Pipeline for Multi-Scale Three-Dimensional Anatomic Study of the Human Heart.

Detailed study of non-failing human hearts rejected for transplantation provides a unique opportunity to perform structural analyses across microscopic and macroscopic scales. These techniques include tissue clearing (modified immunolabeling-enabled three-dimensional (3D) imaging of solvent-cleared organs) and immunohistochemical staining. Mesoscopic examination procedures include stereoscopic dissection and micro-computed tomographic (CT) scanning. Macroscopic examination procedures include gross dissection, photography (including anaglyphs and photogrammetry), CT, and 3D printing of the physically or virtually dissected or whole heart. Before macroscopic examination, pressure-perfusion fixation may be performed to maintain the 3D architecture and physiologically relevant morphology of the heart. The application of these techniques in combination to study the human heart is unique and crucial in understanding the relationship between distinct anatomic features such as coronary vasculature and myocardial innervation in the context of the 3D architecture of the heart. This protocol describes the methodologies in detail and includes representative results to illustrate progress in the research of human cardiac anatomy.

Diagnosis of Advanced Gastric Cancer Occasioned by Persistent Postpartum Fever: A Case Report.

Pregnancy-associated gastric cancer is extremely rare. In many cases, the cancer is already advanced at the time of diagnosis, and the prognosis is often poor. A 39-year-old primigravida, with dichorionic diamniotic twins, was admitted to our hospital for threatened preterm labor at 31 weeks of gestation. At 32 weeks of gestation, she developed a fever and tested positive for influenza A. She recovered from influenza A on the following day but had an emergency cesarean section for premature rupture of the membranes at 32 weeks of gestation. She was discharged on postpartum day six. Thereafter, she was again infected with influenza A. On day 18, she underwent an abdominal ultrasound revealing multiple mass lesions in the liver, because she had an uncomfortable upper gastric with persistent fever. She was referred to the internal medicine team, who made a diagnosis of stage IV gastric cancer. Importantly, non-specific symptoms and physical signs that are not explicable by the normal course of pregnancy may be recognized through conscientious history-taking and physical observations. If gastrointestinal symptoms are prolonged, or if symptoms such as severe weight loss, melena, a tender abdominal mass, or persistent and unexplained fever develop, an endoscopic assessment should be conducted to suspect other diseases. In addition, proactive ultrasound scanning, including the upper abdomen, may detect pregnancy-associated gastric cancer and lead to further in-depth investigations.

Differential Prognostic Impact of Risk-Prediction Models for Heart Failure in Acute Myocardial Infarction: The Original and Revised Heart Failure Time-Points.

Background: We previously developed a risk-scoring system for heart failure (HF) in patients with acute myocardial infarction (MI), namely "HF time-points (HFTPs)". In the original HFTPs, the presence of HF on admission, during hospitalization, and at short-term follow-up was individually scored. This study examined whether the revised HFTPs, with additional scoring of previous HF, provide better predictivity. Methods: This multicenter registry included a total of 1331 patients with acute MI undergoing percutaneous coronary intervention. HF was evaluated at four time-points before and after acute MI onset: (1) a history of HF; (2) elevated natriuretic peptide levels on admission; (3) in-hospital HF events; and (4) elevated natriuretic peptide levels at a median of 31 days after the onset. When HF was present at each time-point, one point was assigned to a risk scoring system, namely the original and revised HFTPs, ranging from 0 to 3 and from 0 to 4. The primary endpoint was a composite of cardiovascular death and HF rehospitalization after discharge. Results: Of the 1331 patients, 65 (4.9%) had the primary outcome events during a median follow-up period of 507 (interquartile range, 335-1106) days. The increase in both original and revised HFTPs was associated with an increased risk of the primary outcomes in a stepwise fashion with similar diagnostic ability. Conclusions: The original and revised HFTPs were both predictive of long-term HF-related outcomes in patients with acute MI undergoing percutaneous coronary intervention. Yet, the original HFTPs may be sufficient to estimate HF risks after MI.

Innervation of the coronary arteries and its role in controlling microvascular resistance.

