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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.MethodsâandâResults: 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.
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COVID-19 , Diabetes Mellitus , Trombosis , Tromboembolia Venosa , Humanos , SARS-CoV-2 , Estudios de Cohortes , Anticoagulantes , Tromboembolia Venosa/prevención & control , Productos de Degradación de Fibrina-Fibrinógeno , Hospitalización , Gravedad del Paciente , Estudios RetrospectivosRESUMEN
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.
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COVID-19 , Anciano , Humanos , Mortalidad Hospitalaria , Hospitalización , Japón/epidemiología , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.MethodsâandâResults: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.
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COVID-19 , Trombosis , Anticoagulantes/uso terapéutico , Coagulación Sanguínea , Enfermedad Crítica/terapia , Humanos , Trombosis/tratamiento farmacológico , Trombosis/etiología , Trombosis/prevención & controlRESUMEN
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.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) reportedly causes venous thromboembolism (VTE), but the status of this complication in Japan was unclear.MethodsâandâResults:The VTE and COVID-19 in Japan Study is a retrospective, multicenter cohort study enrolling hospitalized patients with COVID-19 who were evaluated with contrast-enhanced computed tomography (CT) examination at 22 centers in Japan between March 2020 and October 2020. Among 1,236 patients with COVID-19, 45 (3.6%) were evaluated with contrast-enhanced CT examination. VTE events occurred in 10 patients (22.2%), and the incidence of VTE in mild, moderate, and severe COVID-19 was 0%, 11.8%, and 40.0%, respectively. COVID-19 patients with VTE showed a higher body weight (81.6 vs. 64.0 kg, P=0.005) and body mass index (26.9 vs. 23.2 kg/m2, P=0.04), and a higher proportion had a severe status for COVID-19 compared with those without. There was no significant difference in the proportion of patients alive at discharge between patients with and without VTE (80.0% vs. 88.6%, P=0.48). Among 8 pulmonary embolism (PE) patients, all were low-risk PE. CONCLUSIONS: Among a relatively small number of patients undergoing contrast-enhanced CT examination in Japanese real-world clinical practice, there were no VTE patients among those with mild COVID-19, but the incidence of VTE seemed to be relatively high among severe COVID-19 patients, although all PE events were low-risk without significant effect on mortality risk.
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COVID-19 , Embolia Pulmonar , Tromboembolia Venosa , COVID-19/complicaciones , Humanos , Incidencia , Japón/epidemiología , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/epidemiología , Embolia Pulmonar/virología , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/virologíaRESUMEN
In multicellular organisms, temporal and spatial regulation of cell proliferation is central for generating organs with defined sizes and morphologies. For establishing and maintaining the post-mitotic quiescent state during cell differentiation, it is important to repress genes with mitotic functions. We found that three of the Arabidopsis MYB3R transcription factors synergistically maintain G2/M-specific genes repressed in post-mitotic cells and restrict the time window of mitotic gene expression in proliferating cells. The combined mutants of the three repressor-type MYB3R genes displayed long roots, enlarged leaves, embryos, and seeds. Genome-wide chromatin immunoprecipitation revealed that MYB3R3 binds to the promoters of G2/M-specific genes and to E2F target genes. MYB3R3 associates with the repressor-type E2F, E2FC, and the RETINOBLASTOMA RELATED proteins. In contrast, the activator MYB3R4 was in complex with E2FB in proliferating cells. With mass spectrometry and pairwise interaction assays, we identified some of the other conserved components of the multiprotein complexes, known as DREAM/dREAM in human and flies. In plants, these repressor complexes are important for periodic expression during cell cycle and to establish a post-mitotic quiescent state determining organ size.
