An autopsy case of COVID-19 with a sudden death: Clinico-pathological comparison.

Autopsy was performed on a COVID-19 patient, who suddenly died despite the extensive anti-viral and anti-inflammatory therapies. Although moderate subpleural fibrosis was seen, pathology of DAD, a well-known cause for pulmonary failure, was minimum. Instead, severe hemorrhage was observed. Therapeutic effects were indicated; however, why severe hemorrhage occurred was unclear.

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study.

PURPOSE: The effects of daily teriparatide (20 µg) (D-PTH), weekly high-dose teriparatide (56.5 µg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients. METHODS: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months' treatment compared with baseline. RESULTS: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (-4.1%, -3.0%, -1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (-1.8%, -0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (-0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (-0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%). CONCLUSIONS: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH.

Impact of Door-to-Balloon Time Reduction Depending on the Killip Classification in Patients with ST-Segment Elevation Myocardial Infarction Transported by Emergency Medical Services.

The coronavirus disease 2019 pandemic occurred in several countries, making the conventional medical system difficult to maintain. Recent recommendations aim to prevent nosocomial infections and infections among health care workers. Therefore, establishing a cardiovascular medical system under an emergency for patients with ST-segment elevation myocardial infarction (STEMI) is desired. This study aimed to determine the relationship between prognosis and door-to-balloon time (DBT) shortening based on the severity on arrival.This retrospective, multi-center, observational study included 1,127 consecutive patients with STEMI. These patients were transported by emergency medical services and underwent primary percutaneous coronary intervention. Patients were stratified according to the Killip classification: Killip 1 (n = 738) and Killip ≥ 2 (n = 389) groups.Patients in the Killip ≥ 2 group were older, with more females, and more severity on arrival than those in the Killip 1 group. The 30-day mortality rate in the Killip 1 and Killip ≥ 2 groups was 2.2% and 18.0%, respectively. The Killip ≥ 2 group had a significant difference in the 30-day mortality between patients with DBT ≤ 90 minutes and those with DBT > 90 minutes; however, this did not occur in the Killip 1 group. Furthermore, multivariate analysis revealed that DBT ≤ 90 minutes was not a significant predictive factor in the Killip 1 group; however, it was an independent predictive factor in the Killip ≥ 2 group.DBT shortening affected the 30-day mortality in STEMI patients with Killip ≥ 2, although not those with Killip 1.

New risk factors for early- and late-onset cardiac rupture in ST-elevation myocardial infarction patients after primary percutaneous coronary intervention.

BACKGROUND: Cardiac rupture (CR) is a catastrophic complication of acute myocardial infarction. Primary percutaneous coronary intervention (pPCI) reduces the incidence of CR. This study aimed to investigate the clinical risk factors and characteristics of CR after pPCI. METHODS: This was a retrospective, case-control, multicenter study. We enrolled 2444 consecutive patients with ST-elevation myocardial infarction (STEMI) who had undergone pPCI between 2009 and 2015; 33 patients experienced CR (1.35%): 19 were assigned as early CR (≤72 h) and 14 as late CR (>72 h). The 132 controls were randomly selected from the 2411 STEMI patients without CR, by matching institutions at a 1:4 ratio. RESULTS: Multivariate logistic regression revealed that female sex, acute hyperglycemia, thrombocytopenia (platelets <15 × 104/µL), and incomplete revascularization [post-PCI thrombolysis in myocardial infarction (TIMI) <3] were independent risk factors for CR (p<0.05). Older age, female sex, and emergency surgical repair were strongly associated with in-hospital death, which occurred in 66.7% of CR patients (p<0.05). Univariate logistic regression adjusted for age and sex revealed that low systolic blood pressure, anterior infarction, acute hyperglycemia, Killip class >1, and post-PCI TIMI <3 were significantly associated with early CR, and that Killip class >1 and thrombocytopenia were strongly associated with late CR. Early CR occurred more frequently between 12:00 and 21:00 h, whereas the peak incidence of late CR was bimodal between 6:00-12:00 and 21:00-24:00 h. CONCLUSIONS: In STEMI patients after pPCI, acute hyperglycemia and thrombocytopenia are new risk factors for early and late CR, respectively. Clinical risk factors and time of occurrence of early and late CR may differ in the PCI era.