The coronary circulation plays a crucial role in balancing myocardial perfusion and oxygen demand to prevent myocardial ischemia. Extravascular compressive forces, coronary perfusion pressure, and microvascular resistance are involved to regulate coronary blood flow throughout the cardiac cycle. Autoregulation of the coronary blood flow through dynamic adjustment of microvascular resistance is maintained by complex interactions among mechanical, endothelial, metabolic, neural, and hormonal mechanisms. This review focuses on the neural mechanism. Anatomy and physiology of the coronary arterial innervation have been extensively investigated using animal models. However, findings in the animal heart have limited applicability to the human heart as cardiac innervation is generally highly variable among species. So far, limited data are available on the human coronary artery innervation, rendering multiple questions unresolved. Recently, the clinical entity of ischemia with non-obstructive coronary arteries has been proposed, characterized by microvascular dysfunction involving abnormal vasoconstriction and impaired vasodilation. Thus, measurement of microvascular resistance has become a standard diagnostic for patients without significant stenosis in the epicardial coronary arteries. Neural mechanism is likely to play a pivotal role, supported by the efficacy of cardiac sympathetic denervation to control symptoms in patients with angina. Therefore, understanding the coronary artery innervation and control of microvascular resistance of the human heart is increasingly important for cardiologists for diagnosis and to select appropriate therapeutic options. Advancement in this field can lead to innovations in diagnostic and therapeutic approaches for coronary artery diseases.

Prognostic Impact of Previous Atherosclerotic Cardiovascular Disease on Short- and Long-Term Outcomes in Acute Myocardial Infarction.

Patients with previous atherosclerotic cardiovascular disease (ASCVD) are typically managed by secondary prevention modalities; however, they may experience recurrent events. In acute myocardial infarction (MI), the prognostic effect of preexisting ASCVD on the short- and long-term outcomes remains uncertain. This retrospective, multicenter registry included 2,475 patients with acute MI who underwent percutaneous coronary intervention. Previous ASCVD was defined as a history of ischemic events in the coronary, cerebral, and peripheral arterial territories. Patients were divided into 2 groups according to preexisting ASCVD. The primary end point was major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular death, recurrent MI, and ischemic stroke during hospitalization and after discharge. The bleeding outcomes were also evaluated. Of the 2,475 patients, 475 (19.2%) had previous ASCVD. Patients with previous ASCVD were older and likely to have more co-morbidities than those without ASCVD. During hospitalization, the MACE rates were higher in the ASCVD group than in the non-ASCVD group (16.4% vs 9.6%, p <0.001). Similarly, during a median follow-up of 542 days after discharge, patients with previous ASCVD had an increased risk of MACEs than those without ASCVD (13.4% vs 5.6%, p <0.001). The multivariable analyses identified previous ASCVD as a factor that was significantly associated with MACEs after discharge. Major bleeding events occurred more frequently in the ASCVD group than in the non-ASCVD group. In conclusion, preexisting ASCVD was often observed in patients with acute MI and was particularly associated with long-term ischemic outcomes after discharge; thus, further clinical investigations are needed in this vulnerable patient subset.

The Combinations of the Patterns of Non-adherence to Anti-platelet Regimen in Stented Patients (PARIS) and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) Thrombotic and Bleeding Risk Scores on Clinical Outcomes in Patients with Acute Myocardial Infarction.

Objective The Patterns of Non-adherence to Anti-platelet Regimen in Stented Patients (PARIS) and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic and bleeding risk scores were established to predict ischemic and bleeding events in patients undergoing percutaneous coronary intervention (PCI). However, whether or not the combination of these risk scores is predictive of clinical outcomes is unclear. Methods This bicenter registry included a total of 1,098 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into three groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included the rates of both ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events at two years. Results Two years after primary PCI, ischemic and major bleeding events occurred in 17.3% and 10.2% of patients, respectively. The higher-risk categories of PARIS and CREDO-Kyoto scores were associated with increased risks of ischemic and bleeding events. The rates of ischemic and major bleeding events progressively increased with the increase in risk categories in the two risk scoring systems. In the receiver operating characteristic curve analysis, the addition of CREDO-Kyoto thrombotic and bleeding risk scores to PARIS scores significantly improved diagnostic ability in predicting ischemic (area under the curve: 0.59 vs. 0.63, p=0.01) and bleeding (area under the curve: 0.65 vs. 0.68, p=0.01) events. Conclusion The combinations of the PARIS and CREDO-Kyoto risk scores might be useful for evaluating ischemic and bleeding risks in patients with acute MI undergoing primary PCI.

Diagnostic ability of Japanese version of high bleeding risk criteria for ischemic outcomes in patients with acute myocardial infarction.