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Arabidopsis/fisiología , Ciclo Celular/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Regulación de la Expresión Génica de las Plantas/fisiología , Organogénesis/fisiología , Factores de Transcripción/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Secuencia de Bases , Inmunoprecipitación de Cromatina , Regulación del Desarrollo de la Expresión Génica/genética , Regulación de la Expresión Génica de las Plantas/genética , Espectrometría de Masas , Análisis por Micromatrices , Microscopía Electrónica de Rastreo , Datos de Secuencia Molecular , Complejos Multiproteicos/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Represoras/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: Atrial fibrillation (AF) begets AF in part due to atrial remodeling, the molecular mechanisms of which have not been completely elucidated. This study was conducted to identify microRNA(s) responsible for electrical remodeling in AF. METHODSâANDâRESULTS: The expression profiles of 1205 microRNAs, in cardiomyocytes from patients with persistent AF and from age-, gender-, and cardiac function-matched control patients with normal sinus rhythm, were examined by use of a microRNA microarray platform. Thirty-nine microRNAs differentially expressed in AF patients' atria were identified, including miR-30d, as a candidate responsible for ion channel remodeling by in silico analysis. MiR-30d was significantly upregulated in cardiomyocytes from AF patients, whereas the mRNA and protein levels ofCACNA1C/Cav1.2 andKCNJ3/Kir3.1, postulated targets of miR-30d, were markedly reduced.KCNJ3/Kir3.1 expression was downregulated by transfection of the miR-30 precursor, concomitant with a reduction of the acetylcholine-sensitive inward-rectifier K(+)current (IK.ACh).KCNJ3/Kir3.1 (but notCACNA1C/Cav1.2) expression was enhanced by the knockdown of miR-30d. The Ca(2+)ionophore, A23187, induced a dose-dependent upregulation of miR-30d, followed by the suppression ofKCNJ3mRNA expression. Blockade of protein kinase C signaling blunted the [Ca(2+)]i-dependent downregulation of Kir3.1 via miR-30d. CONCLUSIONS: The downward remodeling ofIK.AChis attributed, at least in part, to deranged Ca(2+)handling, leading to the upregulation of miR-30d in human AF, revealing a novel post-transcriptional regulation ofIK.ACh. (Circ J 2016; 80: 1346-1355).
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Fibrilación Atrial/fisiopatología , MicroARNs/fisiología , Canales de Potasio de Rectificación Interna/metabolismo , Anciano , Estudios de Casos y Controles , Células Cultivadas , Regulación hacia Abajo , Femenino , Proteínas de Unión al GTP , Humanos , Masculino , Persona de Mediana Edad , Miocitos Cardíacos/metabolismo , Canales de Potasio con Entrada de Voltaje/metabolismo , Regulación hacia ArribaRESUMEN
Increased cellular ploidy is widespread during developmental processes of multicellular organisms, especially in plants. Elevated ploidy levels are typically achieved either by endoreplication or endomitosis, which are often regarded as modified cell cycles that lack an M phase either entirely or partially. We identified GIGAS CELL1 (GIG1)/OMISSION OF SECOND DIVISION1 (OSD1) and established that mutation of this gene triggered ectopic endomitosis. On the other hand, it has been reported that a paralog of GIG1/OSD1, UV-INSENSITIVE4 (UVI4), negatively regulates endoreplication onset in Arabidopsis thaliana. We showed that GIG1/OSD1 and UVI4 encode novel plant-specific inhibitors of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. These proteins physically interact with APC/C activators, CDC20/FZY and CDH1/FZR, in yeast two-hybrid assays. Overexpression of CDC20.1 and CCS52B/FZR3 differentially promoted ectopic endomitosis in gig1/osd1 and premature occurrence of endoreplication in uvi4. Our data suggest that GIG1/OSD1 and UVI4 may prevent an unscheduled increase in cellular ploidy by preferentially inhibiting APC/C(CDC20) and APC/C(FZR), respectively. Generation of cells with a mixed identity in gig1/osd1 further suggested that the APC/C may have an unexpected role for cell fate determination in addition to its role for proper mitotic progression.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Ciclo Celular/metabolismo , Mitosis , Complejos de Ubiquitina-Proteína Ligasa/metabolismo , Alelos , Ciclosoma-Complejo Promotor de la Anafase , Arabidopsis/citología , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas Cdc20 , Proteínas de Ciclo Celular/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Cromosomas de las Plantas/genética , Cromosomas de las Plantas/metabolismo , Clonación Molecular , Cotiledón/genética , Cotiledón/metabolismo , Ciclina B/genética , Ciclina B/metabolismo , Citocinesis , Inhibidores Enzimáticos/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Prueba de Complementación Genética , Mutación , Células Vegetales/metabolismo , Epidermis de la Planta/citología , Epidermis de la Planta/genética , Epidermis de la Planta/crecimiento & desarrollo , Epidermis de la Planta/metabolismo , Estomas de Plantas/citología , Estomas de Plantas/genética , Estomas de Plantas/crecimiento & desarrollo , Estomas de Plantas/metabolismo , Plantas Modificadas Genéticamente/citología , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/metabolismo , Plásmidos/genética , Plásmidos/metabolismo , Ploidias , Polen/crecimiento & desarrollo , Polen/metabolismo , Mapeo de Interacción de Proteínas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Activación Transcripcional , Técnicas del Sistema de Dos Híbridos , Complejos de Ubiquitina-Proteína Ligasa/genéticaRESUMEN
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.
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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.
