Histological Evaluation of a Self-Expanding Stent-Graft 23 Months After Implantation in the Superficial Femoral Artery.

PURPOSE: To report histological examination of a Viabahn stent-graft implanted in the superficial femoral artery (SFA) for nearly 2 years. CASE REPORT: A 78-year-old man with peripheral artery disease was treated successfully with a 6.0×250-mm Viabahn self-expanding stent-graft in the right SFA, relieving his lower limb claudication. The patient died suddenly due to acute myocardial infarction 23 months later. Histological evaluation of the stent-graft implantation site revealed moderate neointimal proliferation at both proximal and distal edges of the device. In the middle part of the stent, significant macrophages and multinucleated foreign body giant cells had accumulated, although the stent was entirely patent. Furthermore, no endothelial cell coverage was found. CONCLUSION: Judging from these features, it might be necessary to continue dual antiplatelet therapy after stent-graft implantation over the long term to prevent thrombosis and subsequent restenosis or reocclusion.

Pathology of Neointimal Calcification in Very Late Restenosis After Bare Metal Stent Implantation for Superficial Femoral Artery.

A 60-year-old man, who had claudication in his right limb due to total occlusion of the right superficial femoral artery, received bare metal stents. Although the bare metal stents in the superficial femoral artery did not show restenosis 5 years after stent implantation, angiography revealed significant in-stent restenosis when he developed right critical limb ischemia at 8 years post implantation. Ballooning for in-stent lesions did not result in full expansion. His right limb was amputated above the knee due to progressive limb ischemia. In the pathological findings in the superficial femoral artery, marked calcification was observed in the entire circumference of the luminal surface of the neointima. However, lipid core formation was not identified in the neointima. Although several cracks following balloon angioplasty were observed at the superficial calcified layers, injury to neointimal tissue such as compression was not observed. The neointima exhibited heavy calcification in the very late phase of in-stent restenosis after bare metal stent implantation in superficial femoral artery. Therefore, balloon angioplasty in the very late phase of in-stent restenosis potentially results in underexpansion.

A case of 37 year long Behçet disease resembling Takayasu arteritis: An autopsy report.

A 19-year-old woman with a history of recurrent aphthous stomatitis and genital ulceration was diagnosed with Behçet disease. She was treated with steroids and immunosuppressive agents for more than 30 years, but multiple complications manifested including ileocecal ulcer, aortic valve regurgitation, renal failure, ischemic enterocolitis, and arteriosclerotic obliterans until her death at the age of 56 from pneumonia. An autopsy examination demonstrated an entirely calcified aorta and major aortic branches. The ascending aorta was dilatated 55 mm in diameter and branches were all stenosed. Microscopically, the aortic arch and its branches showed collagenous fibrosis of the outer media and adventitia, whereas coronary and abdominal aortic branches showed conventional atherosclerosis. Although the ante-mortem diagnosis was angio-Behçet disease, its pathophysiology along with her clinical history, morphology of the lead pipe-like aorta, predominant destruction of the outer arteries, and a human leukocyte antigen (HLA) haplotype of B39 were all suggestive of Takayasu arteritis. Thus, this case implies that HLA-B39 may be associated with the pathogenesis of arteritis like Takayasu arteritis, even if the primary disease is Behçet disease.

Risk factors for the occurrence of spina bifida (a case-control study) and the prevalence rate of spina bifida in Japan.

BACKGROUND: The Japanese government recommended in 2000 that women planning pregnancy should take 400 µg of folic acid daily to decrease the risk of having an infant with spina bifida. We aimed to identify risk factors for the occurrence of spina bifida and to evaluate how the prevalence rate has altered over the past 3 decades. METHODS: Subjects comprised 360 women who gave birth to spina bifida-affected offspring and 2333 women who gave birth to offspring without spina bifida between 2001 and 2012. A self-administered questionnaire was used to collect data, which were analyzed by multiple logistic regression models. The prevalence rate of spina bifida was obtained through data provided by international and domestic organizations. RESULTS: Four variables were significantly associated with the increased risk of having newborns afflicted with spina bifida: not taking folic acid supplements (odds ratios [OR], 2.50; 95% confidence interval [CI], 1.72-3.64), presence of spina bifida patients within third-degree relatives (OR, 4.26; 95% CI, 1.12-16.19), taking anti-epileptic drugs without folic acid (OR, 20·20; 95% CI, 2.06-198.17), and low birth weight in the newborns ≤ 2500 g (OR, 4.21; 95% CI, 3.18-5.59). The prevalence rate of spina bifida has remained 5 to 6 per 10,000 total births and has not shown any decreasing trend over the past 11 years. CONCLUSION: Four risk factors were identified among Japanese women. Because recommendations and information have not decreased the occurrence of spina bifida, the Japanese government should implement mandatory food fortification.