Impact of Door-to-Balloon Time in Patients With ST-Elevation Myocardial Infarction Who Arrived by Self-Transport　- Acute Myocardial Infarction-Kyoto Multi-Center Risk Study Group.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) who arrive at a hospital via self-transport reportedly have a delayed door-to-balloon time (DBT). However, the clinical impacts of delayed DBT on in-hospital mortality among such patients are not well known.Methods and Results:In total, 1,172 STEMI patients who underwent primary percutaneous coronary intervention between January 2009 and December 2013 from the Acute Myocardial Infarction (AMI) Kyoto Registry were analyzed. Compared with the emergency medical service (EMS) group (n=804), the self-transport group (n=368) was younger and had a significantly longer DBT (115 min vs. 90 min, P<0.01), with fewer patients having a Killip classification of 2 or higher. The in-hospital mortality rate was lower in the self-transport group than in the EMS group (3.3% vs. 7.1%, P<0.01). A DBT >90 min was an independent predictor of in-hospital mortality in EMS patients (odds ratio (OR)=2.43, P=0.01) but not in self-transport patients (OR=0.89, P=0.87). CONCLUSIONS: The present study demonstrated that there was no relationship between in-hospital prognosis and DBT ≤90 min in STEMI patients using self-transport. The prognosis of these patients cannot be improved by focusing only on DBT. Treatment strategies based on means of transport should also be considered.

A Simple Risk Stratification Model for ST-Elevation Myocardial Infarction (STEMI) from the Combination of Blood Examination Variables: Acute Myocardial Infarction-Kyoto Multi-Center Risk Study Group.

BACKGROUND: Many mortality risk scoring tools exist among patients with ST-elevation Myocardial Infarction (STEMI). A risk stratification model that evaluates STEMI prognosis more simply and rapidly is preferred in clinical practice. METHODS AND FINDINGS: We developed a simple stratification model for blood examination by using the STEMI data of AMI-Kyoto registry in the derivation set (n = 1,060) and assessed its utility for mortality prediction in the validation set (n = 521). We selected five variables that significantly worsen in-hospital mortality: white blood cell count, hemoglobin, C-reactive protein, creatinine, and blood sugar levels at >10,000/µL, <10 g/dL, >1.0 mg/dL, >1.0 mg/dL, and >200 mg/dL, respectively. In the derivation set, each of the five variables significantly worsened in-hospital mortality (p < 0.01). We developed the risk stratification model by combining laboratory variables that were scored based on each beta coefficient obtained using multivariate analysis and divided three laboratory groups. We also found a significant trend in the in-hospital mortality rate for three laboratory groups. Therefore, we assessed the utility of this model in the validation set. The prognostic discriminatory capacity of our laboratory stratification model was comparable to that of the full multivariable model (c-statistic: derivation set vs validation set, 0.81 vs 0.74). In addition, we divided all cases (n = 1,581) into three thrombolysis in myocardial infarction (TIMI) risk index groups based on an In TIME II substudy; the cases were further subdivided based on this laboratory model. The high laboratory group had significantly high in-hospital mortality rate in each TIMI risk index group (trend of in-hospital mortality; p < 0.01). CONCLUSIONS: This laboratory stratification model can predict in-hospital mortality of STEMI simply and rapidly and might be useful for predicting in-hospital mortality of STEMI by further subdividing the TIMI risk index.

Relationship Between Mean Blood Pressure at Admission and In-Hospital Outcome After Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction.

A J-shaped or U-shaped curve phenomenon might exist between systolic blood pressure (SBP) or pulse pressure (PP) at admission and in-hospital mortality in Japanese patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). However, data regarding a relationship between mean blood pressure (MBP) at admission and in-hospital outcome in AMI patients undergoing primary PCI are still lacking in Japan.A total of 1,413 primary PCI-treated AMI patients were classified into quintiles based on admission MBP (< 79 n = 283, 79-91 n = 285, 92-103 n = 285, 104-115 n = 279, and ≥ 116 mmHg n = 281). Patients with MBP < 79 mmHg had a significantly higher in-hospital mortality, while mortality was not significantly different among the other quintiles: 16.6% (< 79), 4.9% (79-91), 3.9% (92-103), 3.2% (104-115), and 5.0% (≥ 116 mmHg). On multivariate analysis, Killip class ≥ 3 at admission, LMT or multivessels as culprit lesions, admission MBP < 79 mmHg, and age were independent positive predictors of in-hospital mortality, whereas hypercholesterolemia and TIMI 3 flow before/after PCI were negative predictors, while the other MBP categories were not.These results suggest that admission MBP < 79 mmHg might be associated with in-hospital death, and the in-hospital prognostic effects of MBP, the steady component of blood pressure, at admission might be different from those of SBP or PP, the pulsatile component of blood pressure, at admission in Japanese AMI patients undergoing primary PCI.

