Mid-term results of cyanoacrylate closure for the treatment of incompetent great and small saphenous veins: Findings from a Japanese prospective consecutive multi-center registry: Mid-term results of cyanoacrylate closure.

OBJECTIVES: We evaluated the efficacy and safety of cyanoacrylate closure (CAC) for endovascular treatment of varicose veins with cyanoacrylate adhesive (VenaSeal® closure system) in Japan. METHODS: A multicenter prospective consecutive registry study was conducted at 12 centers in Japan on 125 patients with primary varicose veins who underwent CAC. The patients were evaluated on target vein occlusion, postoperative complications, Visual Analogue Scale (VAS) for pain, revised Venous Clinical Severity Score (rVCSS), Aberdeen Varicose Vein Questionnaire (AVVQ), and EuroQol 5 dimensions 5-level (EQ-5D-5L) for 1-year after the surgery. RESULTS: The closure rate was 92.6% at 1 year postoperatively, and 95.0% and 90.2% for GSV and SSV respectively with little difference (p = .491). The mean VAS in the immediate postoperative period was 18.9 ± 23.4. Postoperative complications were observed in 20 patients (16%). Hypersensitivity-type phlebitis occurred in 7 patients (5.6%). Infection of the treated vein resulted in resection of GSV. The rVCSS and AVVQ improved significantly after 90 days and 1 year postoperatively (p < .001), while the EQ-5D-5L have not changed. CONCLUSION: Cyanoacrylate Closure was considered generally a safe and minimally invasive treatment with good mid-term outcomes including SSV. However further study is required for some CAC specific complications.

The Beneficial Effect of Brazilian Propolis for Liver Damage through Endoplasmic Reticulum Stress.

There is evidence that propolis exhibits anti-inflammatory, anticancer, and antioxidant properties. We assessed the potential beneficial effects of Brazilian propolis on liver injury in nonalcoholic fatty liver disease (NAFLD). Our findings demonstrate that Brazilian propolis suppresses inflammation and fibrosis in the liver of mice with NAFLD by inhibiting the expression of genes involved in endoplasmic reticulum (ER) stress. Additionally, Brazilian propolis also suppressed the expression of ER stress-related genes in HepG2 cells treated with an excess of free fatty acids, leading to cell apoptosis. A deeper analysis revealed that kaempferol, one of the components present in Brazilian propolis, induces cell proliferation through the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and protects against oxidative stress. In conclusion, Brazilian propolis exhibits hepatoprotective properties against oxidative stress by inhibiting ER stress in NAFLD-induced model mice.

Prophylactic Anticoagulation and Thrombosis in Hospitalized Patients with Clinically Stable COVID-19 at Admission: From the Practice-Based Observational Study.

Objectives: The potential benefit of routine prophylactic anticoagulation for all hospitalized patients with clinically stable coronavirus disease 2019 (COVID-19) is still controversial. Method: The CLOT-COVID Study was a multicenter observational study enrolling 2894 consecutive hospitalized patients with COVID-19. The current study population consisted of 1738 hospitalized patients with mild COVID-19 at admission not requiring oxygen administration, who were divided into 2 groups: patients with prophylactic anticoagulation (n = 326) and those without (n = 1412). Results: Patients with prophylactic anticoagulation had more severe status of the worst severity of COVID-19 during hospitalization compared with those without (mild: 38% versus 82%, moderate: 55% versus 17%, and severe or death at discharge: 6.4% versus 0.7%, P <0.001). During hospitalization, 8 patients (0.5%) developed thrombosis, and the incidences of thrombosis were numerically higher in patients with more severe status of worst severity of COVID-19 during hospitalization (mild: 0.2%, moderate: 1.2%, and severe or death at discharge: 3.2%). Conclusions: Among hospitalized patients with clinically stable COVID-19 at admission, patients who did not worsen in COVID-19 severity after admission rarely developed thrombosis, although patients with worsening of COVID-19 severity after admission more often received prophylactic anticoagulation and might have a higher risk of thrombosis.

Serious Adverse Events with Cyanoacrylate Closure of Varicose Veins: An Initial Report from a Large-Scale National Survey in Japan.

