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2.
Sci Rep ; 14(1): 21815, 2024 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294189

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected or isolated from domestic cats. It is unclear whether cats play an important role in the SARS-CoV-2 transmission cycle. In this study, we examined the susceptibility of cats to SARS-CoV-2, including wild type and variants, by animal experiments. Cats inoculated with wild type, gamma, and delta variants secreted a large amount of SARS-CoV-2 for 1 week after the inoculation from nasal, oropharyngeal, and rectal routes. Only 100 TCID50 of virus could infect cats and replicate well without severe clinical symptoms. In addition, one cat inoculated with wild type showed persistent virus secretion in feces for over 28 days post-inoculation (dpi). The titer of virus-neutralizing (VN) antibodies against SARS-CoV-2 increased from 11 dpi, reaching a peak at 14 dpi. However, the omicron variant could not replicate well in cat tissues and induced a lower titer of VN antibodies. It is concluded that cats were highly susceptible to SARS-CoV-2 infection, but not to the Omicron Variant, which caused the attenuated pathogenicity.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Gatos , Animais , SARS-CoV-2/patogenicidade , SARS-CoV-2/genética , COVID-19/virologia , COVID-19/veterinária , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Doenças do Gato/virologia , Fezes/virologia , Feminino
3.
Vaccine ; 42(23): 126242, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39213922

RESUMO

We established a qualified Madin-Darby canine kidney cell line (qMDCK-Cs) and investigated its suitability for source virus isolation to develop cell-based seasonal influenza vaccine viruses using vaccine manufacturer cells (Manuf-Cs). When inoculated with 81 influenza-positive clinical specimens, the initial virus isolation efficiency of qMDCK-Cs was exceeded 70%. Among the qMDCK-C isolates, 100% of the A/H1N1pdm09, B/Victoria and B/Yamagata strains and >70% of the A/H3N2 strains showed antigenicity equivalent to that of the contemporary vaccine or relevant viruses in haemagglutination inhibition (HI) or virus neutralization (VN) tests using ferret antisera. These qMDCK-C isolates were propagated in Manuf-Cs (MDCK and Vero cells) (Manuf-C viruses) to develop vaccine viruses. In reciprocal antigenicity tests, ferret antisera raised against corresponding reference viruses and Manuf-C viruses recognized 29 of 31 Manuf-C viruses and corresponding reference viruses, respectively at HI or VN titres more than half of the homologous virus titres, which is the antigenicity criterion for cell culture seasonal influenza vaccine viruses specified by the World Health Organization. Furthermore, ferret antisera against these Manuf-C viruses recognized ≥95% of the viruses circulating during the relevant influenza season with HI or VN titres greater than one-quarter of the homologous virus titres. No cell line-specific amino acid substitutions were observed in the resulting viruses. However, polymorphisms at positions 158/160 of H3HA, 148/151 of N2NA and 197/199 of B/Victoria HA were occasionally detected in the qMDCK-C and Manuf-C viruses but barely affected the viral antigenicity. These results indicated that qMDCK-Cs are suitable for isolating influenza viruses that can serve as a source of antigenically appropriate vaccine viruses. The use of the qMDCK-C isolates will eliminates the need for clinical sample collection, virus isolation, and antigenicity analysis every season, and is expected to contribute to the promotion of vaccine virus development using manufacturer cells.


Assuntos
Antígenos Virais , Furões , Testes de Inibição da Hemaglutinação , Vacinas contra Influenza , Animais , Cães , Vacinas contra Influenza/imunologia , Células Madin Darby de Rim Canino , Testes de Inibição da Hemaglutinação/métodos , Antígenos Virais/imunologia , Humanos , Chlorocebus aethiops , Anticorpos Antivirais/imunologia , Testes de Neutralização , Células Vero , Cultura de Vírus/métodos , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Influenza Humana/virologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/genética , Linhagem Celular , Vírus da Influenza B/imunologia , Vírus da Influenza B/genética
4.
J Neurol Sci ; 464: 123154, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39142082