Survivors of acute myocardial infarction at left main trunk undergoing primary percutaneous coronary intervention.

Acute myocardial infarction (AMI) at left main trunk (LMT) is a deteriorated condition with high in-hospital morbidity and mortality; however, detailed data regarding AMI patients with LMT as culprit lesion (LMT-AMI patients) undergoing primary percutaneous coronary intervention (PCI) has been still limited. Using the AMI-Kyoto Multi-Center Risk Study database, clinical background, angiographic findings and results of primary PCI were retrospectively compared between primary PCI-treated LMT-AMI patients without in-hospital death (survivors, n = 21) and those with in-hospital death (non-survivors, n = 19). The survivors had higher values of estimated glomerular filtration rate (eGFR) and systolic blood pressure at admission and lower prevalence of Killip grade 4 than the non-survivors. Pre-procedural thrombolysis in myocardial infarction (TIMI) flow grade ≥2 at the initial coronary angiography (CAG) and post-procedural TIMI flow grade 3 at the final CAG were more frequent in the survivors, compared with the non-survivors. In contrast, age and gender did not differ significantly between the two groups. On multivariate analysis, higher eGFR and Killip grade 4 at admission were found to be independent in-hospital prognostic factors in the LMT-AMI patients. Admission eGFR and Killip grade 4 are tightly associated with in-hospital prognosis in LMT-AMI patients undergoing primary PCI.

Clinical impact of thrombus aspiration during primary percutaneous coronary intervention in acute myocardial infarction with occluded culprit.

Data regarding clinical efficacy of thrombectomy in patients with acute myocardial infarction (AMI) have been still limited in Japan. Using the AMI-Kyoto Multi-Center Risk Study database, the clinical background characteristics, angiographic findings, primary percutaneous coronary intervention (PCI) results and in-hospital prognoses were retrospectively compared between AMI patients with totally occluded infarct-related artery (IRA) (TIMI flow grade 0) undergoing thrombus aspiration during primary PCI (with-aspiration patients, n = 568) and those without thrombus aspiration (without-aspiration patients, n = 266). The with-aspiration patients were more likely to have higher TIMI grade in the IRA immediately after primary PCI, and had a lower in-hospital mortality rate than the without-aspiration patients. According to a multivariate analysis, thrombectomy as well as stent usage was found to be independent predictor of final TIMI flow grade ≥2 in the IRA, and the final TIMI flow grade ≥2 in the IRA was found to be an independent factor for in-hospital survival. These results suggest that among real-world, unselected Japanese AMI patients with totally occluded IRA on initial coronary angiography, thrombus aspiration is an effective adjunctive therapy during primary PCI to improve final epicardial coronary flow in the IRA, which might lead to better in-hospital prognosis.

Prognostic impact of chronic kidney disease and anemia at admission on in-hospital outcomes after primary percutaneous coronary intervention for acute myocardial infarction.

Cardiorenal anemia syndrome has recently been receiving greater attention; however, data regarding the relationship between chronic kidney disease (CKD)/anemia on presentation and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still limited in Japan.A total of 1,447 primary PCI-treated AMI patients were classified into 4 groups according to the presence of CKD and/or anemia on hospital admission (with CKD/with anemia n = 222, with CKD/without anemia n = 299, without CKD/with anemia n = 151, without CKD/without anemia n = 775). Angiographic acute results of primary PCI were similar among the 4 groups. The patients with CKD had a significantly higher in-hospital overall mortality rate than the patients without CKD, and in the presence or absence of CKD, patients with anemia tended to have a higher in-hospital mortality rate than the patients without anemia. According to a multivariate analysis, anemia on admission was found to be an independent predictor of in-hospital mortality, whereas admission CKD and admission eGFR were statistically not independent predictors. Moreover, the multivariable adjusted odds ratio of in-hospital death in AMI patients with CKD alone was 1.855 (95% CI 0.929-3.706), and that in AMI patients with CKD/with anemia was 3.384 (95% CI 1.697-6.748).These results suggest that among real-world, unselected Japanese AMI patients undergoing primary PCI, the combination of CKD and anemia on admission confers significant adverse effects on in-hospital mortality.

Predictors of in-hospital outcomes after primary percutaneous coronary intervention for acute myocardial infarction in patients with a high Killip class.

