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1.
J Virol ; 98(5): e0041624, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38624232

RESUMEN

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, enabling the virus to escape from host immunity by changing its spike antigen, while biased toward the receptor-binding domain and N-terminal domain. Here, we isolated a novel pan-SARS-CoV-2 neutralizing antibody (which we named MO11) for even the recent dominators XBB.1.16 and EG.5.1, from a convalescent patient who had received three doses of an original mRNA COVID-19 vaccination. A cryo-electron microscopy analysis of the spike-MO11 complex at 2.3 Å atomic resolution revealed that it recognizes a conserved epitope hidden behind a glycan shield at N331 on subdomain 1 (SD1), holding both the N- and C-terminal segments comprising SD1. Our identification of MO11 unveiled the functional importance of SD1 for the spike's function, and we discuss the potential availability of a novel common epitope among the SARS-CoV-2 variants.IMPORTANCENovel severe acute respiratory syndrome coronavirus 2 variants with immune evasion ability are still repeatedly emerging, nonetheless, a part of immunity developed in responding to the antigen of earlier variants retains efficacy against recent variants irrespective of the numerous mutations. In exploration for the broadly effective antibodies, we identified a cross-neutralizing antibody, named MO11, from the B cells of the convalescent patient. MO11 targets a novel epitope in subdomain 1 (SD1) and was effective against all emerging variants including XBB.1.16 and EG.5.1. The neutralizing activity covering from D614G to EG.5.1 variants was explained by the conservation of the epitope, and it revealed the importance of the subdomain on regulating the function of the antigen for viral infection. Demonstrated identification of the neutralizing antibody that recognizes a conserved epitope implies basal contribution of such group of antibodies for prophylaxis against COVID-19.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Humanos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Epítopos/inmunología , Microscopía por Crioelectrón , Dominios Proteicos , Vacunas contra la COVID-19/inmunología
2.
J Virol ; 97(6): e0028623, 2023 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-37191569

RESUMEN

We identified neutralizing monoclonal antibodies against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants (including Omicron variants BA.5 and BA.2.75) from individuals who received two doses of mRNA vaccination after they had been infected with the D614G virus. We named them MO1, MO2, and MO3. Among them, MO1 showed particularly high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, BA.2.75, and BA.5. Furthermore, MO1 suppressed BA.5 infection in hamsters. A structural analysis revealed that MO1 binds to the conserved epitope of seven variants, including Omicron variants BA.5 and BA.2.75, in the receptor-binding domain of the spike protein. MO1 targets an epitope conserved among Omicron variants BA.1, BA.2, and BA.5 in a unique binding mode. Our findings confirm that D614G-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants. IMPORTANCE Omicron variants of SARS-CoV-2 acquired escape ability from host immunity and authorized antibody therapeutics and thereby have been spreading worldwide. We reported that patients infected with an early SARS-CoV-2 variant, D614G, and who received subsequent two-dose mRNA vaccination have high neutralizing antibody titer against Omicron lineages. It was speculated that the patients have neutralizing antibodies broadly effective against SARS-CoV-2 variants by targeting common epitopes. Here, we explored human monoclonal antibodies from B cells of the patients. One of the monoclonal antibodies, named MO1, showed high potency against broad SARS-CoV-2 variants including BA.2.75 and BA.5 variants. The results prove that monoclonal antibodies that have common neutralizing epitopes among several Omicrons were produced in patients infected with D614G and who received mRNA vaccination.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , COVID-19 , Epítopos , Animales , Cricetinae , Humanos , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Epítopos/inmunología , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Masculino , Femenino , Persona de Mediana Edad , Vacunas de ARNm
4.
J Infect Dis ; 226(8): 1391-1395, 2022 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-35512332

