differentiated from hypersensitivity reactions to oxaliplatin, and treatment could continue. The first case was that of a 58-year-old woman who developed dyspnea during the first course of combination therapy with capecitabine and oxaliplatin as the primary treatment for advanced rectal cancer. After laryngopharyngeal dysesthesia was differentiated from hypersensitivity reaction based on these typical symptoms, she was considered to have grade 3 (Common Terminology Criteria for Adverse Events [CTCAE] ver. 5) laryngopharyngeal dysesthesia. The second course of oxaliplatin was extended from 2 to 4 h, but symptoms recurred. The third course was performed with a reduced dose of oxaliplatin from 130 mg/m2 to 100 mg/m2, and the patient could complete the treatment without symptom recurrence. The second case involved a 76-year-old woman who developed grade 3 laryngopharyngeal dysesthesia during the first course of combination therapy with capecitabine and oxaliplatin as the primary treatment for localized colon cancer. Based on the experience of the first case, we reduced the oxaliplatin dose from 130 mg/m2 to 100 mg/m2 for the second course, and the patient completed the treatment without symptoms. This dose reduction was effective for grade 3 laryngopharyngeal dysesthesia caused by oxaliplatin without reducing therapeutic efficacy.

Abstract Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults. Although open hematoma removal may be performed for severe subcortical hemorrhage, its safety in patients with cerebral amyloid angiopathy has not been established, and postoperative rebleeding may occur. Therefore, this study aimed to investigate factors associated with postoperative rebleeding. Methods Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan, we examined 109 patients with subcortical hemorrhage who met the inclusion criteria. After excluding 30 patients whose tissue samples were unsuitable for the study, the final study cohort comprised 79 patients. Results Of the 79 patients, 50 (63%) were diagnosed with cerebral amyloid angiopathy (cerebral amyloid angiopathy group) and 29 (37%) were not diagnosed with noncerebral amyloid angiopathy (noncerebral amyloid angiopathy group). Postoperative rebleeding occurred in 12 patients (24%) in the cerebral amyloid angiopathy group and in 2 patients (7%) in the noncerebral amyloid angiopathy group. Preoperative prothrombin time–international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group (odds ratio = 42.4, 95% confidence interval = 1.14–1578; p = 0.042 and odds ratio = 1.005, 95% confidence interval = 1.001–1.008; p = 0.007, respectively). Conclusions Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy, particularly warfarin therapy, are at a high risk of postoperative rebleeding. Trial registration Registry and Registration Number of the study: 19–220, 2019/12/23, retrospectively registered.

A cycloaliphatic tetracarboxylic dianhydride, octahydro-2,3,6,7-anthracenetetracarboxylic dianhydride (OHADA) was synthesized to obtain novel colorless polyimides (PIs). Herein, approaches for decolorizing an OHADA prototype and simplifying the entire process are described, and a plausible steric structure for OHADA is proposed. The polyaddition of OHADA and 2,2′-bis(trifluoromethyl)benzidine (TFMB) was unsuccessful; specifically, the reaction mixture remained inhomogeneous even after prolonged stirring. However, the modified one-pot process was applicable to the OHADA/TFMB system. The isolated PI powder form, as well as those for the other OHADA-based PIs, was highly soluble in numerous solvents and afforded a homogeneous and stable solution with a high solid content (20–30 wt%). Solution casting produced a colorless and ductile PI film with a very high glass transition temperature (Tg~300 °C). Furthermore, the OHADA/TFMB system exhibited remarkable thermal stability compared with those of the other related TFMB-derived semi-cycloaliphatic PIs. However, contrary to our expectations, this PI film did not exhibit a low linear coefficient of thermal expansion (CTE). This PI film also possessed excellent thermoplasticity, probably reflecting its peculiar steric structure. The use of an amide-containing diamine significantly enhanced the Tg (355 °C) and somewhat reduced the CTE (41.5 ppm K−1) while maintaining high optical transparency and excellent solubility.