The Japanese version of high bleeding risk (J-HBR) criteria was domestically proposed to identify patients at HBR after percutaneous coronary intervention (PCI). The applicability of J-HBR on bleeding events has been validated, while whether J-HBR predicts ischemic events is uncertain. This bi-center registry included 904 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were stratified by the J-HBR major (1 point) and minor (0.5 point) criteria. Patients with J-HBR ≥ 1 point were diagnosed as having HBR. The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, recurrent MI, and ischemic stroke, after discharge. Of the 904 patients, 451 (49.9%) had the J-HBR. The primary endpoint more frequently occurred in patients with J-HBR than in those without (10.9% vs. 4.9%, p < 0.001) during the median follow-up period of 522 days. Probability of MACE was progressively increased with the increase in the number of J-HBR major and minor criteria, in which severe anemia, severe chronic kidney disease, prior heart failure, peripheral artery disease, and prior ischemic stroke were identified as significant factors associated with MACE. In patients with acute MI undergoing PCI, the J-HBR criteria were predictive for ischemic outcomes after discharge, suggesting that the J-HBR criteria may be useful to identify patients at high bleeding and ischemic risks.

Broadband design of silica-PLC mode-dependent-loss equalizer for 2LP-mode transmission systems.

A new configuration of mode-dependent-loss (MDL) equalizer for two linearly-polarized mode transmission systems using the silica planar lightwave circuit platform is proposed. This device acts as an LP01-mode attenuator (precisely, LP01/LP21 mode converter) to adjust the MDL keeping a high transmission of the LP11 modes. Almost all components constructing the device are based on the adiabatic mode conversion, which brings broadband operation. Especially, a newly proposed E12/E22 mode converter plays a key role in broadband MDL equalization. It is numerically revealed that the flattened spectra with designated transmission can be obtained for the wavelength from 1200 nm to 1650 nm.

Effect of admission in the stroke care unit versus intensive care unit on in-hospital mortality in patients with acute ischemic stroke.

BACKGROUND/OBJECTIVE: Few reports have directly compared the outcomes of patients with acute ischemic stroke (AIS) who are managed in a stroke care unit (SCU) with those who are managed in an intensive care units (ICU). This large database study in Japan aimed to compare in-hospital mortality between patients with AIS admitted into SCU and those admitted into ICU. METHODS: Patients with AIS who were admitted between April 1, 2014, and March 31, 2019, were selected from the administrative database and divided into the SCU and ICU groups. We calculated the propensity score to match groups for which the admission unit assignment was independent of confounding factors, including the modified Rankin scale (mRS) score. The primary outcome was in-hospital mortality, and secondary outcomes were the mRS score at discharge, length of stay (LOS), and total hospitalization cost. RESULTS: Overall, 8,683 patients were included, and 960 pairs were matched. After matching, the in-hospital mortality rates of the SCU and ICU groups were not significantly different (5.9% vs. 7.9%, P = 0.106). LOS was significantly shorter (SCU = 20.9 vs. ICU = 26.2 days, P < 0.001) and expenses were significantly lower in the SCU group than in the ICU group (SCU = 1,686,588 vs. ICU = 1,998,260 yen, P < 0.001). mRS scores (score of 1-3 or 4-6) at discharge were not significantly different after matching. Stratified analysis showed that the in-hospital mortality rate was lower in the ICU group than in the SCU group among patients who underwent thrombectomy. CONCLUSIONS: In-hospital mortality was not significantly different between the ICU and SCU groups, with significantly lower costs and shorter LOS in the SCU group than in the ICU group.

Insights Into Interaction Between Clip Device and the Mitral Valve Apparatus in the Human Heart.

Precise appreciation of the 3-dimensional relationship between the edge-to-edge clips and mitral valve apparatus remains clinically challenging. We demonstrate the images of clips observed in situ 4 years after implantation. Detailed observation from this case helps improve our understanding of 3-dimensional clinical cardiac anatomy related to transcatheter edge-to-edge mitral valve repair. (Level of Difficulty: Intermediate.).

Bayesian design of mosaic-based mode multiplexers for various wavelength bands.

Ultracompact mode multiplexers based on mosaic structure for various wavelength bands designed by Bayesian technique are investigated. C-, O-, and C + O band, TE0-TE1 2-mode multiplexers can be designed with the same footprint, by only changing the mosaic-pattern, showing the great flexibility of mosaic-based devices. Bayesian direct binary search method is used for the design, and it is demonstrated that the Bayesian technique is superior to conventional design method in terms of the best-structure search for the same number of iterations. The designed devices are fabricated for Si-waveguide platform, and the proof-of-concept results are obtained. These results indicate that the mosaic-based devices are promising candidates for future compact optical transceivers.

