Publications by authors named "Yuichi Saito"

127 Publications

Relation Between Cancer and Vasospastic Angina.

Adv Ther 2021 Jul 9. Epub 2021 Jul 9.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Introduction: Patients with cancer have an increased risk of cardiovascular disease including ischemic heart disease and vice versa. Anticancer drugs and radiotherapy are known to contribute to endothelial injury and vasospasm. However, the relations between vasospastic angina (VSA) and cancer or its treatment are poorly investigated.

Methods: A total of 786 patients underwent intracoronary acetylcholine (ACh) provocation tests to diagnose VSA. The positive ACh provocation test was defined as angiographic coronary artery spasm accompanied by chest pain and/or ischemic electrocardiographic changes. Patients were divided into active cancer, a history of cancer, and no cancer according to the status of malignancy. The impact of types of cancer, anticancer drugs, and radiotherapy on VSA was evaluated.

Results: Of 786 patients, 38 (4.8%) and 84 (10.7%) had active cancer and a history of cancer, respectively, and 401 (51.0%) were diagnosed as VSA. There was no significant difference in rates of positive ACh test among patients with active cancer, a history of cancer, and no cancer (39.5% vs. 57.1% vs. 50.9%, p = 0.20). Types of cancer and cancer treatment also had no impact on positive ACh provocation test.

Conclusions: In this cross-sectional observational study, we did not find an association of active and a history of cancer with the diagnosis of VSA. Anticancer treatment including chemotherapy and radiotherapy was not significantly associated with positive ACh provocation test.
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http://dx.doi.org/10.1007/s12325-021-01854-zDOI Listing
July 2021

Differential Impact of Clinical and Genetic Factors on High Platelet Reactivity in Patients with Coronary Artery Disease Treated with Clopidogrel and Prasugrel.

J Atheroscler Thromb 2021 Jul 8. Epub 2021 Jul 8.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.

Aim: High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear.

Methods: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units >208 were defined as HPR.

Results: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles.

Conclusions: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.
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http://dx.doi.org/10.5551/jat.63035DOI Listing
July 2021

Gene Expression Profiles of Human Cerebral Organoids Identify PPAR Pathway and as Key Markers for Oxygen-Glucose Deprivation and Reoxygenation.

Front Cell Neurosci 2021 8;15:605030. Epub 2021 Jun 8.

Department of Neurology, Nara Medical University, Kashihara, Japan.

Ischemic stroke is one of the most common neurological diseases. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown due to a lack of ischemic human brain samples. In this study, we applied cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). Pathway analysis showed the relationships between vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and complement and coagulation cascades. Combinational verification with transcriptome and gene expression analysis of different cell types revealed fatty acids-related PPAR signaling pathway and pyruvate kinase isoform M2 () as key markers of neuronal cells in response to OGD/R. These findings suggest that, although there remain some limitations to be improved, our ischemic stroke model using human cerebral organoids would be a potentially useful tool when combined with other conventional two-dimensional (2D) mono-culture systems.
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http://dx.doi.org/10.3389/fncel.2021.605030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217463PMC
June 2021

Prognostic Impact of Branch Vessel Involvement on Computed Tomography versus Clinical Presentation of Malperfusion in Patients With Type a Acute Aortic Dissection.

Am J Cardiol 2021 Aug 11;152:158-163. Epub 2021 Jun 11.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Type A acute aortic dissection (AAD) is a life-threatening disease. The use of contrast-enhanced computed tomography (CT) for diagnosing AAD has increased, and CT can provide pathophysiologic information on dissection such as intramural hematoma (IMH), longitudinal extent of dissection, and branch vessel involvement. However, the prognostic impact of these CT findings is poorly investigated. This multicenter registry included 703 patients with type A AAD. The longitudinal extent of dissection and IMH was determined on CT. Branch vessel involvement was defined as dissection extended into coronary, cerebral, and visceral arteries on CT. The evidence of malperfusion was defined based on clinical presentations. The primary endpoint was in-hospital death. Of 703 patients, 126 (18%) died during hospitalization. Based on contrast-enhanced CT findings, longitudinal extent of dissection was not associated with in-hospital death, while patients with IMH had lower in-hospital mortality than those without (13% vs 22%, p = 0.004). Coronary, cerebral, and visceral artery involvement on CT was found in 6%, 55%, and 32%. In patients with coronary artery involvement, 90% had clinical coronary malperfusion, while only 25% and 21% of patients with cerebral and visceral artery involvement had clinical evidence of corresponding organ malperfusion. Multivariable analysis showed evidence of malperfusion as a significant factor associated with in-hospital mortality. In conclusions, branch vessel involvement on CT was not always associated with end-organ malperfusion in patients with type A AAD, especially in cerebral and visceral arteries. Clinical evidence of malperfusion was significantly associated with in-hospital mortality beyond branch vessel involvement on CT.
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http://dx.doi.org/10.1016/j.amjcard.2021.05.005DOI Listing
August 2021

Construction of a computational mechanical model of bronchi for practical simulation of the optimal positive intrathoracic pressure conditions during general thoracic surgery.

