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1.
Circ Res ; 134(12): 1663-1680, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38843286

RESUMO

Over the past 30 years, the field of cardioimmunology has moved from being dismissed as a field that was chasing an epiphenomenon of little biological consequence to a scientific discipline that is providing important new insights into the immunologic basis for hypertension, atherosclerosis, myocarditis, pericarditis, autoimmune heart disease, and heart failure. In this article, we will review the conceptual insights and technical breakthroughs that have allowed the field to move forward, as well as the clinical trials in the cardioimmunology space, to provide a historical context for the articles that will appear in the compendium that is focused on the interface between cardioimmunology, myocardial function, and disease.


Assuntos
Cardiopatias , Humanos , Animais , Cardiopatias/imunologia , Cardiopatias/terapia , Alergia e Imunologia/tendências , Alergia e Imunologia/história , Doenças Cardiovasculares/imunologia , História do Século XXI , História do Século XX
2.
Am J Epidemiol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907283

RESUMO

The assumption that serious adverse events (SAEs) do not affect subsequent exposure might not hold when evaluating 2-dose vaccine safety through a self-controlled case series (SCCS) design. To address this, we developed: 1) propensity score SCCS (PS-SCCS) using a propensity score model involving SAEs during the risk interval after dose 1 (${R}_1\Big)$, and 2) partitioned SCCS (P-SCCS) estimating relative incidence (RI) separately for doses 1 and 2. In simulations, both provided unbiased RIs. Conversely, standard SCCS overestimated RI after dose 2. We applied these approaches to assess myocarditis/pericarditis risks after 2-dose mRNA COVID-19 vaccination in 12-39-year-olds. For BNT162b2, PS-SCCS yielded RIs of 1.85 (95% CI, 0.75-4.59) and 11.05 (95% CI, 6.53-18.68) 14 days after doses 1 and 2 respectively; standard SCCS provided similar RI after dose 1 and RI of 12.92 (95% CI, 7.56-22.09) after dose 2. For mRNA-1273, standard SCCS showed RIs of 1.96 (95% CI, 0.56-6.91) after dose 1 and 7.87 (95% CI, 3.33-18.57) after dose 2. As no mRNA-1273 recipients with SAEs during ${R}_1$ received dose 2, P-SCCS was used, yielding similar RI after dose 1 and RI of 6.48 (95% CI, 2.83-14.83) after dose 2. mRNA vaccines were associated with elevated myocarditis/pericarditis risks following dose 2 in 12-39-year-olds.

3.
Br J Haematol ; 204(4): 1232-1237, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38311378

RESUMO

Among 301 newly diagnosed patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent, 23 (7.6%) experienced major cardiac complications: 15 cardiomyopathy, 5 non-ST elevation myocardial infarction and/or 7 pericarditis/effusions. Four patients had more than one cardiac complication. Baseline characteristics included median age ± interquartile range; 73 ± 5 years; 87% males; 96% with cardiovascular risk factors; and 90% with preserved baseline ejection fraction. In multivariate analysis, males were more likely (p = 0.02) and DNMT3A-mutated cases less likely (p < 0.01) to be affected. Treatment-emergent cardiac events were associated with a trend towards lower composite remission rates (43% vs. 62%; p = 0.09) and shorter survival (median 7.7 vs. 13.2 months; p < 0.01). These observations were retrospectively retrieved and warrant further prospective examination.


Assuntos
Cardiomiopatias , Leucemia Mieloide Aguda , Sulfonamidas , Masculino , Humanos , Feminino , Estudos Retrospectivos , Resultado do Tratamento , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Cardiomiopatias/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
4.
J Med Virol ; 96(6): e29693, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38859751