Objective: Cyanoacrylate closure (CAC) is a minimally invasive technique for the treatment of varicose veins. A recent paper reported serious adverse events (AEs) associated with this use. This triggered an urgent survey to determine the incidence of AEs in Japan. Methods: The CAC-AE survey was sent to all 1,030 institutions authorized for CAC treatments. Cases performed between January 2020 and October 2023 were surveyed. Data on serious AEs and mortality were collected. Results: There were 623 surveys returned. There were 16 cases of proximal deep vein thrombosis, 3 cases of pulmonary embolism (PE), and 0 cases of stroke. Deep vein occlusion due to cyanoacrylate extension was observed in 1 case. Vein resection due to infection was observed in 4 cases. There were 299 cases of localized phlebitis and/or allergic reactions requiring steroid administration. Systemic allergic reactions requiring steroid administration were observed in 66 cases. There was no anaphylaxis associated with cyanoacrylate. There was one postoperative death from PE. Conclusion: This report's intent is to provide real world data on serious AEs following CAC from Japan given current concern over these events. An extensive report investigation of individual complications with analysis including causality will be provided following a full investigation separately.

Achiral 2-pyridone and 4-aminopyridine act as chiral inducers of asymmetric autocatalysis with amplification of enantiomeric excess via the formation of chiral crystals.

Enantiomorphous crystals of achiral 2-pyridone and 4-aminopyridine served as sources of chirality, to induce the asymmetric autocatalysis of 5-pyrimidyl alkanol during the asymmetric addition of diisopropylzinc to the corresponding pyrimidine-5-carbaldehyde, that is, the Soai reaction. Following a significant amplification of enantiomeric excess through asymmetric autocatalysis, highly enantioenriched 5-pyrimidyl alkanol could be synthesized with their corresponding absolute configurations to those of chiral crystals of 2-pyridone and 4-aminopyridine.

Nickel(II) Analogues of Phosphorescent Platinum(II) Complexes with Picosecond Excited-State Decay.

Square-planar NiII complexes are interesting as cheaper and more sustainable alternatives to PtII luminophores widely used in lighting and photocatalysis. We investigated the excited-state behavior of two NiII complexes, which are isostructural with two luminescent PtII complexes. The initially excited singlet metal-to-ligand charge transfer (1 MLCT) excited states in the NiII complexes decay to metal-centered (3 MC) excited states within less than 1 picosecond, followed by non-radiative relaxation of the 3 MC states to the electronic ground state within 9-21 ps. This contrasts with the population of an emissive triplet ligand-centered (3 LC) excited state upon excitation of the PtII analogues. Structural distortions of the NiII complexes are responsible for this discrepant behavior and lead to dark 3 MC states far lower in energy than the luminescent 3 LC states of PtII compounds. Our findings suggest that if these structural distortions could be restricted by more rigid coordination environments and stronger ligand fields, the excited-state relaxation in four-coordinate NiII complexes could be decelerated such that luminescent 3 LC or 3 MLCT excited states become accessible. These insights are relevant to make NiII fit for photophysical and photochemical applications that relied on PtII until now.

Better Covalent Connection in a Molecular Triad Enables More Efficient Photochemical Energy Storage.

Numerous studies have explored the kinetics of light-induced charge separation and thermal charge recombination in donor-acceptor compounds, but quantum efficiencies have rarely been investigated. Here, we report on two essentially isomeric molecular triads, both comprising a π-extended tetrathiafulvalene (ExTTF) donor, a ruthenium(II)-based photosensitizer, and a naphthalene diimide (NDI) acceptor. The key difference between the two triads is how the NDI acceptor is connected. Linkage at the NDI core provides stronger electronic coupling to the other molecular components than connection via the nitrogen atoms of NDI. This change in molecular connectivity is expected to accelerate both energy-storing charge separation and energy-wasting charge recombination processes, but it is not a priori clear how this will affect the triad's ability to store photochemical energy; any gain resulting from faster charge separation could potentially be (over)compensated by losses through accelerated charge recombination. The new key insight emerging from our study is that the quantum yield for the formation of a long-lived charge-separated state increases by a factor of 5 when going from nitrogen- to core-connected NDI, providing the important proof of concept that better molecular connectivity indeed enables more efficient photochemical energy storage. The physical origin of this behavior seems to root in different orbital connectivity pathways for charge separation and charge recombination, as well as in differences in the relevant orbital interactions depending on NDI connection. Our work provides guidelines for how to discriminate between energy-storing and energy-wasting electron transfer reactions in order to improve the quantum yields for photochemical energy storage and solar energy conversion.