RESUMO

INTRODUCTION/AIMS: The common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG). METHODS: A total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation. RESULTS: Among the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use. DISCUSSION: Regarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Miastenia Gravis , Humanos , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Progressão da Doença , Sistema de Registros , Idoso de 80 Anos ou mais , Adulto , Japão/epidemiologia , Estudos de Coortes , Atorvastatina/efeitos adversos , Atorvastatina/uso terapêutico
5.
Laryngoscope ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973571

RESUMO

Cogan's syndrome is a rare disorder first clinically defined in 1945, characterized by nonsyphilitic interstitial keratitis and progressive audiovestibular symptoms. Later, patients with audiovestibular dysfunction and various types of inflammatory eye disease were classified as having atypical Cogan's syndrome. The etiology and pathogenesis of Cogan's syndrome remain largely unknown. Here, we report a case of atypical Cogan's syndrome with a histological assessment of the temporal bone during the acute disease period. Temporal bone histology was compared to age- and gender-matched normal control, and our findings revealed endolymphatic hydrops and degenerative changes in various parts of the inner ear. Laryngoscope, 2024.

6.
Ann Clin Transl Neurol ; 11(5): 1338-1346, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38572524

RESUMO

OBJECTIVE: Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy and tolerability for patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG) in phase 3 clinical trials and subsequent analyses. The purpose of the present study was to evaluate the clinical significance of eculizumab and switching to ravulizumab for refractory AChR+ gMG patients in the real-world experience. METHODS: Among the database of Japan MG registry survey 2021, we studied AChR+ gMG patients who received eculizumab. We also evaluated these patients who switched from eculizumab to ravulizumab. Responder was defined as an improvement of at least 3 points in MG-ADL. We performed a questionnaire of preference between eculizumab and ravulizumab. RESULTS: Among 1,106 patients with AChR+ gMG, 36 patients (3%) received eculizumab (female 78%, mean age 56.0 years). Eculizumab was preferentially used in severe and refractory MG patients. The duration of eculizumab treatment was 35 months on average. MG-ADL improved from 9.4 ± 4.9 to 5.9 ± 5.1, and 25 (70%) of the 36 gMG patients were responders. Postintervention status was markedly improved after the eculizumab treatment. Of 13 patients who did not continue eculizumab, 6 showed insufficiencies. Early onset MG was most effective. However, 15 patients switching from eculizumab to ravulizumab kept favorable response and tolerability. Questionnaire surveys showed preference for ravulizumab over eculizumab. INTERPRETATION: Eculizumab and switching to ravulizumab showed to be effective for refractory AChR+ gMG patients in clinical settings.


Assuntos
Anticorpos Monoclonais Humanizados , Inativadores do Complemento , Miastenia Gravis , Humanos , Miastenia Gravis/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Inativadores do Complemento/administração & dosagem , Inativadores do Complemento/farmacologia , Substituição de Medicamentos , Sistema de Registros , Japão
7.
Sci Rep ; 14(1): 7825, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570621

RESUMO

Diagnosing cardiac sarcoidosis (CS), especially in isolated cases, is challenging, particularly due to the limitations of endomyocardial biopsy, leading to potential undiagnosed cases in pacemaker-implanted patients. This study aims to provide real world findings to support new guideline for CS using 18F-fluoro-deoxyglucose positron-emission tomography computed tomography (FDG-PET/CT) which give a definite diagnosis of isolated CS (iCS) without histological findings. We examined consecutive patients with cardiac pacemakers for atrioventricular block (AV-b) attending our outpatient pacemaker clinic. The patients underwent periodical follow-up echocardiography and were divided into two groups according to echocardiographic findings: those with suspected CS and those without suspected CS. Patients suspected of having nonischemic cardiomyopathy underwent FDG-PET/CT for CS diagnosis. We investigated the utility of the new guideline for CS using FDG-PET/CT. Among the 272 patients enrolled, 97 patients were implanted with cardiac pacemakers for AV-b. Twenty-two patients were suspected of having CS during a median observation period of 5.4 years after pacemaker implantation. Of these, one did not consent, and nine of 21 cases (43%) were diagnosed with definite CS according to the new guidelines. Five of these nine patients were diagnosed with iCS using FDG-PET/CT. The number of patients diagnosed with definite CS using the new guidelines tended to be approximately 2.3 times that of the conventional criteria (p = 0.074). Three of the nine patients underwent steroid treatment. The composite outcome, comprising all-cause death, heart failure hospitalization, and a substantial reduction in left ventricular ejection fraction, were significantly lower in patients receiving steroid treatment compared to those without steroid treatment (p = 0.048). The utilization of FDG-PET/CT in accordance with the new guidelines facilitates the diagnosis of CS, including iCS, resulting in approximately 2.3 times as many diagnoses of CS compared to the conventional criteria. This guideline has the potential to support the early identification of iCS and may contribute to enhancing patient clinical outcomes.