Harpellales (Zoopagomycotina) is a fungal order of which species inhabit the intestine of aquatic arthropods by attaching their thalli to the host’s gut lining. Harpellales consists of 270 species with over half found in Chironomidae larvae. The aim of this research is to document a species, S. pedifer, new to Japan with a chironomid host association and to list all Chironomidae-commensal species of Harpellales with host and country information.

Abstract Background Entrectinib is an effective drug for treating solid tumors with NTRK gene rearrangement and non‐small cell lung cancer (NSCLC) with ROS1 gene rearrangement. However, its efficacy is limited by tolerance and acquired resistance, the mechanisms of which are not fully understood. The growth factors produced by the tumor microenvironment, including hepatocyte growth factor (HGF) produced by tumor‐associated fibroblasts, critically affect the sensitivity to targeted drugs. Methods We investigated whether growth factors that can be produced by the microenvironment affect sensitivity of NTRK1‐rearranged colon cancer KM12SM cells and ROS1‐rearranged NSCLC HCC78 cells to entrectinib both in vitro and in vivo. Results Among the growth factors assessed, HGF most potently induced entrectinib resistance in KM12SM and HCC78 cells by activating its receptor MET. HGF‐induced entrectinib resistance was reversed by the active‐HGF‐specific macrocyclic peptide HiP‐8 and the MET kinase inhibitor capmatinib in vitro. In addition, HGF‐producing fibroblasts promoted entrectinib resistance in vitro (culture model) and in vivo (subcutaneous tumor model). The use of capmatinib circumvented entrectinib resistance in a subcutaneous tumor model inoculated with KM12SM and HGF‐producing fibroblasts. Conclusion Our findings suggest that growth factors in the tumor microenvironment, such as HGF, may induce resistance to entrectinib in tumors with NTRK1 or ROS1 rearrangements. Our results further suggest that optimally co‐administering inhibitors of resistance‐inducing growth factors may maximize the therapeutic efficacy of entrectinib.

Gastroparesis is defined by delayed gastric emptying in the absence of mechanical obstruction of the stomach. Patients experience symptoms of nausea, vomiting, abdominal pain, fullness, and early satiety. The recognition of the disorder has progressed due to availability of gastric emptying scintigraphy and advancements made in understanding its pathophysiology and treatment options. The clinical presentation and treatment of gastroparesis overlap with a more commonly recognized disorder of gut-brain interaction, functional dyspepsia. Recent studies have reenergized the discussion whether these two are separate entities or perhaps reflect a spectrum of gastroduodenal neuromuscular disorders. The societal guidelines conflict on the utility of gastric emptying scintigraphy in assessment of patients with upper gastrointestinal symptoms. A better appraisal of similarities and differences between gastroparesis and functional dyspepsia will allow targeted treatment for these disorders. This is particularly important as specific pharmacological and endoscopic treatment options are being developed for gastroparesis which are unlikely to be helpful for functional dyspepsia. This review makes the case for considering these disorders in a spectrum where identification of both would most ideally position us toward providing the optimal clinical care.

The 3He gas is commonly used for the detection of thermal neutrons. However, with the depletion of 3He gas, there is a need to develop new solid scintillators for thermal neutron detection. Solid scintillators containing 6Li, which have large neutron capture cross-sections and a large amount of energy released by transmutation reactions, are commonly used as alternative candidates. However, only single-crystal scintillators are currently used, and their 6Li concentration is limited by their chemical composition. In this study, we designed, grew, and evaluated a new eutectic scintillator, Rb2CeCl5/LiCl, which can improve the 6Li concentration compared with single-crystal scintillators. Rb2CeCl5, which was selected as the scintillator phase, has excellent scintillator properties (light yield: 36,000 photons/MeV, decay time: mostly 24 ns, slightly 153 ns), and is less deliquescent than other halide scintillators. The crystal grown using the vertical Bridgman method exhibited a eutectic phase composed of Rb2CeCl5 and LiCl. The eutectic crystals exhibited Ce3+ 5d-4f emissions, with a peak between 360 and 370 nm. The Rb2CeCl5 phase was identified as the luminescent phase via cathodoluminescence mapping, and 16,000 photons/neutron of the light yield and 56.1 ns of the decay time were observed. This study indicates that the Rb2CeCl5/LiCl eutectic scintillator is a promising candidate for use in thermal neutron detectors.