RESUMO

Due to the limitation of previous studies examining adverse reports of myocarditis and pericarditis associated with vaccines other than the COVID-19 vaccine, there are challenges in establishing a comprehensive understanding of vaccine safety on a global scale. Hence, the objective of this study was to examine the worldwide burden of vaccine-associated pericarditis and myocarditis and the vaccines associated with these indications. This study utilized the World Health Organization international pharmacovigilance database, from which records of vaccine-associated pericarditis and myocarditis between 1969 and 2023 were extracted (over 130 million reports). We calculated global reporting counts, reported odds ratios (RORs), and information components (ICs) to discern the association between 19 vaccines and the occurrence of pericarditis and myocarditis across 156 countries and territories. We identified 49 096 reports (male, n = 30 013) of vaccine-associated pericarditis and myocarditis among 73 590 reports of all-cause pericarditis and myocarditis. There has been a significant increase in reports of vaccine-related cardiac adverse events over time, with a noteworthy surge observed after 2020, attributed to cases of pericarditis associated with COVID-19 mRNA vaccines. Smallpox vaccines were associated with most pericarditis and myocarditis reports (ROR: 73.68 [95% CI, 67.79-80.10]; IC [IC0.25]: 6.05 [5.91]), followed by COVID-19 mRNA vaccine (37.77 [37.00-38.56]; 3.07 [3.05]), anthrax vaccine (25.54 [22.37-29.16]; 4.58 [4.35]), typhoid vaccine (6.17 [5.16-7.38]; 2.59 [2.29]), encephalitis vaccine (2.00 [1.48-2.71]; 0.99 [0.47]), influenza vaccine (1.87 [1.71-2.04]; 0.90 [0.75]), and Ad5-vectored COVID-19 vaccine (1.40 [1.34-1.46]; 0.46 [0.39]). Concerning age and sex-specific risks, reports of vaccine-associated pericarditis and myocarditis were more prevalent among males and in older age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (median time: 1 day) and fatality rate was 0.44%. Our analysis of global data revealed an increase in pericarditis and myocarditis reports associated with vaccines, particularly live vaccines like smallpox and anthrax, notably in young males. While these adverse events are generally rare and mild, caution is warranted, especially for healthcare workers, due to potential myocardial injury-related in-hospital mortality. Further study with validated reporting is crucial to enhance accuracy in evaluating the correlation between vaccines and cardiac conditions for preventive measures.


Assuntos
Miocardite , Pericardite , Farmacovigilância , Organização Mundial da Saúde , Humanos , Miocardite/epidemiologia , Miocardite/induzido quimicamente , Pericardite/epidemiologia , Pericardite/induzido quimicamente , Masculino , Feminino , Bases de Dados Factuais , Vacinas contra COVID-19/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Saúde Global , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacinas contra Influenza/efeitos adversos , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Vacinas/efeitos adversos
5.
Invest New Drugs ; 42(1): 116-126, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38253746

RESUMO

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.


Assuntos
Antineoplásicos Imunológicos , Miocardite , Humanos , Idoso , Nivolumabe/efeitos adversos , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Miocardite/terapia , Antineoplásicos Imunológicos/efeitos adversos , Estudos Retrospectivos , Peptídeo Natriurético Encefálico/efeitos adversos , Imunossupressores/uso terapêutico , Corticosteroides/efeitos adversos , Creatina Quinase
6.
Eur J Clin Invest ; 54(2): e14110, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37837616

RESUMO

BACKGROUND: An exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs). METHODS: This narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: "acute pericarditis," "recurrent pericarditis," "myocarditis," "cardiac sarcoidosis," "atherosclerosis," "acute myocardial infarction," "inflammation," "NLRP3 inflammasome," "Interleukin-1" and "treatment." RESULTS: Recent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine-rich repeat and pyrin-domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL-1ß, the prototypical pro-inflammatory cytokine involved in CVDs. Other pro-inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL-1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome. CONCLUSION: Tailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies.


Assuntos
Aterosclerose , Miocardite , Pericardite , Sarcoidose , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Citocinas/metabolismo , Interleucina-1beta/metabolismo , Aterosclerose/metabolismo , Pericardite/tratamento farmacológico
7.
Eur Radiol ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467940