Assuntos
Bloqueio Atrioventricular , Cardiomiopatias , Miocardite , Sarcoidose , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Bloqueio Atrioventricular/diagnóstico por imagem , Bloqueio Atrioventricular/terapia , Volume Sistólico , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodos , Função Ventricular Esquerda , Cardiomiopatias/patologia , Sarcoidose/diagnóstico por imagem , Sarcoidose/patologia , Esteroides , Estudos Retrospectivos
8.
BMC Neurol ; 24(1): 139, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664714

RESUMO

BACKGROUND: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. METHODS: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. RESULTS: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. CONCLUSION: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.


Assuntos
Alopecia , Miastenia Gravis , Distúrbios do Paladar , Humanos , Miastenia Gravis/epidemiologia , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Alopecia/epidemiologia , Alopecia/diagnóstico , Feminino , Masculino , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/etiologia , Pessoa de Meia-Idade , Adulto , Idoso , Japão/epidemiologia , Sistema de Registros , Timoma/complicações , Timoma/epidemiologia , Incidência
9.
Neurol Clin Pract ; 14(3): e200276, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38544885

RESUMO

Background and Objectives: Efgartigimod, which has been well tolerated and efficacious in individuals with generalized myasthenia gravis (MG), is available in Japan not only for the treatment of anti-acetylcholine receptor-positive (AChR+) but also anti-muscle-specific receptor tyrosine kinase (MuSK+) and seronegative generalized MG. We report details of the use of efgartigimod for generalized MG in clinical practice in Japan. Methods: We included patients with generalized MG in the 2021 survey of Japan Myasthenia Gravis Registry (JAMG-R) study group who received an initial cycle of efgartigimod between May and September 2022. We defined "responders" as patients who achieved a score ≥2 points for MG activities of daily living (MG-ADL) in the first treatment cycle. The MG composite and the Revised scale of the 15-item Myasthenia Gravis-Quality of Life scale (MG-QOL15-r) were also evaluated. Results: Of 1,343 JAMG-R patients, 36 (2.7%) started efgartigimod (female 68%, age 53 years). Their serologic profiles were as follows: AChR+, n = 19 (53%); MuSK+, n = 6 (17%); and seronegative, n = 11 (31%). Twenty-six patients (72%) had refractory MG. There were 81 cycles of efgartigimod during the 26-week observation in 34 patients (average, 2.4 cycles). The mean interval between cycles was 5.9 weeks. A continuous 4-weekly infusion of efgartigimod was performed in 65 (80%) of 81 cycles. In the first cycle, the MG-ADL score of the 34 patients decreased significantly from 10.5 ± 4.3 to 6.9 ± 5.1 (p = 0.003). Similarly, the mean MG composite and MG-QOL15-r decreased from 18.4 ± 13.6 to 11.8 ± 9.6 (p = 0.004) and from 19.2 ± 6.3 to 14.2 ± 8.3 (p = 0.007), respectively. Twenty-one (62%) patients were responders. Therapeutic responses were observed in the subsequent cycles. The duration of effectiveness of efgartigimod was varied among the responders; 4 responders had only a single effective cycle. Significant improvement was observed in the MuSK+ patients. Prednisolone dose of 7 patients was reduced. Our examination of the patients' postintervention status revealed that 6 patients achieved minimal manifestations. COVID-19 occurred in 5 patients. We failed to detect clinical or laboratory findings associated with responders. Discussion: Efgartigimod can be considered for the treatment of patients with generalized MG who do not achieve minimal manifestations, with a broad flexibility of patient selection and treatment schedules.