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant omicron is now under investigation. We evaluated cross-neutralizing activity against omicron in coronavirus disease 2019 (COVID-19) convalescent patients (n = 23) who had received 2 doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Intriguingly, after the second vaccination, the neutralizing antibody titers of subjects against SARS-CoV-2 variants, including omicron, all became seropositive, and significant fold-increases (21.1-52.0) were seen regardless of the disease severity. Our findings thus demonstrate that 2 doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against omicron.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Humanos , Pruebas de Neutralización , ARN Mensajero , Vacunación
5.
Front Immunol ; 13: 773652, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35281007

RESUMEN

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. The emergence of variants of concern (VOCs) has become one of the most pressing issues in public health. To control VOCs, it is important to know which COVID-19 convalescent sera have cross-neutralizing activity against VOCs and how long the sera maintain this protective activity. Methods: Sera of patients infected with SARS-CoV-2 from March 2020 to January 2021 and admitted to Hyogo Prefectural Kakogawa Medical Center were selected. Blood was drawn from patients at 1-3, 3-6, and 6-8 months post onset. Then, a virus neutralization assay against SARS-CoV-2 variants (D614G mutation as conventional strain; B.1.1.7, P.1, and B.1.351 as VOCs) was performed using authentic viruses. Results: We assessed 97 sera from 42 patients. Sera from 28 patients showed neutralizing activity that was sustained for 3-8 months post onset. The neutralizing antibody titer against D614G significantly decreased in sera of 6-8 months post onset compared to those of 1-3 months post onset. However, the neutralizing antibody titers against the three VOCs were not significantly different among 1-3, 3-6, and 6-8 months post onset. Discussion: Our results indicate that neutralizing antibodies that recognize the common epitope for several variants may be maintained for a long time, while neutralizing antibodies having specific epitopes for a variant, produced in large quantities immediately after infection, may decrease quite rapidly.


Asunto(s)
COVID-19/inmunología , SARS-CoV-2/fisiología , Anciano , Anticuerpos Antivirales/sangre , Anticuerpos ampliamente neutralizantes , Reacciones Cruzadas , Femenino , Humanos , Inmunidad Humoral , Epítopos Inmunodominantes/inmunología , Masculino , Persona de Mediana Edad , Factores de Tiempo
6.
Ann Transl Med ; 10(3): 130, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35284557

RESUMEN

Background: We developed and validated a machine learning diagnostic model for the novel coronavirus (COVID-19) disease, integrating artificial-intelligence-based computed tomography (CT) imaging and clinical features. Methods: We conducted a retrospective cohort study in 11 Japanese tertiary care facilities that treated COVID-19 patients. Participants were tested using both real-time reverse transcription polymerase chain reaction (RT-PCR) and chest CTs between January 1 and May 30, 2020. We chronologically split the dataset in each hospital into training and test sets, containing patients in a 7:3 ratio. A Light Gradient Boosting Machine model was used for the analysis. Results: A total of 703 patients were included, and two models-the full model and the A-blood model-were developed for their diagnosis. The A-blood model included eight variables (the Ali-M3 confidence, along with seven clinical features of blood counts and biochemistry markers). The areas under the receiver-operator curve of both models [0.91, 95% confidence interval (CI): 0.86 to 0.95 for the full model and 0.90, 95% CI: 0.86 to 0.94 for the A-blood model] were better than that of the Ali-M3 confidence (0.78, 95% CI: 0.71 to 0.83) in the test set. Conclusions: The A-blood model, a COVID-19 diagnostic model developed in this study, combines machine-learning and CT evaluation with blood test data and performs better than the Ali-M3 framework existing for this purpose. This would significantly aid physicians in making a quicker diagnosis of COVID-19.

7.
Ann Clin Epidemiol ; 4(4): 110-119, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-38505255

RESUMEN

BACKGROUND: We aimed to develop and externally validate a novel machine learning model that can classify CT image findings as positive or negative for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR). METHODS: We used 2,928 images from a wide variety of case-control type data sources for the development and internal validation of the machine learning model. A total of 633 COVID-19 cases and 2,295 non-COVID-19 cases were included in the study. We randomly divided cases into training and tuning sets at a ratio of 8:2. For external validation, we used 893 images from 740 consecutive patients at 11 acute care hospitals suspected of having COVID-19 at the time of diagnosis. The dataset included 343 COVID-19 patients. The reference standard was RT-PCR. RESULTS: In external validation, the sensitivity and specificity of the model were 0.869 and 0.432, at the low-level cutoff, 0.724 and 0.721, at the high-level cutoff. Area under the receiver operating characteristic was 0.76. CONCLUSIONS: Our machine learning model exhibited a high sensitivity in external validation datasets and may assist physicians to rule out COVID-19 diagnosis in a timely manner at emergency departments. Further studies are warranted to improve model specificity.