Biomed Mater Eng 2021 May 6. Epub 2021 May 6.

Laboratory of Fluid-Structural Simulation and Design, Strategic Innovation and Research Center, Teikyo University, Tokyo, Japan.

Background: Thoracic CO2 insufflation with positive intrathoracic pressure is usually effective during thoracoscopic surgery, however, lung collapse is sometimes insufficient. We hypothesized that inappropriate bronchial collapse might cause this unsuccessful lung collapse.

Objective: The objective of this study was to construct a computational mechanical model of bronchi for practical simulation to discover the optimal conditions of positive intrathoracic pressure during thoracoscopic surgery.

Methods: Micro-focus high-resolution X-ray computed tomography measurements of lungs from just-slaughtered swine were extracted, and the three-dimensional geometries of the bronchi under pressurized and depressurized conditions were measured accurately. The mechanical properties of the bronchus were also measured. Computational fluid dynamics (CFD) and computational structural mechanics (CSM) analyses were conducted.

Results: The CSM results indicated that the present structural model could simulate bronchial occlusion. The CFD results showed that airflows from pressed lung alveoli might cause low-internal-pressure regions when suddenly or heterogeneously pushed airflow was injected from a small branching bronchus to a large bronchus. A preliminary computational mechanical model of bronchi was constructed.

Conclusions: We demonstrated the performance of the mechanical model of bronchi in rough simulations of bronchial occlusions. However, this model should be verified further using human data to facilitate its introduction to clinical use.
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http://dx.doi.org/10.3233/BME-211228DOI Listing
May 2021

Impact of CADILLAC and GRACE risk scores on short- and long-term clinical outcomes in patients with acute myocardial infarction.

J Cardiol 2021 May 1. Epub 2021 May 1.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: Recent guidelines recommend risk stratification using objective scoring systems in patients with acute coronary syndrome. In this context, the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) and GRACE (Global Registry of Acute Coronary Events) risk scores were both originally established to predict short-term mortality. However, their impact on short- and long-term clinical outcomes in a contemporary cohort of patients with acute myocardial infarction (MI) is unclear.

Methods: This bi-center registry included 809 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into three groups according to the pre-defined thresholds and tertiles of the CADILLAC and GRACE scores. The study endpoints included all-cause death and major adverse cardiovascular events (MACE) during the index hospitalization and after discharge.

Results: Of 809 patients, 323 (39.9%) and 255 (31.5%) had high CADILLAC and GRACE risk scores. During the index hospitalization, 61 (7.5%) patients died and 262 (32.4%) had MACE. Both CADILLAC and GRACE risk scores were associated with in-hospital mortality and MACE rates. After discharge, out of 683 patients with available follow-up information who survived to discharge, 42 (6.1%) died and 123 (18.0%) had MACE during the median follow-up period of 632 days. Significantly higher incidence of MACE in higher CADILLAC and GRACE risk scores was observed in a stepwise manner.

Conclusion: Both CADILLAC and GRACE risk scores were predictive for short- and long-term mortality and MACE rates in a contemporary cohort of acute MI patients undergoing primary percutaneous coronary intervention.
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http://dx.doi.org/10.1016/j.jjcc.2021.04.005DOI Listing
May 2021

Oncological issues in staging mediastinal lymph node metastases in left lung cancer.

Asian J Surg 2021 Apr 30. Epub 2021 Apr 30.

Department of General Thoracic Surgery, Southern Tohoku General Hospital, Research Institute for Neuroscience & Respirology, Koriyama, Japan.

Objective: We aimed to discuss the underlying oncological issues in staging of mediastinal lymph node metastasis in patients with left lung cancer who underwent extended radical lymphadenectomy (ERL).

Methods: This multi-institutional retrospective study analyzed 116 patients with left non-small-cell lung cancer who underwent bilateral paratracheal lymph node dissection (ERL) via median sternotomy. The clinicopathological records of patients with mediastinal lymph node metastasis were examined for prognostic factors, including age, sex, histology, tumor size, cN number, preoperative data, metastatic stations (number and distribution), pT, and adjuvant chemotherapy.

Results: Mediastinal lymph node metastases were found in 43 patients, and right paratracheal lymph node metastases (pN3) were found in 13 patients. The 5-year overall survival rate was 25.2% in patients with pN3 tumors (n = 13) and 23.1% in patients with pN2 tumors (n = 30). The prognosis did not differ between patients with pN3 and pN2. Univariate analyses showed that histology, cN, and adjuvant chemotherapy were significant prognostic factors in patients with mediastinal lymph node metastasis. In these 43 patients, cN and adjuvant chemotherapy were significant independent prognostic factors in multivariate analysis.

Conclusions: The prognostic factors for left lung cancer with mediastinal lymph node metastasis were cN status and adjuvant chemotherapy, and not pN status (pN2 or pN3). We hope that the study results, which suggest that there may be no difference in prognosis between pN2 and pN3, would broaden the discussion of oncological issues in the staging of mediastinal lymph node metastasis of left lung cancer.
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http://dx.doi.org/10.1016/j.asjsur.2021.04.003DOI Listing
April 2021

Layered coronary plaque associated with coronary vasospasm.

