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A man in his 60s developed a pancreatic pseudocyst postoperatively after an open graft replacement for a ruptured abdominal aortic aneurysm. Endoscopic drainage was performed; however, this led to an aortic graft infection due to macroscopic communication with the perigraft cavity. Percutaneous drainage was performed to manage the pancreatic fistula and graft infection simultaneously. Although the pancreatic pseudocyst diminished, the aortic graft infection persisted. Subsequently, partial aortic graft replacement with greater omental flap coverage was performed. He was discharged with oral antibiotics, with no recurrence of infections at 10 months., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist, leading to increased mortality. A cryoballoon-based approach is a potential treatment for patients with HF because of its safety and efficacy., Objectives: The authors sought to evaluate the optimal timing of cryoballoon ablation after the first clinical diagnosis of AF and its prognosis for patients with HF., Methods: This large-scale multicenter study retrospectively collected data of patients with HF who underwent cryoballoon ablation for AF from 17 Japanese institutions. Patients were divided into 2 groups depending on the duration between the first diagnosis and ablation using a median time of 0.5 year (IQR: 0.3-2.0 years). Clinical endpoints of recurrence, mortality, and HF hospitalization were compared between the 2 groups., Results: Among 3,655 patients, 543 with HF were included for analysis. During a median follow-up period of 21.3 months (IQR: 12.0-36.8 months), 151 of 520 patients (29%) had a recurrence. The AF recurrence rate was significantly lower in the early-ablation group (≤0.5 year) than in the delayed-ablation group (>0.5 year) (24% [65/266] vs 34% [86/254], respectively; P  = 0.018). In the multivariable analysis, early ablation ≤ 0.5 year was independently associated with an absence of recurrence (HR: 0.581; 95% CI: 0.401-0.842; P  = 0.004). Delayed time for cryoballoon ablation incrementally increased the risk of postablation recurrence. Antiarrhythmic drug use was independently associated with delayed ablation. No significant differences in mortality or HF hospitalization were observed between the 2 groups., Conclusions: Early cryoablation reduced the risk of recurrence in patients with HF, which may help improve clinical management., Competing Interests: Drs Yanagisawa and Shibata are affiliated with a department sponsored by Medtronic Japan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

The link between changes in astrocyte function and the pathological progression of Alzheimer's disease (AD) has attracted considerable attention. Interestingly, activated astrocytes in AD show abnormalities in their lipid content and metabolism. In particular, the expression of apolipoprotein E (ApoE), a lipid transporter, is decreased. Because ApoE has anti-inflammatory and amyloid β (Aβ)-metabolizing effects, the nuclear receptors, retinoid X receptor (RXR) and LXR, which are involved in ApoE expression, are considered promising therapeutic targets for AD. However, the therapeutic effects of agents targeting these receptors are limited or vary considerably among groups, indicating the involvement of an unknown pathological factor that modifies astrocyte and ApoE function. Here, we focused on the signaling lipid, sphingosine-1-phosphate (S1P), which is mainly produced by sphingosine kinase 2 (SphK2) in the brain. Using astrocyte models, we found that upregulation of SphK2/S1P signaling suppressed ApoE induction by both RXR and LXR agonists. We also found that SphK2 activation reduced RXR binding to the APOE promoter region in the nucleus, suggesting the nuclear function of SphK2/S1P. Intriguingly, suppression of SphK2 activity by RNA knockdown or specific inhibitors upregulated lipidated ApoE induction. Furthermore, the induced ApoE facilitates Aβ uptake in astrocytes. Together with our previous findings that SphK2 activity is upregulated in AD brain and promotes Aβ production in neurons, these results indicate that SphK2/S1P signaling is a promising multifunctional therapeutic target for AD that can modulate astrocyte function by stabilizing the effects of RXR and LXR agonists, and simultaneously regulate neuronal pathogenesis., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Right ventricular outflow tract reconstruction is repeatedly required after the Rastelli procedure. However, standard right ventricular outflow tract reconstruction using direct anastomosis on the posterior right ventricular outflow tract wall is unfeasible in cases with severe calcification. Herein, we present a novel technique called the "lantern procedure," which can fix the prosthetic pulmonary valve without anastomosis to the calcified right ventricular outflow tract wall., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Obesity and diabetes mellitus are associated with increased risk of arterial thrombosis and venous thromboembolism. Tsumura Suzuki Obese Diabetes (TSOD) mice are useful models for elucidating the molecular mechanisms of these diseases. We investigated normoglycemic [Ng]-TSOD mice with a metabolic abnormality that was accompanied by a coagulative and fibrinolytic state with a phenotype that distinctly differed from that of standard TSOD mice. As in TSOD mice, plasminogen activation inhibitor-1 (PAI-1) that inhibits fibrinolysis was substantially augmented in Ng-TSOD mice, suggesting that they are hypofibrinolytic. However, blood clotting parameters were within the normal range in Ng-TSOD mice. These findings indicated that Ng-TSOD mice are novel models with a hypofibrinolytic phenotype that is not associated with hyperglycemia.