8.
PLoS One ; 16(11): e0258760, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34735458

RESUMEN

Ali-M3, an artificial intelligence program, analyzes chest computed tomography (CT) and detects the likelihood of coronavirus disease (COVID-19) based on scores ranging from 0 to 1. However, Ali-M3 has not been externally validated. Our aim was to evaluate the accuracy of Ali-M3 for detecting COVID-19 and discuss its clinical value. We evaluated the external validity of Ali-M3 using sequential Japanese sampling data. In this retrospective cohort study, COVID-19 infection probabilities for 617 symptomatic patients were determined using Ali-M3. In 11 Japanese tertiary care facilities, these patients underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. They also underwent chest CT to confirm a diagnosis of COVID-19. Of the 617 patients, 289 (46.8%) were RT-PCR-positive. The area under the curve (AUC) of Ali-M3 for predicting a COVID-19 diagnosis was 0.797 (95% confidence interval: 0.762‒0.833) and the goodness-of-fit was P = 0.156. With a cut-off probability of a diagnosis of COVID-19 by Ali-M3 set at 0.5, the sensitivity and specificity were 80.6% and 68.3%, respectively. A cut-off of 0.2 yielded a sensitivity and specificity of 89.2% and 43.2%, respectively. Among the 223 patients who required oxygen, the AUC was 0.825. Sensitivity at a cut-off of 0.5% and 0.2% was 88.7% and 97.9%, respectively. Although the sensitivity was lower when the days from symptom onset were fewer, the sensitivity increased for both cut-off values after 5 days. We evaluated Ali-M3 using external validation with symptomatic patient data from Japanese tertiary care facilities. As Ali-M3 showed sufficient sensitivity performance, despite a lower specificity performance, Ali-M3 could be useful in excluding a diagnosis of COVID-19.


Asunto(s)
Prueba de COVID-19/métodos , COVID-19/diagnóstico , Aprendizaje Profundo , Diagnóstico por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Algoritmos , Área Bajo la Curva , Estudios de Cohortes , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Japón/epidemiología , Masculino , Persona de Mediana Edad , Probabilidad , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Sensibilidad y Especificidad
9.
Open Forum Infect Dis ; 8(10): ofab430, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34631915

RESUMEN

BACKGROUND: As of March 2021, Japan is facing a fourth wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but has not been firmly established. METHODS: We investigated the neutralizing potency of 81 coronavirus disease 2019 (COVID-19) patients' sera from the first to fourth waves of the pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses. RESULTS: Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the fourth wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less severe patients was lower than that of more severe patients for all variants. CONCLUSIONS: The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351. The high neutralizing activity specific to B.1.1.7 in the fourth wave suggests that mutations in the virus might cause conformational change of its spike protein, which affects immune recognition of D614G. Our results indicate that individuals who recover from COVID-19 could be protected from the severity caused by infection with newly emerging variants.