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COVID-19 , Trombosis , Humanos , Estudios de Cohortes , COVID-19/complicaciones , Hemorragia , Hospitalización , Estudios Retrospectivos , SARS-CoV-2 , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Niño , Adolescente , Recién Nacido , Lactante , PreescolarRESUMEN
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 18â¯years with available body mass index (BMI), who were divided into an obesity group (BMI ≥30) (Nâ¯=â¯457) and a non-obesity group (BMI <30) (Nâ¯=â¯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: 2.6â¯% versus non-obesity group: 1.9â¯%, pâ¯=â¯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 (20.1â¯% versus 15.0â¯%, pâ¯<â¯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; 95â¯% CI, 0.68-2.84, pâ¯=â¯0.37), while the adjusted risk of obesity relative to non-obesity for the composite outcome was significant (adjusted OR, 1.85; 95â¯% CI, 1.39-2.47, pâ¯<â¯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.
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COVID-19 , Trombosis , Humanos , Adulto , Persona de Mediana Edad , COVID-19/complicaciones , SARS-CoV-2 , Incidencia , Estudios de Cohortes , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Obesidad/complicaciones , Obesidad/epidemiología , Hospitalización , Trombosis/epidemiología , Trombosis/etiologíaRESUMEN
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.
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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.
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Background: To date, there are no large-scale data on the association between D-dimer levels at admission and the occurrence of venous thromboembolism (VTE) in Japanese patients with coronavirus disease 2019 (COVID-19). MethodsâandâResults: The CLOT-COVID study was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 across 16 centers in Japan from April 2021 to September 2021. Among 2,894 enrolled patients, 2,771 (96%) had D-dimer levels measured at admission. Patients were divided into 3 groups based on tertiles of D-dimer levels at admission (1st tertile, D-dimer ≤0.5 µg/mL, n=949; 2nd tertile, D-dimer 0.51-1.09 µg/mL, n=894; 3rd tertile, D-dimer ≥1.1 µg/mL, n=928). The higher the tertile group, the more severe the COVID-19 status at admission. The incidence of VTE during hospitalization was highest in the 3rd tertile group (1st tertile, 0.3%; 2nd tertile, 0.3%; 3rd tertile, 3.6%; P<0.001). Even after adjusting for confounders in the multivariable logistic regression model, the higher D-dimer levels in the 3rd tertile (≥1.1 µg/mL) were independently associated with a higher risk of VTE during hospitalization (adjusted odds ratio 4.83 [95% confidence interval 1.93-12.11; P<0.001]; reference=1st tertile). Conclusions: Higher D-dimer levels at admission were associated with a higher risk of VTE events during hospitalization in Japanese patients with COVID-19. This could be helpful in determining patient-specific anticoagulation management strategies for COVID-19 in Japan.
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INTRODUCTION: There has been limited data on the influence of sex on development of thrombosis in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: 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 the men (N = 1885) and women (N = 1009) groups. RESULTS: There were no significant differences in D-dimer levels at admission between men and women. Men had more severe status of the COVID-19 at admission compared with women (Mild: 57% versus 66%, Moderate: 34% versus 29%, and Severe: 9.1% versus 5.7%, P < 0.001). Men more often received pharmacological thromboprophylaxis than women (47% versus 35%, P < 0.001). During the hospitalization, men more often developed thrombosis than women (2.5% [95%CI, 1.9-3.3%] versus 0.8% [95%CI, 0.4-1.6%], P = 0.001). Men had numerically higher incidences of thrombosis than women in all subgroups of the worst severity of COVID-19 during the hospitalization (Mild: 0.3% versus 0.0%, Moderate: 1.6% versus 1.0%, and Severe: 11.1% versus 4.3%). Even after adjusting confounders in the multivariable logistic regression model, the excess risk of men relative to women remained significant for thrombosis (adjusted OR, 2.51; 95%CI, 1.16-5.43, P = 0.02). CONCLUSIONS: In the current large observational study of patients with COVID-19, men had more severe status of the COVID-19 than women, and the risk of development of thrombosis was higher in men compared with women, which could be helpful in determining the patient-specific optimal management strategies for COVID-19.
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COVID-19 , Trombosis , Tromboembolia Venosa , Anticoagulantes/uso terapéutico , COVID-19/complicaciones , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Masculino , Estudios Retrospectivos , SARS-CoV-2 , Trombosis/tratamiento farmacológico , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19.
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COVID-19 , Trombosis , Tromboembolia Venosa , Anticoagulantes/efectos adversos , Estudios de Cohortes , Humanos , Japón/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Trombosis/epidemiología , Trombosis/etiología , Trombosis/prevención & control , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
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.