Purpose: There is controversy regarding which internal thoracic artery (ITA) should be anastomosed to the left anterior descending artery (LAD). Here, we propose an optimal graft design based on measurement of blood flow in the ITA., Methods: Sixty-one patients (53 men, median age 68 [62-75] years) undergoing first elective coronary artery bypass grafting were enrolled. Fifty-seven left ITAs (LITAs) and 28 right ITAs (RITAs) were harvested in either a semi-skeletonized manner using a harmonic scalpel covered with papaverine-soaked gauze (group-A, n = 45) or a fully skeletonized manner using electrocautery with intraluminal papaverine injection (group-B, n = 41). Free flow of 33 ITAs was measured after pharmacological dilatation and in situ ITA-LAD flow was measured in 59 patients by transit-time flowmetry., Results: RITA and LITA free flow were 147.0 [87.8-213.0] mL/min and 108.0 [90.0-144.0] mL/min, respectively (P = 0.199). The group-B had significantly higher ITA free flow (135.0 [102.0-171.0] mL/min) than group-A (63.0 [36.0-96.0] mL/min, P = 0.009). In 13 patients with bilateral ITA harvesting, free flow of the RITA (138.0 [79.5-204.0] mL/min) was also significantly higher than the LITA (102.0 [81.0-138.0] mL/min, P = 0.046). There was no significant difference between RITA and LITA flow anastomosed to the LAD. The group-B had significantly higher ITA-LAD flow (56.5 [32.3-73.6] mL/min) than group-A (40.9 [20.1-53.7] mL/min, P = 0.023)., Conclusion: RITA provides significantly higher free flow than LITA but similar blood flow to the LAD. Full skeletonization with intraluminal papaverine injection maximizes both free flow and ITA-LAD flow., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Aducanumab, co-developed by Eisai (Japan) and Biogen (U.S.), has received Food and Drug Administration approval for treating Alzheimer's disease (AD). In addition, its successor antibody, lecanemab, has been approved. These antibodies target the aggregated form of the small peptide, amyloid-β (Aβ), which accumulates in the patient brain. The "amyloid hypothesis" based therapy that places the aggregation and toxicity of Aβ at the center of the etiology is about to be realized. However, the effects of immunotherapy are still limited, suggesting the need to reconsider this hypothesis. Aβ is produced from a type-I transmembrane protein, Aβ precursor protein (APP). One of the APP metabolites, the 99-amino acids C-terminal fragment (C99, also called βCTF), is a direct precursor of Aβ and accumulates in the AD patient's brain to demonstrate toxicity independent of Aβ. Conventional drug discovery strategies have focused on Aβ toxicity on the "outside" of the neuron, but C99 accumulation might explain the toxicity on the "inside" of the neuron, which was overlooked in the hypothesis. Furthermore, the common region of C99 and Aβ is a promising target for multifunctional AD drugs. This review aimed to outline the nature, metabolism, and impact of C99 on AD pathogenesis and discuss whether it could be a therapeutic target complementing the amyloid hypothesis.

Given its limited accessibility, the CA2 area has been less investigated compared to other subregions of the hippocampus. While the development of transgenic mice expressing Cre recombinase in the CA2 has revealed unique features of this area, the use of mouse lines has several limitations, such as lack of specificity. Therefore, a specific gene delivery system is required. Here, we confirmed that the AAV-PHP.eB capsid preferably infected CA2 pyramidal cells following retro-orbital injection and demonstrated that the specificity was substantially higher after injection into the lateral ventricle. In addition, a tropism for the CA2 area was observed in organotypic slice cultures. Combined injection into the lateral ventricle and stereotaxic injection into the CA2 area specifically introduced the transgene into CA2 pyramidal cells, enabling us to perform targeted patch-clamp recordings and optogenetic manipulation. These results suggest that AAV-PHP.eB is a versatile tool for specific gene transduction in CA2 pyramidal cells., (© 2023. The Author(s).)

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder and the most common cause of dementia in the elderly. The presence of large numbers of senile plaques, neurofibrillary tangles, and cerebral atrophy is the characteristic feature of AD. Amyloid β peptide (Aβ), derived from the amyloid precursor protein (APP), is the main component of senile plaques. AD has been extensively studied using methods involving cell lines, primary cultures of neural cells, and animal models; however, discrepancies have been observed between these methods. Dissociated cultures lose the brain's tissue architecture, including neural circuits, glial cells, and extracellular matrix. Experiments with animal models are lengthy and require laborious monitoring of multiple parameters. Therefore, it is necessary to combine these experimental models to understand the pathology of AD. An experimental platform amenable to continuous observation and experimental manipulation is required to analyze long-term neuronal development, plasticity, and progressive neurodegenerative diseases. In the current study, we provide a practical method to slice and cultivate rodent hippocampus to investigate the cleavage of APP and secretion of Aβ in an ex vivo model. Furthermore, we provide basic information on Aβ secretion using slice cultures. Using our optimized method, dozens to hundreds of long-term stable slice cultures can be coordinated simultaneously. Our findings are valuable for analyses of AD mouse models and senile plaque formation culture models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kamikubo, Jin, Zhou, Niisato, Hashimoto, Takasugi and Sakurai.)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the SFTS virus (SFTSV). SFTSV causes severe symptoms both in humans and cats. In this study, we report the clinical and pathological findings of 4 fatal cases of cats with high SFTS viremia levels. These cats showed an acute onset of fever, leukopenia, thrombocytopenia, and increased serum amyloid A and pro-inflammatory cytokine levels. A high viral copy number was detected in the blood, oral swabs, rectal swabs, conjunctiva swabs, and urine. Histopathologically, necrotizing lymphadenitis, splenitis with lymphoblastoid cell proliferation, and hemophagocytosis were observed in all 4 cats. Immunohistochemistry revealed the presence of SFTSV antigen on lymphoblastoid B cells. SFTSV-RNA was detected in systemic tissues, including the brain. The present findings provide useful information for understanding the features of fatal SFTS in cats. To elucidate the mechanisms of severe progress of SFTS cats, as well as its role as a source of human infection, further research is needed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 ( RUNX1 ) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo . We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo . Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.