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Alzheimer disease (AD) is the most common type of dementia and accounts for the largest proportion of dementia cases. The amyloid cascade hypothesis is known for the pathogenesis of AD, in which excessive accumulation of amyloid-β (Aβ) leads to the formation of senile plaques and ultimately to AD. Inhibition of β-secretase (BACE1) may contribute to the treatment of AD by suppressing Aβ production. In this study, we isolated and characterized the activity of new and known BACE1-inhibiting compounds from two mushrooms of the Boletales order, Suillus bovinus and Boletinus cavipes, using a BACE1-inhibitory activity-guided separation approach. Three compounds (1-3) were isolated from Suillus bovinus CHCl 3 extract and three compounds (4-6) were isolated from Boletinus cavipes CHCl 3 extract. Compound 1 was a new compound. The structures were elucidated using MS, IR, and NMR. Compounds 1-6 showed BACE1-inhibitory activity (IC 50 ; 21.2, 17.8, 1.0, 1.6, 23.7, and 22.8 μM, respectively). To examine the structure-activity relationship, we also evaluated the activity of geranylgerniol, farnesol, 2,5-dihydroxy-1,4-benzoquinone and mesaconic acid. These compounds showed no activity, and these results indicate that chain terpenes alone do not show BACE1-inhibitory activity, but only when mesaconic acid or a quinone with a hydroxyl group is bound. In addition, the mode of inhibition of 2 and 3 were competitive and 4 was uncompetitive inhibition, respectively, as determined by analysis of Lineweaver-Burk and Dixon plots., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

The number of patients with Alzheimer's disease (AD) is expected to increase as the population ages. The amyloid cascade hypothesis is proposed as the pathogenic mechanism of AD. We report the isolation and structural determination of three new p-terphenyl compounds, thelephantin P (1), thelephantin Q (2), and thelephantin R (3), with four known compounds (4-7), from the fruiting bodies of Thelephora aurantiotincta Corner. We evaluated Aβ aggregation and BACE1 inhibitory activities and neuroprotective activities of these isolated compounds. Compound 1 was shown to be multi-inhibitors for AD. Compound 1 had an IC 50  = 12.9 μM (Aβ), 6.3 μM (BACE1), and EC 50  = 8.0 μM (neuroprotection), respectively. Therefore, these compounds are potential therapeutic agents for AD., Competing Interests: Declarations. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Persistent inflammation during chronic human immunodeficiency virus (HIV) infection may affect the immune response against severe acute respiratory syndrome-coronavirus 2 (SARS- CoV-2) infection. Plasma levels of multiple proinflammatory cytokines during acute SARS-CoV-2 infection were measured in people with HIV (PWH) with effective combination antiretroviral therapy. There were no significant differences in any of the measured cytokines between severity levels of coronavirus disease 2019 (COVID-19) in PWH, while most were significantly higher in HIV-uninfected individuals with severe COVID-19, suggesting that excess cytokines release by hyperinflammatory responses do not occur in individuals with severe COVID-19 with HIV infection. The strong associations between the cytokines observed in HIV-uninfected individuals, particularly between IFN-α/TNF-α and other cytokines, were lost in PWH. The steady-state plasma levels of IP-10, ICAM-1, and CD62E were significantly higher in PWH, indicating that they were in an enhanced inflammatory state. The absence of several inter-cytokine correlations was observed in in vitro lipopolysaccharide stimulus-driven cytokine production in PWH. These data suggest that inflammatory responses during SARS-CoV-2 infection in PWH are distinct from those in HIV-uninfected individuals, partially because of the underlying inflammatory state and/or impairment of innate immune cells.

Sialidases (or neuraminidases) catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly the removal of the terminal Sia on glycans (desialylation) of either glycoproteins or glycolipids. Therefore, sialidases can modulate the functionality of the target glycoprotein or glycolipid and are involved in various biological pathways in health and disease. In mammalian cells, there are four kinds of sialidase, which are Neu1, Neu2, Neu3, and Neu4, based on their subcellular locations and substrate specificities. Neu1 is the lysosomal sialidase, Neu2 is the cytosolic sialidase, Neu3 is the plasma membrane-associated sialidase, and Neu4 is found in the lysosome, mitochondria, and endoplasmic reticulum. In addition to specific subcellular locations, sialidases can translocate to different subcellular localizations within particular cell conditions and stimuli, thereby participating in different cellular functions depending on their loci. Lysosomal sialidase Neu1 can translocate to the cell surface upon cell activation in several cell types, including immune cells, platelets, endothelial cells, and epithelial cells, where it desialylates receptors and thus impacts receptor activation and signaling. On the other hand, cells secrete sialidases upon activation. Secreted sialidases can serve as extracellular sialidases and cause the desialylation of both extracellular glycoproteins or glycolipids and cell surface glycoproteins or glycolipids on their own and other cells, thus playing roles in various biological pathways as well. This review discusses the recent advances and understanding of sialidase translocation in different cells and secretion from different cells under different conditions and their involvement in physiological and pathological pathways., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interests with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Photochemical reactions are powerful tools for synthesizing organic molecules. The input of energy provided by light offers a means to produce strained and unique molecules that cannot be assembled using thermal protocols, allowing for the production of immense molecular complexity in a single chemical step. Furthermore, unlike thermal reactions, photochemical reactions do not require active reagents such as acids, bases, metals, or enzymes. Photochemical reactions play a central role in green chemistry. This article reports the isolation and structure determination of four new compounds (1-4) from the photoreaction products of the Polyozellus multiplex MeOH ext. The structures of the new compounds were elucidated using MS, IR, comprehensive NMR measurements and microED. The four compounds were formed by deacetylation of polyozellin, the main secondary metabolite of P. multiplex, and addition of singlet oxygen generated by sunlight. To develop drugs for treating Alzheimer's disease (AD) on the basis of the amyloid cascade hypothesis, the compounds (1-4) obtained by photoreaction were evaluated for BACE1 inhibitory activity. The hydrolysates (5 and 6) of polyozellin, the main secondary metabolites of P. multiplex, were also evaluated. The photoreaction products (3 and 4) and hydrolysates (5 and 6) of polyozellin showed BACE1 inhibitory activity (IC 50 : 2.2, 16.4, 23.3, and 5.3 μM, respectively)., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Purpose: To examine the surgical findings of ruptured abdominal aortic aneurysm (RAAA) based on the open-first strategy in the last decade, and to analyze the predictors of in-hospital mortality for RAAA in the endovascular era., Methods: The subjects of this retrospective study were 116 patients who underwent RAAA repair, for whom sufficient data were available [25% female, median age 76 (70-85) years]. Sixteen (13.8%) patients were managed with endovascular aneurysm repair (EVAR) and 100 patients (86.2%) were managed with open surgical repair (OSR)., Results: Univariate analysis identified base excess (BE) (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.79-0.96; p = 0.006), and preoperative cardiopulmonary arrest (CPA) [OR] 15.4; 95% [CI] 1.30-181; p = 0.030), BE (OR 0.88; 95% CI 0.79-0.96; p = 0.006), shock index (OR 2.44; 95% CI 1.01-5.94; p = 0.050), lactic acid (Lac) (OR 1.18; 95% CI 1.02-1.36; p = 0.026), and blood sugar (BS) > 215 (OR 3.46; 95% CI 1.10-10.9; p = 0.034) as positive predictors of hospital mortality., Conclusions: The findings of this study suggest that a first-line strategy of OSR for ruptured AAAs is acceptable. Poor preoperative conditions, including a high shock index, CPA, low BE, high Lac, and a BS level > 215 mg/dl, were identified as predictors of hospital mortality, rather than the procedures themselves., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Ethnopharmacological Relevance: The terrestrial stems of Ephedra (Ephedra spp.; including Ephedra sinica Stapf and Ephedra przewalskii Stapf) extracts are used in traditional medicines in East Asia. In Japan, the Kampo formula containing E. sinica extract is prescribed for the treatment of the common cold, influenza virus infections, and mild symptoms of coronavirus disease 2019 (COVID-19). Although ephedrine alkaloids in E. sinica exert antitussive effects, they may have side effects associated with the sympathetic nervous system. E. przewalskii extract, a drug used in traditional Uyghur and Mongolian medicine, is considered to be free of ephedrine alkaloids and is a promising candidate for the treatment of infectious diseases. However, its use is currently limited because evidence of its antiviral efficacy remains inconclusive., Aim of the Study: We compared the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) effects of E. przewalskii and E. sinica extracts in vitro. Additionally, we examined the differences in their antiviral effects against different SARS-CoV-2 strains., Materials and Methods: VeroE6/TMPRSS2 cells were infected with SARS-CoV-2 (Conventional, Delta, and Omicron strains-BA.1, BA.2, BA.4, and BA.5), and lysates prepared from each herbal extract were added. The infectious titer was determined using the 50% tissue culture infectious dose (TCID 50 ) method; in turn, the half-maximal inhibitory concentration (IC 50 ) was calculated for each extract to compare the antiviral efficacy of E. sinica and E. przewalskii extracts. Further, the extracts were compared with remdesivir for their antiviral efficacy against the conventional viral strain. To verify the effect of the inactivation of virus particles, these extracts were added to each SARS-CoV-2 strain, and the infectious titers were determined using the TCID 50 method., Results: The antiviral efficacy (i.e., IC 50 ) of the E. przewalskii extract against each SARS-CoV-2 strain was 2.7-10.8-fold greater than that of the E. sinica extract. The antiviral efficacy of the E. przewalskii extract against conventional viral strains was compared with that of remdesivir, which was 1/27.6 of remdesivir's efficacy. The E. sinica extract showed minimal inactivation of virus particles of each strain, whereas the E. przewalskii extract resulted in substantial viral inactivation., Conclusions: The E. przewalskii extract showed higher antiviral activity against SARS-CoV-2 than the E. sinica extract. Overall, our study suggests that E. przewalskii extract can be used for the treatment of viral infections, including COVID-19., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The human skin microbiome consists of many species of bacteria, including Staphylococcus aureus and S. epidermidis. Individuals with atopic dermatitis (AD) have an increased relative abundance of S. aureus, which exacerbates the inflammation of AD. Although S. epidermidis, a main component of healthy skin microbiota, inhibits the growth of S. aureus, the balance between S. epidermidis and S. aureus is disrupted in the skin of individuals with AD. In this study, we found that Citrobacter koseri isolated from patients with AD produces substances that inhibit the growth of S. epidermidis. Heat-treated culture supernatant (CS) of C. koseri inhibited the growth of S. epidermidis but not S. aureus. The genome of C. koseri has gene clusters related to siderophores and the heat-treated CS of C. koseri contained a high concentration of siderophores compared with the control medium. The inhibitory activity of C. koseri CS against the growth of S. epidermidis was decreased by the addition of iron, but not copper or zinc. Deferoxamine, an iron-chelating agent, also inhibited the growth of S. epidermidis, but not that of S. aureus. These findings suggest that C. koseri inhibits the growth of S. epidermidis by interfering with its iron utilization., 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 © 2023 Elsevier Inc. All rights reserved.)

