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The relationship between in-stent calcified nodules (IS-CN) and second-generation drug-eluting stent (G2-DES) stent thrombosis (ST) remains uncertain.We aimed to evaluate the prevalence, clinical demographic and long-term clinical outcomes after G2-DES ST with IS-CN.The prespecified substudy of the REAL-ST registry (a retrospective, multicentre registry of patients with definite ST after first- and G2-DES implantation) enrolled patients who experienced definite G2-DES ST and who underwent pre-intervention intravascular ultrasound imaging at index ST events.IS-CN was observed in 15 out of 118 (13%) definite G2-DES ST cases. The multiple logistic regression model demonstrated that haemodialysis (odds ratio [OR] 12.27, 95% confidence interval [CI]: 1.56-94.54; p=0.02), proximal or mid-right coronary artery lesions (OR 12.79, 95% CI: 1.78-92.13; p=0.01) and severe calcification (OR 13.01, 95% CI: 1.18-142.94; p=0.04) were independently associated with ST with IS-CN. The cumulative 5-year incidence of target lesion revascularisation (TLR) after ST was significantly higher in the IS-CN group than in the non-IS-CN group (p=0.02). Independent predictors of TLR after the index ST events were female sex (hazard ratio [HR] 3.05, 95% CI: 1.20-7.74; p=0.02), diabetes mellitus (HR 3.26, 95% CI: 1.26-8.41; p=0.01) and IS-CN (HR 3.07, 95% CI: 1.16-8.14; p=0.02).IS-CN may be one of the underlying mechanisms of G2-DES ST. Notably, IS-CN was associated with a higher TLR rate after the index ST events, suggesting the need for careful clinical follow-up of ST patients with IS-CN.

In the near future, hypertensive disorders of pregnancy (HDP) have been diagnosed by home blood pressure monitoring (HBPM) instead of clinic BP monitoring. A multicenter study of HBPM was performed in pregnant Japanese women in the non-high risk group for HDP. Participants were women (n = 218), uncomplicated pregnancy who self-measured and recorded their HBP daily. Twelve women developed HDP. HBP was appropriate (100 mmHg in systole and 63 mmHg in diastole), bottoming out at 17 to 21 weeks of gestation. It increased after 24 weeks of gestation and returned to non-pregnant levels by 4 weeks of postpartum. The upper limit of normal HBP was defined as the mean value +3 SD for systolic and mean +2 SD for diastolic with reference to the criteria for non-pregnant women. Using the polynomial equation, the hypertensive cut-off of systolic HBP was 125 mmHg at 15 weeks and 132 mmHg at 30 weeks of gestation, while it for diastolic HBP was 79 mmHg at 15 weeks and 81 mmHg at 30 weeks of gestation. Systolic HBP in women who developed HDP was higher after 24 weeks of gestation, and diastolic HBP was higher during most of the pregnancy compared to normal pregnancy. When the variability of individual HBP in women developed HDP compared to normal pregnant women was examined using the coefficient of variation (CV), the CV was lower in HDP before the onset of HDP. HBPM can be used not only for HDP determination, but also for early detection of HDP.

All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal outcomes. The cause(s) of pre-eclampsia and the optimal clinical management of the hypertensive disorders of pregnancy remain uncertain; therefore, we recommend that every hypertensive pregnant woman be offered an opportunity to participate in research, clinical trials and follow-up studies.

Among mammalian species, human reproduction has 2 outstanding features. The human hemochorial placentation is characterized by a very deep endovascular trophoblast invasion in the spiral arteries, reaching deep into the myometrium. This requires an agonistic direct cell-cell interaction between the maternal immune system and semiallogeneic trophoblast. The second feature is preeclampsia, a heterogeneous syndrome, a uniquely human condition. The human female is one of the few mammals exposed to her partner's semen on multiple occasions before conception. Regulatory T cells, especially paternal antigen-specific regulatory T cells, play an important role in the maintenance of pregnancy. Sexual intercourse increases the number of dendritic cells in the uterus that play an important role in the induction of paternal antigen-specific regulatory T cells. Paternal antigen-specific regulatory T cells maintain pregnancy by inducing tolerance. In the decidua basalis of preeclamptic cases, clonal regulatory T cells are reduced; these would normally monoclonally expand to recognize fetal or paternal antigens. Programmed cell death-1 expressed on T cells regulate cytotoxic T-cell activity and protect the fetus against maternal rejection. Programmed cell death-1 expression on clonal cytotoxic T cells is reduced in preeclampsia especially in early-onset preeclampsia, making the fetus and placenta vulnerable to attack by cytotoxic T cells. These phenomena can explain the epidemiologic phenomenon that preeclampsia is more common in couples using condom contraception, with shorter cohabitation periods, first pregnancies, first pregnancies in multiparous women when they change partner, and pregnancies after assisted reproduction using donated gametes. In contrast to its importance in early-onset preeclampsia, shallow trophoblast invasion does not play a role in the development of preeclampsia, that is, immune maladaptation does not seem to be involved. Late-onset preeclampsia (34 weeks' gestation), representing 80% to 90% of preeclampsia in most developed countries with a "Western lifestyle," is strongly associated with maternal cardiometabolic variables (metabolic syndrome). Although the underlying pathophysiology might be quite different, syncytiotrophoblast stress is the final common pathway leading to the maternal syndrome among the subtypes of preeclampsia by causing an imbalance between proangiogenic factors (placental growth factor and vascular endothelial growth factor) and antiangiogenic factors (soluble fms-like tyrosine kinase-1 and soluble endoglin). Low-dose aspirin, started before 16 week's gestation, will prevent up to 60% of early-onset preeclampsia but will not prevent late-onset preeclampsia. Optimizing prepregnancy weight and controlling gestational weight gain may be the most effective ways to prevent preeclampsia.

BACKGROUND The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied. METHODS We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding. RESULTS A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P���=���0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P���=���0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11). CONCLUSIONS In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).

A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimers disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe a novel, sensitive assay that detects serum protein aggregates from patients with PE (n=33 early onset and 33 late onset) and gestational age-matched controls (n=77) as well as AD in both dementia and prodromal mild cognitive impairment (MCI, n=24) stages with age-matched controls (n=19). The assay employs exposure of genetically engineered, autophagy-deficient human trophoblasts (ADTs) to serum from patients. The aggregated protein complexes and their individual components, including transthyretin, amyloid beta -42, alpha -synuclein, and phosphorylated tau231, can be detected and quantified by co-staining with ProteoStat, a rotor dye with affinity to aggregated proteins, and respective antibodies. Detection of protein aggregates in ADTs was not dependent on transcriptional upregulation of these biomarkers. The ROC curve analysis validated the robustness of the assay for its specificity and sensitivity (PE; AUC: 1, CI: 0.949-1.00; AD; AUC: 0.986, CI: 0.832-1.00). In conclusion, we have developed a novel, noninvasive diagnostic and predictive assay for AD, MCI and PE. Funding Agencies|NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P20 GM121298, 3P20GM121298-04W1, P30 GM114750]; Brown University DEANS Award; Brown University Seed Award; William and Mary Oh-William and Elsa Zopfi Professorship Award

BACKGROUND The effect of sex on mortality is controversial; furthermore, sex differences in left ventricular (LV) remodeling after transcatheter aortic valve implantation (TAVI) remain unknown.Methods and Results:This study included 2,588 patients (1,793 [69.3%] female) enrolled in the Optimized CathEter vAlvular iNtervention (OCEAN)-TAVI Japanese multicenter registry between October 2013 and May 2017. We retrospectively analyzed the effect of sex on mortality, and evaluated changes in the LV mass index (LVMI) after TAVI. Female sex was significantly associated with lower all-cause and cardiovascular mortality (log-rank P