Cardiovasc Interv Ther 2021 Apr 23. Epub 2021 Apr 23.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.

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http://dx.doi.org/10.1007/s12928-021-00780-9DOI Listing
April 2021

Prognostic value of baseline and change in neutrophil-to-lymphocyte ratio for survival in advanced non-small cell lung cancer patients with poor performance status receiving PD-1 inhibitors.

Transl Lung Cancer Res 2021 Mar;10(3):1397-1407

Department of Medical Oncology, Chinese PLA General Hospital, Beijing, China.

Background: Advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS) are likely to receive programmed cell death 1 (PD-1) inhibitors, despite limited evidence. The aim of the present study was to report the clinical outcomes and potential prognostic biomarkers in advanced NSCLC patients with poor PS receiving PD-1 inhibitors.

Methods: We conducted a retrospective study enrolling 101 advanced NSCLC patients from our hospital. Data of patients with poor PS 2-4 receiving PD-1 inhibitors were retrieved from medical records. Patients were stratified based on dichotomized baseline neutrophil-to-lymphocyte ratio (NLR), change in NLR (ΔNLR; 6 weeks post-treatment NLR minus baseline NLR), and their combination. The receiver-operating characteristic curve was used to assess the best cutoff for NLR. Multivariate Cox analysis was used to evaluate the prognostic value of NLR and ΔNLR for patients' survival.

Results: The optimal cutoff for NLR was 4.5. The median follow-up was 25.7 months, baseline NLR ≥4.5, and ΔNLR ≥0, which were independently and significantly associated with shorter overall survival (both P=0.002) and progression-free survival (P=0.004 for NLR and P<0.001 for ΔNLR). Furthermore, simultaneous elevation of the 2 factors was associated with worsened prognosis; patients with both NLR ≥4.5 and ΔNLR ≥0 had significantly increased risk of death [hazards ratio (HR): 10.79, 95% confidence interval (CI): 4.30-27.10] and disease progression (HR: 10.49, 95% CI: 4.39-25.09), compared with both low NLR and ΔNLR patients. Patients with either NLR ≥4.5 or ΔNLR ≥0 showed an intermediate risk for death (HR: 3.12, 95% CI: 1.35-7.21) and progression (HR: 3.45, 95% CI: 1.62-7.36).

Conclusions: High baseline NLR and increased post-treatment NLR might aid in the stratification of high progression and death risk groups in advanced NSCLC patients with poor PS receiving PD-1 inhibitors.
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http://dx.doi.org/10.21037/tlcr-21-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044483PMC
March 2021

Academic Research Consortium Definition of High Bleeding Risk in Clinical Practice - Validation and Beyond.

Circ J 2021 May 15;85(6):806-807. Epub 2021 Apr 15.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.

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http://dx.doi.org/10.1253/circj.CJ-21-0192DOI Listing
May 2021

Impact of in-hospital blood pressure variability on clinical outcomes in patients with symptomatic peripheral arterial disease.

Hypertens Res 2021 Apr 13. Epub 2021 Apr 13.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Various types of blood pressure (BP) variability have been recognized as risk factors for future cardiovascular events. However, the prognostic impact of in-hospital BP variability in patients with symptomatic peripheral arterial disease (PAD) has not yet been thoroughly investigated. A total of 386 patients with PAD who underwent endovascular therapy in two hospitals were retrospectively included. BP variability was assessed by the coefficient of variation (CV) of systolic BP measured during hospitalization by trained nurses. The primary endpoint was a composite of major adverse cardiovascular events (cardiovascular death, acute coronary syndrome, stroke, and hospitalization for heart failure) and major adverse limb events (major amputation, acute limb ischemia, and surgical limb revascularization). The mean systolic BP and the CV of systolic BP during hospitalization were 130.8 ± 15.7 mmHg and 11.2 ± 4.1%, respectively. During the median follow-up period of 22 months, 80 patients (21%) reached the primary endpoint. Receiver operating characteristic curve analysis showed that the CV of systolic BP significantly predicted major adverse cardiovascular and limb events (area under the curve 0.60, best cutoff value 9.8, P = 0.01). Using the best cutoff value, patients with high BP variability (n = 242) had a higher risk of clinical events than those with low BP variability (n = 144) (26% vs. 12%, P < 0.001). Multivariable analysis indicated that the CV of systolic BP, age, hemodialysis, and atrial fibrillation were associated with the primary endpoint. In conclusion, greater in-hospital systolic BP variability was associated with major adverse cardiovascular and limb events in patients with symptomatic PAD undergoing endovascular therapy.
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http://dx.doi.org/10.1038/s41440-021-00648-8DOI Listing
April 2021

Clinical implications and debates on the ISCHEMIA trial.

Cardiol Rev 2021 Mar 19. Epub 2021 Mar 19.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan Department of Cardiovascular Medicine, Gifu Heart Center, Gifu, Japan.