We present a diagnostically challenging case of intimal sarcoma of the pulmonary artery (PA) due to the histologic finding of a sclerosing appearance with no appreciable spindle/pleomorphic cell proliferation. Initial endarterectomy specimens were composed of sclerosing extracellular matrix with a few bland cells, some recanalization, and fibrin thrombi, impeding the confirmation of intimal sarcoma as these findings were also consistent with chronic thromboembolic pulmonary hypertension. However, the patient experienced recurrence 5 years later, and the second endarterectomy specimens revealed more firm and solid mass and the proliferation of atypical spindle/pleomorphic cells within a myxomatous matrix in the distal PA, leading to the definitive diagnosis of undifferentiated intimal sarcoma of the PA. The archival specimens from the endarterectomy confirmed intense MDM2 expression by immunohistochemistry, suggesting its role as a potential diagnostic marker for intimal sarcoma. This case highlights that prominent sclerosing extracellular matrix with very few atypical cells should raise the possibility of intimal sarcoma of the PA and that high index of suspicion, generous sampling, and ancillary tests are critical for accurate diagnosis. In this case, the tumor was incidentally removed by endarterectomy, resulting in 5 years of survival., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Candidemia is a life-threatening disease common in immunocompromised patients, and is generally caused by the pathogenic fungus Candida albicans. C. albicans can change morphology from yeast to hyphae, forming biofilms on medical devices. Biofilm formation contributes to the virulence and drug tolerance of C. albicans, and thus compounds that suppress this morphological change and biofilm formation are effective for treating and preventing candidemia. Marine organisms produce biologically active and structurally diverse secondary metabolites that are promising lead compounds for treating numerous diseases. In this study, we explored marine-derived fungus metabolites that can inhibit morphological change and biofilm formation by C. albicans. Enniatin B (1), B1 (2), A1 (3), D (4), and E (5), visoltricin (6), ergosterol peroxide (7), 9,11-dehydroergosterol peroxide (8), and 3β,5α,9α-trihydroxyergosta-7,22-dien-6-one (9) were isolated from the marine-derived fungus Fusarium sp. Compounds 1-5 and 8 exhibited inhibitory activity against hyphal formation by C. albicans, and compounds 1-3 and 8 inhibited biofilm formation by C. albicans. Furthermore, compounds 1-3 decreased cell surface hydrophobicity and expression of the hypha-specific gene HWP1 in C. albicans. Compound 1 was obtained in the highest yield. An in vivo evaluation system using silkworms pierced with polyurethane fibers (a medical device substrate) showed that compound 1 inhibited biofilm formation by C. albicans in vivo. These results indicate that enniatins could be lead compounds for therapeutic agents for biofilm infections by C. albicans., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Aims: In COVID-19 pneumonia, early detection and appropriate treatment are essential to prevent severe exacerbation. Therefore, it is important to understand the initiating events of COVID-19 pneumonia. However, at present, the literature about early stage disease has been very limited. Here, we investigated the earliest histopathological changes and gene expression profiles associated with COVID-19 pneumonia., Methods and Results: We carefully examined 25 autopsied cases with different clinical courses. Dilation of capillaries and edematous thickening of the alveolar septa were found even in areas that macroscopically looked almost normal. Pneumocytes, histocytes/macrophages, and vascular endothelial cells were immunohistochemically positive for tissue factor, which is an important early responder to tissue injuries. Comprehensive gene expression analyses revealed that those lesions presented differential profiles compared to those of control lungs and were associated with a significant upregulation of the lysosomal pathway., Conclusions: Alveolar capillary dilation and edematous thickening may be the earliest histopathological change detected in COVID-19 pneumonia. Intensive investigations of such lesions may lead to an understanding of the initiating event of not only COVID-19 pneumonia but also of general diffuse alveolar damage., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Alzheimer's disease (AD) is an important human disease that mainly causes cognitive impairments. Growing evidence has shown that amyloid-β (Aβ) peptide plays a key role in AD pathogenesis in what is known as the Aβ cascade hypothesis. This hypothesis suggests the importance of suppressing Aβ aggregation and Aβ production. The latter process is governed by β-site APP Cleaving Enzyme1 (BACE1) and γ-secretase. We, therefore, focused on Aβ aggregation inhibitory activity, initially assessing numerous extracts derived from our marine-derived fungus collections. One EtOAc extract derived from an Aspergillus sp. exhibited Aβ aggregation inhibitory activity. Eleven known compounds (1-11) were isolated from CHCl 3 and EtOAc extracts derived from the fungus, and the structures were identified based on MS, NMR, and ECD spectra. Compounds 2, 6, and 10 inhibited Aβ aggregation with IC 50 values of 2.8, 3.9, and 8.1 μM, respectively. The protective effect on SH-SY5Y cells against Aβ toxicity was also evaluated, and compounds 6 and 10 significantly alleviated Aβ toxicity. BACE1 inhibitory activity was also examined, and compounds 4, 5, 7, 10, and 11 inhibited BACE1 activity with IC 50 values of 14.9, 70.0, 36.5, 28.0, and 72.8 μM, respectively. These data suggest that compound 10 could be useful in AD treatment., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Objectives: This study aimed to reveal the association between lower-profile stent graft (LPSG) and embolism during thoracic endovascular aortic repair for non-dissecting distal arch and descending thoracic aortic aneurysm., Methods: This study reviewed data of 35 patients who underwent thoracic endovascular aortic repair with LPSG (27 males; age: 77 ± 9.2 years) and 312 who underwent thoracic endovascular aortic repair with conventional-sized stent graft (CSSG) (247 males; age: 77 ± 7.4 years) from 2009 to 