Background: Accelerated endothelial healing after targeted antiproliferative drug delivery may limit the long-term inflammatory response of drug-eluting stents (DESs). The novel Supreme DES is designed to synchronize early drug delivery within 4 to 6 weeks of implantation, leaving behind a prohealing permanent base layer. Whether the Supreme DES is safe and effective in the short term and can improve long-term clinical outcomes is not known. Methods: In an international, 2:1 randomized, single-blind trial, we compared treatment with Supreme DES to durable polymer everolimus-eluting stents (DP-EES) in patients with acute and chronic coronary syndromes. The primary end point was target lesion failure—a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. The trial was designed to demonstrate noninferiority (margin of 3.58%) of the Supreme DES at 12 months compared with DP-EES (URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03168776). Results: From October 2017 to July 2019, a total of 1629 patients were randomly assigned (2:1) to the Supreme DES (N=1086) or DP-EES (N=543). At 12 months, target lesion failure occurred in 57 of 1057 patients (5.4%) in the Supreme DES group and in 27 of 532 patients (5.1%) in the DP-EES group (absolute risk difference, 0.32% [95% CI, −1.87 to 2.5]; P non inferiority =0.002]. There were no significant differences in rates of device success, clinically driven target lesion revascularization, or stent thrombosis at 12 months, and the safety composite of cardiovascular death and target vessel myocardial infarction was 3.5% versus 4.6% (hazard ratio, 0.76 [95% CI, 0.46–1.25]) with Supreme DES compared with DP-EES, although rates of combined clinically and non–clinically driven target lesion revascularization at 12 months were higher with Supreme DES. Conclusions: Among patients with acute and chronic coronary syndromes undergoing percutaneous coronary intervention, the Supreme DES proved to be noninferior to the standard DP-EES. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03168776.

BACKGROUND: Japanese patients undergoing transcatheter aortic valve replacement (TAVR) are often female and have a small body size, potentially impacting bleeding risk with antithrombotic therapy. Outcomes of direct oral anticoagulant use in these patients with atrial fibrillation (AF) need to be clarified.Methods and Results: This prespecified analysis included Japanese patients from ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial that compared treatment with edoxaban and vitamin K antagonists (VKAs) in patients with AF after TAVR. The primary efficacy and safety outcomes were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, ischemic stroke, systemic embolic event, valve thrombosis, and International Society on Thrombosis and Haemostasis [ISTH]-defined major bleeding) and ISTH-defined major bleeding, respectively. Intention-to-treat (ITT) and on-treatment analyses were performed. Overall, 159 Japanese patients were enrolled (edoxaban group: 82, VKA group: 77) and followed for on average 483 days. Mean patient age was 83.8 years; 52.2% were female. In the ITT analysis, NACE rates were 10.9%/year with edoxaban and 12.5%/year with VKA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.38-1.90); major bleeding occurred in 8.9%/year and 7.3%/year, respectively (HR, 1.17; 95% CI, 0.45-3.05). In edoxaban- and VKA-treated patients, rates of ischemic stroke were 1.8%/year and 1.0%/year, respectively; fatal bleeding rates were 0.9%/year and 2.0 %/year. On-treatment results were similar to ITT. CONCLUSIONS: In Japanese patients with AF after successful TAVR, edoxaban and VKA treatment have similar safety and efficacy profiles.

Recent studies showed the favorable outcomes of transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve (BAV) stenosis. However, data on the rela-tion between BAV morphology and optimal transcatheter heart valve (THV) selection are limited. This study sought to evaluate the determinants of device performance in patients with BAV who underwent TAVI. Consecutive patients with BAV who under-went TAVI with the SAPIEN 3 from multicenters were evaluated. Outcomes were the incidence and predictors of device failure. Device failure was defined as peak aortic velocity > 3.0 m/s, mean pressure gradient > 20 mm Hg, moderate or severe paravalvular leakage and/or procedure mortality. A total of 187 patients with BAV were identified, aged 77 years, and 38.0% were women. A total of 37 patients (19.8%) were treated with 23-mm valve, 58 (31.0%) with 26-mm valve, and 92 (49.2%) with 29-mm valve. Predis -charge echocardiogram demonstrated 37 patients (19.8%) with device failure. BAV with excessive leaflet calcification plus calcified raphe (EC-BAV) (OR 16.7, 95% CI 1.99 to 39.6) and smaller THV (OR 4.41, 95% CI 1.43 to 13.6) were independently associated with increased risk of device failure. In addition, 4.0%, 5.1%, and 11.1% of device fail-ures were observed in patients without EC-BAV who underwent TAVI with 23-, 26-and 29-mm THV (p = 0.47), respectively, and 91.7%, 31.6% and 23.2% in those with EC-BAV, respectively (p < 0.001). In conclusion, EC-BAV morphology was the major deter-minant of a device failure after TAVI. Moreover, TAVI in patients with EC-BAV requir-ing small SAPIEN 3 could be challenging. Further data on device and treatment selection in patients with BAV are still warranted. (C) 2022 The Author(s). Published by Elsevier Inc.

Regulatory T (Treg) cells play an important role in implantation of the embryo and maintenance of pregnancy after allogeneic mating. Implantation failure, miscarriage, and preeclampsia are associated with decreased numbers of Treg cells or with dysfunctional Treg cells. Treg cells are classified into naturally occurring Treg (nTreg) cells or thymus-derived Treg (tTreg) cells that differentiate in the thymus and induce tolerance to self-antigens, while induced Treg (iTreg) or peripheral Treg (pTreg) cells differentiate in the periphery and induce transient tolerance to foreign antigens. Memory nTreg or iTreg cells were recently reported to accumulate in the uterus during early pregnancy and contribute to the establishment of pregnancy. Miscarriage is characterized by the downregulation of the total numbers of Treg cells rather than a downregulation of the numbers of paternal/fetal antigen-specific Treg cells. In addition to the volume of paternal/fetal antigen-specific CD8+ T cells, the number of paternal/fetal antigen-specific Treg cells, which protect the fetus/placenta against maternal immune cell attack, increases after the second trimester of pregnancy. Clonal Treg cells which are surrogate markers of paternal/fetal antigen-specific Treg cells in humans may be involved in the development of preeclampsia during the mid- to late pregnancy stage, as evidenced by their downregulation in the decidua of preeclamptic cases. This review summarizes recent findings on Treg cells and discusses the roles, in the maintenance of pregnancy, of different types of Treg cells such as paternal/fetal antigen-specific Treg, pregnancy-associated memory Treg, nTreg (or tTreg), and iTreg (or pTreg cells).