Clinical Features Comparing Arterial Thrombosis and Venous Thromboembolism in Hospitalized Patients with COVID-19: Result from the CLOT-COVID Study.

Objectives: This study aimed to investigate the clinical features of arterial thrombosis and venous thromboembolism (VTE) in coronavirus disease 2019 (COVID-19). Methods: The CLOT-COVID Study was a retrospective, multicenter cohort study that enrolled 2,894 consecutively hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We compared the clinical features of arterial thrombosis and VTE. Results: Thrombosis was observed in 55 patients (1.9%) during hospitalization. Arterial thrombosis and VTE occurred in 12 (0.4%) and 36 (1.2%) patients, respectively. Among the 12 patients with arterial thrombosis, 9 (75%), 2 (17%), and 1 developed ischemic cerebral infarction, myocardial infarction, and acute limb ischemia, respectively, and there were five patients (42%) without comorbidities. Among 36 patients with VTE, 19 (53%) and 17 (47%) developed pulmonary embolism (PE) and deep vein thrombosis (DVT), respectively. PE was common in the early stages of hospitalization; whereas, DVT was common beyond the early stages of hospitalization. Conclusion: Among patients with COVID-19, arterial thrombosis was less common than VTE, although ischemic cerebral infarction seemed to be relatively common, and a certain number of patients developed arterial thrombosis even in the absence of known atherosclerosis risk factors.

Impact of increased plasma levels of calreticulin on prognosis of patients with advanced lung cancer undergoing combination treatment of chemotherapy and immune checkpoint inhibitors.

BACKGROUND: Damage-associated molecular pattern (DAMP)-related immunogenic cell death triggers secondary adaptive immune responses. The relationship between DAMP levels and prognosis in patients with non-small cell lung cancer (NSCLC) who undergo a combination therapy of immune checkpoint inhibitors (ICI) and chemotherapy remains unclear. METHODS: Serial plasma samples were prospectively collected from 45 patients treated with ICI combination therapy for advanced NSCLC. Plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), annexin A1, and heat shock protein 70 were measured. Associations between increases in plasma DAMP levels and the efficacy of the ICI combination therapy were evaluated. RESULTS: The maximum fold changes in plasma levels differed across individuals but demonstrated a marked increase, especially for CRT (mean ± SEM, 11.61 ± 46.15). Increased plasma DAMP levels were not clearly associated with clinical responses. There was a significant correlation between the maximum fold change in CRT levels and progression-free survival (PFS; r = 0.49, P < 0.001). Median PFS and overall survival (OS) rates were higher in patients with a ≥ 2-fold increase in plasma CRT levels than in those with a < 2-fold increase (PFS, 14.9 versus 6.0 months, hazard ratio (HR), 0.58; P = 0.17; OS, not reached versus 21.6 months, HR, 0.31, P = 0.02). CONCLUSIONS: Plasma CRT level monitoring has the potential to predict the efficacy of ICI combination therapy and shed light on the mechanisms underlying DAMP-related immunogenic cell death.

Risk Factors and Impact on Outcomes of Thrombosis in Patients with COVID-19 in Japan: From the CLOT-COVID Study.

Objectives: The relationship between the thrombotic event and prognosis in patients with coronavirus disease 2019 (COVID-19) has not yet been fully investigated in Japan. Our study aimed to investigate the clinical outcomes and risk factors for thrombosis in hospitalized patients with COVID-19 in Japan. Materials and Methods: We compared the patient characteristics and clinical outcomes among patients with thrombosis (N=55) and those without thrombosis (N=2839) by using a large-scale data of CLOT-COVID study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800). Thrombosis included venous thromboembolism, ischemic stroke, myocardial infarction, and systemic arterial thromboembolism. Results: Higher rates of mortality and bleeding events were shown in hospitalized patients with COVID-19 with thrombosis compared to those without thrombosis (all-cause mortality, 23.6% vs. 5.1%, P<0.001; major bleeding, 23.6% vs. 1.6%, P<0.001). Multivariable analysis revealed that the independent risk factors of thrombosis were male sex, D-dimer level on admission>1.0 µg/mL, and moderate and severe COVID-19 status on admission. Conclusions: The development of thrombosis in hospitalized patients with COVID-19 was related to higher mortality and major bleeding, and several independent risk factors for thrombosis could help determine the patient-appropriate treatment for COVID-19.