2021., Results: The rate of total embolic events was significantly lower in the LPSG group (0/35 [0%]) than the CSSG group (34/312 [11.2%]) (P = 0.035). Shaggy aorta (odds ratio: 5.220; P < 0.001) were identified as positive embolic event predictors. The rate of total embolic events in 68 patients with shaggy aorta (12 in LPSG/56 in CSSG) was significantly lower in the LPSG group (0/12 [0%]) than the CSSG group (19/56 [34%]) (P = 0.015). The rate of total embolic events in 279 patients with the non-shaggy aorta (23 in LPSG/256 in CSSG) reveals no difference between the 2 groups (0 [0%]/16 [6.3%]) (P = 0.377)., Conclusions: LPSG usage could reduce embolism in thoracic endovascular aortic repair, and the difference was more pronounced in patients with the shaggy aorta. LPSG might be beneficial in preventing embolism in thoracic endovascular aortic repair for patients with a shaggy aorta., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: The optimal treatment for acute type A aortic dissection (AAAD) with thrombosed false lumen (T-FL) of the ascending aorta remains controversial. The goal of this study was to evaluate clinical outcomes of initial medical treatment (IMT) and the effectiveness of thoracic endovascular aortic repair (TEVAR) for AAAD with T-FL., Methods: We retrospectively analysed 60 patients with AAAD with T-FL. Emergency aortic repair was performed in 33 patients, and IMT was selected in 27 uncomplicated patients with ascending aortic diameter < 50 mm and ascending T-FL thickness ≤ 10 mm., Results: Among the 27 patients who received IMT, 14 had intramural haematomas at admission; however, new ulcer-like projections appeared in 7 (50%) during hospitalization. Before discharge, 12 (44%) were given medical treatment only, and 15 (56%) required delayed aortic repair including TEVAR in 8 and open repair in 7. The median interval from onset to delayed repair was 9 days, and significantly more patients received TEVAR compared to those receiving emergency repair (53% vs 21%; P = 0.043). Between the TEVAR (n = 15) and the open repair (n = 33) groups, 1 (7%) 30-day death occurred in the TEVAR group, whereas no in-hospital deaths occurred in the open repair group. During the median follow-up time of 24.8 months, no aorta-related death was observed, and there were no statistically significant differences in the rate of freedom from aortic events (TEVAR: 92.8%/3 years vs open repair: 88.4%/3 years; P = 0.871)., Conclusions: Our management, using a combination of emergency aortic repair, IMT and delayed aortic repair for AAAD with T-FL, achieved favourable clinical outcomes. Among the selected Japanese patients, IMT with repeated multidetector computed tomography could detect a new intimal tear that could be closed by TEVAR in some cases. Using EVAR for this pathology resulted in acceptable early and midterm outcomes. Further investigations are required to validate the safety and efficacy of this management procedure., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The early and long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been established by several high-volume centers, but the impact of postoperative residual pulmonary hypertension affecting postoperative clinical parameters remains unclear. This study aims to investigate the institutional surgical results of PEA and to evaluate the efficacy of additional balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension., Patients and Methods: We retrospectively reviewed 222 patients (57.7 ± 12.9 years old, 141 female) who underwent PEA for CTEPH at the National Cerebral and Cardiovascular Center between 2000 and 2020., Results: The preoperative mean pulmonary artery pressure (mPAP) was 45.6 ± 9.7 mmHg and pulmonary vascular resistance (PVR) was 1062 ± 451 dyne*sec/cm -5 . Postoperative mPAP (23.4 ± 11 mmHg, 204 patients, P < 0.001) and PVR (419 ± 291 dyne*sec/cm -5 , 199 patients, P < 0.001) significantly improved after PEA. Since 2011, 62 patients (28%) underwent BPA after PEA for "catecholamine dependent" residual PH 1 month after PEA in 14, "scheduled" BPA with residual PH 1 year after PEA in 32, and 16 "symptomatic" patients without residual PH. Their mPAP had significantly improved by PEA (48.1 ± 7.7 to 32.0 ± 10.2 mmHg, P < 0.001), and further improved (33.8 ± 11.1 to 26.5 ± 9.1 mmHg, P < 0.001) after BPA., Conclusions: PEA provided immediate and substantial improvements in pulmonary hemodynamics and favorable long-term survival. In addition, postoperative BPA improved postoperative clinical parameters for eligible patients regardless of the presence of residual PH., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Objectives: The optimal indications and contraindications for thoracic endovascular aortic repair of retrograde Stanford type A acute aortic dissection (R-AAAD) are not well known. The goal of this study was to determine the outcomes of thoracic endovascular aortic repair for R-AAAD at our institution and to discuss optimal indications., Methods: The medical records of 359 patients admitted to our institution for R-AAAD between December 2016 and December 2022 were reviewed, and 83 patients were finally diagnosed with R-AAAD. We selected thoracic endovascular aortic repair as an alternative, considering the anatomy of aortic dissection and the risk to patients undergoing open surgery., Results: Nineteen patients underwent thoracic endovascular aortic repair for R-AAAD. No in-hospital deaths or neurologic complications occurred. A type Ia endoleak was detected in 1 patient. All other primary entries were successfully closed. All dissection-related complications, such as cardiac tamponade, malperfusion distal to the primary entry and abdominal aortic rupture, were resolved. One patient required open conversion for intimal injury at the proximal edge of the stent graft; all other ascending false lumens were completely thrombosed and contracted at discharge. During the follow-up period, no aortic-related deaths or aortic events proximal to the stent graft occurred., Conclusions: The indications for thoracic endovascular aortic repair were expanded to low-risk and emergency cases at our institution. The early- and midterm outcomes of thoracic endovascular aortic repair for R-AAAD were acceptable. Further long-term follow-up is required., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