According to the 2004 Japanese definition, early-onset (EO) preeclampsia (PE) is defined as PE occurring at32 weeks of gestation. This was based on the presence of "dual peaks" (30-31 and 34-35 weeks) in the prevalence of severe forms of hypertension. In contrast, the international definition adopted a cutoff of 34 weeks based on the consensus. Our aim was to investigate whether there were "dual peaks" in the gestational-age-specific incidence or prevalence of PE onset in pregnant women who underwent maternal check-ups at20 weeks of gestation in a multicenter retrospective cohort study. Diagnoses of PE and superimposed preeclampsia (SPE) were based on the new Japanese definition. A total of 26,567 pregnant women with singleton pregnancy were investigated. The best fitting equations for the distribution of the onset of gestational-age-specific incidence (hazard) rates of PE/SPE, PE, and PE with severe hypertension (a systolic blood pressure ≥160 and/or a diastolic blood pressure ≥110 mmHg) were investigated using the curve estimation function in SPSS. PE/SPE occurred in 1.83% of the patients. EO-PE/SPE with onset at32 and34 weeks of gestation and preterm PE/SPE occurred in 0.38, 0.56, and 1.07% of the patients, respectively. Gestational-age-specific incidence rates of PE/SPE, PE, and PE with severe hypertension showed exponential increases, with very high R

AIM The purpose of this study was to evaluate the current state and clinical characteristics of spontaneous hemoperitoneum in pregnancy (SHiP) in Japan by performing a comprehensive survey. METHODS We reviewed data on pregnant women who developed SHiP during 2013-2017 (for 5 years), and were admitted to any of the perinatal centers in Japan. The survey assessed maternal background and maternal and neonatal prognosis. We divided the cases into two groups, favorable and poor prognosis groups, and made comparisons between the two groups. RESULTS Of the 407 facilities in Japan, 267 (66%) facilities responded to our survey. Overall, 31 cases of SHiP were registered. Maternal death occurred in one case (3%) due to liver bleeding with an unknown cause. Of 23 cases with a SHiP onset during pregnancy, 12 (53%) had been misdiagnosed as placental abruption. The prognosis for the fetuses included miscarriage or stillbirth in three cases (10%) and asphyxia in 12 cases (42%). There was no significant correlation between the amount of intra-abdominal blood loss and neonatal prognosis based on umbilical artery pH. Incidences of preterm birth

Cytotrophoblasts differentiate in two directions during early placentation: syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). STBs face maternal immune cells in placentas, and EVTs, which invade the decidua and uterine myometrium, face the cells in the uterus. This situation, in which trophoblasts come into contact with maternal immune cells, is known as the maternal-fetal interface. Despite fetuses and fetus-derived trophoblast cells being of the semi-allogeneic conceptus, fetuses and placentas are not rejected by the maternal immune system because of maternal-fetal tolerance. The acquired tolerance develops during normal placentation, resulting in normal fetal development in humans. In this review, we introduce placental development from the viewpoint of molecular biology. In addition, we discuss how the disruption of placental development could lead to complications in pregnancy, such as hypertensive disorder of pregnancy, fetal growth restriction, or miscarriage.

We have previously described that placental activation of autophagy is a central feature of normal pregnancy, whereas autophagy is impaired in preeclampsia (PE). Here, we show that hypoxia–reoxygenation (H/R) treatment dysregulates key molecules that maintain autophagy–lysosomal flux in primary human trophoblasts (PHTs). Ultrastructural analysis using transmission electron microscopy reveals a significant reduction in autophagosomes and autolysosomes in H/R-exposed PHTs. H/R-induced accumulation of protein aggregates follows a similar pattern that occurs in PHTs treated with a lysosomal disruptor, chloroquine. Importantly, the placenta from early-onset PE deliveries exhibits the same features as seen in H/R-treated PHTs. Taken together, our results indicate that H/R disrupts autophagic machinery in PHTs and that impaired autophagy in the placenta from early-onset PE deliveries mimics the events in H/R-treated PHTs. Notably, assessment of key regulators at each stage of autophagic processes, especially lysosomal integrity, and verification of autophagic ultrastructure are essential for an accurate evaluation of autophagy activity in human trophoblasts and placental tissue from PE deliveries.

Item does not contain fulltext BACKGROUND: COMBO (OrbusNeich Medical, Hong Kong) is a dual-therapy coronary stent featuring sirolimus as antiproliferative drug and an anti-CD34+ antibody coating to attract endothelial progenitor cells favoring rapid stent re-endothelization. The Mega COMBO collaboration aimed to evaluate the performance of the COMBO stent in a large contemporary cohort of patients undergoing percutaneous coronary intervention (PCI). METHODS: Patient-level data of subjects undergoing PCI with the COMBO stent from the REMEDEE-Trial, REMEDEE-OCT, HARMONEE, REDUCE, SORT OUT X, REMEDEE-Registry and MASCOT studies were pooled together. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction (TV-MI) or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes were the individual components of the primary endpoint and stent thrombosis (ST). Endpoints were evaluated against performance goals based on the EAPCI (the European Association of Percutaneous Coronary Intervention) recommendations for new drug-eluting stents. RESULTS: A total of 6753 patients (mean age 63.7 ± 11.4 years, 23% women) were included. At 1-year follow-up, TLF occurred in 303 (4.6%) patients. The rates of cardiovascular death, TV-MI, and CD-TLR were 1.3%, 1.8%, and 2.5%, respectively. The rate of definite/probable ST was 0.73%, early ST (

Background The practice pattern and outcome of medical devices following their regulatory approval may differ by country. The aim of this study is to compare postapproval national clinical registry data on transcatheter aortic valve replacement between the United States and Japan on patient characteristics, periprocedural outcomes, and the variability of outcomes as a part of a partnership program (Harmonization‐by‐Doing) between the 2 countries. Methods and Results The patient‐level data were extracted from the US Society of Thoracic Surgeons /American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) and the J‐TVT (Japanese Transcatheter Valvular Therapy) registry, respectively, to analyze transcatheter aortic valve replacement outcomes between 2013 and 2019. Data entry for these registries was mandated by the federal regulators, and the majority of variable definitions were harmonized to allow direct data comparison. A total of 244 722 transcatheter aortic valve replacements from 646 institutions in the United States and 26 673 transcatheter aortic valve replacements from 171 institutions in Japan were analyzed. Median volume per site was 65 (interquartile range, 45–97) in the United States and 28 (interquartile range, 19–41) in Japan. Overall, patients in J‐TVT were older (United States: mean‐age, 80.1±8.7 versus Japan: 84.4±5.2; P P P P P P Conclusions This collaborative analysis between the United States and Japan demonstrated the feasibility of international comparison using the national registries coded under mutual variable definitions. Both countries obtained excellent outcomes, although the Japanese had lower 30‐day mortality and major morbidity. Harmonization‐by‐Doing is one of the key steps needed to build global‐level learning to improve patient outcomes.

Limited data exist on the comparison of clinical outcomes after first- and second-generation drug-eluting stent (DES) thrombosis. From the Retrospective Multicenter Registry of Stent Thrombosis (ST) After First- and Second-Generation DES Implantation registry, this study evaluated 655 ST patients (first-generation DES thrombosis [G1-ST], n = 342; second-generation DES thrombosis [G2-ST], n = 313). After propensity score matching, the final study population consisted of 159 matched patients. The primary end point was the cumulative 1-year incidence of mortality. The mortality after G2-ST at 1 year was similar to that after G1-ST (23.0% vs 22.9%, p = 0.76). Also, the G2-ST group showed a significantly lower rate of target lesion revascularization than the G1-ST group (9.7% vs 17.1%, p = 0.01). Risk factors of 1-year mortality included cardiogenic shock or arrest at the time of ST, multivessel ST, left ventricular ejection fraction ≤40%, advanced age, and final thrombolysis in myocardial infarction flow grade ≤2. In conclusion, patients with G2-ST showed a similar 1-year mortality to those with G1-ST, highlighting that ST remains a life-threatening complication in the second-generation DES era.