OBJECTIVE: The predictors of in-hospital outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated with heart failure or cardiogenic shock at presentation remain unclear. METHODS: Using the AMI-Kyoto Multi-Center Risk Study database, the clinical background characteristics, angiographic findings, primary PCI results, and in-hospital prognoses were retrospectively compared between primary PCI-treated AMI patients with a Killip class status of ≥2 (Killip 2-4 patients, n=390) and those with a Killip class 1 status (Killip 1 patients, n=1,057). RESULTS: The Killip 2-4 patients were more likely to have a higher age and proportion of women and exhibited a higher prevalence of previous myocardial infarction, diabetes mellitus and chronic kidney disease or anemia on admission, lower systolic blood pressure (SBP) values on admission, a higher rate of multivessels or left main trunk as the culprit artery, a larger number of diseased vessels, a lower Thrombolysis In Myocardial Infarction (TIMI) grade in the infarct-related artery (IRA) before/after primary PCI and a significantly higher in-hospital mortality rate than the Killip 1 patients. According to a multivariate analysis, age was found to be an independent positive predictor of in-hospital mortality, while admission SBP was an independent positive predictor of in-hospital survival in both groups. In contrast, anemia on admission was found to be an independent predictor of in-hospital death, while the TIMI 3 flow in the IRA after PCI was found to be an independent factor for survival in the Killip 2-4 patients, but not the Killip 1 patients. CONCLUSION: Anemia on admission and the final TIMI 3 flow in the IRA are critical determinants of in-hospital death in AMI patients with a Killip class status of ≥2 undergoing primary PCI.

Unusual stability of acetonitrile-based superconcentrated electrolytes for fast-charging lithium-ion batteries.

The development of a stable, functional electrolyte is urgently required for fast-charging and high-voltage lithium-ion batteries as well as next-generation advanced batteries (e.g., Li-O2 systems). Acetonitrile (AN) solutions are one of the most promising electrolytes with remarkably high chemical and oxidative stability as well as high ionic conductivity, but its low stability against reduction is a critical problem that hinders its extensive applications. Herein, we report enhanced reductive stability of a superconcentrated AN solution (>4 mol dm(-3)). Applying it to a battery electrolyte, we demonstrate, for the first time, reversible lithium intercalation into a graphite electrode in a reduction-vulnerable AN solvent. Moreover, the reaction kinetics is much faster than in a currently used commercial electrolyte. First-principle calculations combined with spectroscopic analyses reveal that the peculiar reductive stability arises from modified frontier orbital characters unique to such superconcentrated solutions, in which all solvents and anions coordinate to Li(+) cations to form a fluid polymeric network of anions and Li(+) cations.

General observation of lithium intercalation into graphite in ethylene-carbonate-free superconcentrated electrolytes.

Lithium-ion batteries have exclusively employed an ethylene carbonate (EC)-based electrolyte to ensure the reversibility of the graphite negative electrode reaction. Because of the limitation of electrolyte compositions, there has been no remarkable progress in commercial lithium-ion batteries despite active research on positive electrode materials. Herein, we present a salt-superconcentrating strategy as a simple and effective method of universalizing a graphite negative electrode reaction in various organic solvents. A dilute electrolyte (e.g., 1 mol dm(-3)) of sulfoxide, ether, and sulfone results in solvent cointercalation and/or severe electrolyte decomposition at a graphite electrode, whereas their superconcentrated electrolyte (e.g., >3 mol dm(-3)) allows for highly reversible lithium intercalation into graphite. We have found a unique coordination structure in the superconcentrated solution and an anion-based inorganic SEI film on the cycled graphite electrode, which would be the origin of the reversible graphite negative electrode reaction without EC. Our salt-superconcentrating strategy, expanding the graphite negative electrode reaction in various organic solvents other than EC, will contribute to the development of advanced lithium-ion batteries with high-voltage and fast-charging characters based on new EC-free functional electrolytes.

Prognostic impact of pulse pressure at admission on in-hospital outcome after primary percutaneous coronary intervention for acute myocardial infarction.