Serum chemokine levels as prognostic markers in patients with early systemic sclerosis: a multicenter, prospective, observational study.

OBJECTIVE: To assess the utility of serum chemokine levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease. METHODS: Seventy Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicenter, observational study. Concentrations of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in serum samples from all patients were measured using cytometric beads array. In 33 patients, chemokine levels were measured each year for 4 years. The ability of baseline chemokine levels to predict changes in clinical features were evaluated statistically by multiple regression analysis. RESULTS: At their first visit, serum levels of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 were significantly elevated in patients with SSc compared with healthy controls. There were significant associations between CCL2 and CXCL8 levels and between CXCL9 and CXCL10 levels in patients. The initial serum CXCL8 levels were significantly associated with the HAQ-DI at the fourth year while the %VC of baseline tended to be negatively associated with HAQ-DI at the fourth year. Initial chemokine levels were not associated with other clinical features including skin thickness score and the respiratory function. CONCLUSION: Serum CXCL8 level may serve as a prognostic indicator of the physical dysfunction in SSc. Further longitudinal studies of larger populations are needed to confirm these findings.

[Effectiveness of acupuncture and moxibustion therapy for the treatment of refractory interstitial cystitis].

The efficacy of acupuncture and moxibustion treatment was examined on eight female patients with refractory interstitial cystitis (IC) who had been treated conservatively with hydrodistension, intravesical instillation of dimethyl sulfoxide, or oral medication. These patients had received hydrodistension on an average of 2.3±1.8 times. Moxa needles were applied to Ciliao in bladder meridian 32 and Xialiao in bladder meridian 34, and electroacupuncture was performed on Zhongliao in bladder meridian 33 at 3 Hz for 20 min once a week. The bladder condition was assessed by the visual analogue scale (VAS) score, the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI), the Interstitial Cystitis Problem Index (ICPI), and the maximum voided volume (MVV). After 3 months, patients who showed a reduction of >2 in their VAS score, reduction of <30% of ICSI and ICPI, and increase of >100 ml MVV were considered responders. There were three responders, and after repeated therapy to maintain these effects, they no longer required hydrodistension. Two responders had no recurrence for 48 months or more. Acupuncture and moxibustion resulted in improvement in 38% of the patients (3/8) with refractory IC, and repeated therapy maintained the therapeutic effects. This therapy is traditional and relatively noninvasive. Although its precise mechanism of action is unclear, this study suggests that acupuncture and moxibustion treatment may be a complementary and alternative therapeutic option for refractory IC.

Gene network inference from single-cell omics data and domain knowledge for constructing COVID-19-specific ICAM1-associated pathways.

Introduction: Intercellular adhesion molecule 1 (ICAM-1) is a critical molecule responsible for interactions between cells. Previous studies have suggested that ICAM-1 triggers cell-to-cell transmission of HIV-1 or HTLV-1, that SARS-CoV-2 shares several features with these viruses via interactions between cells, and that SARS-CoV-2 cell-to-cell transmission is associated with COVID-19 severity. From these previous arguments, it is assumed that ICAM-1 can be related to SARS-CoV-2 cell-to-cell transmission in COVID-19 patients. Indeed, the time-dependent change of the ICAM-1 expression level has been detected in COVID-19 patients. However, signaling pathways that consist of ICAM-1 and other molecules interacting with ICAM-1 are not identified in COVID-19. For example, the current COVID-19 Disease Map has no entry for those pathways. Therefore, discovering unknown ICAM1-associated pathways will be indispensable for clarifying the mechanism of COVID-19. Materials and methods: This study builds ICAM1-associated pathways by gene network inference from single-cell omics data and multiple knowledge bases. First, single-cell omics data analysis extracts coexpressed genes with significant differences in expression levels with spurious correlations removed. Second, knowledge bases validate the models. Finally, mapping the models onto existing pathways identifies new ICAM1-associated pathways. Results: Comparison of the obtained pathways between different cell types and time points reproduces the known pathways and indicates the following two unknown pathways: (1) upstream pathway that includes proteins in the non-canonical NF-κB pathway and (2) downstream pathway that contains integrins and cytoskeleton or motor proteins for cell transformation. Discussion: In this way, data-driven and knowledge-based approaches are integrated into gene network inference for ICAM1-associated pathway construction. The results can contribute to repairing and completing the COVID-19 Disease Map, thereby improving our understanding of the mechanism of COVID-19.