Background : Anastomotic leakage after esophagectomy is significantly associated with more severe complications, such as sepsis and mortality. Early prediction for anastomotic leakage is usually difficult and needs to be treated rapidly. In the current study, we investigated the correlation between hemodynamic and several complications after esophagectomy in patients with esophageal cancer, using the FloTrac system. Materials and Methods : Between April 2013 and December 2014, 39 patients with a mean age of 66.6 ± 8.9 years underwent postoperative supervision using the FloTrac sensor / Vigileo monitoring system after curative surgery for esophageal cancer. We retrospectively evaluated the association between the number of aberrant cardiac index (CI) along with stroke volume variability (SVV) values and clinicopathological parameters of postoperative complications in this report. Results : There were significant positive correlations between the number of aberrant values of CI along with SVV and depth of invasion during pathological stage. Concerning major postoperative complications, there was a significant positive correlation between the number of aberrant values of CI and anastomotic leakage. Discussion: The hemodynamic change by employing the FloTrac system could predicts the complication of anastomotic leakage after esophagectomy. Adequate management of hemodynamic stability by utilizing it will reduce the complications of anastomotic leakage. J. Med. Invest. 67 : 240-245, August, 2020.

This study aimed to elucidate the association between postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) and clinicopathological factors and intraoperative and postoperative epidural or intravenous patient-controlled analgesia (IV-PCA). We reviewed data of 116 patients who underwent distal pancreatectomy at Gunma University Hospital from October 2000 to October 2019. Clinical POPF was defined as the International Study Group of Pancreatic Fistula grade B or C. Intraoperative and postoperative analgesia included fentanyl-mediated IV-PCA (n = 37, 32%), fentanyl-mediated epidural analgesia (n = 39, 34%), and morphine-mediated epidural analgesia (n = 40, 34%). All patients had received analgesia. Clinical POPF occurred in 34 of the 116 (29%) DP cases. Male sex (P = 0.035) and the length of operation time (P = 0.0070) were significant risk factors of clinical POPF. Furthermore, a thick pancreas was more likely to cause clinical POPF than a thin one (P = 0.052). No statistically significant difference was found between other factors, including intraoperative and postoperative analgesia (P = 0.95), total median oral morphine equivalents (P = 0.23), and clinical POPF. Intraoperative and postoperative epidural analgesia and IV-PCA are not associated with clinical POPF after DP. Our results suggest that morphine and fentanyl can be used as IV-PCA or epidural analgesia.

TAKAYASU'S ARTERITIS (TA) is a rare clinical condition, with an incidence of 1-2 cases per million in Japan 1 . It is characterized by chronic panarteritis of the aorta and its primary branches, including the subclavian, common carotid, coronary and renal arteries, and may result in localized stenosis, vascular occlusion, dilatation and aneurysm formation 2 . The disease can cause various circulatory complications, such as hypertension, heart failure, aortic regurgitation, coronary stenosis and aortic aneurysm.Among these, aortic dissection is very rare, accounting for 0.87% of patients with TA 3 . Further, there are only few reports of peripartum aortic dissection in pregnant patients with TA requiring combined treatment with cesarean delivery and TEVAR at the same time 4 . If aortic dissection occurs during pregnancy, ensuring the safety of both mother and fetus is quite challenging in this potentially lethal situation. Here, the authors report successful anesthetic management of emergency cesarean delivery immediately followed by TEVAR for a dissecting aortic aneurysm with impending rupture in a pregnant patient with TA. Written informed consent was obtained from the patient for publication of this case report

Japanese patients have shown improved outcomes after treatment with drug eluting stents compared with Western patients. Outcomes with the ridaforolimus-eluting EluNIR stent in Japanese patients are unknown. This was a multi-center trial in Japanese patients undergoing PCI with the ridaforolimus eluting EluNIR stent. A propensity-score matched analysis was performed with the EluNIR arm of the BIONICS trial. The matched cohort was compared with the Japanese patients for the primary endpoint of target lesion failure (TLF) in a non-inferiority study. 104 Japanese patients were compared with 410 matched patients from BIONICS. Baseline characteristics were similar except for more frequent multi-vessel disease in the BIONICS cohort. Post dilation was more likely in Japanese patients (90.4% vs. 64.6%, p

BACKGROUND Approximately 10% of female athletes have a history of stress fractures, which most commonly occur between the ages of 16 and 17 years old. PURPOSE We investigated whether tartrate-resistant acid phosphatase 5b (TRACP-5b), which is a bone resorption marker, can serve as a valid predictor of stress fractures in female athletes in their teens and 20s. METHODS Three hundred and sixteen elite female athletes were recruited between 2013 and 2015. Serum TRACP-5b and various hormones were examined in blood samples. The serum TRACP-5b level was compared between athletes with and without stress fractures within 3 months after the initial collection of their blood samples. RESULTS The 316 athletes were divided into two age groups: 13-19 years old and 20-29 years old. Thirty-six athletes (11.4%) experienced new stress fractures within 3 months after the initial collection of their blood samples. The median serum TRACP-5b level was significantly higher in teenage athletes with new stress fractures than in teenage athletes without new stress fractures. In univariate logistic regression analysis, the Z-score of serum TRACP-5b was a significant predictive factor of stress fractures in teenage athletes only (odds ratio: 1.87; 95% CI: 1.31-2.66; P

Coronary artery disease is common in patients on dialysis; there is a high rate of bleeding events after percutaneous coronary intervention (PCI) in such patients. We investigated the impact of bleeding events after PCI on mortality in patients on hemodialysis. We included 386 consecutive hemodialysis patients who underwent PCI using a drug-eluting stent (DES) between September 2004 and December 2017 in our hospital, and investigated the impact of bleeding events on all-cause mortality after PCI. Bleeding events were assessed by the Thrombolysis in Myocardial Infarction (TIMI) bleeding definition within 24 months after PCI. A total of 42 patients experienced bleeding events. Of these, 30 patients (71.4%) had TIMI major bleeding events and 12 patients (28.6%) had TIMI minor bleeding events. Patients with bleeding events had significantly higher mortality than patients without bleeding events (survival rate, 55.1% vs 81.5%, log-rank: p

Objective To evaluate the short-, long-term clinical and angiographic outcomes after treatment of true bifurcation lesions using a modified jailed balloon technique (MJBT). Background Percutaneous coronary intervention (PCI) for true bifurcation lesions has high risk for adverse events. Side branch (SB) occlusion is one of the most serious complications. Therefore, novel strategies to avoid SB occlusion during main branch stenting and to keep its patency are important. Methods and results Between February 2015 and February 2018, 328 patients with 349 true bifurcation lesions underwent PCI using MJBT. True bifurcation lesions were defined as Medina classifications (1.1.1), (1.0.1) or (0.1.1) lesions. We investigated the procedural and long-term clinical outcomes. Furthermore, angiographic outcomes were assessed at follow-up diagnostic angiography. The mean age of patients was 71.6 ± 9.9 years. Procedural success was achieved in all patients; postoperative SB occlusion was noted in only one patient (0.3%). The cumulative incidence of all-cause death was 23 patients (7.0%) in the follow-up period (median 717 days). Target lesion revascularization was performed in 19 patients (5.8%) with 23 lesions (6.6%), and 0.6% of myocardial infarction and 0% of definite stent thrombosis were observed. Angiographic follow-up was performed in 243 patients (74.1%); the percent diameter stenosis in SB was not significantly different between after the index procedure and follow-up angiography. Conclusions This MJBT is safe and effective in preserving SB patency for true bifurcation lesions. Furthermore, long-term clinical and angiographic outcomes after MJBT are feasible.