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged

DNMT1 is an essential for maintaining genomic DNA methylation. Here, we report the cryo-EM structure of DNMT1 bound to ubiquitinated H3 and hemimethylated DNA, revealing structural insight into the activation mechanism of DNMT1.

Abstract How do large-bodied frugivores contribute to seed dispersal of large-diaspore plants? This study examined seed dispersal effectiveness for two large-diaspore tree species, Astrotrichilia asterotricha (AA) and Abrahamia deflexa (AD), in a Madagascan forest. I evaluated fruit removal rates through focal tree observations and factors affecting seedling recruitment up to the 2-year-old seedling stage. I confirmed brown lemur (Eulemur fulvus) as the sole disperser, removing 58.8% and 26.0% of fruits produced by AA and AD. Brown lemurs frequently visited large-crowned AA trees with high density of fallen fruits and more adjacent fruiting trees during seasons with low fruit diversity. Most AA seedlings were removed by predators, although canopy openness slightly improved seedling establishment. Although AD seeds were severely attacked by predators under mother trees, the seedlings survived under dispersal conditions distant from the mother trees, and with low density of diaspores. AD had a higher cumulative probability from fruit removal to seedling recruitment (6.5%) than AA (1.5%) in the first rainy season. This study clarifies the significance of seed dispersal to tree recruitment strategies, which vary among different combinations of tree species and large frugivores, i.e. quantitative dispersal to reach suitable microhabitats, and qualitative dispersal to escape from dangerous zones near mother trees.

Abstract Background The desired depth of sedation during flexible bronchoscopy is one in which verbal contact is possible whenever necessary. Although it is common that the depth of sedation is assessed by validated instruments such as the modified observer's assessment of alertness and sedation (MOAA/S) score, the repeated stimulation associated with the assessment can affect the sedation. The bispectral index (BIS) has been widely used for general anesthesia due to its objective and noninvasive nature. However, the utility of BIS monitoring and a target BIS value for use during bronchoscopy have not been fully elucidated. Methods We performed a retrospective observational study to assess the utility of the BIS value for monitoring conscious sedation during bronchoscopy at Kobe University Hospital from August 2020 to April 2021. Results Eighteen patients underwent bronchoscopy with BIS monitoring. The BIS value significantly correlated with the MOAA/S score (r = 0.2, p

Abstract Background Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with εγδβ-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. Case presentation A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with εγδβ-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. Conclusions We reported that an infant with εγδβ-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia.

Abstract A 70‐year‐old woman who had cardiac sarcoidosis and severe tethering mitral regurgitation (MR) and had been implanted with a biventricular pacemaker experienced recurrent hospitalisation due to decompensated heart failure (HF). Application of MultiPoint™ pacing reduced the MR volume and maintained the symptoms under control; however, the predicted longevity of the device significantly decreased because of the very high threshold of the added pacing site. Transcatheter mitral valve repair (TMVR) using MitraClip® was performed to further diminish the severe MR, thereby enabling the switch from highly consumptive multipoint pacing (MPP) to energy‐saving single‐point pacing. MPP could further reduce MR compared to the conventional single‐point pacing, and this could be a bridging therapy to TMVR in some patients implanted with a biventricular pacemaker. This is the first case to report that switching from conventional single‐point pacing to MPP decreased the MR, to some extent, resulting in the improvement of HF symptoms.