RESUMO

OBJECTIVE: Our study aimed to explore with cardiovascular magnetic resonance (CMR) the impact of left atrial (LA) and left ventricular (LV) myocardial strain in patients with acute pericarditis and to investigate their possible prognostic significance in adverse outcomes. METHOD: This retrospective study performed CMR scans in 36 consecutive patients with acute pericarditis (24 males, age 52 [23-52]). The primary endpoint was the combination of recurrent pericarditis, constrictive pericarditis, and surgery for pericardial diseases defined as pericardial events. Atrial and ventricular strain function were performed on conventional cine SSFP sequences. RESULTS: After a median follow-up time of 16 months (interquartile range [13-24]), 12 patients with acute pericarditis reached the primary endpoint. In multivariable Cox regression analysis, LA reservoir and LA conduit strain parameters were all independent determinants of adverse pericardial diseases. Conversely, LV myocardial strain parameters did not remain an independent predictor of outcome. With receiving operating characteristics curve analysis, LA conduit and reservoir strain showed excellent predictive performance (area under the curve of 0.914 and 0.895, respectively) for outcome prediction at 12 months. CONCLUSION: LA reservoir and conduit mechanisms on CMR are independently associated with a higher risk of adverse pericardial events. Including atrial strain parameters in the management of acute pericarditis may improve risk stratification. CLINICAL RELEVANCE STATEMENT: Atrial strain could be a suitable non-invasive and non-contrast cardiovascular magnetic resonance parameter for predicting adverse pericardial complications in patients with acute pericarditis. KEY POINTS: • Myocardial strain is a well-validated CMR parameter for risk stratification in cardiovascular diseases. • LA reservoir and conduit functions are significantly associated with adverse pericardial events. • Atrial strain may serve as an additional non-contrast CMR parameter for stratifying patients with acute pericarditis.

8.
Rev Med Virol ; 33(4): e2443, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36998233

RESUMO

Mpox (previously known as monkeypox) continues to raise concerns since many cases are still being recorded globally. Various reports have shown changing epidemiology of the disease, together with different atypical clinical characteristics of affected patients. The condition has reportedly been self-limited since most patients do not usually require hospitalisation. However, recent reports showed that some patients might suffer from related complications and require hospitalisation. Different systems were reportedly affected, including cardiac, neurological, respiratory, and renal events. In the present literature review, we aim to review these complications, discuss their potential mechanisms, and provide insight into the currently recommended diagnostic and management practices.


Assuntos
Mpox , Humanos , Hospitalização
9.
BMC Cardiovasc Disord ; 24(1): 154, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481129

RESUMO

BACKGROUND: Purulent pericarditis (PP)- a purulent infection involving the pericardial space-requires a high index of suspicion for diagnosis as it often lacks characteristic signs of pericarditis and carries a mortality rate as high as 40% even with treatment. Common risk factors include immunosuppression, diabetes mellitus, thoracic surgery, malignancy, and uremia. Most reported cases of PP occur in individuals with predisposing risk factors, such as immunosuppression, and result from more commonly observed preceding infections, such as pneumonia, osteomyelitis, and meningitis. We report a case of PP due to asymptomatic bacteriuria in a previously immunocompetent individual on a short course of high-dose steroids. CASE PRESENTATION: An 81-year-old male presented for severe epigastric pain that worsened with inspiration. He had been on high-dose prednisone for presumed inflammatory hip pain. History was notable for urinary retention requiring intermittent self-catheterization and asymptomatic bacteriuria and urinary tract infections due to methicillin-sensitive Staphylococcus aureus (MSSA). During the index admission he was found to have a moderate pericardial effusion. Pericardial fluid cultures grew MSSA that had an identical antibiogram to that of the urine cultures. A diagnosis of purulent pericarditis was made. CONCLUSION: PP requires a high index of suspicion, especially in hosts with atypical risk factors. This is the second case of PP occurring as a result of asymptomatic MSSA bacteriuria. Through reporting this case we hope to highlight the importance of early recognition of PP and the clinical implications of asymptomatic MSSA bacteriuria in the setting of urinary instrumentation and steroid use.


Assuntos
Bacteriúria , Mediastinite , Derrame Pericárdico , Pericardite , Esclerose , Infecções Estafilocócicas , Masculino , Humanos , Idoso de 80 Anos ou mais , Meticilina/uso terapêutico , Staphylococcus aureus , Bacteriúria/complicações , Bacteriúria/patologia , Pericárdio/patologia , Pericardite/diagnóstico , Pericardite/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Derrame Pericárdico/terapia , Derrame Pericárdico/tratamento farmacológico , Dor
10.
BMC Cardiovasc Disord ; 24(1): 200, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582827