Background It currently remains unknown whether the resection of cervical polyps during pregnancy leads to miscarriage and/or preterm birth. This study evaluated the risk of spontaneous PTB below 34 or 37 weeks and miscarriage above 12 weeks in patients undergoing cervical polypectomy during pregnancy. Methods This was a retrospective monocentric cohort study of patients undergoing cervical polypectomy for clinical indication. Seventy-three pregnant women who underwent polypectomy were selected, and risk factors associated with miscarriage above 12 weeks or premature delivery below 34 or 37 weeks were investigated. A multivariable regression looking for predictors of spontaneous miscarriage > 12 weeks and PTB Results Sixteen patients (21.9%, 16/73) had spontaneous delivery at p = 0.004], polyp width ≥ 12 mm (OR 4.0, 95% CI 1.2–13.1, p = 0.005), the proportion of decidual polyps (OR 8.1, 95% CI 1.00–65.9, p = 0.024), and polypectomy at ≤10 weeks (OR 5.2, 95% CI 1.3–20.3, p = 0.01) were significantly higher in delivery at p = 0.001), genital bleeding before polypectomy (OR 6.5, 95% CI 1.2–55.7, p = 0.025), and polypectomy at ≤10 weeks (OR 5.9, 95% CI 1.2–45.0, p = 0.028) as independent risk factors for predicting delivery at Conclusions Our cohort of patients undergoing polypectomy in pregnancy have high risks of miscarriage or spontaneous premature delivery. It is unclear whether these risks are given by the underlying disease, by surgical treatment or both. This study establishes clinically relevant predictors of PTB are polyp size> 12 mm, bleeding and first trimester polypectomy. PTB risks should be exposed to patients and extensively discussed with balancing against the benefits of intervention in pregnancy.

Background and aims: Clinical atherosclerosis manifestations are different in women compared to men. Since endothelial shear stress (ESS) is known to play a critical role in coronary atherosclerosis development, we investigated differences in anatomical characteristics and endothelial shear stress (ESS)–related plaque growth in human coronary arteries in men compared to women. Methods: 1183 coronary arteries (male/female: 944/239) from the PREDICTION study were studied for differences in artery/plaque and ESS characteristics, and ESS-related plaque progression (6–10 months follow-up) among men and women and after stratification for age. All characteristics were derived from IVUS-based vascular profiling and reported per 3 mm-segments (13,030 3-mm-segments (male/female: 10,465/2,565)). Results: Coronary arteries and plaques were significantly smaller in females compared to males; but no important differences were observed in plaque burden, ESS and rate of plaque progression. Change in plaque burden was inversely related to ESS (p

The etiology of preeclampsia (PE), a serious pregnancy complication, remains an enigma. We have demonstrated that proteinopathy, a pathologic feature of neurodegenerative diseases, is a key observation in the placenta and serum from PE patients. We hypothesize that the macroautophagy/autophagy machinery that mediates degradation of aggregated proteins and damaged organelles is impaired in PE. Here, we show that TFEB (transcription factor EB), a master transcriptional regulator of lysosomal biogenesis, and its regulated proteins, LAMP1, LAMP2, and CTSD (cathepsin D), were dysregulated in the placenta from early and late onset PE deliveries. Primary human trophoblasts and immortalized extravillous trophoblasts (EVTs) showed reduced TFEB expression and nuclear translocation as well as lysosomal protein content in response to hypoxia. Hypoxia-exposed trophoblasts also showed decreased PPP3/calcineurin phosphatase activity and increased XPO1/CRM1 (exportin 1), events that inhibit TFEB nuclear translocation. These proteins were also dysregulated in the PE placenta. These results are supported by observed lysosomal ultrastructural defects with decreased number of autolysosomes in hypoxia-treated primary human trophoblasts. Autophagy-deficient human EVTs exhibited poor TFEB nuclear translocation, reduced lysosomal protein expression and function, and increased MTORC1 activity. Sera from PE patients induced these features and protein aggregation in EVTs. Importantly, trophoblast-specific conditional atg7 knockout mice exhibited reduced TFEB expression with increased deposition of protein aggregates in the placenta. These results provide compelling evidence for a regulatory link between accumulation of protein aggregates and TFEB-mediated impaired lysosomal biogenesis and autophagy in the placenta of PE patients. Abbreviation:atg7: autophagy related 7; CTSD: cathepsin D; ER: endoplasmic reticulum; EVTs: extravillous trophoblasts; KRT7: keratin 7; LAMP1: lysosomal associated membrane protein 1; LAMP2: lysosomal associated membrane protein 2; mSt: mStrawberry; MTORC1: mechanistic target of rapamycin complex 1; NP: normal pregnancy; NPS: normal pregnancy serum; PE: preeclampsia; PES: preeclampsia serum; p-RPS6KB: phosphorylated ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TFEB: transcription factor EB; XPO1/CRM1: exportin 1

To clarify the perinatal outcome of retained products of conception (RPOC) after 22 weeks or more.The retrospective cohort study reviewed medical records of patients with RPOC without placenta previa at 186 Japanese perinatal centers.Of the 323 patients with RPOC, pregnancies after assisted reproductive technology (ART) accounted for 43%. Transfusion at delivery was required in 33% of the patients. Logistic regression analyses revealed that transfusion was significantly required in the following situations: ART pregnancy (aOR: 6.0, 95%CI: 2.3-16, P 0.001), and RPOC length ≥4 cm (aOR: 5.3, 95%CI: 2.1-13, P 0.001). Transarterial embolization (TAE) and/or hysterectomy for subsequent RPOC-related bleeding was performed in 60 patients with RPOC. Logistic regression analysis revealed that additional interventions were significantly required in the following situations: multiparity (aOR: 6.1, 95%CI: 2.1-17.2, P 0.001), and hypervascular RPOC (aOR: 12.8, 95%CI: 3.2-51.1, P 0.001). TAE and/or hysterectomy was also frequently employed in ART pregnancy, although this was not significant (aOR: 2.8, 95%CI: 0.9-8.2, P = 0.063).Patients with RPOC were significantly more likely to require transfusion at delivery in the presence of large RPOC and ART. They were also more likely to require hemostatic procedures for subsequent bleeding in the presence of hypervascular RPOC and ART.

A large cohort study of Japanese women reported that the rate of recurrent spontaneous preterm delivery (sPTD) in the next pregnancy was 22.3%; therefore, it is important to prevent recurrent sPTD. The present study investigated the rate of recurrent sPTD in pregnant women treated with probiotics.This was a retrospective study. Fifty-one pregnant women with a history of sPTD and who had been taking probiotics before 14 weeks of gestation were selected. The rate of sPTD in the next pregnancy among 255 pregnant women with a history of sPTD who had not taken probiotics was compared with that in the probiotics group.The rate of recurrent sPTD was 9.8% (5/51), which was lower than previously reported values. Furthermore, the rate of recurrent sPTD was significantly lower in the probiotics group (9.8%) than in the nonprobiotics group (31.0% [79/255]; p = 0.002).Probiotics may reduce the rate of recurrent sPTD.

Background Ventricular‐arterial coupling predicts outcomes in patients with heart failure. The arterial elastance to end‐systolic elastance ratio (Ea/Ees) is a noninvasively assessed index that reflects ventricular‐arterial coupling. We aimed to determine the prognostic value of ventricular‐arterial coupling assessed through Ea/Ees after transcatheter aortic valve replacement to predict clinical events. Methods and Results We retrieved data on 1378 patients (70% women) who underwent transcatheter aortic valve replacement between October 2013 and May 2017 from the OCEAN‐TAVI (Optimized transCathEter vAlvular iNtervention) Japanese multicenter registry. We determined the association between Ea/Ees and the composite end point of hospitalization for heart failure and cardiovascular death by classifying the patients into quartiles based on Ea/Ees values (group 1: 0.666) during the midterm follow‐up after transcatheter aortic valve replacement. During a median follow‐up period of 736 days (interquartile range, 414–956), there were 247 (17.9%) all‐cause deaths, 89 (6.5%) cardiovascular deaths, 130 (9.4%) hospitalizations for heart failure, and 199 (14.4%) composite events of hospitalization for heart failure and cardiovascular death. The incidence of the composite end point was significantly higher in group 2 (hazard ratio [HR], 1.76; 95% CI, 1.08–2.87 [ P =0.024]), group 3 (HR, 2.43; 95% CI, 1.53–3.86 [ P P P =0.015]). Conclusions These findings suggest that a higher Ea/Ees at discharge after transcatheter aortic valve replacement is associated with adverse clinical outcomes during midterm follow‐up. Registration URL: https://www.upload.umin.ac.jp/ . Unique identifier: UMIN000020423.