10.
Rinsho Shinkeigaku ; 64(2): 109-112, 2024 Feb 23.
Artigo em Japonês | MEDLINE | ID: mdl-38281749

RESUMO

A 74-year-old woman developed myasthenia gravis (MG) at the age of 32. She had a thymoma removed the following year, but her MG symptoms did not stabilize, and she required frequent hospitalization for fast-acting treatment (FT). She started eculizumab in March of two years ago and was followed up on an outpatient basis as her MG symptoms became milder. In February of this year, she was admitted to our hospital due to mild COVID-19-associated pneumonia with general malaise and fever. Her COVID-19-associated pneumonia was treated with intravenous sotrovimab, dexamethasone, and unfractionated heparin, and oral therapy for MG stayed the same. Eculizumab was not administered during hospitalization due to the combination of stable MG symptoms and the fact that the drug is not paid for by the Japanese insurance system. The patient's MG and COVID-19-associated pneumonia were not severe during hospitalization. However, the risk of myasthenic crisis and death is high when patients with MG develop COVID-19-associated pneumonia. Several reports suggest that the condition of patients with eculizumab-treated MG who develop COVID-19-associated pneumonia is not severe, and that that inhibition of the complement pathway with eculizumab is effective for COVID-19-associated pneumonia. Complement deposition in organ microvessels has been observed in patients with COVID-19, which suggests that complement overload may be a risk factor for COVID-19-associated pneumonia. Excessive complement activation may be involved in the pathogenesis; thus, eculizumab may function by inhibiting this pathway. In this case, eculizumab was discontinued while the patient had COVID-19-associated pneumonia, however, CH50, which is an indicator of complement, was suppressed during hospitalization due to the COVID-19-associated pneumonia. Therefore, eculizumab may have interfered with this course of events. This case demonstrates that eculizumab may be safe for and tolerated by patients with MG and COVID-19-associated pneumonia, but more cases need to be accumulated to support this conclusion.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Miastenia Gravis , Pneumonia , Humanos , Feminino , Idoso , Heparina , COVID-19/complicações , Miastenia Gravis/complicações , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/diagnóstico , Pneumonia/tratamento farmacológico , Pneumonia/etiologia , Progressão da Doença
11.
J Neuroimmunol ; 385: 578241, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37952282

RESUMO

This study included 51 patients with muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) from a Japanese multicenter survey to examine clinical features and outcomes. Median onset age was 37 years and female predominance was observed. All patients developed generalized symptoms and almost all (50/51) patients had bulbar symptoms. About half of the patients met the criteria for refractory MG. The refractory group had a lower age of onset, higher severity scores, and higher maximum daily doses of oral prednisolone compared to the nonrefractory group. The outcomes for MuSK-MG patients in Japan are not favorable, indicating the need for more aggressive treatment.


Assuntos
Miastenia Gravis , Humanos , Feminino , Adulto , Masculino , Japão , Miastenia Gravis/tratamento farmacológico , Miastenia Gravis/diagnóstico , Prednisolona/uso terapêutico , Músculos , Autoanticorpos/uso terapêutico
12.
Sci Rep ; 13(1): 17204, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821563

RESUMO

Catheter ablation for atrial fibrillation (AF) during pulmonary vein isolation (PVI) is performed under general anesthesia (GA) or conscious sedation (CS). GA during PVI may improve treatment outcomes by improving catheter stability. However, the magnitude of GA-derived catheter stability compared with that of CS is unclear. We directly assessed catheter movement and determined the impact of GA compared with that of CS on ablation catheter stability during PVI. Patients who underwent initial ablation using the EnSite Precision™ mapping system were recruited and divided into two groups (GA and CS groups). The two groups were compared for ablation catheter stability during PVI based on the distance traveled by the catheter distal tip per second, clinical periprocedural characteristics, and periprocedural complications. Among 69 consecutively admitted patients, data of 30 patients (17 in the GA group and 13 in the CS group) and the distance traveled per second by the catheter on 148,976 points/patient were evaluated. The GA group had a significantly smaller catheter tip travel distance than the CS group (0.92 [0.82‒1.16] vs. 1.25 [1.14‒1.38], p = 0.01). Therefore, GA during PVI for AF provides greater catheter stability than CS and will contribute to more accessible and safer PVI procedures.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Veias Pulmonares/cirurgia , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Ablação por Cateter/métodos , Anestesia Geral/métodos , Catéteres , Recidiva
13.
Intern Med ; 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37779069