The ISCHEMIA was eagerly awaited study in the field of ischemic heart disease. Following the presentation and publication of ISCHEMIA, multiple opinions and viewpoints get complicated. The ongoing debates have been including the relevance of coronary revascularization, non-invasive diagnostic methods, and invasive ischemic testing in patients with stable ischemic heart disease (SIHD). Prior to ISCHEMIA, observational studies indicated the potential of coronary revascularization for improving clinical outcomes, while the randomized COURAGE trial did not support the plausible concept. Although the FAME 2 trial implied the superiority of percutaneous coronary intervention over medical therapy alone, the clinical relevance of coronary revascularization to improve outcomes and quality of life has been questioned. As a consequence, the ISCHEMIA trial did not demonstrate clear benefits in reducing clinical events but showed antianginal effects of revascularization. This landmark trial also suggested the difficulties of non-invasive ischemia testing rather than computed tomography angiography. Despite the complex results, the ISCHEMIA trial may simplify the clinical indications of coronary revascularization in patients with SIHD. Future publications from the ISCHEMIA trial and debates on the results will sharpen our thinking and understanding.
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http://dx.doi.org/10.1097/CRD.0000000000000389DOI Listing
March 2021

Generation and characterization of CD19-iCre mice as a tool for efficient and specific conditional gene targeting in B cells.

Sci Rep 2021 Mar 9;11(1):5524. Epub 2021 Mar 9.

Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

The Cre/loxP system is a powerful tool for generating conditional gene knockout (KO) mice and elucidate gene function in vivo. CD19-Cre and Mb1-iCre transgenic mice are commonly used for generating B cell-specific KO mice and investigate the development, as well as the physiological and pathophysiological roles of B cells. However, the CD19-Cre line low efficiency and the Mb1-iCre line occasional ectopic recombination represent challenges for their use. Thus, we developed a CD19-codon-improved Cre (CD19-iCre) knock-in mouse with the T2A-iCre sequence inserted into the Cd19 locus, just before the stop codon. The CD19-iCre mice were compared with existing models, crossed with the Rosa26-EYFP reporter mice, and their recombination activity in B cells carrying different Cre alleles was assessed. CD19-iCre mice showed more effective Cre recombination in the early B cell developmental stages compared with the CD19-Cre mice. The efficiencies of the CD19-iCre and Mb1-iCre lines were similar; however, the B lineage-specific recombination was more stringent in the CD19-iCre line. Furthermore, the utility value of the CD19-iCre model was superior than that of the CD19-Cre mice regarding deletion efficiency in IL10-floxed mice. Thus, the CD19-iCre line is a valuable tool for highly efficient gene targeting specific to the B cell compartment.
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http://dx.doi.org/10.1038/s41598-021-84786-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943778PMC
March 2021

Comparative study of the loop-mediated isothermal amplification method and the QIAGEN PCR kit for the detection of EGFR mutations in non-small cell lung cancer.

J Thorac Dis 2021 Feb;13(2):743-753

Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.

Background: Epidermal growth factor receptor () mutations are important biomarkers in the treatment of patients with advanced or metastatic diseases. The EGFR Rotor-Gene Q (RGQ) PCR Kit (Qiagen, Inc.) is an approved diagnostic test for EGFR mutations in non-small cell lung cancer (NSCLC). This study aims to investigate the diagnostic capability of a loop-mediated isothermal amplification (LAMP) assay as an accurate, efficient, and cost-effective alternative to the assay.

Methods: EGFR mutations were investigated by LAMP and assays using tissue samples that were surgically resected or biopsied from 117 consecutive patients with NSCLC tumors. The EGFR status from the LAMP assay was compared with that of the . Next-generation sequencing (NGS) was performed to confirm EGFR status of tumors that did not match in both assays. To establish an optimal LAMP AUC value, receiver operating characteristics (ROC) curve analysis was performed within tumors with exon 19 deletion or L858R point mutation.

Results: Of the 117 tumors assayed, 45 tumors with mutations and 68 tumors with wild type were matched in both assays, four tumors having mismatched EGFR statuses. NGS further confirmed that two of the four discordant tumors had the same EGFR status that was determined by the LAMP assay. The AUC values were 0.973 (95% CI: 0.929-1.00) in exon 19 deletion, and 0.952 (95% CI: 0.885-1.00) in L858R point mutation. In exon 19 deletion, sensitivity, specificity, and accuracy were 89.3%, 98.9%, and 96.6%, respectively, and 94.7%, 95.9%, and 95.7%, respectively, in L858R using AUC value of 0.222.

Conclusions: The LAMP assay compared favorably with the assay and has potential as an effective, simple, rapid, and low-cost diagnostic alternative. Based on these results, a liquid biopsy LAMP system should be developed for point-of-care testing of oncogenes in the near future.
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http://dx.doi.org/10.21037/jtd-20-2642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947485PMC
February 2021

A Pedicled Posterior Septal-Nasal Floor Flap and a Novel Rescue Flap for Skull Base Reconstruction.