Understanding of sterile inflammation and its associated biological triggers and diseases is still at the elementary stage. This becomes more warranted in cases where infections are not associated with the pathology. Detrimental effects of bacterial and viral infections on the immune responses at the maternal-fetal interface as well as pregnancy outcomes have been well documented. However, an infection-induced etiology is not thought to be a major contributing component to severe pregnancy complications such as preeclampsia (PE) and gestational diabetes. How is then an inflammatory signal thought to be associated with these pregnancy complications? It is not clear what type of inflammation is involved in the onset of PE-like features. We opine that sterile inflammation regulated by the inflammasome-gasdermins-caspase-1 axis is a contributory factor to the onset of PE. We hypothesize that increased production and release of damage-associated molecular patterns (DAMPs) or Alarmins such as high-mobility group box1 (HMGB1), cell-free fetal DNA, uric acid, the NOD-like receptor pyrin-containing receptor 3 (NLRP3) inflammasome, IL-1β and IL-18 occur in the PE placenta. Some of these molecules have already been observed in the placenta from women with PE. Mechanistically, emerging evidence has demonstrated that excessive placental endoplasmic reticulum (ER) stress, impaired autophagy and gasdermine D (GSDMD)-mediated intrinsic pyroptosis are key events that contribute to systemic sterile inflammation in patients with PE, especially early-onset PE (e-PE). In this review, we highlight the advances on the roles of sterile inflammation and inflammatory signaling cascades involving ER stress, autophagy deficiency and pyroptosis in PE pathophysiology. Deciphering the mechanisms underlying these inflammatory pathways may provide potential diagnostic biomarkers and facilitate the development of therapeutic strategies to treat this devastating disease.

Background Percutaneous coronary intervention of calcified lesions was associated with worse outcomes in the era of bare‐metal and first‐generation drug‐eluting stents. Data on percutaneous coronary intervention of calcified lesions with newer‐generation drug‐eluting stents are scarce. Therefore, we investigated the impact of lesion calcification on clinical outcomes in patients undergoing percutaneous coronary intervention with a bioresorbable‐polymer sirolimus‐eluting stent or a durable‐polymer everolimus‐eluting stent. Methods and Results Patients (n=2361) from BIOFLOW II, IV, and V trials were categorized into moderate/severe versus none/mild lesion calcification by a core laboratory. End points were target‐lesion failure (TLF) (cardiac death, target‐vessel myocardial infarction, or target‐lesion revascularization) and probable/definite stent thrombosis at 2 years. The agreement in calcification assessment between the operator and the core laboratory was weak (weighted κ, 0.23). Patients with moderate/severe calcification (n=303; 16%) had higher TLF (13.5% versus 8.4%; P =0.003) and stent thrombosis rates (2.1% versus 0.2%; P P =0.302). After adjustment, calcification did not emerge as an independent predictor of TLF (adjusted hazard ratio [aHR], 1.37; 95% CI, 0.89–2.08; P =0.148) but did for target‐vessel myocardial infarction (aHR, 1.66; 95% CI, 1.03–2.68; P =0.037). TLF rates were similar between bioresorbable‐polymer sirolimus‐eluting stent and durable‐polymer everolimus‐eluting stent (12.6% versus 15.4%, P =0.482) in moderate/severe calcification. In none/mild calcification, the bioresorbable‐polymer sirolimus‐eluting stent showed lower TLF (7.5% versus 10.3%, P =0.045). Conclusions With newer‐generation drug‐eluting stents, moderate/severe lesion calcification was not associated with more TLF after adjustment for the higher risk of patients with coronary calcification, whereas the rate of target‐vessel myocardial infarction was higher. The bioresorbable‐polymer sirolimus‐eluting stent and durable‐polymer everolimus‐eluting stent were equally effective and safe in calcified lesions. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT01356888, NCT01939249, NCT02389946.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, five of which are summarised in this report. These workshops discussed new perspectives and knowledge in the following areas of research: 1) preeclampsia; 2) abnormally invasive placenta; 3) placental infection; 4) gestational trophoblastic disease; 4) drug delivery to treat placental dysfunction.

Aim To clarify the risk factors and pregnancy outcomes for each risk factor of recurrent pregnancy loss (RPL) in Japan. Methods Using a prospective RPL database collected from 16 facilities in Japan, the prevalence of risk factors for RPL, their treatments and pregnancy outcomes were examined. Results Of 6663 patients registered in our database, 5708 patients had RPL. All examinations for risk factors were performed for 1340 patients (23.5%). The prevalences of positive antiphospholipid antibodies (aPL), malformation of the uterus, thyroid dysfunction, parental karyotype abnormality, factor XII deficiency, protein S deficiency and unknown risk factors were 8.7%, 7.9%, 9.5%, 3.7%, 7.6%, 4.3% and 65.1%, respectively. Although factor XII deficiency and protein S deficiency are not recognized as risk factors for RPL in general, low-dose aspirin (LDA) or unfractionated heparin + LDA therapy improved live birth rates. In transiently aPL-positive patients, the live birth rate with LDA therapy was similar to that with heparin + LDA. For unknown risk factors of RPL, the live birth rate in normal fetal karyotype in the none treatment group was similar to that in all other treatments group (81.3% vs 86.0%). Of 5708 RPL patients, pregnancy outcomes were known for 2261 patients and 1697 patients (75.1%) had at least one live birth. Conclusion The risk factors and pregnancy outcomes for each risk factor of RPL are useful for clinicians and patients. Factor XII deficiency and protein S deficiency may be risk factors of RPL.

ObjectivesTo assess the long-term safety and efficacy of a sirolimus-eluting stent with bioresorbable polymer (BP-SES; Ultimaster), in comparison to a benchmark everolimus-eluting, permanent polymer stent (PP-EES; Xience), in a prespecified subgroup of patients with multivessel coronary artery disease (MVD) enrolled in the CENTURY II trial. BackgroundThe use of coronary stenting in high-risk subgroups, like MVD patients, is rising. The clinical evidence, including long-term comparative analysis of the efficacy and safety benefits of different new-generation drug eluting stents, however, remains insufficient. MethodsAmong 1,119 patients (intention-to-treat) enrolled in the CENTURY II prospective, randomized, single-blind, multicenter trial, a prespecified subgroup of 456 MVD patients were allocated by stratified randomization to treatment with BP-SES (n =225) or PP-EES (n =231). The previously reported primary endpoint of this study was freedom from target lesion failure (TLF: a composite of cardiac death, target vessel-related myocardial infarction [MI] and clinically-indicated target lesion revascularization) at 9months. ResultsIn this MVD substudy, baseline patient, lesion and procedure characteristics were similar between the treatment arms. At 1 and 5 years, both BP-SES and PP-EES displayed low and comparable rates of TLF (5.3 vs. 7.8%; p =.29 and 10.2 vs. 13.4%; p =.29), and definite or probable stent thrombosis (0.4 vs. 1.3%; p =.33 and 0.9 vs. 1.7%; p =.43), respectively. Composite endpoint of cardiac death and MI, and patient-oriented composite endpoint of any death, MI, and coronary revascularizations were also similar. ConclusionsThese results confirm good long-term safety and efficacy of the studied bioresorbable polymer stent in this high-risk patient population.