RESUMO

Streptococcus agalactiae is a rare cause of meningitis in healthy adults. We herein report a case of culture-negative Streptococcus agalactiae meningitis in a healthy adult which was diagnosed using the FilmArray Meningitis and Encephalitis Panel. A healthy 22-year-old man presented with a fever, headache, and neck stiffness. Despite negative results from blood and cerebrospinal fluid cultures, the diagnosis was confirmed using the FilmArray Meningitis and Encephalitis Panel. The patient was treated with dexamethasone, vancomycin, and ceftriaxone, and thereafter recovered completely. This report highlights the importance of being aware that Streptococcus agalactiae meningitis can occur in healthy individuals, and summarizes these features.

14.
Influenza Other Respir Viruses ; 17(2): e13093, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36824396

RESUMO

Background: The antigenicity of SARS-CoV-2 is a critical issue for the effectiveness of the vaccine, and thus, it should be phenotypically evaluated by serological assays as new field isolates emerge. The hemagglutination/hemagglutination inhibition (HA/HI) tests are well known as a representative method for antigenic analysis of influenza viruses, but SARS-CoV-2 does not agglutinate human or guinea pig red blood cells. Therefore, the antigenic analysis requires complicated cell-based assays using special equipment such as plate reader or ELISPOT analyzer. Methods: Based on the HA/HI tests for influenza viruses, we developed the particle agglutination/particle agglutination inhibition (PA/PAI) test to easily and rapidly quantify the virus and antibody using human angiotensin-converting enzyme 2 (hACE2)-bound latex beads. The virus titers were determined by mixing the beads and the virus from culture supernatant, settling it overnight, and then observing the sedimentation/agglutination pattern (PA test). The neutralization antibody titers were determined by mixing virus-infected hamster antisera in addition to the beads and virus (PAI test). Results: The PA titer was positively correlated with the plaque-forming units. The PAI titer using the hamster antisera clearly revealed the antigenic difference between the omicron and previous variants. The antigenic differences were supported by the results shown in other methods. Conclusions: The PAI test is an easy and rapid method to analyze the antigenicity of SARS-CoV-2.


Assuntos
COVID-19 , Orthomyxoviridae , Animais , Humanos , Cobaias , SARS-CoV-2 , Testes de Inibição da Hemaglutinação , Aglutinação , Soros Imunes , Glicoproteínas de Hemaglutininação de Vírus da Influenza
15.
J Neurol Neurosurg Psychiatry ; 94(6): 467-473, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36693723

RESUMO

BACKGROUND: Early fast-acting treatment (EFT) is the aggressive use of fast-acting therapies such as plasmapheresis, intravenous immunoglobulin and/or intravenous high-dose methylprednisolone (IVMP) from the early phases of treatment. EFT is reportedly beneficial for early achievement of minimal manifestations (MM) or better status with ≤5 mg/day prednisolone (MM5mg), a practical therapeutic target for myasthenia gravis (MG). OBJECTIVE: The current study aimed to clarify which specific EFT regimen is efficacious and the patient characteristics that confer sensitivity to EFT. METHODS: We recruited a total of 1710 consecutive patients with MG who enrolled in the Japan MG Registry for this large-cohort study. Among them, 1066 with generalised MG who had received immunotherapy were analysed. Prognostic background factors were matched in a 1:1 ratio using propensity score matching analysis between patients treated with EFT (n=350) and those treated without EFT (n=350). The clinical course and time to first achieve MM5mg after starting immunotherapy was analysed in relation to treatment combinations and patient characteristics. RESULTS: Kaplan-Meier analyses showed that EFT had a significant effect on the achievement of MM5mg (p<0.0001, log-rank test; HR 1.82, p<0.0001). Notably, EFT was efficacious for any type of MG, and the inclusion of IVMP resulted in earlier and more frequent achievement of MM5mg (p=0.0352, log-rank test; HR 1.46, p=0.0380). In addition, early administration of calcineurin inhibitors also promoted MM5mg achievement. CONCLUSION: Early cycles of intervention with EFT and early use of calcineurin inhibitors provides long-term benefits in terms of achieving therapeutic targets for generalised MG, regardless of clinical subtype.