Abstract Backgrounds The pharynx has no muscularis mucosae, so it is unclear whether diagnostic techniques used for the esophagus can be applied to the pharynx. This study investigated the usefulness of magnifying endoscopy with narrowband imaging using the Japan Esophageal Society (JES) classification for predicting the depth of invasion and lymph node metastasis (LNM) in pharyngeal cancer. Methods A total of 123 superficial pharyngeal carcinoma lesions that had been observed preoperatively with magnifying endoscopy with narrowband imaging between January 2014 and June 2021 were analyzed. Predictors of subepithelial invasion (SEP) and LNM were sought based on endoscopic findings, including microvascular morphology, using the JES classification. Results The lesions were divided into carcinoma in situ (n = 41) and SEP (n = 82). Multivariate analysis identified B2–B3 vessels (odds ratio [OR] 6.54, 95% confidence interval [CI] 1.74–24.61, p = 0.005) and a middle/large avascular area (OR 4.15, 95% CI 1.18–14.62, p = 0.027) as independent predictors of SEP. Significant predictors of LNM were protruding type, B2–B3 vessels, middle/large avascular area, SEP, venous invasion, lymphatic invasion, and tumor thickness > 1000 μm. Median tumor thickness increased significantly in the order of B1

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.

Abstract Background The optimal management for peritoneal dissemination in patients with hepatocellular carcinoma remains unclear. Although several reports have described the usefulness of surgical resection, the indications should be carefully considered. Herein, we report the case of a patient with hepatocellular carcinoma with peritoneal recurrence who underwent surgical resection using an indocyanine green fluorescence navigation system and achieved favorable disease control. Case presentation A 45-year-old Asian woman underwent left hemihepatectomy for a ruptured hepatocellular carcinoma. Seventeen months after the initial surgery, a single nodule near the cut surface of the liver was detected on computed tomography, along with elevation of tumor markers. The patient was diagnosed with peritoneal metastasis and underwent a surgical resection. Twelve months later, a single nodule on the dorsal side of the right hepatic lobe was detected on computed tomography, and we performed surgical resection. Indocyanine green (0.5 mg/kg) was intravenously administered 3 days before surgery, and the indocyanine green fluorescence imaging system revealed clear green fluorescence in the tumor, which helped us perform complete resection. Indocyanine green fluorescence enabled the detection of additional lesions that could not be identified by preoperative imaging, especially in the second metastasectomy. There was no further recurrence at 3 months postoperatively. Conclusion When considering surgical intervention for peritoneal recurrence in patients with hepatocellular carcinoma, complete resection is mandatory. Given that disseminated nodules are sometimes too small to be detected by preoperative imaging studies, intraoperative indocyanine green fluorescence may be an essential tool for determining the indications for surgical resection.

Abstract Background Adenomatoid mesothelioma is a rare subtype of malignant mesothelioma that can be confused with adenomatoid tumors, which are classified as benign. The clinical features and optimal management of adenomatoid mesothelioma have not been elucidated in the literature. In this report, we present an extremely rare case of adenomatoid mesothelioma that developed on the peritoneal surface of the diaphragm as well as a literature review of adenomatoid mesothelioma in the abdominal cavity. Case presentation The patient was a 61-year-old Japanese woman who had undergone resection of a malignant peripheral nerve sheath tumor of the hand 18 years prior. She was diagnosed with clinical stage I lung adenocarcinoma on follow-up chest radiography. Simultaneously, a 20-mm enhancing nodule with slow growth on the right diaphragm was detected on contrast-enhanced computed tomography. She presented no specific clinical symptoms. At this point, the lesion was suspected to be a hypervascular tumor of borderline malignancy, such as a solitary fibrous tumor. After a left upper lobectomy for lung adenocarcinoma, she was referred to our department, and laparoscopic tumor resection was performed. Adenomatoid tumors were also considered based on the histopathological and immunohistochemical analyses, but we made the final diagnosis of adenomatoid mesothelioma using the results of the genetic profile. The patient remains alive, with no recurrence noted 6 months after surgery. Conclusion We encountered a valuable case of adenomatoid mesothelioma of peritoneal origin. There are some previously reported cases of adenomatoid mesothelioma and adenomatoid tumors that may need to be recategorized according to the current classification. It is important to accumulate and share new findings to clarify the clinicopathological characteristics and genetic status of adenomatoid mesothelioma.