Incidence, risk factors, and clinical sequelae of angiographic peri-stent contrast staining after sirolimus-eluting stent implantation.

BACKGROUND: We have noted abnormal angiographic findings--at the sites of drug-eluting stent implantation, suggesting contrast staining outside the stent struts--that do not fulfill the classic definition of coronary artery aneurysm. We propose a new term, peri-stent contrast staining (PSS), for these abnormal angiographic findings and assess their incidence, risk factors, and clinical sequelae. METHODS AND RESULTS: Peri-stent contrast staining was defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter. The study population consisted of 3081 lesions (1998 patients) that were treated exclusively with sirolimus-eluting stents and were evaluated by follow-up angiography within 12 months after sirolimus-eluting stent implantation in a single center. Late acquired PSS was observed in 58 lesions (1.9%) in 49 patients (2.5%). Independent risk factors of PSS included chronic total occlusion, whereas negative risk factors for PSS were left circumflex coronary artery lesion and in-stent restenosis lesion. Stent fracture was more frequently observed in lesions with PSS than in lesions without PSS (43.1% versus 5.4%, P<0.0001). Excluding 269 lesions with target-lesion revascularization within 12 months, the study population for long-term follow-up consisted of 51 lesions (42 patients) with PSS and 2761 lesions (1751 patients) without PSS. Cumulative incidence of target-lesion revascularization and definite very late stent thrombosis at 3 years in the PSS group was higher than that in the non-PSS group (15.0% versus 6.5%, and 8.2% versus 0.2%, respectively). CONCLUSIONS: Peri-stent contrast staining found within 12 months after sirolimus-eluting stent implantation appeared to be associated with subsequent target-lesion revascularization and very late stent thrombosis.

Investigation of prognostic factors for skin sclerosis and lung function in Japanese patients with early systemic sclerosis: a multicentre prospective observational study.

OBJECTIVE: To clarify the clinical course of SSc in Japanese patients with early-onset disease. It is well known that ethnic variations exist in the clinical features and severity of SSc. However, neither the clinical course nor prognostic factors have been thoroughly investigated in the Japanese population. METHODS: Ninety-three Japanese patients of early-onset SSc (disease duration: <3 years) with diffuse skin sclerosis and/or interstitial lung disease were registered in a multi-centre observational study. All patients had a physical examination with laboratory tests at their first visit and at each of the three subsequent years. Factors that could predict the severity of skin sclerosis and lung involvement were examined statistically by multiple regression analysis. RESULTS: Two patients died from SSc-related myocardial involvement and four patients died from other complications during the 3-year study. Among various clinical data assessed, the initial modified Rodnan total skin thickness score (MRSS) and maximal oral aperture were associated positively and negatively with MRSS at Year 3, respectively. Additionally, initial ESR tended to be associated with final MRSS. Pulmonary vital capacity (VC) in the third year was significantly associated with initial %VC. Furthermore, patients with anti-topo I antibody tended to show reduced %VC at Year 3. CONCLUSIONS: Several possible prognostic factors for skin sclerosis and lung function were detected in Japanese patients with early SSc. Further longitudinal studies of larger populations will be needed to confirm these findings.

Diffuse in-stent restenosis of CYPHER® stent due to hypersensitivity reaction confirmed by pathohistological findings.

The use of drug-eluting stents (DES) reduces the risk of repeat revascularization without increase of death and myocardial infarction compared to standard bare metal stents. However, in-stent restenosis (ISR) after DES implantation still occurs. Here, we report a rare case with a diffuse ISR after CYPHER® stent implantation because of chronic inflammation and hypersensitivity reactions, confirmed by pathohistological findings.

Explainable Model Fusion for Customer Journey Mapping.