SARS-CoV-2 continues to spread worldwide. Patients with COVID-19 show distinct clinical symptoms. Although many studies have reported various causes for the diversity of symptoms, the underlying mechanisms are not fully understood. Peripheral blood mononuclear cells from COVID-19 patients were collected longitudinally, and single-cell transcriptome and T cell receptor repertoire analysis was performed. Comparison of molecular features and patients' clinical information revealed that the proportions of cells present, and gene expression profiles differed significantly between mild and severe cases; although even among severe cases, substantial differences were observed among the patients. In one severely-infected elderly patient, an effective antibody response seemed to have failed, which may have caused prolonged viral clearance. Naïve T cell depletion, low T cell receptor repertoire diversity, and aberrant hyperactivation of most immune cell subsets were observed during the acute phase in this patient. Through this study, we provided a better understanding of the diversity of immune landscapes and responses. The information obtained from this study can help medical professionals develop personalized optimal clinical treatment strategies for COVID-19., (© 2023. The Author(s).)

Objective: Debranching thoracic endovascular aortic repair (d-TEVAR) for zone 0 landing (Z0-TEVAR) remained challenging in aortic arch aneurysms. This study aimed to compare the mid-term outcomes between Z0-TEVAR and Z1/2-TEVAR to assess the appropriateness of Z0-TEVAR as the first-line therapy for aortic arch aneurysms in high-risk patients., Methods: Medical records of 200 patients who underwent d-TEVAR from 2007 to 2019 were retrospectively reviewed. Of these, 40 patients who underwent Z0-TEVAR (70% males; the median age of 82 years) and 160 Z1/2-TEVAR (78% males; the median age of 77 years) were compared. In each group, 39 patients were matched using propensity scores (PS) to adjust for differences in patient backgrounds., Results: Freedom from all-cause mortality (p < 0.001), aorta-related mortality (p < 0.001), and stroke (p = 0.001) were significantly lower in Z0-TEVAR than in Z1/2-TEVAR. Freedom from reintervention was similar between the two groups (p = 0.326). Type A dissection post-TEVAR was observed in 3 (7.5%) of Z0-TEVAR, but none in Z1/2-TEVAR (p = 0.006). Pneumonia was also more frequent in Z0-TEVAR (n = 8, 30%) than Z1/2-TEVAR (n = 4, 2.5%) (p < 0.001). PS matching also yielded worse outcomes (all-cause mortality, p = 0.017; aorta-related mortality, p = 0.046; and stroke, p = 0.027) in Z0-TEVAR than Z1/2-TEVAR., Conclusions: Higher mid-term mortality and stroke rates after Z0-TEVAR were confirmed by PS matching. Z0-TEVAR would be an alternative for high-risk patients with arch aneurysms requiring zone 0 landing but not a reliable method., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Skin infections caused by Panton-Valentine leukocidin (PVL)-positive methicillin-resistant Staphylococcus aureus (MRSA), especially the USA300 clone, have been increasing in Japan. To prevent an epidemic of PVL-positive MRSA, rapid diagnosis and effective antimicrobial therapy are essential. However, the clinical features of, and antimicrobial efficacy against, these skin infections are not well understood in Japan. Here, we report 10 cases of skin infections caused by PVL-positive MRSA that presented over a two-year period in our clinic. Genetic analyses revealed that 90% of the PVL-positive MRSA strains were identified as USA300 and its related clones. Notably, 70% of the patients had atopic dermatitis (AD) as an underlying disease. Average durations of antimicrobial therapy for AD patients (10.6 weeks) were 2.9-fold longer than those for non-AD patients (3.7 weeks). However, all cases were improved by a long-term course of fosfomycin, minocycline, doxycycline, and/or rifampicin. Our data suggest that AD may be an important risk factor for intractable skin infections caused by PVL-positive MRSA., (© 2022 Japanese Dermatological Association.)

We performed a pilot study to assess the immunogenicity and safety of intradermal hepatitis B (HB) virus vaccines in people living with HIV (PLWH). This single-center prospective study was conducted in Yokohama, Japan. Adult PLWH with serum antibodies against HB surface antigen (anti-HBs) <10 mIU/mL at all time points after standard HB vaccination were included. We administered HB surface antigen (total dose of 10 μg) at 5 separate sites intradermally at baseline, one month, and 6-9 months and measured anti-HBs 1-3 months after administration. Eleven PLWH were included in this study. The mean age was 36 years, and all patients were men. At baseline, all patients were on antiretroviral therapy, and the mean CD4+ lymphocyte count was 588 /μL and plasma HIV-RNA was <20 copies/mL, except for one patient. Anti-HB levels were elevated to >10 mIU/mL in one patient after one dose, 6 patients after 2 doses, and 4 patients after 3 doses of the intradermal vaccines. Eight patients experienced grade 1 local adverse events. Additional vaccination via the intradermal route induced an anti-HBs level >10 mIU/mL in all patients, without serious adverse events.

We report the first case with COVID-19-like acute respiratory distress syndrome after mRNA-1273 SARS-CoV-2 vaccination. An 88-year-old woman developed dyspnea several hours after vaccination with the second dose of mRNA-1273. She was hospitalized on day nine due to worsening dyspnea. Chest computed tomography showed bilateral ground-glass opacities and consolidations, mainly in the peripheral lung areas. Repeat polymerase chain reaction tests for SARS-CoV-2 were negative, although the serum level of antibodies against spike protein was extremely elevated. Her condition did not improve with high-dose corticosteroids and high-flow nasal cannula oxygen therapy; she died on day 18. Autopsy findings revealed very early-phase diffuse alveolar damage in the whole lung without other lung diseases. The clinical and pathological findings suggested vaccine-induced acute respiratory distress syndrome. Serological and pathological tests might be useful to differentiate the disease from COVID-19., Competing Interests: Conflict of Interest Department of Infectious Disease and Respiratory Medicine of Yokohama Municipal Citizen's Hospital, to which Yukihiro Yoshimura, Hiroaki Sasaki, Nobuyuki Miyata, Kazuhito Miyazaki, and Natsuo Tachikawa belong, have received research funding from three companies, Gilead Sciences, Inc., Eli Lilly Japan K.K, and Ono Pharmaceutical Co., Ltd. in the last two years., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this study was to disclose the differences of surgical outcomes between Marfan syndrome with mutations in fibrillin-1 gene and Loeys-Dietz syndrome with mutations in transforming growth factor-beta receptor 1 and 2., Methods: We reviewed 368 patients aged less than 50 years who underwent surgery for thoracic aortic diseases between 1988 and 2019, and enrolled 99 patients with Marfan syndrome (26.9%; 57 men, 33 ± 7.5 years) and 24 patients with Loeys-Dietz syndrome (6.5%; 13 men, 28 ± 11 years)., Results: Freedom from all causes of mortality was similar between the 2 groups (P = .40, log-rank). The cumulative incidence of reintervention was significantly lower in the Marfan syndrome group than in the Loeys-Dietz syndrome group (P = .016, Gray). The cumulative incidence of first aortic arch reoperation for aortic arch aneurysm was significantly lower in the Marfan syndrome group than in the Loeys-Dietz syndrome group (P < .001, Gray). The cumulative incidence of first aortic root reoperation for aortic root aneurysm (P = .57, Gray) and first descending aorta reoperation for descending aortic aneurysm (P = .76, Gray) was similar between the 2 groups. The cumulative incidence of aortic dissection after initial surgery was significantly lower in Marfan syndrome than in Loeys-Dietz syndrome (P = .0059, Gray)., Conclusions: Loeys-Dietz syndrome with mutations in transforming growth factor-beta receptor 1 and 2 revealed higher rates of reoperation, and more specifically the arch reoperation was higher in those with Loeys-Dietz syndrome than those with Marfan syndrome. Aggressive arch surgery in the initial operation on the proximal aorta is recommendable in Loeys-Dietz syndrome to avoid additional aortic events. In Marfan syndrome, this is controversial in patients without dissection because of a low possibility to expand., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

It is sometimes difficult to identify the culprit lesion and treatment strategy in patients with acute coronary syndrome who have complex coronary lesions and jeopardized left internal mammary artery graft. This report describes a heart team approach for a non-ST-segment elevation myocardial infarction case with complex coronary vasculature. A 73-year-old man presented to the emergency department with crescendo angina. He had a history of total aortic arch replacement with concomitant coronary artery bypass graft using left internal mammary artery. Emergent coronary angiography demonstrated severe stenosis at left main trunk bifurcation caused by calcified nodule. While the bypass graft to left anterior descending coronary artery was patent, the proximal segment of left subclavian artery was occluded. Following the prompt discussion with our heart team, we performed percutaneous coronary intervention in the first step for treating the left main stenosis using rotational atherectomy into the unprotected left circumflex artery. After clinical recovery, stress myocardial scintigraphy identified the presence of anteroseptal ischemia, which indicated coronary subclavian steal syndrome due to left subclavian artery occlusion. Contrast-enhanced CT visualized that the occlusion originated from the anastomosis, suggesting the potential procedural risk of endovascular treatment by dilatation. Our heart team discussed again and decided to undergo axillo-axillary artery bypass surgery. He was discharged 8 days after the surgery without any sequelae. This is the rare case report of non-ST-segment elevation myocardial infarction who had similar condition to coronary subclavian steal syndrome after total aortic arch replacement. This case highlights the importance of a collaborative approach of the heart team to identify the best therapeutic strategy in a patient with complex coronary vasculature., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Nobunari Tomura et al.)