Abstract Background Bronchoscopy can be a distress for the patient. There have been few studies on the combination of sedatives and opioids. The aim of this study was to demonstrate the usefulness and safety of administration of the combination of midazolam and pethidine during bronchoscopy. Methods In this prospective randomized single (patient)-blind study, we randomly assigned 100 patients who were scheduled to undergo bronchoscopy biopsy to receive treatment with either the midazolam/pethidine combination (combination group) or midazolam alone (midazolam group) during examinations. After the end of bronchoscopy, patients completed a questionnaire and the visual analogue scale was measured. The primary outcome was the patients’ acceptance of re-examination assessed by visual analogue scale. We also assessed pain levels, vital signs, midazolam use, xylocaine use, and adverse events. Univariate analyses were performed using Fisher’s exact test for categorical data, and the t-test or Mann-Whitney test was carried out for analysis of numeric data. All P-values were two-sided, and values

Abstract Ellis–van Creveld syndrome is an autosomal recessive skeletal dysplasia that is characterized by thoracic hypoplasia, polydactyly, oral abnormalities, and congenital heart disease. It is caused by pathogenic variants in the EVC or EVC2 genes. We report a case of a newborn with a compound heterozygous variant comprising NM_147127.5: c.1991dup:[p.Lys665Glufs*10] in the EVC2 gene and a novel large deletion involving exon 1 in EVC and exons 1–7 in EVC2.

Abstract Background The outcome of catheter ablation could probably differ among patients with atrial fibrillation (AF), depending on age and AF type. We aimed to investigate the difference in predictors of outcome after catheter ablation for AF among the patient categories divided by age and AF type. Methods and Results A total of 396 patients with AF (mean age 65.69 ± 11.05 years, 111 women [28.0%]) who underwent catheter ablation from January 2018 to December 2019 were retrospectively analyzed. We divided the patients into four categories: patients with paroxysmal AF (PAF) or persistent AF (PeAF) who were 75 years or younger (≤75 years) or older than 75 years (>75 years). Kaplan–Meier survival analysis demonstrated that patients with PAF aged ≤75 years had the lowest AF recurrence among the four groups (log‐rank test, p = .0103). In the patients with PAF aged ≤75 years (N = 186, 46.7%), significant factors associated with recurrence were female sex (p = .008) and diabetes (p = .042). In the patients with PeAF aged ≤75 years (N = 142, 35.9%), the only significant factor associated with no recurrence was medication with a renin‐angiotensin system inhibitor (p = .044). In the patients with PAF aged >75 years (N = 53, 14.4%), diabetes was significantly associated with AF recurrence (p = .021). No significant parameters were found in the patients with PeAF aged >75 years (N = 15, 4.1%). Conclusions Our findings indicate that the risk factors for AF recurrence after catheter ablation differed by age and AF type.

Placement of guiding catheters (GCs) in older patients who undergo thrombectomy is often difficult owing to age-related atherosclerotic changes. Herein, we propose a unique technique of balloon guide catheter (BGC) implantation for thrombectomy termed the AC-Amplatz wire method (Aspiration Catheter – Amplatz Super-Stiff Guidewire method). Using the AC-Amplatz wire method, AC was first guided to the C5 portion of the internal carotid artery followed by passing this Amplatz wire through it. Using this novel method, flow control with BGC and good recanalization were achieved. The AC-Amplatz wire method was very effective in GC placement in patients with torturous and atherosclerotic vasculature.

The outbreak of coronavirus disease (COVID-19) resulted in implementation of social distancing and other public health measures to control the spread of infection and improve prevention, resulting in a decrease in respiratory syncytial virus (RSV) and pediatric respiratory tract infection rates. However, there was a rapid and large re-emergence of RSV infection in Japan. Notably, we were faced with a difficult situation wherein there was a shortage of hospital beds. This study aimed to examine the epidemiological patterns of RSV-related hospitalizations among children before and after the COVID-19 pandemic onset at two pediatric emergency referral hospitals covering the entire Tokushima Prefecture. Data were extracted from electronic medical records of children hospitalized with RSV infection between January 1, 2018, and December 31, 2021. All patients meeting the eligibility criteria were included in this study. The rates of study outcomes were documented annually during 2018-2021 and compared between the 2018-2020 and 2021 periods. In 2020, there was no RSV infection outbreak. Hospitalizations at the peak week in 2021 were 2.2- and 2.8-fold higher than those in 2018 and 2019, respectively. Hospitalizations in 2021 were concentrated within a short period. In addition, there was a significant increase in hospitalizations among children aged 3-5 months and those older than 24 months. The high-flow nasal cannula (HFNC) use rate nearly doubled in 2021. A new pandemic in the future may cause an outbreak of RSV infection that can result in an intensive increase in the number of hospitalizations of pediatric patients requiring respiratory support, especially in infants aged