RESUMO

BACKGROUND: IgG4-related disease is a fibro-inflammatory disorder with an unknown etiology, which can affect multiple organ systems, including the cardiovascular system. While most reported cases of cardiovascular involvement are primarily associated with the aorta, there have been sporadic reports of isolated cardiac involvement. CASE PRESENTATION: This paper presents a documented case of IgG4-related systemic disease with symptoms indicative of restrictive cardiomyopathy. Subsequent Cardiac Magnetic Resonance imaging revealed diffuse myopericardial involvement, characterized by pericardial thickening and enhancement, accompanied by subepicardial and myocardial infiltration. Considering the rarity of cardiac involvement in our case, we conducted a thorough review of the existing literature pertaining to various patterns of cardiac involvement in IgG4-related disease, as well as the diagnostic modalities that can be employed for accurate identification and assessment. CONCLUSIONS: This case report sheds light on the importance of recognizing and evaluating cardiac manifestations in IgG4-related systemic disease to facilitate timely diagnosis and appropriate management.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Pericárdio/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imunoglobulina G
11.
BMC Cardiovasc Disord ; 24(1): 122, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389040

RESUMO

BACKGROUND: Immunoglobulin G4 (IgG4)-related effusive constrictive pericarditis (ECP) is a rare manifestation of IgG4-related disease (IgG4-RD). It can lead to persistent pericardial fibrosis, resulting in cardiac tamponade, diastolic dysfunction, and heart failure. Glucocorticoids are the primary treatment for effectively reducing inflammation and preventing fibrosis. However, guidelines for monitoring treatment response are lacking and tapering glucocorticoid therapy for specific target organs remains a challenge. Recent studies on IgG4-RD have demonstrated that semiquantitative measurements of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in the main involved organs in positron emission tomography/computed tomography (PET/CT) scanning are correlated to disease activity. We present a case of IgG4-related ECP to demonstrate the usefulness of 18F-FDG PET/CT for diagnosing and treatment follow-up of IgG4-related ECP. CASE PRESENTATION: Herein, a 66-year-old woman diagnosed with IgG4-related ECP presented with breathlessness, leg swelling, rales, and fever. Laboratory tests revealed markedly elevated levels of C-reactive protein, and transthoracic echocardiography revealed constrictive physiology with effusion. High IgG4 levels suggested an immune-related pathogenesis, while viral and malignant causes were excluded. Subsequent pericardial biopsy revealed lymphocyte and plasma cell infiltration in the pericardium, confirming the diagnosis of IgG4-related ECP. 18F-FDG PET/CT revealed increased uptake of 18F-FDG in the pericardium, indicating isolated cardiac involvement of IgG4-RD. Treatment with prednisolone and colchicine led to a rapid improvement in the patient's condition within a few weeks. Follow-up imaging with 18F-FDG PET/CT after 3 months revealed reduced inflammation and improved constrictive physiology on echocardiography, leading to successful tapering of the prednisolone dose and discontinuation of colchicine. CONCLUSION: The rarity of IgG4-related ECP and possibility of multiorgan involvement in IgG4-RD necessitates a comprehensive diagnostic approach and personalized management. This case report highlights the usefulness of 18F-FDG PET/CT in the diagnosis and treatment follow-up of isolated pericardial involvement in IgG4-RD.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Pericardite Constritiva , Feminino , Humanos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Glucocorticoides/uso terapêutico , Pericardite Constritiva/diagnóstico por imagem , Pericardite Constritiva/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Compostos Radiofarmacêuticos , Inflamação , Prednisolona/uso terapêutico , Imunoglobulina G , Fibrose , Colchicina
12.
J Clin Ultrasound ; 52(5): 529-534, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38476017

RESUMO

PURPOSE: To analyze ultrasound features of cervical thoracic duct for patients with constrictive pericarditis and chylothorax. METHODS: Patients were retrospectively assessed. The patients were divided into a non-pleural effusion (PE) group (n = 54), a chylothorax group (n = 23), and non-chylothorax group (n = 28). Conventional ultrasound was used to obtain the maximum inner diameter and collapse of the inferior vena cava, the inner diameter of left cervical thoracic duct, and the frequency of opening of the valve at the end of the left thoracic duct. Contrast ultrasonography was used to score the reverse flow of the thoracic tube. RESULTS: The percentage of PE was 48.5%, and the percentage of chylothorax was 21.9%. The three groups had significant differences in five parameters. The inner diameter of left cervical thoracic duct was correlated with the degree of central venous pressure. Contrast ultrasonography was effective in quantitative assessment of the degree of intravenous-thoracic cord reverse flow which correlated with all parameters of central venous pressure. CONCLUSION: Thoracic duct dilation and regurgitation secondary to central venous pressure can lead to chyloreflux disorder and may be the mechanism of chylothorax occurrence in constrictive pericarditis.