World Neurosurg 2021 Jun 6;150:197-204.e1. Epub 2021 Mar 6.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: We devised a new surgical alternative to the conventional nasoseptal flap, a pedicled posterior septal-nasal floor flap that we named the Kegon flap. We evaluated the effectiveness of this flap for skull base reconstruction in patients with high-flow cerebrospinal fluid (CSF) leakage after sellar/parasellar tumor resection.

Methods: The Kegon flap with a novel rescue flap was designed to preserve blood flow and mucosa anterior to the nasal septum and to avoid flap damage during surgery. We retrospectively evaluated postoperative flap perfusion with T1-weighted contrast-enhanced magnetic resonance imaging and characterized complications and wound healing in 5 patients who experienced high-flow CSF leakage after sellar/parasellar tumor resection requiring reconstruction.

Results: Postoperative T1-weighted contrast-enhanced magnetic resonance imaging demonstrated good flap perfusion in all patients. The area reconstructed with the Kegon flap healed within the first month following surgery. No postoperative CSF leakage or nasal hemorrhage was observed. There was no perforation of the anterior nasal septum after surgery. The mucosal defect had completely epithelialized in all patients by 3 months after surgery. There were no instances of prolonged nasal crusting or any subjective decrease in olfactory function 3 months after surgery.

Conclusions: The use of a Kegon flap with a novel rescue flap was effective and helped preserve nasal structure and function in patients undergoing skull base reconstruction after sellar/parasellar tumor resection associated with high-flow CSF leakage.
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http://dx.doi.org/10.1016/j.wneu.2021.02.138DOI Listing
June 2021

Radiological imaging and pathological findings of small lung adenocarcinoma: a narrative review.

J Thorac Dis 2021 Jan;13(1):366-371

Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.

The eighth edition of the Lung Cancer Handling Regulations defines the pathological findings of "invasion" in the pathological diagnosis of lung adenocarcinoma and terms it as adenocarcinoma in situ/minimally invasive carcinoma. In addition, the invasion diameter (tumor diameter excluding the lepidic growth region) was adopted as the pT factor, and the classification further reflected prognosis (degree of invasion/progression). Meanwhile, computed tomography imaging-based classification, where the consolidation (nodule) diameter excluding the ground glass shadow area was defined as cT, and the classification reflected the pathological invasion diameter. It is clear that the revision of the eighth edition has reduced discrepancies in the pathological findings of lung adenocarcinoma in CT imaging and assessment of the degree of invasion and progression. At the same time, the 8th edition is not yet accurate enough. Therefore, we will discuss imaging techniques to better predict the extent of adenocarcinoma invasion and progression, based on our own findings and the literature.
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http://dx.doi.org/10.21037/jtd-20-844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867796PMC
January 2021

Differential impact of abluminal groove-filled biodegradable-polymer sirolimus-eluting stent versus durable-polymer everolimus-eluting stent on and off dual antiplatelet therapy.

Catheter Cardiovasc Interv 2021 Jan 27. Epub 2021 Jan 27.

Yale University School of Medicine, New Haven, Connecticut.

Background: Current guidelines recommend dual antiplatelet therapy (DAPT) following percutaneous coronary intervention for 6-12 months in patients with acute coronary syndrome (ACS) and 3-6 months in those with chronic coronary syndromes (CCS). Whether DAPT duration has a differential effect on outcomes following treatment of ischemic coronary disease with durable versus biodegradable drug-eluting stent (DES) is poorly defined.

Methods: The TARGET All Comer study was a randomized trial of patients with ischemic coronary artery disease assigned to treatment with either a biodegradable polymer DES (Firehawk) or a durable polymer DES (XIENCE). This pre-specified TARGET AC sub-analysis sought to evaluate the 2-year clinical outcomes before and after DAPT discontinuation. The primary endpoint was target lesion failure (TLF).

Results: A total of 1,296 (78.4%) of 1,653 randomized patients were included in this substudy, of which 1,210 (93.4%) remained on DAPT at 6 months, 863 (66.6%) at 12 months, and 409 (31.6%) at 2 years. There was no difference in TLF between patients treated with Firehawk and XIENCE stents from index procedure to DAPT discontinuation (8.0 and 7.7%, p > .99) or after DAPT discontinuation (2.9 vs. 3.8%, p = .16). After DAPT discontinuation, target vessel myocardial infarction (1.3 vs. 3.3%, p = .07), and ischemia-driven target lesion revascularization (0.5 vs. 1.9%, p = .06) favored treatment with Firehawk.

Conclusions: Although TLF was comparable for both Firehawk and XIENCE stent groups before and after DAPT discontinuation, after DAPT discontinuation, there was a trend for less target vessel myocardial infarction and ischemia-driven revascularization with the biodegradable polymer DES.
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http://dx.doi.org/10.1002/ccd.29468DOI Listing
January 2021

Long-term effectiveness, safety, and quality of life outcomes following endoscopic posterior nasal neurectomy with submucosal turbinectomy for the treatment of intractable severe chronic rhinitis.