Objectives: The management of acute type A aortic dissection with malperfusion syndrome remains challenging. To evaluate preoperative condition, symptoms might be subjective and objective evaluation of cerebral artery has not yet been established. For quantitative evaluation, this study focused on brain computed tomography perfusion (CTP), which has been recommended by several guidelines of acute ischaemic stroke., Methods: In the last 2 years, 147 patients hospitalized due to acute type A aortic dissection were retrospectively reviewed. Among the 23 (16%) patients with cerebral malperfusion, 14 who underwent brain CTP (6 preoperative and 8 postoperative) were enrolled. CTP parameters, including regional blood flow and time to maximum, were automatically computed using RApid processing of Perfusion and Diffusion software. The median duration from the onset to hospital arrival was 129 (31-659) min., Results: Among the 6 patients who underwent preoperative CTP, 4 with salvageable ischaemic lesion (penumbra: 8-735 ml) without massive irreversible ischaemic lesion (ischaemic core: 0-31 ml) achieved acceptable neurological outcomes after emergency aortic replacement regardless of preoperative neurological severity. In contrast, 2 patients with an ischaemic core of >50 ml (73, 51 ml) fell into a vegetative state or neurological death due to intracranial haemorrhage. CTP parameters guided postoperative blood pressure augmentation without additional supra-aortic vessel intervention in the 8 patients who underwent postoperative CTP, among whom 6 achieved normal neurological function regardless of common carotid true lumen stenosis severity., Conclusions: CTP was able to detect irreversible ischaemic core, guide critical decisions in preoperative patients and aid in determining the blood pressure augmentation for postoperative management focusing on residual brain ischaemia., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Purpose: Casirivimab/imdevimab (REGN-COV), a cocktail of neutralizing antibodies against the receptor-binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, was shown to be an effective treatment and post-exposure prophylaxis measure for coronavirus disease 2019 (COVID-19). We assessed the antibody titers among patients who received REGN-COV with the purpose of evaluating this therapeutic and prophylactic option from the serological point of view., Methods: We collected serological data of patients with COVID-19 who were treated with REGN-COV 1200 mg (casirivimab 600 mg/imdevimab 600 mg). Antibody titers were assessed within 24 h before and within 48 h after the administration of REGN-COV using ARCHITECT SARS-CoV-2 immunoglobulin (Ig)G (IgG NC ), which is against nucleocapsid protein, and ARCHITECT SARS-CoV-2 IgG II Quant (IgG SP ), which is against spike protein., Results: A total of nine patients were evaluated. IgG SP was elevated after REGN-COV administration with a median of 208,370 Arbitrary Units/mL while simultaneous IgG NC remained low. With the simple linear regression model, the IgG SP after the REGN-COV administration was correlated with the reciprocal of ideal body weight., Conclusion: The high titer of IgG SP supports the clinical benefit of therapeutic and prophylactic use of REGN-COV from the serological point of view., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The rapid introduction of teleworking due to the coronavirus disease 2019 pandemic has led to concerns about increases in cyberbullying (CB) worldwide. However, little is known about workplace CB in non-Western countries. The first objective was to clarify the prevalence and characteristics regarding workplace CB victimization in Japan. The second objective was to demonstrate the psychological outcomes of CB victimization in combination with traditional bullying (TB)., Methods: We conducted an anonymous, cross-sectional, Internet-based survey targeting regular employees in Japan (N = 1200) in January 2021. We investigated CB victimization using the Inventory of Cyberbullying Acts at Work and TB victimization by using the Short Negative Act Questionnaire. Possible explanatory factors for TB/CB victimization were sociodemographic variables, personality trait, chronic occupational stress, organizational climate, and gratitude at work. We also measured psychological distress, insomnia, and loneliness to assess adverse effects of workplace bullying. Two-step cluster analysis was used in determining the patterns combined with TB and CB victimization. Hierarchical binomial logistic regression analysis was used., Results: In total, 8.0% of employees reported experiencing CB on a weekly basis. CB victimization was associated with younger age, managerial position, higher qualitative workload, and active information dissemination via the Internet, and frequency of teleworking. Three clusters based on TB and CB victimization patterns were identified: those who belong to the first cluster suffered neither from TB and CB (81.0%), the second cluster suffered only from TB (14.3%), and the third cluster suffered from both TB and CB (4.8%). The third cluster exhibited higher odds ratios (ORs) and 95% confidence intervals (CIs) for psychological distress (OR = 12.63, 95% CI = 4.20-38.03), insomnia (OR = 6.26, 95% CI = 2.80-14.01), and loneliness (OR = 3.24, 95% CI = 1.74-6.04) compared to the first cluster., Conclusions: These findings firstly clarify the prevalence and correlated factors of CB victimization among employees in Japan. Further, we showed that psychological wellbeing can be impaired by the coexistence of TB and CB. Our research could be the first step to develop the effective countermeasures against workplace CB., (© 2022. The Author(s).)