10.
Circ Rep ; 3(7): 375-380, 2021 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-34250278

RESUMEN

Background: The COVID-19 pandemic has challenged healthcare systems, at times overwhelming intensive care units (ICUs). We aimed to describe the length and rate of ICU admission, and explore the clinical variables influencing ICU use, for COVID-19 patients with known cardiovascular diseases or their risk factors (CVDRF). Methods and Results: A post hoc analysis was performed of 693 Japanese COVID-19 patients with CVDRF enrolled in the nationwide CLAVIS-COVID registration system between January and May 2020 (mean [±SD] age 68.3±14.9 years; 35% female); 199 patients (28.7%) required ICU management. The mean (±SD) ICU length of stay (LOS) was 19.3±18.5 days, and the rate of in-hospital death and hospital LOS were significantly higher (P<0.001) and longer (P<0.001), respectively, in the ICU than non-ICU group. Logistic regression analysis revealed that clinical variables reflecting impaired general condition (e.g., high C-reactive protein, low Glasgow Coma Scale score, SpO2, albumin level), male sex, and previous use of ß-blockers) were associated with ICU admission (all P<0.001). Notably, age was inversely associated with ICU admission, and this was particularly prominent among elderly patients (OR 0.97, 95% confidence interval 0.95-0.99; P=0.0018). Conclusions: One-third of COVID patients with CVDRF required ICU care during the first phase of the pandemic in Japan. Other than anticipated clinical variables, such as hypoxia and altered mental status, age was inversely associated with the use of the ICU, warranting further investigation.

11.
JMA J ; 4(1): 1-7, 2021 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-33575497

RESUMEN

Patients with coronavirus disease 2019 (COVID-19) exhibit a wide clinical spectrum ranging from mild respiratory symptoms to critical and fatal diseases, and older individuals are known to be more severely affected. The underlying mechanism of this phenomenon is unknown. A neutralizing antibody against viruses is known to be important to eliminate the virus. In addition, this antibody is induced at high levels in patients with severe COVID-19, followed by a termination of virus replication. Severe COVID-19 patients exhibit high levels of cytokines/chemokines, even after the disappearance of the virus. This indicates that cytokines/chemokines play significant roles in disease severity. These findings also suggest that antiviral therapy (monoclonal antibody and/or convalescent plasma therapy) should be administered early to eliminate the virus, followed by steroid treatment after viral genome disappearance, especially in patients with severe symptoms.

12.
J Infect Dis ; 223(7): 1145-1149, 2021 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-33411935

RESUMEN

Most patients with coronavirus disease 2019 (COVID-19) experience asymptomatic disease or mild symptoms, but some have critical symptoms requiring intensive care. It is important to determine how patients with asymptomatic or mild COVID-19 react to severe acute respiratory syndrome coronavirus 2 infection and suppress virus spread. Innate immunity is important for evasion from the first virus attack, and it may play an important role in the pathogenesis in these patients. We measured serum cytokine levels in 95 patients with COVID-19 during the infection's acute phase and report that significantly higher interleukin 12 and 2 levels were induced in patients with asymptomatic or mild disease than in those with moderate or severe disease, indicating the key roles of these cytokines in the pathogenesis of asymptomatic or mild COVID-19.


Asunto(s)
COVID-19/inmunología , Inmunidad Innata , Interleucina-12/sangre , Interleucina-2/sangre , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Asintomáticas , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Estudios de Casos y Controles , Femenino , Voluntarios Sanos , Humanos , Interleucina-12/inmunología , Interleucina-2/inmunología , Masculino , Persona de Mediana Edad , ARN Viral/aislamiento & purificación , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Adulto Joven
13.
Infect Chemother ; 53(4): 767-775, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34979607