Understanding Cardiac Anatomy and Imaging to Improve Safety of Procedures: The Right Ventricle.

Right ventricular perforation is a catastrophic complication of catheter-based intracardiac interventions. In this context, appreciation of 5 attachments of the right ventricle to the aortoventricular unit is essential to recognize extent of right ventricular free wall. We herein present progressive dissection and virtual and photographic endoscopic images of the hearts without distortion. Real dissection images show us how and where to avoid this complication by indicating the true muscular component of the ventricular septum. Both virtual and photographic endoscopic images, when combined with transillumination, beautifully shows the thin wall regions and trabeculations with unprecedented clarity. We believe recognition of these anatomical nuances can reduce the likelihood of right ventricular perforation.

Photogrammetry of Perfusion-Fixed Heart: Innovative Approach to Study 3-Dimensional Cardiac Anatomy.

Photogrammetry generates a 3-dimensional high-resolution model from multiple 2-dimensional photographs. Herein, we demonstrate a photogrammetry of a perfusion-fixed cardiac sample around the left ventricular summit. The single photogrammetric model can be observed from almost all directions and illustrates important anatomical features for the general cardiologist. (Level of Difficulty: Advanced.).

Clinical characteristics and outcomes of patients with chronic systemic inflammatory disease in acute myocardial infarction.

BACKGROUND: Chronic systemic inflammatory diseases (CSIDs) such as rheumatoid arthritis (RA) are reportedly associated with an increased risk of ischemic cardiovascular events including acute myocardial infarction (MI). However, data are limited on clinical characteristics and ischemic and bleeding outcomes after acute MI in patients with CSIDs. METHODS: This bi-center registry included a total of 1001 patients with acute MI undergoing percutaneous coronary intervention. CSIDs included inflammatory rheumatological conditions (RA, systemic lupus erythematosus, vasculitis, etc.) and organ-specific diseases (chronic hepatitis, psoriasis, inflammatory bowel disease, etc.). The primary endpoint was net adverse clinical events (NACE), a composite of ischemic (all-cause death, MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events, during hospitalization and after discharge. RESULTS: Of the 1001 patients, 58 (5.8%) had CSIDs. The proportion of women was higher in patients with CSIDs than those without (37.9% vs. 22.1%, p = 0.009). During the hospitalization, no significant differences in the primary endpoint of NACE were observed between patients with and without CSIDs (10.3% vs. 12.7%, p = 0.84). During the median follow-up of 42.6 months after discharge, patients with CSIDs had a higher risk of NACE (22.5% vs. 10.1%, p = 0.01) than those without, mainly driven by an increased risk of ischemic events (18.4% vs. 8.4%, p = 0.03). CONCLUSIONS: A small but significant proportion of patients with acute MI (5.8%) had CSIDs. While the incidence of in-hospital events was similar, patients with CSIDs had worse outcomes after discharge, suggesting that further clinical investigations and therapeutic approaches are needed in this patient subset.

Characterising the performance of an ultrawide field-of-view 3D atom probe.

The CAMECA Invizo 6000 atom probe microscope uses ion optics that differ significantly from the local electrode atom probe (LEAP). It uses dual antiparallel deep ultraviolet lasers, a flat counter electrode, and a series of accelerating and decelerating lenses to increase the field-of-view of the specimen without reducing the mass resolving power. In this work we characterise the performance of the Invizo 6000 using three material case studies: a model Al-Mg-Si alloy, a commercially-available Ni-based superalloy, and a Zr alloy, using a combination of air and vacuum-transfer between instruments. The ion optics of the Invizo 6000 significantly increase the field-of-view compared to the same specimen on a LEAP 4000 X Si. We also observe a significant increase in specimen yield, especially for the Zr alloy. These results combine to make the Invizo 6000 well-suited to research projects requiring large analysis volumes, particularly so for traditionally difficult samples such as oxides.

Design of silica-PLC LP11 mode rotator based on adiabatic mode conversion.

A silica-based LP11 mode rotator, which is one of the basic and indispensable optical components for space division multiplexing, with multiple tapered trenches is proposed. Compared with the conventional interference-based LP11 mode rotator with a simple L-shape waveguide, the proposed LP11 mode rotator has many advantages in a mode conversion efficiency, an insertion loss, and a fabrication tolerance because the operation principle is based on the adiabatic mode conversion. By using an approach of the shortcut to adiabaticity, the proposed device is effectively miniaturized rather than the standard tapered structures. Among the LP11 mode rotators in the silica-based mode multi/demultiplexers, the proposed type will be a considerably promising candidate.