Auris Nasus Larynx 2021 Aug 11;48(4):636-645. Epub 2021 Jan 11.

Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Objective: In recent decades, posterior nasal neurectomy (PNN) with submucosal inferior turbinectomy (ST) has been increasingly used for the treatment of intractable severe rhinitis; however, to the best of our knowledge, there have been few studies regarding its long-term therapeutic effects or its influence on patient quality of life (QOL). Therefore, this study examined the long-term therapeutic effects in patients who underwent PNN with ST, as well as their QOL and medication use after surgery.

Methods: This retrospective cohort study initially included 16 consecutive patients who underwent PNN with ST from January 2010 to December 2011. Ten of the 16 patients participated in a paper-based survey questionnaire between June 2018 and November 2018; the responses of these 10 patients were used for analysis in this study. To clarify the effects of surgical treatment on symptoms, QOL, and medication status, data recorded before and 3 months after surgery were compared with data recorded at 8 years after surgery using the Japan Rhinoconjunctivitis Quality of Life Questionnaire No. 1 and Classification of the Severity of Allergic Rhinitis Symptoms I and II.

Results: Nasal symptoms including runny nose and nasal congestion, medication score, respective total symptoms medication scores (i.e., combined average total symptoms score and medication score), and the scores of troubles with daily life and total QOL were significantly improved at 3 months and 8 years after surgery, compared with before surgery; scores were not significantly worsened at 8 years after surgery, compared with 3 months after surgery. In addition, there were no adverse events requiring treatment after surgery.

Conclusion: Our findings suggest that PNN with ST is effective and safe for long-term treatment of severe chronic rhinitis symptoms, as well as reduction of medication use and improvement of QOL.
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http://dx.doi.org/10.1016/j.anl.2020.12.009DOI Listing
August 2021

IVUS Tells a Potential of Late Lumen Enlargement After CTO PCI: The Story so Far.

Cardiovasc Revasc Med 2021 Apr 31;25:18-19. Epub 2020 Dec 31.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.carrev.2020.12.029DOI Listing
April 2021

Uric acid and cardiovascular disease: A clinical review.

J Cardiol 2021 Jul 30;78(1):51-57. Epub 2020 Dec 30.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.

Uric acid, the end-product of purine metabolism in humans, is not only a cause of gout, but also may play roles in developing cardiovascular diseases such as hypertension, atrial fibrillation, chronic kidney disease, heart failure, coronary artery disease, and cardiovascular death. Several clinical investigations have reported serum uric acid as a predictive marker for cardiovascular outcomes. Although the causal relationship of hyperuricemia to cardiovascular diseases remains controversial, there has been a growing interest in uric acid because of the increased prevalence of hyperuricemia worldwide. This review article summarizes current evidence concerning the relation between hyperuricemia and cardiovascular diseases.
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http://dx.doi.org/10.1016/j.jjcc.2020.12.013DOI Listing
July 2021

Selection of Pathological N0 (pN0) in Clinical IA (cIA) Lung Adenocarcinoma by Imaging Findings of the Main Tumor.

Ann Thorac Cardiovasc Surg 2020 Dec 18. Epub 2020 Dec 18.

Department of Surgery, Teikyo University Hospital, Tokyo, Japan.

Objectives: We would like to clarify the imaging findings of the main tumor that may omit the requirement for lymph node dissection in clinical IA (cIA) lung adenocarcinoma.

Methods: A total of 336 patients with cIA lung adenocarcinomas with normal preoperative carcinoembryonic antigen (CEA) who underwent surgical resection were analyzed. We investigated the association between various computed tomography (CT) imaging findings or the maximum standardized uptake value (SUVmax) of fluorodeoxyglucose-position emission tomography (FDG-PET) and lymph node metastasis. The maximum tumor diameter was calculated from the CT images using both the lung window setting (LD) and mediastinal window setting (MD). The diameter of the solid component (CD) was defined as consolidation diameter in lung window setting. The solid component ratio (C/T) was defined as CD/LD.

Results: SUVmax, MD, and C/T were independent factors related to lymph node metastasis, but CD was not (p = 0.38). The conditions required for the positive predictive value (PPV) to reach 100% were 10.6 mm for MD, 12.5 mm for CD, and 0.55 for C/T. SUVmax did not reach 100%.

Conclusions: In cIA lung adenocarcinoma with CEA in the normal range, we found that it may be possible for lymph node dissection to be omitted by MD, CD, and C/T.
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http://dx.doi.org/10.5761/atcs.oa.20-00240DOI Listing
December 2020

Deep Neck Infection Complicated by Phlegmonous Esophagitis and Mediastinitis.

Ann Thorac Surg 2021 06 21;111(6):e403-e406. Epub 2020 Nov 21.

Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.