BACKGROUND SYMPLICITY HTN-Japan is a prospective, randomized, controlled trial comparing renal denervation (RDN) with standard pharmacologic therapy for treatment of uncontrolled hypertension (HTN). Methods and Results: Patients enrolled had uncontrolled HTN, defined as office systolic blood pressure (SBP) ≥160 mmHg and 24-h ambulatory SBP ≥135 mmHg, on ≥3 antihypertensive drugs of maximally tolerated dose for at least 6 weeks prior to enrollment. Randomization was 1:1 to RDN or maintenance of current medical therapy (control). Patients were followed every 6 months post-randomization for up to 36 months. There were 22 patients randomized to RDN and 19 to control, and 11 patients were crossed over and received RDN at 6 months post-randomization. For the RDN group (n=22), office SBP reduction was -32.8±20.1 mmHg and office DBP reduction was -15.8±12.6 mmHg at 36 months post-procedure, both P

OBJECTIVE To determine the cutoff of antithrombin activity for predicting the interval from diagnosis of early-onset pre-eclampsia to delivery. METHODS At Hokkaido University Hospital, Japan, data were retrospectively assessed on antithrombin activity measured at both diagnosis of pre-eclampsia and delivery among women with singleton pregnancy and pre-eclampsia (defined by combined gestational hypertension and proteinuria) between 2009 and 2017. The timing of delivery was determined by maternal and fetal well-being. RESULTS Among 2904 singleton deliveries, antithrombin activity was measured for 94 (3.2%) women diagnosed with pre-eclampsia. The median (range) interval was significantly longer for 38 (40%) women with early-onset than for 56 (60%) women with late-onset pre-eclampsia (6.5 [0-27] vs 1 [0-29] days, respectively; P

We aimed to clarify how maternal physical characteristics explains the association between adolescent pregnancy and adverse birth outcomes, focusing on their height. We used a national multicenter-based delivery registry among 30,831 women under age 25 years with a singleton pregnancy between 2005 and 2011. Adolescent pregnancy was defined as younger than 20 years of age, and categorized into “junior adolescent” (aged ≤15 years) and “senior adolescent” (aged 16–19 years). We used multivariate Poisson regression and mediation analysis to assess the extent to which maternal height explained the association between adolescent pregnancy and risk of adverse birth outcomes. Risks for preterm birth [(adjusted risk ratio (aRR) 1.17, 95% confidence interval (95% CI), 1.08–1.27], low birthweight (aRR 1.08, 95% CI, 1.01–1.15), and low Apgar score (aRR 1.41 95%CI, 1.15–1.73) were significantly higher among adolescent women compared to women of 20–24 years of age. The mediation effect of maternal height on these outcomes were moderate for low birthweight (45.5%) and preterm birth (10.5%), and smaller for low Apgar score (6.6%). In all analyses, we did not detect significant differences between junior adolescent and senior adolescent. Adolescent women have higher risk of adverse birth outcomes. This association is partially mediated by shorter maternal height.

Objectives To assess the longer‐term safety and efficacy of the IN.PACT Admiral (MDT‐2113) drug‐coated balloon (DCB) for the treatment of de novo and non‐stented restenotic lesions in the superficial femoral and/or proximal popliteal arteries versus uncoated percutaneous transluminal angioplasty (PTA) in a Japanese cohort. Background Although DCBs are the newest endovascular strategy for patients with peripheral artery disease presenting with femoropopliteal lesions, there remains a paucity of results in non‐Caucasian populations. Methods IN.PACT SFA Japan is an independently‐adjudicated, prospective, multicenter, randomized, single‐blinded trial. Endpoints through 2 years included primary patency and a composite safety endpoint of freedom from device‐ and procedure‐related death through 30 days, freedom from target limb major amputation and freedom from clinically‐driven target vessel revascularization at 24 months. Results One hundred patients were assigned by 2:1 randomization to treatment with the IN.PACT Admiral DCB (n = 68) or PTA (n = 32). The groups were well‐matched at baseline. Mean lesion length for the DCB and PTA groups were 9.15 ± 5.85 and 8.89 ± 6.01 cm (P = 0.838), respectively. Patients treated with DCB exhibited superior 24‐month primary patency compared to PTA (79.8% vs. 46.9%; log rank P

Background/aim Esophagectomy is more invasive compared to other gastrointestinal surgery types. Perioperative circulatory management is important to avoid postoperative heart complications. The FloTrac sensor along with the Vigileo monitor is a minimally invasive haemodynamic monitoring device. Here, we examined different surgical procedures affecting hemodynamics using the FloTrac system in esophageal cancer patients following esophagectomy. Patients and methods Thirty-one patients undergoing postoperative monitoring with the FloTrac sensor/Vigileo monitor system following esophagectomy were included. Evaluation of cardiac index (CI) and stroke volume variation (SVV) measurements were performed by analyzing the number of aberrant values. We evaluated the correlation between the number of aberrant values of CI, SVV and surgical methods of esophagectomy and perioperative factors. Results There was no significant correlation between the number of aberrant values of CI, SVV and operative approach or fields of lymphadenectomy. Regarding the reconstruction route following esophagectomy, there was a significant correlation between the number of aberrant values of CI, SVV and retrosternal route compared with other routes. There was a significant correlation between the number of aberrant values of SVV and preoperative heart complication. Conclusion Hemodynamic stability management using FloTrac/Vigileo system following esophagectomy is useful for safe performance of postoperative management of esophageal cancer patients.

INTRODUCTION Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. MATERIAL AND METHODS Patients with early-onset severe de novo preeclampsia who are ≥24 to

Aggrephagy is defined as the selective degradation of aggregated proteins by autophagosomes. Protein aggregation in organs and cells has been highlighted as a cause of multiple diseases, including neurodegenerative diseases, cardiac failure, and renal failure. Aggregates could pose a hazard for cell survival. Cells exhibit three main mechanisms against the accumulation of aggregates: protein refolding by upregulation of chaperones, reduction of protein overload by translational inhibition, and protein degradation by the ubiquitin–proteasome and autophagy–lysosome systems. Deletion of autophagy-related genes reportedly contributes to intracellular protein aggregation in vivo. Some proteins recognized in aggregates in preeclamptic placentas include those involved in neurodegenerative diseases. As aggregates are derived both intracellularly and extracellularly, special endocytosis for extracellular aggregates also employs the autophagy machinery. In this review, we discuss how the deficiency of aggrephagy and/or macroautophagy leads to poor placentation, resulting in preeclampsia or fetal growth restriction.