Due to advances in computing power and internet technology, various industrial sectors are adopting IT infrastructure and artificial intelligence (AI) technologies. Recently, data-driven predictions have attracted interest in high-stakes decision-making. Despite this, advanced AI methods are less often used for such tasks. This is because AI technology is a black box for the social systems it is meant to support; trustworthiness and fairness have not yet been established. Meanwhile in the field of marketing, strategic decision-making is a high-stakes problem that has a significant impact on business trends. For global marketing, with its diverse cultures and market environments, future decision-making is likely to focus on building consensus on the formulation of the problem itself rather than on solutions for achieving the goal. There are two important and conflicting facts: the fact that the core of domestic strategic decision-making comes down to the formulation of the problem itself, and the fact that it is difficult to realize AI technology that can achieve problem formulation. How can we resolve this difficulty with current technology? This is the main challenge for the realization of high-level human-AI systems in the marketing field. Thus, we propose customer journey mapping (CJM) automation through model-level data fusion, a process for the practical problem formulation known as explainable alignment. Using domain-specific requirements and observations as inputs, the system automatically outputs a CJM. Explainable alignment corresponds with both human and AI perspectives and in formulating the problem, thereby improving strategic decision-making in marketing. Following preprocessing to make latent variables and their dynamics transparent with latent Dirichlet allocation and a variational autoencoder, a post-hoc explanation is implemented in which a hidden Markov model and learning from an interpretation transition are combined with a long short-term memory architecture that learns sequential data between touchpoints for extracting attitude rules for CJM. Finally, we realize the application of human-AI systems to strategic decision-making in marketing with actual logs in over-the-top media services, in which the dynamic behavior of customers for CJM can be automatically extracted.

Acute mitral regurgitation after non-ischemic papillary muscle rupture: A case report.

Papillary muscle rupture (PMR) is a life-threatening cardiac emergency that is generally associated with inadequate myocardial perfusion after acute myocardial infarction. Nonischemic spontaneous PMR occurs less frequently and is mostly caused by myocarditis, infections, or trauma. We report a patient with spontaneous PMR resulting in severe mitral regurgitation with refractory heart failure showing no specific causes but deterioration of the mitral leaflet and papillary muscle. The integration of pathologic and echocardiographic findings describes the details of the disease. .

Association between nail-fold capillary findings and disease activity in dermatomyositis.

OBJECTIVE: Although findings of nail-fold capillary changes and reduced red blood cell velocity in SSc patients are well established, studies in adult-onset DM patients are scarce. Our objective was to assess the changes and red blood cell velocity in finger nail-fold capillaries using nail-fold video capillaroscopy (NVC) in patients with adult-onset DM. METHODS: This study included 50 patients with adult-onset DM and 20 healthy subjects. A semi-quantitative rating scale was used to score capillaroscopy changes. Red blood cell velocity was evaluated using frame-to-frame determination of the position of capillary plasma gaps. RESULTS: Thirty-seven (74%) patients showed the scleroderma NVC pattern. Patients with the scleroderma pattern exhibited elevated serum creatine kinase levels more frequently and increased visual analogue scale of muscle disease activity. Scores of loss of capillaries were associated with muscle and global disease activity, whereas scores of haemorrhages were associated with skin disease activity. However, NVC findings were not significantly associated with lung involvement. The scores of irregularly enlarged capillaries, haemorrhages and loss of capillaries were reduced after stabilization of disease activity by treatment. The mean red blood cell velocity was not significantly reduced in DM patients compared with healthy controls and was not changed by treatment. CONCLUSION: Our results suggest that changes in nail-fold capillaries reflect disease activity in DM. Furthermore, the differences found in red blood cell velocity may reflect somewhat distinct microcirculation injuries in DM and SSc.

Identification of three factors influencing trail making test performance using multichannel near-infrared spectroscopy.

Recent advances in medical care have facilitated the survival of patients with stroke or traffic-related injuries. However, such patients may suffer from higher brain dysfunction; i.e., an impaired ability to plan and perform behaviors based on prior knowledge. The Trail Making Test (TMT) is a cognitive task that is used to evaluate higher brain dysfunction caused by frontal lobe injury. TMT consists of two tasks; TMT-A involves connecting consecutive numbers, and TMT-B involves connecting numbers and letters alternately. In this study, using near-infrared spectroscopy (NIRS) and the achievement value (TMT score), we investigated the effects of three factors on TMT performance: knowledge of the TMT, the order of TMT-A and TMT-B performance, and gender. The subjects were 48 healthy adults, consisting of college graduates and undergraduates (age: 22.8 ± 2.5 years, education: 16.0 ± 1.2 years, 24 males and 24 females). We measured the changes in oxygenated hemoglobin (oxy-Hb) levels using NIRS, showing that the increase in oxy-Hb was higher in subjects who had no knowledge of the TMT than those who had prior knowledge. In both TMT-A and TMT-B, the subjects who performed their first task displayed higher oxy-Hb levels. Moreover, the oxy-Hb level in males was higher than that in females. In contrast, only the order of TMT performance showed noticeable effect on the TMT score. In the present study, using NIRS we have shown that either knowledge of the TMT, the order of the TMT, or gender affects TMT performance, providing invaluable information for interpreting TMT results.