Data regarding relationship between pulse pressure (PP) at admission and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still lacking. A total of 1413 primary PCI-treated AMI patients were classified into quintiles based on admission PP (<40, n = 280; 40-48, n = 276; 49-57, n = 288; 58-70, n = 288; and ≥71 mmHg, n = 281). The patients with PP < 40 mmHg tended to have higher prevalence of male, smoking, and Killip class ≥3 at admission; right coronary artery, left main trunk (LMT), or multivessels as culprit lesions; larger number of diseased vessels; lower Thrombolysis in Myocardial Infarction (TIMI) grade in the infarct-related artery before/after primary PCI; and higher value of peak creatine phosphokinase concentration. Patients with PP < 40 mmHg had highest mortality, while patients with PP 49-57 mmHg had the lowest: 11.8 % (<40), 7.2 % (40-48), 2.8 % (49-57), 5.9 % (58-70), and 6.0 % (≥71 mmHg). On multivariate analysis, Killip class ≥3 at admission, LMT or multivessels as culprit lesions, chronic kidney disease, and age were the independent positive predictors of the in-hospital mortality, whereas admission PP 49-57 mmHg, hypercholesterolemia, and TIMI 3 flow before/after PCI were the negative ones, but admission PP < 40 mmHg was not. These results suggest that admission PP 49-57 mmHg might be correlated with better in-hospital prognosis in Japanese AMI patients undergoing primary PCI.

Prognostic impact of systolic blood pressure at admission on in-hospital outcome after primary percutaneous coronary intervention for acute myocardial infarction.

BACKGROUND: Data regarding the relationship between systolic blood pressure (SBP) at admission and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still lacking in Japan. METHODS AND RESULTS: A total of 1475 primary PCI-treated AMI patients were classified into quintiles based on admission SBP (<105 mmHg, n=300; 105-125 mmHg, n=294; 126-140 mmHg, n=306; 141-158 mmHg, n=286; and ≥159 mmHg n=289). The patients with SBP<105 mmHg tended to have higher age, previous myocardial infarction, chronic kidney disease (CKD), Killip class≥3 at admission, right coronary artery, left main trunk (LMT), or multivessels as culprit lesions, larger number of diseased vessels, lower Thrombolysis In Myocardial Infarction (TIMI) grade in the infarct-related artery before primary PCI, and higher value of peak creatine phosphokinase concentration. Patients with SBP<105 mmHg had a significantly higher mortality, while mortality was not significantly different among the other quintiles: 24.3% (<105 mmHg), 4.8% (105-125 mmHg), 4.9% (126-140 mmHg), 2.8% (141-158 mmHg), and 5.2% (≥159 mmHg) (p<0.001). On multivariate analysis, Killip class≥3 at admission, LMT or multivessels as culprit lesions, admission SBP<105 mmHg, CKD, and age were the independent positive predictors of in-hospital mortality, whereas admission SBP 141-158 mmHg and TIMI 3 flow after PCI were the negative ones, but admission SBP 105-125 mmHg, admission SBP 126-140 mmHg, and admission SBP≥159 mmHg were not. CONCLUSIONS: These results suggest that admission SBP 141-158 mmHg might be correlated with better in-hospital prognosis, whereas admission SBP<105 mmHg was associated with in-hospital death in Japanese AMI patients undergoing primary PCI.

Primary human bone marrow adipocytes support TNF-α-induced osteoclast differentiation and function through RANKL expression.

PURPOSE: In previous reports, it was demonstrated that bone marrow adipocytes were related to steroid osteoporosis through osteoclastogenesis induced by Receptor Activator of Nuclear factor κ-B Ligand (RANKL) expression. The purpose of this study was to evaluate the effect of Tumor necrosis factor-alpha (TNF-α) on RANKL expression in bone marrow adipocytes, and osteoclast differentiation supported by human bone marrow adipocytes. METHODS: RANKL, osteoprotegerin (OPG), and macrophage-colony stimulating factor (M-CSF) mRNA expression in bone marrow adipocytes and their regulation by TNF-α treatment were measured by real-time RT-PCR. Co-cultures of bone marrow adipocytes and osteoclast precursors were performed with or without TNF-α, and osteoclast differentiation was evaluated morphologically and functionally. RESULTS: RANKL expression and an increase in the RANKL/OPG ratio in bone marrow adipocytes were stimulated by TNF-α treatment. In co-culture of bone marrow adipocytes and osteoclast precursors with TNF-α, the number of TRAP-positive multinuclear cells and resorption cavity formations of calcium phosphate film were increased. Osteoclast differentiation was suppressed by anti-RANKL antibody treatment. In co-culture with non-cell-contact conditions, no TRAP-positive cells or resorption cavity formations were observed. CONCLUSIONS: TNF-α increased RANKL expression in primary human bone marrow adipocytes. TNF-α induced the ability of bone marrow adipocytes to promote osteoclast differentiation and activity in a manner directly related to RANKL expression.