Assuntos
Inibidores de Calcineurina , Miastenia Gravis , Humanos , Inibidores de Calcineurina/uso terapêutico , Estudos de Coortes , Miastenia Gravis/tratamento farmacológico , Metilprednisolona/uso terapêutico , Imunoterapia
16.
PLoS One ; 18(1): e0280811, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36662890

RESUMO

Manufactured influenza vaccines have to contain a defined amount of hemagglutinin (HA) antigen. Therefore, vaccine viruses with a high HA antigen yield (HAY) are preferable for manufacturing vaccines, particularly vaccines in response to a pandemic, when vaccines need to be rapidly produced. However, the viral properties associated with a high HAY have not yet been fully clarified. To identify the HAY-associated traits, we first propagated 26 H5 candidate vaccine viruses (CVVs) in eggs, which were previously developed based on genetic reassortment methods using master viruses, to determine their total protein yield (TPY), ratio of HA to total viral protein (%-HA content) and HAY. The results revealed that the HAY was correlated with the TPY but not with the %-HA content. We further found that altering the sequences of the 3' noncoding region of HA vRNA or replacing the master virus improved the HAYs and TPYs of the low-HAY CVVs to approximately double the values of the original CVVs but did not change the %-HA content, which a previous study suggested was associated with the HAY. Analyses based on real-time PCR assays and scanning electron microscopy revealed that the virus samples with an improved HAY contained more copies of the virus genome and viral particles than the original samples. The results suggest that an improvement in virus growth (i.e., an increase in the amount of viral particles) leads to an increase in the TPY and thus in the HAY, regardless of the %-HA content. The approximately twofold increase in the HAY shown in this study may not appear to represent a large improvement, but the impact will be significant given the millions of chicken eggs used to produce vaccines. These findings will be informative for developing high-HAY vaccine viruses.


Assuntos
Vacinas contra Influenza , Orthomyxoviridae , Animais , Hemaglutininas/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Galinhas , Anticorpos Antivirais
17.
Neurotherapeutics ; 20(2): 518-523, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36607596

RESUMO

The efficacy of intravenous high-dose methylprednisolone (IVMP) in ocular myasthenia gravis (MG) has not been fully established. This study aimed to elucidate the effects of early intervention with IVMP for achieving the therapeutic targets (minimal manifestations [MM] or MM or better status with prednisolone ≤ 5 mg/day [MM5mg]) in ocular MG. In this observational study, we included a total of 1710 consecutive patients with MG enrolled in the Japan MG Registry in 2021. Of these, 204 patients with ocular MG who received immunotherapy were analyzed. The clinical course and time to first achieve MM or MM5mg after starting immunotherapy were compared between the early IVMP group (treated with IVMP within 3 months of treatment initiation) and the non-early IVMP group. Despite having greater clinical severity before immunotherapy and lower oral prednisolone doses throughout the course, the early IVMP group (n = 55) showed a higher rate of achievement of MM (P = 0.0040, log-rank test; hazard ratio 1.58, 95% confidence interval [CI] 1.13-2.20, P < 0.0001) and MM5mg (P = 0.0005, log-rank test; hazard ratio 1.78, 95% CI 1.27-2.51, P < 0.0001) compared with the non-early IVMP group (n = 149). In conclusion, an early intervention with IVMP is likely to increase the probability of achieving a better long-term outcome and reducing the total dose of corticosteroids in ocular MG.


Assuntos
Metilprednisolona , Miastenia Gravis , Humanos , Metilprednisolona/uso terapêutico , Resultado do Tratamento , Administração Intravenosa , Miastenia Gravis/tratamento farmacológico , Imunoterapia
18.
Ren Replace Ther ; 8(1): 58, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407492