[Absence of cortical lesions after the first seizure in a patient with anti-myelin oligodendrocyte glycoprotein-associated cortical encephalitis].

A 31-year-old man developed headache and generalized convulsions. At the time of the first seizure, there was no distinct MRI abnormality. He was admitted to the hospital with repeated seizures, left-sided hemiparesis, and left-sided neglect. He had a slight fever, elevated cerebrospinal fluid (CSF) pressure, and increased CSF cell count with predominance of mononuclear cells. A repeat MRI scan on day 8 after the recurrent seizure showed cortical edema in the right cerebral hemisphere on fluid-attenuated inversion recovery (FLAIR), abnormal high signal on DWI, and decreased apparent diffusion coefficient. The patient was diagnosed with aseptic meningoencephalitis and treated with antiviral drugs and methylprednisolone pulse therapy. Serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody was subsequently detected, and prednisolone was added to treat the FLAIR-hyperintense lesions in anti-MOG antibody associated encephalitis with seizures (FLAMES). It is important to identify the clinical picture and typical images of FLAMES to allow early treatment.

[A case of primary progressive multiple sclerosis with improvement in cognitive impairment by anti-CD20 monoclonal antibody therapy].

The patient was a 44-year-old man who developed cognitive impairment beginning at the age of 35 years that gradually worsened. The cognitive impairment led to a difficult social life, and he retired from his company. After hospitalization and workup, he was diagnosed with primary progressive multiple sclerosis (PPMS) that presented only with cognitive impairment for 10 years. Since he had multiple predictive factors for poor prognosis, anti-CD20 monoclonal antibody therapy was implemented. Cognitive impairment and cerebral blood flow SPECT findings improved, and he returned to a social life 3 months later. Anti-CD20 monoclonal antibody therapy was effective in improving cognitive impairment in a case of an advanced stage of PPMS.

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

AIM: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. RESULTS: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. CONCLUSIONS: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission.

Association Between the Development of Thrombosis and Worsening of Disease Severity in Patients With Moderate COVID-19 on Admission　- From the CLOT-COVID Study.

BACKGROUND: The worsening of coronavirus disease 2019 (COVID-19) severity is a critical issue in current clinical settings and may be associated with the development of thrombosis.Methods and Results: This study used patient data obtained in the CLOT-COVID study, a retrospective multicenter cohort study. The demographics of patients with moderate COVID-19 on admission with and without worsened severity during hospitalization were compared and predictors were identified. Of 927 patients with moderate COVID-19 on admission, 182 (19.6%) had worsened severity during hospitalization. Patients with worsening of severity were older, more likely to have hypertension, diabetes, heart disease, and active cancer, and more likely to use pharmacological thromboprophylaxis. Patients with worsening of severity had higher D-dimer levels on admission and were more likely to develop thrombosis and major bleeding during hospitalization than those without worsening. Increased age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, P=0.005), diabetes (OR: 1.63, 95% CI: 1.11-2.33, P=0.012), D-dimer levels >1.0 µg/mL on admission (OR: 2.10, 95% CI: 1.45-3.03, P<0.001), and thrombosis (OR: 6.28, 95% CI: 2.72-14.53, P<0.001) were independently associated with worsening of COVID-19 severity. CONCLUSIONS: Approximately 20% of patients with moderate COVID-19 had worsened severity during hospitalization. Increased age, diabetes, D-dimer levels >1.0 µg/mL on admission, and the development of thrombosis during hospitalization were significantly associated with worsened COVID-19 severity.

Influence of obesity on incidence of thrombosis and disease severity in patients with COVID-19: From the CLOT-COVID study.