Abstract Background Mixed neuroendocrine-non-neuroendocrine neoplasm (MINEN) is a rare disease and there is scarce literature on its diagnosis, treatment, and prognosis. We encountered two unusual cases of MINEN in the biliary tract, one in the ampulla of Vater and the other in the distal bile duct. In this report, we describe the clinical course of these two cases in detail. Case presentation Case 1: A 69-year-old woman presented with a chief complaint of epigastric pain. When endoscopic sphincterotomy and retrograde biliary drainage were performed for gallstone pancreatitis, an ulcerated lesion was found in the ampulla of the Vater. Based on the biopsy results, the lesion was diagnosed as the ampulla of Vater carcinoma and subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed. Postoperative histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, consistent with the diagnosis of MINEN. In addition, lymph node metastasis was found on the dorsal side of the pancreas and the metastatic component was adenocarcinoma. Adjuvant chemotherapy with etoposide and cisplatin was administered for 6 months, and presently the patient is alive without recurrence 64 months after surgery. Case 2: A 79-year-old man presented with a chief complaint of anorexia. Cholangiography showed severe stenosis of the distal bile duct. A biopsy was conducted from the stenotic lesion and it revealed the lesion to be adenocarcinoma. A diagnosis of distal bile duct carcinoma was made, and SSPPD was performed. Histopathological examination revealed the coexistence of adenocarcinoma and neuroendocrine carcinoma components, and the tumor was confirmed as MINEN of the distal bile duct. No adjuvant chemotherapy was administered due to the poor performance status. 7 months later, the patient was found to have a liver metastasis. Conclusion We experienced two valuable cases of biliary MINEN. To identify better treatments, it is important to consider the diversity of individual cases and to continue sharing a variety of cases with different presentations.

Abstract Type III interferons (IFNs) play an important role in respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to determine whether the expression of serum type III IFNs predicted disease severity among patients with the coronavirus disease (COVID-19). A retrospective cohort study was conducted of patients admitted to a single hospital between March 21, 2020, and March 31, 2021. Patients were divided into mild to moderate I (MM) and moderate II to severe (MS) groups based on the COVID-19 severity classification developed by the Japanese Ministry of Health, Labor and Welfare. A total of 257 patients were included in the analysis. Human interleukin-28A (IL-28A/IFN-λ2) expression was significantly lower, and interleukin (IL)-6 expression was significantly higher in the MS group than in the MM group (both p

Abstract Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

Abstract Background Chemotherapy for advanced gastric cancer is recommended in the guidelines; however, later‐line treatment remains controversial. Since immune checkpoint inhibitors have been used for the treatment of various malignancies, trials have been performed for gastric cancer. A phase 3 trial indicated the survival benefit of nivolumab monotherapy for gastric cancer patients treated with prior chemotherapy regimens. Patients and methods A regional cohort study was undertaken to determine the real‐world data of nivolumab treatment for patients with advanced or recurrent gastric cancer. The patients were enrolled for 2 years from October 2017 to October 2019 and were prospectively followed for 1 year to examine the overall survival (OS). The patient characteristics were analyzed in a multivariate analysis and a nomogram to predict the probability of survival was generated. Results In total, 70 patients who received nivolumab as ≥third‐line chemotherapy were included in the Asahikawa Gastric Cancer Cohort. The median OS was 7.5 (95% CI, 4.8–10.2) months and the response rate was 18.6%. Diffuse type classification, bone metastasis, high neutrophil/lymphocyte ratio, and high CRP were associated with poor OS/prognosis in the multivariate analysis. A nomogram was developed based on these clinical parameters and the concordance index was 0.80 (95% CI, 0.68–0.91). The responders were aged and were frequently diagnosed with intestinal type gastric cancer, including patients with a HER2‐positive status (27.3%) or microsatellite instability‐high (27.3%) status. Conclusions The regional cohort study of nivolumab monotherapy for gastric cancer patients revealed prognostic factors and a nomogram was developed that could predict the probability of survival.