RESUMEN

BACKGROUND: Neutralizing antibody cocktail therapy, REGN-COV2, is promising in preventing a severe form of coronavirus disease 2019 (COVID-19), but its effectiveness in Japan has not been fully investigated. MATERIALS AND METHODS: To evaluate the effectiveness of REGN-COV2, clinical data of 20 patients with COVID-19 who received REGN-COV2 was compared with the control by matching age and sex. The primary outcome was the time from the onset to defervescence, the duration of hospitalization, and oxygen requirement. A sensitivity analysis using Bayesian analysis was also conducted. RESULTS: The time to defervescence was significantly shorter in the treatment group (5.25 vs. 7.95 days, P = 0.02), and so was the duration of hospitalization (7.115 vs. 11.45, P = 0.0009). However, the oxygen therapy requirement did not differ between the two groups (15% vs. 35%, P = 0.27). For Bayesian analysis, the median posterior probability of the time to defervescence since the symptom onset on the REGN-COV2 group was 5.28 days [95% credible interval (CrI): 4.28 - 6.31 days], compared with the control of 7.99 days (95% CrI: 6.81 - 9.24 days). The posterior probability of the duration of the hospitalization on the REGN-COV2 group was 7.17 days (95% CrI: 5.99 - 8.24 days), compared with the control of 11.54 days (95% CrI: 10.28 - 13.14 days). The posterior probability of the oxygen requirement on the REGN-COV2 group was 18% (95% CrI: 3 - 33%), compared with the control of 36% (95% CrI: 16 - 54%). CONCLUSION: REGN-COV2 may be effective in early defervescence and shorter hospitalization. Its effectiveness for preventing a severe form of infection needs to be evaluated by further studies.

14.
Am J Case Rep ; 18: 324-328, 2017 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-28360410

RESUMEN

BACKGROUND A free-floating ball thrombus in the left atrium is a rare clinical condition. However, the diagnosis of this condition has been facilitated by the advent and development of echocardiography and multi-detector row computed tomography (MDCT) and several cases have been reported. CASE REPORT We report a case of a 75-year-old woman who had recurrent giant spherical thrombi in the left atrium. She was diagnosed with chronic atrial fibrillation at 52 years of age. A pacemaker implantation was performed at 54 years of age because of a complete atrioventricular block; and mitral valve replacement was performed for severe mitral regurgitation at 62 years of age. She had a history of cerebral infarction and she was under treatment for chronic heart failure. Despite intensive anticoagulant therapy, she developed ball thrombi in the left atrium three times in six months. During hospitalization for acute myocardial infarction treated with percutaneous catheter intervention, transthoracic echocardiography and computed tomography (CT) revealed a free-floating giant spherical thrombus in the left atrium. She was treated with intensive anticoagulation therapy and the left atrial ball thrombus disappeared; however, two ball thrombi in the left atrium and left atrial appendage recurred after three months. Surgical removal of the thrombi and closure of the left atrial appendage were performed. Unfortunately, a ball thrombus in the left atrium recurred again after a further three months. CONCLUSIONS The present case highlights the difficulty of treating refractory thrombi in the left atrium.


Asunto(s)
Atrios Cardíacos/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Anciano , Anticoagulantes/uso terapéutico , Femenino , Humanos , Recurrencia , Trombosis/tratamiento farmacológico
15.
Intern Med ; 55(9): 1071-5, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27150857

RESUMEN

Objective Karoshi, which is the Japanese term for death from over-work, is usually the extreme result of cardiovascular diseases, and occupational stress plays a pivotal role in the pathogenesis. Depression is closely associated with atherosclerotic cardiovascular disease. The present study was undertaken to examine the relationship between occupational stress and depression. Methods We enrolled 231 consecutive outpatients with lifestyle-related diseases such as diabetes, hyperlipidemia and hypertension were enrolled. Occupational stress was measured by qualitative constructs assessing job control, job demands, and worksite social support using a job content questionnaire (JCQ). The job strain index measured by the ratio of job demands to job control was used as an indicator of the occupational stress. Depression was evaluated by the Self-rating Depression Scale (SDS). Results A univariate linear regression analysis showed the SDS scores to be positively correlated with job demands and the job strain index and negatively correlated with job control and worksite social support. Multiple regression analyses to predict the SDS scores demonstrated that job demands were positively associated with SDS scores and job control and worksite social support were negatively associated with SDS scores after controlling for other variables. The job strain index was positively related to SDS scores. Conclusion Occupational stress expressed as the job strain index was strongly associated with depression. By simultaneously using the SDS and JCQ, the health conditions of patients could be classified based on occupational stress and mental stress, and this classification could help to promote a healthy work environment and guide individual workers.


Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Depresión/complicaciones , Estilo de Vida , Enfermedades Profesionales/complicaciones , Enfermedades Profesionales/psicología , Estrés Psicológico/complicaciones , Tolerancia al Trabajo Programado/psicología , Carga de Trabajo/psicología , Pueblo Asiatico/psicología , Enfermedades Cardiovasculares/psicología , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Hiperlipidemias/complicaciones , Hipertensión/complicaciones , Japón , Masculino , Persona de Mediana Edad , Salud Laboral , Calidad de Vida , Apoyo Social , Encuestas y Cuestionarios
16.
Thromb J ; 13: 39, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26648789

RESUMEN

BACKGROUND: Dabigatran is an alternative to warfarin (WF) for the thromboprophylaxis of stroke in patients with non-valvular atrial fibrillation (NVAF). The advantage of dabigatran over WF is that monitoring is not required; however, a method to monitor the effect and the safety of dabigatran is not currently available. The Global Thrombosis Test (GTT) is a novel method to assess both clot formation and lysis activities under physiological conditions. OBJECTIVE: The aim of this study was to evaluate whether treatment with dabigatran might affect shear-induced thrombi (occlusion time [OT], sec) by the GTT, and to investigate the possibility that the GTT could be useful as a monitoring system for dabigatran. PATIENTS/METHODS: The study population consisted of 50 volunteers and 43 NVAF patients on WF therapy, who were subsequently switched to dabigatran. Using the GTT, the thrombotic status was assessed one day before and 1 month after switching anticoagulation from WF to dabigatran. RESULTS: The OT was 524.9 ± 17.0 sec in volunteers whereas that of NVAF patients on WF therapy was 581.7 ± 26.3 sec. The switch from WF to dabigatran significantly prolonged OT (784.5 ± 19.3 sec). One patient on WF therapy and 12 patients on dabigatran therapy were shown to have OT > 900 sec. CONCLUSION: The GTT could be used to assess the risk of dabigatran-related bleeding complications.

17.
Am J Case Rep ; 16: 598-602, 2015 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-26347942

RESUMEN

BACKGROUND: The clinical conditions of various diseases, including coronary artery disease, are determined by genetics and the environment. Previous investigations noted the significance of genetic mutations and polymorphisms in cases of coronary spasm. CASE REPORT: We report on monozygotic identical twins who almost simultaneously presented with vasospastic angina. The 58-year-old younger twin was admitted to our hospital because of persistent chest pain. An electrocardiogram showed an inverted T wave in the left precordial leads. Coronary angiographies revealed a short left main trunk (LMT) and 50% stenosis at the proximal portion of the left anterior descending artery (LAD). Infusion of acetylcholine to his left coronary artery caused marked vasoconstriction associated with a sensation of chest oppression. Nitroglycerine completely reversed this response. Based on these findings, we diagnosed Twin A with vasospastic angina. At nearly the same time, his identical twin brother was diagnosed with vasospastic angina at another hospital. Comparison of both coronary angiograms indicated similar structure of coronary vessels, including short LMT and mild stenosis at the proximal portion of LAD. CONCLUSIONS: These 2 cases highlight the importance of genetic factors in the pathogenesis of vasospastic angina. It may be important for individuals to receive medical attention if their identical twin presents with vasospastic angina.


Asunto(s)
Angina de Pecho/diagnóstico , Vasoespasmo Coronario/diagnóstico , Enfermedades en Gemelos , Gemelos Monocigóticos , Angina de Pecho/etiología , Angina de Pecho/terapia , Vasoespasmo Coronario/etiología , Vasoespasmo Coronario/terapia , Humanos , Masculino , Persona de Mediana Edad
18.
Am J Case Rep ; 16: 191-5, 2015 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-25819539