Objectives: The goal of this study was to evaluate the surgical outcomes of a valve-sparing root replacement using the reimplantation technique for annuloaortic ectasia in patients with Marfan syndrome (MFS) and in those with Loeys-Dietz syndrome (LDS)., Methods: We reviewed 103 patients with MSF with mutations in the fibrillin-1 gene and 28 patients with LDS with mutations in the transforming growth factor-beta receptor and 2, SMAD3 and transforming growth factor beta-2 from 1988 to 2020., Results: Forty-four (42.7%) patients with MFS [26 men, 31 (7.6) years] and 10 (35.7%) patients with Loeys-Dietz syndrome (LDS) [7 men, 22 (standard deviation: 8.6) years] who had no aortic dissection and underwent valve-sparing root replacement were included. The preoperative sinus diameter [46 (45-50.5) mm in those with MFS vs 48 (47-50) mm in those with LDS, p = 0.420] and the percentage of aortic insufficiency > grade 2+ [31.8% (10/44) in patients with MFS vs 10.0% (1/10) in those with LDS, p = 0.667] revealed no significant differences between the 2 groups. The cumulative incidences of aortic insufficiency greater than grade 1 (p = 0.588) and aortic valve reoperation (p = 0.310) were comparable between the 2 groups. Patients with LDS had a higher tendency towards aortic dissection after the initial operation (p = 0.061) and a significantly higher cumulative incidence of aortic reoperation (p = 0.003) versus those with MFS., Conclusions: Patients with MFS and those with LDS showed similar cumulative incidences of recurrent aortic valve insufficiency and aortic valve reoperation. Those with LDS revealed a higher cumulative incidence of aortic reoperation and a greater tendency towards aortic dissection after the initial operation compared with those with MFS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Neopterin (NP) is a biomarker for activated cellular immunity and is elevated in diseases including viral and bacterial infections, autoimmune diseases, and cancer. However, the clinical assessment of neopterin has not been used for these disorders because the physiological significance of measuring NP is obscure. It would be important to compare the NP profiles with those of other inflammation markers especially in relatively early phase of patients to reveal the significance of NP measurements in pathological states., Methods: Plasma NP, biopterin, CRP, and IL-6 levels were measured in 46 patients with Coronavirus Disease 2019 (COVID-19) and 23 patients with non-COVID-19 disorders. The correlations between these markers were analyzed in the COVID-19 and non-COVID-19 patients independently., Results: The NP levels were significantly higher in the COVID-19 patients than in the non-COVID-19 patients, while biopterin, CRP and IL-6 were not changed significantly. The NP levels were found to show a weak negative correlation against the days after onset in the COVID-19 patients ( rs = -0.348, p = 0.0192), suggesting that the elevation of NP would be an early event of viral infection. Correlations between NP and CRP, or between NP and IL-6 in COVID-19 patients were weaker than that between CRP and IL-6., Conclusions: The elevation of NP levels was supposed to be distinct from those of CRP and IL-6 in relatively early and mild COVID-19 patients. Our data suggest that NP is produced at the early phase of infection by different signaling pathways and/or cells from those of CRP and IL-6. Further study on the signaling pathway to induce NP is expected., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Purpose: This observational retrospective study aimed to identify preoperative blood test data capable of predicting preoperative shock in ruptured abdominal aortic aneurysm (rAAA)., Methods: A total of 104 patients who underwent surgery for rAAA between 2007 and 2018 were reviewed. Preoperative shock, defined as a shock index (heart rate/blood pressure) exceeding 1.5 or a maximum blood pressure < 80 mmHg, was observed in 44 patients (42%)., Results: Blood sugar (BS) (odds ratio [OR] 1.02; p < 0.001), C-reactive protein (CRP) (OR 0.57; p = 0.005), and hemoglobin (OR 0.60; p = 0.001) levels were identified as independent positive predictors of preoperative shock, and a BS level ≥ 300 mg/dl (OR 13.2; 95% CI 3.56-48.6; p < 0.001) was identified as a positive predictor of preoperative shock. The receiver operating characteristics curve analysis for BS showed that the area under the curve for the predicted probabilities was 0.84, and at a cut-off value of 215 mg/dl, the sensitivity of minimum BS for predicting preoperative shock was 86% with a specificity of 79%., Conclusions: The BS level is as an independent predictor of preoperative shock in patients with rAAA. Patients with preoperative BS levels ≥ 300 mg/dl have an extremely high risk of preoperative shock., (© 2021. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Remdesivir has been shown to reduce recovery time and mortality among patients with coronavirus disease 2019 (COVID-19). However, data regarding the efficacy and safety of remdesivir use are limited in Japan. We conducted a single-center retrospective cohort study at Yokohama Municipal Citizen's Hospital, Kanagawa, Japan. Patients with COVID-19 pneumonia treated with remdesivir were included. The onset of acute pancreatitis and increased pancreatic enzyme levels and clinical, laboratory, treatment, and outcome data were collected and analyzed. A total of 201 patients were included. Among the 201 patients treated with remdesivir, 177 recovered from COVID-19. Increased pancreatic enzyme levels of grade 3 or higher or acute pancreatitis developed in 23 of the 201 patients. The potential etiopathogenetic effects of remdesivir on increased pancreatic enzyme levels of grade 3 or higher or acute pancreatitis were ascertained by reviewing the characteristics of patients hospitalized for COVID-19 who did not receive remdesivir treatment. Only 3 of 159 patients had increased pancreatic enzyme levels of grade 3 or higher during the treatment course. Multivariate analysis indicated remdesivir administration and severe COVID-19 infection by National Institute of Health standards as independent risk factors. Acute pancreatitis and severe increases in pancreatic enzyme levels were observed among patients with COVID-19 treated with remdesivir., (© 2022. The Author(s).)

Left coronary artery malperfusion is a fatal complication of acute type A aortic dissection. However, effective treatment strategies have not yet been established. Herein, we report two cases of left coronary artery malperfusion successfully treated with different preoperative catheter interventions, followed by a central aortic repair. Preoperative coronary intervention ensuring the blood flow to the left coronary artery might be essential if a coronary angiogram was performed prior to the diagnosis and treatment., (© 2021. The Japanese Association for Thoracic Surgery.)

Lymphoma has been reported to worsen the prognosis of COVID-19 partly because it disturbs the normal production of antibodies. We treated a man with mantle cell lymphoma treated with rituximab, who developed severe COVID-19 with viral shedding that lasted for 78 days. He stayed in the intensive care unit for 28 days and did not respond to any treatment against COVID-19. His increased oxygen demand at rest eventually resolved despite the absence of anti-SARS-CoV-2-IgG. This case illustrates that recovery from COVID-19 can occur without antibody production, and that even patients with an inability to produce antibodies can recover from severe COVID-19. It also illustrates that lymphoma patients who develop severe COVID-19 while on rituximab therapy can recover from a prolonged viral shedding state if the acute lung injury can be overcome., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Ibaraki's Amabie-chan is a COVID-19 infection control system unique to Ibaraki prefecture, Japan. It requires residents to register each time they visit events, commercial facilities, and restaurants. The number of registrations has been limited, and its function alerting about people positive for COVID-19 infection seems not to be working. Nevertheless, registration with the system might have some impact on the user's behavior. In the current preliminary survey, the possible impact of Ibaraki's Amabie-chan on infection prevention behavior and fear of COVID-19 was investigated., Methods: A cross-sectional, web-based, anonymous, and self-administered survey was conducted at two workplaces in Tsukuba Science City, Ibaraki, Japan. The first survey was conducted at one of the workplaces in November 2020, and the second survey, at the other workplace in February 2021. Variables of interest were sex, age group, marital status, employment status, Ibaraki's Amabie-chan use, COVID-19 Contact-Confirming Application use, ten items of infection prevention behaviors, and fear of COVID-19. Hierarchical linear regression analysis was performed., Results: In both surveys, use of Ibaraki's Amabie-chan was significantly associated with COCOA use and with "physical condition management such as body temperature measurement." No association was found with other infection prevention behaviors or with fear of COVID-19., Conclusions: Our findings did not provide sufficient evidence for the effectiveness of Ibaraki's Amabie-chan in regard to users' infection control behavior. Further detailed study is needed to investigate the effectiveness in terms of infection prevention and the cost-effectiveness of Ibaraki's Amabie-chan.

Background: Vaccination is one of the most important tools to control the COVID-19 pandemic. However, there is little information on the antibody response in humans after the COVID-19 vaccination., Methods: This single-center, prospective study was conducted in Yokohama, Japan. We included health care workers who had received two doses of COVID-19 vaccination (BNT162b2) 21 days apart. We measured serum immunoglobulin G (IgG) to nucleoprotein and spike protein of SARS-CoV-2 with commercially available kits before and 7, 14, and 35 days after the first dose of vaccination., Results: A total of 104 workers participated in this study. Of these, 7 participants were seropositive with antibodies to spike protein at baseline and 4 of the 7 seropositive participants had COVID-19 history. The mean level of IgG to spike protein (QT) was 45.2, 1219, 2845, and 23489 AU/mL at baseline, on days 7, 14, and 35, respectively, although the values for nucleoprotein (NG) were 0.2, 0.21, 0.22, and 0.19 S/C, respectively. On day 7, QT in seropositive participants at baseline was elevated, whereas it was not elevated in seronegative participants at baseline until day 14., Conclusions: QT was elevated over the cutoff in all the participants at day 35, but NG did not change between baseline and day 35., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Although endovascular repair has become an alternative treatment for coarctation of the aorta (CoA) in adults, open repair provides concomitant repair of other cardiac complications, including post-stenotic aneurysm, ascending aortic aneurysm, and intracardiac diseases. We evaluated open anatomical repair for CoA repair in adults., Methods: Eleven patients (6 men, age range 21-63 years) underwent primary CoA repair. Complicating conditions included post-stenotic aortic aneurysm in the descending aorta in 5 patients (45.5%) and ascending aortic aneurysm in 3 (27.3%). Two patients (18.2%) had a bicuspid aortic valve, and one (9.1%) had a quadricuspid aortic valve. Ventricular septal defect was detected in 1 patient (9.1%). Eight patients (72.7%) underwent descending aorta replacement through a left thoracotomy, comprising partial cardiopulmonary bypass in 4 and deep hypothermic circulatory arrest in 4. Of those, the left subclavian artery was reconstructed in 4 patients. The remaining 3 patients (27.3%) underwent total arch replacement, through a median sternotomy in 1 and using a combination of median sternotomy and thoracotomy in 2., Results: No in-hospital mortality was observed. No spinal cord ischemia or neurological events were encountered, but 1 patient (9.1%) who underwent CoA repair via median sternotomy and thoracotomy required prolonged ventilatory support for more than 48 h. During the follow-up of 90 months (interquartile range 65-124 months), no patient died or required reintervention for the repaired segment., Conclusions: CoA in adults could be anatomically repaired with graft replacement both through the median sternotomy, the left thoracotomy, and the combination of both approaches, according to the complicated aortic or intracardiac lesions., (© 2021. The Japanese Association for Thoracic Surgery.)