RESUMO

Background: The Japan Society for Blood Purification in Critical Care (JSBPCC) has reported survey results on blood purification therapy (BPT) for critically ill patients in 2005, 2009, and 2013. To clarify the current clinical status, including details of the modes used, treated diseases, and survival rate, we conducted this cohort study using data from the nationwide JSBPCC registry in 2018. Methods: We analyzed data of 2371 patients who underwent BPT in the intensive care units of 43 facilities to investigate patient characteristics, disease severity, modes of BPTs, including the dose of continuous renal replacement therapy (CRRT) and hemofilters, treated diseases, and the survival rate for each disease. Disease severity was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores. Results: BPT was performed 2867 times in the 2371 patients. Mean APACHE II and SOFA scores were 23.5 ± 9.4 and 10.0 ± 4.4, respectively. The most frequently used mode of BPT was CRRT (67.4%), followed by intermittent renal replacement therapy (19.1%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (7.3%). The most commonly used anticoagulant was nafamostat mesilate (78.6%). Among all patients, the 28-day survival rate was 61.7%. CRRT was the most commonly used mode for many diseases, including acute kidney injury (AKI), multiple organ failure (MOF), and sepsis. The survival rate decreased according to the severity of AKI (P = 0.001). The survival rate was significantly lower in patients with multiple organ failure (MOF) (34.6%) compared with acute lung injury (ALI) (48.0%) and sepsis (58.0%). Multivariate logistic regression analysis revealed that sepsis, ALI, acute liver failure, cardiovascular hypotension, central nervous system disorders, and higher APACHE II scores were significant predictors of higher 28-day mortality. Conclusion: This large-scale cohort study revealed the current status of BPT in Japan. It was found that CRRT was the most frequently used mode for critically ill patients in Japan and that 28-day survival was lower in those with MOF or sepsis. Further investigations are required to clarify the efficacy of BPT for critically ill patients.Trial Registration : UMIN000027678. Supplementary Information: The online version contains supplementary material available at 10.1186/s41100-022-00445-0.

19.
Circ Rep ; 4(9): 439-446, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36120484

RESUMO

Background: Physiological assessments using fractional flow reserve (FFR) and resting full-cycle ratio (RFR) have been recommended for revascularization decision making. Previous studies have shown a 20% rate of discordance between FFR and RFR. In this context, the correlation between RFR and FFR in patients with renal dysfunction remains unclear. This study examined correlations between RFR and FFR according to renal function. Methods and Results: In all, 263 consecutive patients with 370 intermediate lesions were enrolled in the study. Patients were classified into 3 groups according to renal function: Group 1, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; Group 2, 30 mL/min/1.73 m2≤eGFR<60 mL/min/1.73 m2; Group 3, eGFR <30 mL/min/1.73 m2. The discordance between FFR and RFR was assessed using known cut-off values for FFR (≤0.80) and RFR (≤0.89). Of the 370 lesions, functional significance with FFR was observed in 154 (41.6%). RFR was significantly correlated with FFR in all groups (Group 1, R2=0.62 [P<0.001]; Group 2, R2=0.67 [P<0.001]; Group 3, R2=0.46 [P<0.001]). The rate of discordance between RFR and FFR differed significantly among the 3 groups (Group 1, 18.8%; Group 2, 18.5%; Group 3, 42.9%; P=0.02). Conclusions: The diagnostic performance of RFR differed based on renal function. A better understanding of the clinical factors contributing to FFR/RFR discordance, such as renal function, may facilitate the use of these indices.

20.
BMJ Case Rep ; 15(7)2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35863858

RESUMO

Ventricular arrhythmias are a life-threatening factor in cardiac sarcoidosis (CS), posing a significant therapeutic challenge. Stellate ganglion phototherapy (SGP), a non-invasive procedure for modification of the sympathetic nervous system, is an effective treatment for refractory ventricular tachycardia (RVT). However, there are limited data on the efficacy of SGP for RVT in patients with CS. In our case report, we found that SGP was effective for treating RVT in a patient with CS.We present the case of a man in his 60s with multiple cardioversions of implantable cardioverter defibrillator for ventricular tachycardia. The patient was administered prednisolone for the management of CS, which subsequently led to an increase in anti-tachycardia pacing for ventricular tachycardias. We introduced SGP to suppress RVT and anti-tachycardia pacing decreased from 371 to 25 events. Thus, SGP could be a feasible option for the management of RVT in patients with CS.


Assuntos
Desfibriladores Implantáveis , Miocardite , Sarcoidose , Taquicardia Ventricular , Desfibriladores Implantáveis/efeitos adversos , Humanos , Masculino , Miocardite/complicações , Fototerapia , Sarcoidose/complicações , Sarcoidose/terapia , Gânglio Estrelado , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/terapia
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