RESUMEN

BACKGROUND: Complete calcification of the left atrium (LA) is called "coconut atrium", which decreases the compliance of LA, leading to the elevation of LA pressure that is transmitted to the right-side of the heart. The pathogenesis of LA calcification in patients with rheumatic heart disease is unknown; however, possible mechanisms include chronic strain force in the atrial wall and inflammation. We report here a patient with long-standing rheumatic valvular heart disease with coconut atrium. CASE REPORT: A 76-year-old man presented with breathlessness and leg edema due to right-sided heart failure. He was diagnosed with rheumatic fever at 8 years of age. Mitral commissurotomy and the mitral and aortic valve replacement were previously performed to treat mitral and aortic valvular stenosis. The profile view of the chest X-ray indicated a diffuse calcified outline of the LA wall. A transthoracic echocardiogram revealed pulmonary hypertension and dilatation of both atria. Moreover, computed tomography showed nearly circumferential calcification of the LA wall. Despite intense medical treatment, he succumbed to heart failure. An autopsy demonstrated that the LA was markedly dilated, its wall was calcified, and its appearance was similar to the surface of an atherosclerotic aorta. Microscopic examination revealed intensive calcification in the endocardium. Minimal accumulation of inflammatory cells was noted. Although slight fibrosis was observed, the cardiac musculature was preserved. CONCLUSIONS: To the best of our knowledge, this is the first report that identifies the histological changes of LA calcification associated with long-standing rheumatic valvular heart disease.


Asunto(s)
Calcinosis/etiología , Cardiomiopatías/etiología , Atrios Cardíacos , Insuficiencia Cardíaca/complicaciones , Enfermedades de las Válvulas Cardíacas/complicaciones , Cardiopatía Reumática/complicaciones , Anciano , Calcinosis/diagnóstico , Cardiomiopatías/diagnóstico , Resultado Fatal , Humanos , Masculino
19.
J Cardiol Cases ; 11(2): 48-51, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30534257

RESUMEN

Chronic disseminated intravascular coagulation (DIC) is a well-known complication of aortic aneurysm. A 91-year-old Japanese woman was admitted to our hospital because of massive purpura of the lower limbs. The presence of abdominal aortic aneurysm (AAA) had been pointed out from the age of 80 years, and its diameter had gradually increased. The AAA was composed of two portions, that is, a large upper and a small lower portion, and a large mural thrombosis was observed in the lower portion. The laboratory data led to the diagnosis of DIC, and AAA was the only identifiable cause of coagulopathy. The time course of exacerbation of AAA was consistent with the progression of thrombocytopenia and purpura. Therefore, we concluded that AAA was the underlying cause of DIC. Since DIC in aortic aneurysms is associated with excessive fibrinolysis, tranexamic acid was administered as anti-fibrinolytic therapy. After that, coagulopathy was drastically improved. Our patient responded successfully to anti-fibrinolytic therapy for coagulopathy. The present case illustrates the importance of evaluation of the diameter of an aneurysm as well as intraluminal thrombosis, which may play an important role in coagulopathy including DIC. It is necessary to monitor coagulation and fibrinolysis for the follow-up of patients with AAA. .

20.
Circ J ; 71(6): 911-4, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17526989

RESUMEN

BACKGROUND: The ability to evaluate coronary stenosis using multi-detector computed tomography (MDCT) has been well discussed. In contrast, several studies demonstrated that the plaque burden measured by intravascular ultrasound (IVUS) has a relationship to the risk of cardiovascular events. the accuracy of MDCT was studied to determine plaque and vessel size compared with IVUS. METHODS AND RESULTS: Fifty-six proximal lesions (American College of Cardiology/American Heart Association classification: segment 1, 5, 6) from 33 patients were assessed using MDCT and IVUS. The plaque and vessel area were measured from the cross-sectional image using both MDCT and IVUS. Eight coronary artery lesions with motion artifacts and heavily calcified plaques were excluded from the analysis. The vessel and lumen size evaluated using MDCT were closely correlated with those evaluated by IVUS (R(2)=0.614, 0.750 respectively). Furthermore, there was a strong correlation between percentage plaque area assessed by MDCT and IVUS (R(2)=0.824). CONCLUSION: MDCT can noninvasively quantify coronary atherosclerotic plaque with good correlation compared with IVUS in patients with atherosclerosis.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Vasos Coronarios/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Ultrasonografía Intervencional
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