A stereogenic π-system based on dimer (2) and trimer (3) of [2.2]paracyclophane (PC) and biphenyl was prepared and its structural, photophysical, and chiroptical properties were investigated. X-ray analysis revealed that the quaterphenyl moieties in 2 adopt a double helical structure anchoring [2.2]PC from both sides. Furthermore, 3 forms a isosceles triangle structure with a large chiral cavity. A homodesmotic reaction using DFT calculations revealed that 2 has a larger strain energy than 3 owing to its highly twisted phenylene linkers. Electronic and circular dichroic (CD) spectra were recorded in CH 2 Cl 2 solution. The spectra of both 2 and 3 are similar, and their longest absorption band accompanying a remarkable Cotton effect is attributed to the transition from HOMO to LUMO, which is delocalized to the quaterphenyl moiety. These compounds exhibit fairly high fluorescence quantum yields (ϕ=0.70-0.83) and moderate dissymmetry factor (|g CPL |=1.6×10 -3 ) in circularly polarized luminescence (CPL)., (© 2021 Wiley-VCH GmbH.)

Objectives: Aortic graft infection (AGI) is a serious condition associated with a high mortality rate. However, optimal surgical options have not been identified. Therefore, we retrospectively reviewed AGI cases, including those in the thoracic and abdominal regions, with or without fistula formation, to investigate the various options for better outcomes., Methods: We reviewed 50 patients who underwent surgical interventions for AGI out of 97 patients with arterial infective disease. The mean patient age was 67 ± 17 years. Fourteen patients (28%) had a fistula with the gastrointestinal tract or lung. A combination of graft excision and vascularized tissue flap coverage was performed in 25 cases (50%). Tissue flap alone, graft excision alone and cleansing alone were performed in 9 (18%), 10 (20%), and 6 cases (12%), respectively., Results: Total in-hospital mortality rate was 32% (n = 16). In-hospital mortalities in patients with and without fistulas were 43% (6/14) and 28% (10/36), respectively (P = 0.33). Subgroup analysis among patients without fistula demonstrated that the in-hospital mortality rate of the patients with vascularized tissue flap (3/21, 14%) was significantly lower than that of the patients without vascularized tissue flap (7/14, 50%, P = 0.026). Overall 1- and 5-year survival rates were 66% and 46%, respectively. In multivariable analysis, an independent factor associated with in-hospital mortality was vascularized tissue flap (odds ratio 0.20, P = 0.024)., Conclusions: Vascularized tissue flaps could provide better outcomes for AGI. Graft preservation with vascularized tissue flaps could be a useful option for AGI without fistula., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: This study aimed to reveal additional factors potentially contributing to the multifactorial ethiopathogenesis of spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) for descending thoracic aortic aneurysm (TAA)., Methods: The medical records of 293 patients who underwent TEVAR without debranching procedures for descending TAA between 2011 and 2018 were retrospectively reviewed. We excluded the following cases from the study: 72 patients with aortic dissection; 15 with rupture; 14 with anastomotic pseudoaneurysm; 22 with re-TEVAR; 34 without evaluation of the artery of Adamkiewicz (AKA). Sufficient data were available for 136 patients (79% men; mean age of 76 ± 7.4 years). We conducted univariable and multivariable analyzes using the logistic regression analysis to assess the relationship between pre-/intraoperative factors and postoperative SCI., Results: SCI was observed in nine patients (6.8%). Severe intraluminal atheroma [odds ratio (OR), 6.23; p = 0.014] and iliac artery access (OR 4.65; p = 0.043) were identified as the positive predictors of SCI by univariable analysis. Risk factors of SCI were determined additionally as follows: coverage of the intercostal artery branching AKA (ICA-AKA) (OR 4.89; p = 0.054); coverage of the ICA-AKA combined with iliac access (OR 10.1; p = 0.002); that combined with severe intraluminal atheroma (OR 13.7; p = 0.001)., Conclusion: Severe intraluminal atheroma and iliac artery access were the independent predicting factors of SCI after TEVAR for degenerative descending TAA. In patients with complicated aortoiliofemoral access route, coverage of the ICA-AKA is associated with the risk of SCI., (© 2021. The Japanese Association for Thoracic Surgery.)

Background: This study aimed to clarify how SARS-CoV-2 RNAemia is related to COVID-19 critical condition development and mortality in comparison with other predictive markers and scoring systems., Methods: This is a retrospective cohort study conducted at Yokohama Municipal Citizen's Hospital and National Institute of Infectious Diseases. We recruited adult patients with COVID-19 admitted between March 2020 and January 2021. We compared RNAemia with clinical status on admission including scoring systems such as the 4C Mortality, CURB-65, and A-DROP, as well as the Ct value of the nasopharyngeal PCR, in predicting COVID-19 mortality and critical condition development., Results: Of the 92 recruited patients (median age, 58; interquartile range, 45-71 years), 14 (14.9%) had RNAemia. These patients had an older age (median, 68 years vs. 55.5 years; p = 0.011), higher values of lactated dehydrogenase (median, 381 U/L vs. 256.5 U/L, p < 0.001), C-reactive protein (median, 10.9 mg/dL vs. 3.8 mg/dL; p < 0.001), D-dimer (median, 2.07 μg/mL vs. 1.28 μg/mL; p = 0.015), lower values of lymphocyte (median, 802/μL vs. 1007/μL, p = 0.025) and Ct of the nasopharyngeal PCR assay (median, 20.59 vs. 25.54; p = 0.021) than those without RNAemia. Univariate analysis showed RNAemia was associated with mortality (odds ratio [OR], 18.75; 95% confidence interval [CI], 3.92-89.76; area under the receiver operating characteristic curve [AUC], 0.7851; p = 0.002) and critical condition (OR, 72.00; 95% CI, 12.98-399.29; AUC, 0.8198; p < 0.001). Plus, multivariate analysis also revealed the association of RNAemia with critical condition (adjusted OR, 125.71; 95% CI, 11.47-1377.32; p < 0.001)., Conclusion: On-admission SARS-CoV-2 RNAemia is a potent predictive marker of COVID-19 critical condition and mortality. The adjusted OR for critical condition was as high as 125.71., Competing Interests: The authors have declared that no competing interests exist.

HLA-A, -C, -B, and -DRB1 genotypes were analyzed in 178 Japanese COVID-19 patients to investigate the association of HLA with severe COVID-19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA-DRB1*09:01 and severe COVID-19 (odds ratio [OR], 3.62; 95% CI, 1.57-8.35; p = 0.00251 [permutation p value = 0.0418]) when age, sex, and other common HLA alleles at the DRB1 locus were adjusted. The DRB1*09:01 allele was more significantly associated with risk for severe COVID-19 compared to preexisting medical conditions such as hypertension, diabetes, and cardiovascular diseases. These results indicate a potential role for HLA in predisposition to severe COVID-19., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: This study aimed to determine the optimal surgical procedure for arch aneurysm in the elderly based on preoperative comorbidities, especially focusing on renal function., Methods: The medical records of 374 patients who experienced arch surgery between 2008 and 2019 were reviewed. Among the 374 patients, 92 who underwent total arch replacement (TAR) were assigned to the TAR group and the remaining 152 who underwent debranching thoracic endovascular aortic repair (DTEVAR) were assigned to the DTEVAR group., Results: Chronic kidney disease (CKD) was an independent risk factor of mortality (hazard ratio, 2.85; p = 0.029) in the TAR group but not in the DTEVAR. In the Grade I/II category CKD (estimated glomerular filtration rate (eGFR) > 60 mL/min), freedom from all-cause mortality was significantly higher in the TAR group than in the DTEVAR group (p = 0.0155, log-rank). Freedom from all-cause mortality was comparable between the two groups in the Grade IIIa CKD (eGFR, 45-60) (p = 0.584, log-lank), Grade IIIb (eGFR, 30-45) (p = 0.822), and Grade IV/V (eGFR < 30) (p = 0.548)., Conclusion: In elderly patients who underwent TAR, CKD was the independent risk factor of the mortality, but not in the patients who underwent debranching TEVAR. Conversion of surgical strategy from TAR to debranching TEVAR in the treatment of aortic arch aneurysms in the elderly with CKD below Grade IIIa is acceptable considering that less-invasiveness. While, in the elderly with Grade I/II CKD, TAR still remains as a primary choice for the arch repair for better mid-term survival.