BACKGROUND: The influence of obesity on the development of thrombosis and severity of coronavirus disease 2019 (COVID-19) remains unclear. METHOD: The CLOT-COVID study was a retrospective multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 between April 2021 and September 2021 among 16 centers in Japan. The present study consisted of 2690 patients aged over 18 years with available body mass index (BMI), who were divided into an obesity group (BMI ≥30) (N = 457) and a non-obesity group (BMI <30) (N = 2233). RESULTS: The obesity group showed more severe status of COVID-19 at admission compared with the non-obesity group. The incidence of thrombosis was not significantly different between the groups (obesity group: 2.6 % versus non-obesity group: 1.9 %, p = 0.39), while the incidence of a composite outcome of all-cause death, or requirement of mechanical ventilation or extracorporeal membrane oxygenation during hospitalization was significantly higher in the obesity group (20.1 % versus 15.0 %, p < 0.01). After adjusting confounders in the multivariable logistic regression model, the risk of obesity relative to non-obesity for thrombosis was not significant (adjusted OR, 1.39; 95 % CI, 0.68-2.84, p = 0.37), while the adjusted risk of obesity relative to non-obesity for the composite outcome was significant (adjusted OR, 1.85; 95 % CI, 1.39-2.47, p < 0.001). CONCLUSIONS: In the present large-scale observational study, obesity was not significantly associated with the development of thrombosis during hospitalization; however, it was associated with severity of COVID-19.

Mortality-associated Risk Factors in Hospitalized COVID-19 Patients in Japan: Findings of the CLOT-COVID Study.

BACKGROUND: Reports of mortality-associated risk factors in patients with the novel coronavirus disease 2019 (COVID-19) are limited. METHODS: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (n = 158) and those who were alive at discharge (n = 2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study, which enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study. RESULTS: Patients who died were older (71.1 years vs 51.6 years, P < 0.001), had higher median D-dimer values on admission (1.7 µg/mL vs 0.8 µg/mL, P < 0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% vs 63%, moderate: 47% vs 31%, and severe: 37% vs 6.2%, P < 0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs 1.5%, P < 0.001; major bleeding: 12.7% vs 1.4%, P < 0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk. CONCLUSION: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.

Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.

Background: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. Objectives: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. Methods: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). Results: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). Conclusions: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

Coordination polymer-forming liquid Cu(2-isopropylimidazolate).

The structure of the melt state of one-dimensional (1D) coordination polymer crystal Cu(isopropylimidazolate) (melting temperature T m = 143 °C) was characterized by DSC, variable temperature PXRD, solid-state NMR (SSNMR), viscoelastic measurements, XAS, and DFT-AIMD calculations. These analyses suggested "coordination polymer-forming liquid" formation with preserved coordination bonds above T m. Variable chain configurations and moderate cohesive interaction in adjacent chains are the keys to the rarely observed polymer-forming liquid. The melt structure is reminiscent of the common 1D organic polymer melts such as entanglement or random coil structures.

Molecular Design Principles to Elongate the Metal-to-Ligand Charge Transfer Excited-State Lifetimes of Square-Planar Nickel(II) Complexes.

Square-planar NiII complexes and their electronically excited states play key roles in cross-coupling catalysis and could offer new opportunities to complement well-known isoelectronic PtII luminophores. Metal-to-ligand charge transfer (MLCT) excited states and their deactivation pathways are particularly relevant in these contexts. We sought to extend the lifetimes of 3MLCT states in square-planar NiII complexes by creating coordination environments that seemed particularly well adapted to the 3d8 valence electron configuration. Using a rigid tridentate chelate ligand, in which a central cyclometalated phenyl unit is flanked by two coordinating N-heterocyclic carbenes, along with a monodentate isocyanide ligand, a very strong ligand field is created. Bulky substituents at the isocyanide backbone furthermore protect the NiII center from nucleophilic attack in the axial directions. UV-Vis transient absorption spectroscopies reveal that upon excitation into 1MLCT absorption bands and ultrafast intersystem crossing to the 3MLCT excited state, the latter relaxes onward into a metal-centered triplet state (3MC). A torsional motion of the tridentate ligand and a NiII-carbon bond elongation facilitate 3MLCT relaxation to the 3MC state. The 3MLCT lifetime gets longer with increasing ligand field strength and improved steric protection, thereby revealing clear design guidelines for square-planar NiII complexes with enhanced photophysical properties. The longest 3MLCT lifetime reached in solution at room temperature is 48 ps, which is longer by a factor of 5-10 compared to previously investigated square-planar NiII complexes. Our study contributes to making first-row transition metal complexes with partially filled d-orbitals more amenable to applications in photophysics and photochemistry.

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear. METHOD: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events. RESULTS: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6-14] vs 28 [19-43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001). CONCLUSIONS: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.