Botulinum toxin A submucosal injection for refractory non-neurogenic overactive bladder: early outcomes.

The objective of the present study was to assess the short-term effects of botulinum toxin A (BTX-A) injection for refractory non-neurogenic overactive bladder (OAB) in the setting of a prospective multicenter clinical trial. Refractory OAB was defined as persistent urgency urinary incontinence (UUI) ≥ once a week despite taking anticholinergic agents, or the incapability to continue the agents because of the adverse effects. A total of 100 U of BTX-A were reconstituted in 15 mL of normal saline and an aliquot of 0.5 mL was injected at 30 submucosal sites of the bladder wall. Nine men and eight women aged 67 ± 12 years were included. Subjective daytime frequency, urgency and UUI significantly decreased after treatment. On a 3-day frequency-volume chart, the daytime and night-time frequency of UUI significantly decreased from 5.5 and 0.5 pre-injection to 2.0 and 0.3 postinjection, respectively. Daytime urinary incontinence completely disappeared in six subjects. A urodynamic study showed the disappearance of detrusor overactivity in eight patients and a decrease in five patients. Maximum bladder capacity significantly increased from 179.9 to 267.3 mL. Difficulty on micturition or feeling of incomplete emptying was reported by 23.5% and 43.8% of patients at weeks 2 and 4, respectively. Postvoid residual urine increased to >100 mL in seven patients and >200 mL in one patient after injection; however, none of the patients required clean intermittent catheterization. These findings suggest promising efficacy of BTX-A in Japanese OAB patients.

[Investigation of pharmacokinetics of crushed imidafenacin 0.1-mg tablet after single oral administration in healthy men].

The crushing of tablets and opening of capsules should not be performed without proper care, as these actions may adversely affect the pharmaceutical release mechanisms. However, various clinical circumstances occasionally necessitate these actions. The long-term stability of the commercial formulation of imidafenacin was confirmed after crushing of tablets. For the safe administration of crushed imidafenacin tablets, we examined the pharmacokinetics of crushed imidafenacin 0. 1-mg tablet after single oral administration in healthy men. Plasma concentrations were measured in 6 male volunteers (age, 33.3 ± 10.6 years) orally administered crushed imidafenacin under fasting conditions. Imidafenacin was rapidly absorbed and plasma concentrations peaked (Cmax) at 414 ± 108 pg/ml after 1.5 h (Tmax ; median), after which the drug was rapidly eliminated with a half-life (t1/2) of 2.8 ± 0. 3 h. Area under the plasma concentration-time curve (AUC0-10) was 1,680 ± 334 pgï½¥h/ml. There were no significant differences in Cmax, Tmax and t1/2 between the crushed and tablet medications. Thus, crushing has almost no influence on the pharmacokinetics of imidafenacin. Consequently, this study was made available as information for patients requiring crushed anticholinergic agents.

Modeling viral dynamics in SARS-CoV-2 infection based on differential equations and numerical analysis.

Computational modeling and simulation of viral dynamics would explain the pathogenesis for any virus. Such computational attempts have been successfully made to predict and control HIV-1 or hepatitis B virus. However, the dynamics for SARS-CoV-2 has not been adequately investigated. The purpose of this research is to propose different SARS-CoV-2 dynamics models based on differential equations and numerical analysis towards distilling the models to explain the mechanism of SARS-CoV-2 pathogenesis. The proposed four models formalize the dynamical system of SARS-CoV-2 infection, which consists of host cells and viral particles. These models undergo numerical analysis, including sensitivity analysis and stability analysis. Based on the sensitivity indices of the four models' parameters, the four models are simplified into two models. In advance of the following calibration experiments, the eigenvalues of the Jacobian matrices of these two models are calculated, thereby guaranteeing that any solutions are stable. Then, the calibration experiments fit the simulated data sequences of the two models to two observed data sequences, SARS-CoV-2 viral load in mild cases and that in severe cases. Comparing the estimated parameters in mild cases and severe cases indicates that cell-to-cell transmission would significantly correlate to the COVID-19 severity. These experiments for modeling and simulation provide plausible computational models for the SARS-CoV-2 dynamics, leading to further investigation for identifying the essential factors in severe cases.