Descending necrotizing mediastinitis is a life-threatening disease that extends into the pretracheal, perivascular, retrovisceral, and/or prevertebral spaces, generally sparing the esophagus. We report a case of deep neck abscess complicated by phlegmonous esophagitis and mediastinitis. The patient was successfully treated with antibiotics and surgery, combining transcervical and bilateral thoracoscopic transthoracic mediastinal drainage. However, a pseudo-lumen with a large amount of pus remained in the esophagus. The septum between the true and the pseudo-lumen was cut endoscopically, after which the patient recovered well without any complications.
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http://dx.doi.org/10.1016/j.athoracsur.2020.08.101DOI Listing
June 2021

Validation of the ABCD-GENE score to identify high platelet reactivity in east Asian patients undergoing percutaneous coronary intervention.

Int J Cardiol 2021 03 19;327:15-18. Epub 2020 Nov 19.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: High platelet reactivity (HPR) is associated with subsequent thrombotic events in patients undergoing percutaneous coronary intervention (PCI). Recently, the ABCD-GENE score was developed to identify patients at risk for HPR, incorporating both clinical and genetic factors. However, this score was derived and validated in mostly Caucasian subjects and it has not been validated in an East Asian population.

Method: Individual patient data from 4 prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay on clopidogrel and genotyping of CYP2C19 was performed after PCI. Study populations included patients with general stable coronary artery disease, hemodialysis, age ≥75 and/or body weight <50 kg, and acute coronary syndrome. VerifyNow P2Y12 reactivity units >208 was defined as HPR.

Results: Of 184 patients, 111 (60%) had HPR on clopidogrel. In the receiver operating characteristics curve analyses, the ABCD-GENE score significantly predicted HPR on clopidogrel (AUC 0.78, best cut-off value 9, p < 0.001). Across the 4 studies and their combinations, the diagnostic ability and cut-off values of ABCD-GENE score for HPR on clopidogrel were consistent.

Conclusions: The ABCD-GENE score had significant and moderate diagnostic ability for HPR on clopidogrel in Japanese patients undergoing PCI. The predictivity was consistent across a broad spectrum of patient populations, suggesting the applicability of this novel scoring system in clinical practice worldwide.
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http://dx.doi.org/10.1016/j.ijcard.2020.11.022DOI Listing
March 2021

Greater coronary lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound in patients with elevated xanthine oxidoreductase: a mechanistic insight.

Heart Vessels 2021 May 20;36(5):597-604. Epub 2020 Nov 20.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, 260-8677, Japan.

Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play an important role in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear. Patients with stable coronary artery disease undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities: low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4 ± 171.6 vs. 347.4 ± 181.6 vs. 294.0 ± 155.9, p = 0.04) and maxLCBI (102.1 ± 56.5 vs. 65.6 ± 48.5 vs. 55.6 ± 37.8, p = 0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI. There were also no relations between XOR activity and C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio. In conclusion, elevated XOR activity was associated with greater coronary lipid core plaque in patients with stable coronary artery disease, without significant relations to systemic endothelial function and inflammation.
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http://dx.doi.org/10.1007/s00380-020-01730-wDOI Listing
May 2021

Impact of clinical presentations on lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound.

Int J Cardiovasc Imaging 2021 Apr 17;37(4):1151-1158. Epub 2020 Nov 17.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.
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http://dx.doi.org/10.1007/s10554-020-02107-wDOI Listing
April 2021

P63-negative pulmonary NUT carcinoma arising in the elderly: a case report.

Diagn Pathol 2020 Nov 11;15(1):134. Epub 2020 Nov 11.

Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.

Background: Pulmonary NUT carcinoma is rare, but lethal, thus, must not be overlooked. The definitive diagnosis is made by a NUT monoclonal antibody or gene analysis, but these are not always routinely available. Therefore, the diagnosis depends on this rare disease being suspected from the clinical and pathological findings. Generally, NUT carcinoma of the lung occurs near the hilum in younger adults with severe subjective symptoms. Histologically, it is characterized by the monomorphic growth of small cells which showed positivity of p63 immunohistochemistry.

Case Presentation: An 82-year-old man was referred for an incidental finding of an abnormal shadow at the peripheral apex of the right lung on computed tomography for a regular follow-up examination of renal cancer. Microscopically, small cell carcinoma was initially suspected; however, immunohistochemistry was not typical. NUT carcinoma with BRD4-NUT fusion was ultimately diagnosed using a NUT monoclonal antibody, fluorescence in situ hybridization, and RNA-seq. p63 and p40 protein expression was not detected.

Conclusions: This is the first case of pulmonary NUT carcinoma to show negativity for p63 and is the oldest among previously reported cases. The present case suggests that NUT carcinoma should be suspected when the morphology of monomorphic growth of small cells without lineage-specific differentiation, regardless of age, clinical symptoms, the tumor location, or p63 expression.
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http://dx.doi.org/10.1186/s13000-020-01053-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657348PMC
November 2020

Contemporary coronary drug-eluting and coated stents: a mini-review.

Cardiovasc Interv Ther 2021 Jan 10;36(1):20-22. Epub 2020 Nov 10.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.