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Objectives: To establish the reference values for PAPP-A and total hCG between 11 and 13 weeks of gestation for the use of risk assessment of fetal aneuploidy in Japanese pregnant women.Methods: A multicenter prospective study was conducted. The subjects included only Japanese pregnant women with viable singleton who requested the first trimester combined (nuchal translucency and maternal serum marker) screening for fetal aneuploidy. Reference values of PAPP-A and total hCG in Japanese population were made and compared with them in Caucasian.Results: Overall 1,751 Japanese pregnant women were analyzed. Median vales of maternal serum concentration in Japanese pregnant women from 11 + 0-13 + 6 weeks' gestation were ranged from 3.01 to 9.51 mIU/mL for PAPP-A and from 70.2 to 58.3 IU/mL for total-hCG, respectively. Regression curve of median maternal serum PAPP-A and total-hCG concentration against gestational days are significantly higher in Japanese comparing with Caucasian. At most distant values, Japanese serum concentration indicated 1.45 MoM for total-hCG and 1.70 MoM for PAPP-A based on Caucasian regression curves.Conclusion: A modification of the equations by specific reference values is necessary for Japanese pregnant women at the risk assessment of chromosomal abnormalities using the first trimester maternal serum marker.
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Gonadotropina Coriónica/sangre , Síndrome de Down/diagnóstico , Medida de Translucencia Nucal , Proteína Plasmática A Asociada al Embarazo/análisis , Adulto , Aneuploidia , Pueblo Asiatico , Femenino , Humanos , Japón , Embarazo , Estudios Prospectivos , Estándares de Referencia , Medición de RiesgoRESUMEN
OBJECTIVE: We developed a "simplified elephant trunk (SET) graft technique" as a refinement of the original elephant trunk. A cuff is created in a single 4-branched graft, which is used for the distal anastomosis; the residual distal graft is used as the trunk. We expected the SET would secure the anastomosis and promote the thrombo-occlusion of the false lumen in the down stream of the aorta. In this paper, we highlight the usage of the SET for arch replacement of acute aortic dissection cases in comparison with the same arch replacement without the SET method. PATIENTS AND METHODS: Between March 1996 and March 2002, 35 patients underwent arch replacement for acute aortic dissection. Twenty-two of them had a patent false lumen in the downstream aorta at the operation and 17 (SET: 8, non-SET (NSET) : 9) out of 22 underwent enhanced computed tomography (CT) scan 2 weeks after and 1 year after operation. We calculated the ratio of the false lumen in the aorta (F ratio) and the ratio of the patent false lumen in the whole false lumen (E ratio) by CT scan. These values were calculated every 3 cm down to 15 cm below the anastomosis, thus resulting in 5 segments. RESULTS: The false lumen throughout all segments disappeared (F ratio =0) in none of both group 2 weeks after operation. One year thereafter, in 5 (63%) patients in the SET group, no false lumen in any segment existed, while in contrast a false lumen still existed in some of the segments in all NSET patients. Although neither the F and E ratio of the NSET group change during this period in any segments, those of the SET group decreased significantly in all the segments except for the E ratio of segment 5. CONCLUSION: The SET promoted thrombo-occlusion thus leading to the disappearance of the residual false lumen, possibly by avoiding persistent endoleakage at the anastomotic site.
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Aneurisma Falso/cirugía , Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/métodos , Adulto , Anciano , Anastomosis Quirúrgica , Disección Aórtica/diagnóstico por imagen , Aneurisma Falso/diagnóstico por imagen , Aorta Torácica/diagnóstico por imagen , Prótesis Vascular , Embolización Terapéutica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
A 78-year-old woman who had previously undergone prosthetic graft replacement of the total aortic arch was admitted to repair a chronic expanding type IIIb dissecting aneurysm. Firstly the patient's abdominal aorta was replaced with a prosthetic graft without any complications, then the thoracicdescending aorta was repaired five months later. Surgery for the thoracic descending aorta was performed with distal perfusion, cerebrospinal fluid drainage, somatosensory evoked potential (SEP) monitoring and reimplantation of three pairs of intercostal arteries. During surgery, SEP showed no significant changes, and the patient awoke without paraplegia three hours after the surgery. However, she developed bilateral complete paraplegia eight hours after the surgery. Reexploration demonstrated thrombo-occlusion of the sidearm graft for reimplantation of the Th10 intercostal artery. After thrombectomy of the sidearm graft, there was gradual neurological recovery and the patient was ambulatory when discharged. Quick treatment to restore the spinal cord blood supply promoted recovery from paraplegia.