Splenic hemangiosarcoma is one of the most common malignant tumors in dogs, and early diagnosis is of great importance for achieving a good prognosis. DNA methylation plays an important role in cancer development. Long interspersed nuclear element 1 (LINE-1) is the most abundant repetitive element in the genome. LINE-1 hypomethylation has been shown to be related to carcinogenesis in humans, and it has been used as a novel cancer biomarker. This study aimed to evaluate the methylation status of LINE-1 in tumor tissue and circulating cell-free DNA and assess its clinical significance in canine splenic hemangiosarcoma. Genomic DNA was isolated from splenic masses of 13 dogs with hemangiosarcoma, 11 with other malignant tumors, and 15 with benign lesions. LINE-1 methylation was quantified using methylation-sensitive and -insensitive restriction enzyme digestion followed by real-time polymerase chain reaction. Additionally, blood samples were collected from eight patients to isolate cell-free DNA to determine LINE-1 methylation status changes during the treatment course. LINE-1 methylation in tumor samples was significantly lower in patients with hemangiosarcoma than in those with other malignant tumors and benign lesions. Non-significant but similar results were observed for the cell-free DNA samples. Our results demonstrate that LINE-1 methylation status is a potential biomarker for splenic hemangiosarcoma.

Acute subdural hemorrhage caused by ruptured cerebral aneurysms is rare. Herein, we report an atypical case of subdural hemorrhage caused by ruptured anterior communicating artery aneurysm in a 49-year-old woman. Computed tomography revealed subarachnoid, intracerebral, and subdural hemorrhages. After the treatment with endovascular coiling significantly decreased the patient's subdural hemorrhage. However, the subdural hemorrhage revealed and became iso-attenuation compared with the white matter on the 11th day, and hypo-attenuation on the 19th day. On the 33rd day, this subdural hemorrhage completely resolved after discontinuation of dual antiplatelet therapy. Due to rapid changes in the radiologic features of SDH, frequent computed tomography scans at least once a week may be needed especially in patients who receive antiplatelet therapy during the vasospasm phase.

Background: Kawasaki disease is suspected to be triggered by previous infection. The prevention measures for coronavirus disease 2019 (COVID-19) have reportedly reduced transmission of certain infectious diseases. Under these circumstances, the prevention measures for COVID-19 may reduce the incidence of Kawasaki disease. Methods: We conducted a retrospective study using registration datasets of patients with Kawasaki disease who were diagnosed in all 11 inpatient pediatric facilities in Yamanashi Prefecture. The eligible cases were 595 cases that were diagnosed before the COVID-19 pandemic (from January 2015 through February 2020) and 38 cases that were diagnosed during the COVID-19 pandemic (from March through November 2020). Incidence of several infectious disease were evaluated using data from the Infectious Disease Weekly Report conducted by the National Institute of Infectious Diseases. Results: Epidemics of various infectious diseases generally remained at low levels during the first 9 months (March through November 2020) of the COVID-19 pandemic. Moreover, the incidence of COVID-19 was 50–80 times lower than the incidence in European countries and the United States. The total number of 38 cases with Kawasaki disease for the 9 months during the COVID-19 pandemic was 46.3% (−3.5 standard deviations [SDs] of the average [82.0; SD, 12.7 cases] for the corresponding 9 months of the previous 5 years. None of the 38 cases was determined to be triggered by COVID-19 based on their medical histories and negative results of severe acute respiratory syndrome coronavirus 2 testing at admission. Conclusion: These observations provide a new epidemiological evidence for the notion that Kawasaki disease is triggered by major infectious diseases in children.