Percutaneous coronary intervention has become a standard-of-care procedure in patients with acute and chronic coronary syndromes, in which coronary stent technology is commonly used. In this mini-review article, we summarize the characteristics of contemporary coronary drug-eluting and coated stents.
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http://dx.doi.org/10.1007/s12928-020-00731-wDOI Listing
January 2021

Coronary Flow Reserve and Glycemic Variability in Patients with Coronary Artery Disease.

Intern Med 2021 Apr 2;60(8):1151-1158. Epub 2020 Nov 2.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Japan.

Objective Glycemic variability is being increasingly recognized as an early indicator of glucose metabolic disorder and may contribute to the development of diabetic vascular complications, such as coronary microvascular dysfunction. The present study sought to investigate the relationship between coronary microvascular function assessed by intracoronary thermodilution method and glycemic variability on a continuous glucose monitoring system (CGMS). Methods We prospectively enrolled 40 patients with or without known diabetes mellitus who had epicardial coronary artery disease referred for coronary angiography and were not treated with diabetic medications. Of these, two had a significant stenosis in the left main coronary artery and were therefore excluded from the analyses. In the end, 38 patients were equipped with a CGMS and underwent intracoronary physiological assessments in the unobstructed left anterior descending artery. The mean amplitude of glycemic excursion (MAGE) and standard deviation were calculated from the obtained CGMS data as indicators of glucose variability. Results Coronary flow reserve (CFR) was negatively correlated with MAGE (r=-0.328, p=0.044) and standard deviation (r=-0.339, p=0.037) on CGMS, while the index of microcirculatory resistance showed no such correlation. Multivariable linear regression analyses showed that MAGE on CGMS was significantly associated with CFR after adjusting for age, sex, fractional flow reserve and hemoglobin A1c. Conclusion Higher MAGE on CGMS was associated with reduced CFR in stable patients with coronary artery disease, suggesting a potential effect of glycemic variability on coronary microvascular flow regulation. A further study with a larger sample size needs to be conducted to confirm our findings.
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http://dx.doi.org/10.2169/internalmedicine.6158-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112971PMC
April 2021

Left upper lobectomy for cancer of the left lung with a rare mediastinal left basal pulmonary artery.

Gen Thorac Cardiovasc Surg 2021 Apr 28;69(4):748-751. Epub 2020 Oct 28.

Department of Thoracic Surgery, Saitama Cardiovascular and Respiratory Center, Itai 1696, Kumagaya, 360-0197, Japan.

We report a rare case wherein a mediastinal left basal pulmonary artery was detected during surgery. Intraoperative findings revealed mediastinal left lingular and basal segments of the pulmonary artery (A + A) just dorsal to the superior pulmonary vein. The mediastinal left basal pulmonary artery is classified by its branching type, (1) complete type-wherein the entire that all basal pulmonary artery flow lies between the superior pulmonary vein and the left upper bronchus, as in like this case, (2) incomplete type-wherein that a part of the left basal pulmonary artery segment is on the flow mediastinal side. It is important to understand this rare aberration for undergoing safe surgery.
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http://dx.doi.org/10.1007/s11748-020-01528-7DOI Listing
April 2021

Intrathoracic use of a small ultrasonic probe for localizing small lung tumors in thoracoscopic surgery: Empirical results and comparison with preoperative CT images.

Gen Thorac Cardiovasc Surg 2021 Mar 20;69(3):516-524. Epub 2020 Oct 20.

Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan.

Objective: To evaluate the use of a small mobile ultrasound probe to localize small lung tumors during thoracoscopic surgery under thoracic CO insufflation.

Methods: We prospectively enrolled 20 patients (26 tumors) scheduled to undergo thoracoscopic pulmonary wedge resection between April 2016 and October 2018. Ultrasonographic tumor detection was performed with an ARIETTA 850 and L51K probe (Hitachi, Tokyo, Japan). Ultrasonography was repeated after achieving adequate lung collapse under a positive intrathoracic pressure of 8-15 mmHg. The appearance on preoperative CT versus the ultrasonographic localization was compared for each tumor. The receiver operating characteristic curves were compared for the tumor dimension of the lung window, consolidation dimension of the lung window, tumor dimension of the mediastinal window (MD), and tumor depth from the lung surface.

Results: The average age was 62 years (range 42-79 years), average pathological tumor size was 9 mm (range 3-22 mm), and average tumor depth was 6 mm (range 1-25 mm). Although no tumors could be visualized before lung collapse, 22 tumors (85%) were detectable with ultrasonography after lung collapse. Of these 22 tumors, 16 were well-depicted, while six were poorly delineated. MD showed the largest area under the receiver operating characteristic curve (0.81), and tumors with a MD of ≤ 6 mm had a high risk of difficult localization using ultrasonography.

Conclusion: This ultrasonographic method obtained high tumor detection rates, especially for tumors with a MD > 6 mm. Tumors with a MD ≤ 6 mm may require another localization method.

Clinical Registration Number: University Hospital Medical Information Network Clinical Trials Registry (UMIN000036921).
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http://dx.doi.org/10.1007/s11748-020-01514-zDOI Listing
March 2021