To develop drugs to treat Alzheimer's disease (AD) on the basis of the amyloid cascade hypothesis, the amyloid-β (Aβ) aggregation inhibitory activities of 110 extracts from mushrooms were evaluated by thioflavin T (Th-T) assays. The MeOH extract of Albatrellus yasudae inhibited Aβ aggregation, and the bioactivity-guided fractionation of the extract afforded four novel meroterpenoids, named scutigeric acid ( 1 ), albatrelactone methyl ester ( 2 ), albatrelactone ( 3 ), and 10',11'-dihydroxygrifolic acid ( 4 ), together with two known compounds, grifolin ( 5 ) and grifolic acid ( 6 ). The structures of 1 - 4 were elucidated using NMR, MS, UV, IR, and induced ECD spectral data. The structure of 1 was determined as a methyl ester ( 1a ) by 2D NMR spectroscopy. Th-T assays showed that compounds 1 - 4 and 1a possessed inhibitory activities against Aβ aggregation, with IC 50 values of 6.6, 40.7, 51.4, 53.3, and 50.3 μM, respectively. Notably, 1 possessed an inhibitory activity against Aβ aggregation comparable to that of myricetin as a positive control. Moreover, 1 - 6 exhibited inhibitory activities against BACE1, with IC 50 values of 1.6, 10.9, 10.5, 34.4, 6.1, and 1.4 μM, respectively.

Competing Interests: None disclosed.

Objectives: The surgical indications for acute type A aortic dissection (AAAD) in patients in cardiopulmonary arrest remain controversial. Outcomes of AAAD for patients who underwent cardiopulmonary resuscitation (CPR) were evaluated., Methods: Between 2004 and 2018, of the 519 patients who underwent AAAD repair, 34 (6.6%) required CPR before or on starting AAAD repair. The patients were divided into 2 groups, survivors (n = 13) and nonsurvivors (n = 21), to compare the early operative outcomes, including mortality and neurological events., Results: The major cause of cardiovascular collapse requiring CPR was aortic rupture/cardiac tamponade (n = 21 [61.8%]), followed by coronary malperfusion (n = 12 [35.3%]) and acute aortic valve regurgitation (n = 3 [8.8%]). There were 3 (23.1%) patients in the survivors group and 11 (52.4%) in the nonsurvivors group who required ongoing CPR at the beginning of AAAD repair (P = .039). Of these patients, 1 survivor and 6 nonsurvivors could not achieve return of spontaneous circulation after pericardiotomy (P = .045). Although the duration from onset or arrival to the operating room was similar (P = .35 and P = .49, respectively), overall duration of CPR was shorter in survivors (10 minutes [range, 7.5-16 minutes] vs 16.5 minutes [range, 15-20 minutes]; P = .044). All survivors without any neurological deficits showed return of spontaneous circulation after pericardiotomy. Multivariate regression modeling showed that CPR duration >15 minutes was a significant risk factor for in-hospital mortality (P = .0040)., Conclusions: CPR duration beyond 15 minutes may be a contraindication for AAAD repair. Moreover, we should reconsider surgery for patients who cannot achieve return of spontaneous circulation after pericardiotomy., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19). However, data regarding myeloid cell expansion have been collected in Europe, where the mortality rate by COVID-19 is greater than those in other regions including Japan. Thus, characteristics of COVID-19-induced myeloid cell subsets remain largely unknown in the regions with low mortality rates. Here, we analyzed cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis, using blood samples from Japanese COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, but not other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Contrary to previous studies in Europe, this subset selectively expanded in survivors of severe cases and subsided before discharge, but such transient expansion was not observed in non-survivors in Japanese cohort. Analysis of plasma cytokine/chemokine levels revealed positive correlation of PMN-MDSC frequencies with IL-8 levels, indicating the involvement of IL-8 on recruitment of PMN-MDSCs to peripheral blood following the onset of severe COVID-19. Our data indicate that transient expansion of the PMN-MDSC subset results in improved clinical outcome. Thus, this myeloid cell subset may be a predictor of prognosis in cases of severe COVID-19 in Japan., (© The Japanese Society for Immunology. 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pregnancy with a mechanical heart valve (MHV) is high risk for valve thrombosis because pregnancy is a hyper-coagulation state. In addition, warfarin use during pregnancy is restricted due to its fetotoxicity, and postpartum bleeding may be increased with anticoagulation. In particular, placenta previa under anticoagulation may cause massive postpartum bleeding. The optimal anticoagulation for a pregnant woman with mitral and aortic double MHVs is not known. In addition, suitable techniques for control of bleeding in a case of placenta previa under anticoagulation are not known. Thus, a case of a pregnant woman with mitral and aortic double MHVs and placenta previa is presented. The case was managed without valve thrombosis through precise unfractionated heparin dose adjustment and frequent activated partial thromboplastin time monitoring, along with maintenance of antithrombin levels. Compression sutures were found to be effective for controlling bleeding from the attachment site of placenta previa even under anticoagulation.

Six new triterpene saponins (1-5,7) and 3 known saponins (6,8,9) were isolated from MeOH extracts of the cactus Stenocereus pruinosus. The structures of the isolated saponins were elucidated using MS, IR, and comprehensive NMR measurements. To develop drugs for treating Alzheimer's disease (AD) on the basis of the amyloid cascade hypothesis, the isolated saponins were evaluated for inhibition of BACE1 activity and amyloid beta (Aβ) aggregation using thioflavin-T assay, and triterpenes as an aglycone moiety and an alkaline hydrolysate of the saponins were also evaluated. One saponin, stenoside A (7), exhibited inhibitory activity related to Aβ aggregation and its degree of Aβ aggregation was 40.6% at 100 μM.

Objective: The purpose of this study was to determine the clinical outcomes of thoracic endovascular aortic repair in 8 patients with acute type A aortic dissection with an entry tear in the descending aorta., Subjects and Methods: From January 2016 to December 2018, eight patients (mean age 76 years; range 54-92 years) were treated by thoracic endovascular aortic repair due to high operative risk for conventional open repair. All patients had significant comorbidities, and two had critical organ malperfusion due to aortic dissection. Surgical outcomes were retrospectively reviewed., Results: All procedures were technically successful with complete coverage of the entry tear. The proximal landing zone was Zone 1 in 2, Zone 2 in 1, Zone 3 in 4, and Zone 4 in 1 patient. Patients requiring Zone 1 and 2 thoracic endovascular aortic repair underwent aortic arch bypass simultaneously. Mean operation time was 132 min. There were no hospital deaths and no serious complications, including stroke and spinal cord ischemic injury. All patients had complete thrombosis and shrinkage of the false lumen in the ascending aorta before discharge. During up to 36-month follow-up (mean 20 ± 12 months), there were no adverse aortic events except one who died due to ischemic colitis 4 months after the procedure., Conclusion: Thoracic endovascular aortic repair could be a useful alternative surgical option for patients with retrograde acute type A aortic dissection with an entry in the descending aorta who are not suitable for conventional open surgery. Careful follow-up of such patients is mandatory.