Patient: Female, 43-year-old Final Diagnosis: Portopulmonary hypertension Symptoms: Dyspnea Medication:— Clinical Procedure: — Specialty: Critical Care Medicine • Medicine, General and Internal Objective: Rare disease Background: Pulmonary arterial hypertension (PAH), which is caused by increased pulmonary artery pressure, results in right-heart failure and presents with shortness of breath, chest pain, and syncope. PAH has idiopathic, heritable, and drug/toxin causes and is accompanied by other conditions, including connective tissue disease, congenital heart disease, and portal hypertension. Rarely, portal hypertension causes a type of PAH called porto-pulmonary hypertension (POPH). Portal hypertension can be triggered by liver cirrhosis, which can result from non-alcoholic steatohepatitis (NASH), a metabolic syndrome caused by hypopituitarism. Although an association between hypopituitarism and POPH has been suggested, few reports have described this relationship. Case Report: A 43-year-old woman with hypopituitarism received hormone replacement therapy after partial hypothalamic resection at age 4 years. At age 32 years, she developed liver cirrhosis from NASH due to adult growth hormone (GH) deficiency. Despite restarting GH replacement therapy, she refused the required GH doses for economic reasons. She was hospitalized with abdominal pain and dyspnea and was found to have severe POPH. She received PAH-specific therapies, including endothelin receptor antagonist and prostacyclin analog. Pulmonary hypertension improved on day 3 of hospitalization while the cardiac index increased gradually. On day 12, her respiratory status rapidly worsened and percutaneous cardiopulmonary support was applied. On day 18, she died of multiple organ failure and disseminated intravascular coagulation despite intensive care management. Conclusions: Severe PAH, particularly POPH, remains incurable despite the use of PAH-specific therapies and intensive care management. For hypopituitarism patients, careful observation, including of the cardiopulmonary system, can improve the prognosis after completing hormone replacement therapy.

In endometriosis, M2 MΦs are dominant in endometriotic lesions, but the actual role of M2 MΦ is unclear. CD206 positive (+) MΦ is classified in one of M2 type MΦs and are known to produce cytokines and chemokines. In the present study, we used CD206 diphtheria toxin receptor mice, which enable to deplete CD206+ cells with diphtheria toxin (DT) in an endometriosis mouse model. The depletion of CD206+ MΦ decreased the total weight of endometriotic-like lesions significantly (p

BACKGROUND The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) among patients at high bleeding risk (HBR) is unknown. OBJECTIVES The purpose of this analysis was to compare 1 vs 3 months of DAPT in HBR patients undergoing drug eluting stent implantation. METHODS The XIENCE Short DAPT program comprised 3 prospective, multicenter, single-arm studies of HBR patients treated with a short DAPT course followed by aspirin monotherapy after PCI with a cobalt-chromium everolimus-eluting stent. In this exploratory analysis, patients who received 1-month DAPT (XIENCE 28 USA and 28 Global) were compared with those on 3-month DAPT (XIENCE 90) using propensity score stratification. Ischemic and bleeding outcomes were assessed between 1 and 12 months after index PCI. RESULTS A total of 3,652 patients were enrolled and 1,392 patients after 1-month DAPT and 1,972 patients after 3 month DAPT were eligible for the analyses. The primary endpoint of all-cause mortality or myocardial infarction was similar between the 2 groups (7.3% vs 7.5%; difference-0.2%; 95% CI:-2.2% to 1.7%; P = 0.41). The key secondary endpoint of BARC (Bleeding Academic Research Consortium) type 2-5 bleeding was lower with 1-month DAPT compared with 3-month DAPT (7.6% vs 10.0%; difference-2.5%; 95% CI:-4.6% to-0.3%; P = 0.012). Major BARC type 3-5 bleeding did not differ at 12 months (3.6% vs 4.7%; difference-1.1%; 95% CI:-2.6% to 0.4%; P = 0.082), but was lower with 1-month DAPT at 90 days (1.0% vs 2.1%; P = 0.015). CONCLUSIONS Among HBR patients undergoing PCI, 1 month of DAPT, compared with 3 months of DAPT, was associated with similar ischemic outcomes and lower bleeding risk. (XIENCE 90 Study; NCT03218787; XIENCE 28 USA Study; NCT03815175; XIENCE 28 Global Study; NCT03355742) (J Am Coll Cardiol 2021;78:2060-2072) (c) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Objective Preterm birth (PTB) is the leading cause of infant morbidity and mortality worldwide. Canada and Japan each have strengths that can inform clinical decision-making, research, and health care policy regarding the prevention of PTB and its sequelae. Our objectives were to: 1) compare PTB rates, risk factors, management, and outcomes between Japan and Canada; 2) establish research priorities while fostering future collaborative opportunities; and 3) undertake knowledge translation of these findings. Methods We conducted a literature review to identify publications that examined PTB rates, risk factors, prevention and management techniques, and outcomes in Japan and Canada. We conducted site visits at 4 Japanese tertiary centres and held a collaborative stakeholder meeting of parents, neonatologists, maternal–fetal medicine specialists, and researchers. Results Japan reports lower rates of PTB, neonatal mortality, and several PTB risk factors than Canada. However, Canadian PTB data is population-based, whereas, in Japan, the rate of PTB is population-based, but outcomes are not. Rates of severe neurologic injury and necrotizing enterocolitis were lower in Japan, while Canada's rates of bronchopulmonary dysplasia and retinopathy of prematurity were lower. PTB prevention approaches differed, with less progesterone use in Japan and more long-term tocolysis. In Japan, there were lower rates of neonatal transfers and non-faculty overnight care, but also less use of antenatal corticosteroids and deferred cord clamping. Research priorities identified through the stakeholder meeting included early skin-to-skin contact, parental well-being after PTB, and transitions in care for the child. Conclusion We identified key differences between Japan and Canada in the factors affecting PTB management and patient outcomes, which can inform future research efforts.

Data on ischemic and bleeding outcomes after percutaneous coronary intervention (PCI) in high bleeding risk (HBR) patients with chronic kidney disease (CKD) are scarce. We aimed to evaluate the association between CKD and ischemic and bleeding outcomes in HBR patients who underwent PCI. Among 10,502 patients in the four post-approval registries evaluating patients undergoing PCI, 2,300 patients presented with at least one major or two minor ARC-HBR criteria. CKD was defined as eGFR

Dendritic cells (DCs) are essential for successful embryo implantation. However, the properties of uterine DCs (uDCs) during the implantation period are not well characterized. In this study, we investigated the dynamic changes in the uDC phenotypes during the period between coitus and implantation. In virgin mice, we evaluated the expressions of CD103 and XCR1, this is the first report to demonstrate uDCs expressing CD103 in XCR1+cDC1s and XCR1+cDC2s. On day 0.5 post coitus (pc), the number of uterine CD11c+CD103-MHC classIIhighCD86high-mature DCs rapidly increased and then decreased to non-pregnancy levels on days 1.5 and 2.5 pc. On day 3.5 pc just before implantation, the number of CD11c+CD103+MHC class IIdimCD86dim-immature DCs increased in the uterus. The increase in mature uDCs on day 1.5 pc was observed in both allogeneic- and syngeneic mating, suggesting that sexual intercourse, or semen, play a role in this process. Meanwhile, the increase in immature uDCs on day 3.5 pc was only observed in allogeneic mating, suggesting that allo-antigens in the semen contribute to this process. Next, to understand the turnover and migration of uDCs, we monitored DC movement in the uterus and uterine draining lymph nodes (dLNs) using photoconvertible protein Kikume Green Red (KikGR) mice. On day 0.5 pc, uDCs were composed of equal numbers of remaining DCs and migratory DCs. However, on day 3.5 pc, uDCs were primarily composed of migratory DCs, suggesting that most of the uDCs migrate from the periphery just before implantation. Finally, we studied the expression of PD-L2-which induces immunoregulation-on DCs. On day 3.5 pc, PD-L2 was expressed on CD103+-mature and CD103--mature DCs in the uterus. However, PD-L2 expression on CD103--immature DCs and CD103+-immature DCs was very low. Furthermore, both remaining and migratory DCs in the uterus and uterus-derived-DCs in the dLNs on day 3.5 pc highly expressed PD-L2 on their surface. Therefore, our study findings provide a better understanding of the dynamic changes occurring in uterine DCs and dLNs in preparation for implantation following allogeneic- and syngeneic mating.