Assuntos
Quilotórax , Pericardite Constritiva , Ducto Torácico , Ultrassonografia , Humanos , Pericardite Constritiva/diagnóstico por imagem , Pericardite Constritiva/complicações , Pericardite Constritiva/fisiopatologia , Ducto Torácico/diagnóstico por imagem , Quilotórax/diagnóstico por imagem , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Ultrassonografia/métodos , Adulto
13.
Int J Mol Sci ; 25(12)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38928231

RESUMO

Ibogaine is an organic indole alkaloid that is used in alternative medicine to combat addiction. Numerous cases of life-threatening complications and sudden deaths associated with ibogaine use have been reported, and it has been hypothesized that the adverse effects are related to ibogaine's tendency to induce cardiac arrhythmias. Considering that the bioavailability of ibogaine and its primary metabolite noribogaine is two to three times higher in female rats than in male rats, we here investigated the effect of a single oral dose (1 or 20 mg/kg) of ibogaine on cardiac histopathology and oxidative/antioxidant balance. Our results show that ibogaine induced dose-dependent cardiotoxic necrosis 6 and 24 h after treatment and that this necrosis was not a consequence of inflammation. In addition, no consistent dose- and time-dependent changes in antioxidant defense or indicators of oxidative damage were observed. The results of this study may contribute to a better understanding of ibogaine-induced cardiotoxicity, which is one of the main side effects of ibogaine use in humans and is often fatal. Nevertheless, based on this experiment, it is not possible to draw a definitive conclusion regarding the role of redox processes or oxidative stress in the occurrence of cardiotoxic necrosis after ibogaine administration.


Assuntos
Ibogaína , Necrose , Oxirredução , Estresse Oxidativo , Animais , Ibogaína/análogos & derivados , Ibogaína/farmacologia , Ibogaína/efeitos adversos , Ratos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Feminino , Cardiotoxicidade/etiologia , Cardiotoxicidade/patologia , Antioxidantes/farmacologia , Miocárdio/metabolismo , Miocárdio/patologia , Ratos Wistar
14.
Int J Mol Sci ; 25(7)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38612407

RESUMO

A small fraction of people vaccinated with mRNA-lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1ß < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1ß, and TNF-α, suggesting C-dependence of these cytokines' induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents.


Assuntos
COVID-19 , Inativadores do Complemento , Nanopartículas , Humanos , Lipossomos , Vacinas contra COVID-19/efeitos adversos , Leucócitos Mononucleares , Citocinas , Fator de Necrose Tumoral alfa , Vacina BNT162 , Ativação do Complemento , Lipídeos
15.
Z Rheumatol ; 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277021

RESUMO

OBJECTIVE: Idiopathic recurrent pericarditis (IRP) is defined by recurring episodes of pericardial inflammation without a known cause. This study investigates the safety and efficacy of anakinra, an interleukin­1 inhibitor, as a successful therapy for IRP in cases resistant to conventional treatment. METHODS: A retrospective evaluation of patients treated at our autoinflammatory center between 2011 and 2023 was conducted. Patient files were examined for demographic, clinical, and treatment response data, including nonsteroid anti-inflammatory drugs (NSAIDs), corticosteroids, and colchicine. Monogenic autoinflammatory disease screening was performed for Mediterranean Fever (MEFV), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase (MVK), nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and nucleotide-binding oligomerization domain-containing protein 2 (NOD2). Patients who experienced multiple episodes of pericarditis were diagnosed with recurrent pericarditis. The study evaluated anakinra treatment in IRP patients unresponsive to conventional therapy. RESULTS: The study included 21 participants, 9 (42.9%) female and 12 (57.1%) male. The average age of the participants was 43.1 ± 16.5 years. The MEFV mutation analysis revealed that 2 (9.5%) had a mutation in exon 10 and 4 (19.0%) had one in exon 2. Out of the 16 cases, 15 successfully discontinued steroid treatment. Four patients (19.0%) experienced injection site reactions. C­reactive protein (CRP) levels were measured at an average of 196 ± 67.8 mg/l before and 2.6 ± 3.15 mg/l after anakinra treatment. CONCLUSION: In conclusion, the study adds to the growing evidence for the efficacy of interleukin-1 inhibitors, such as anakinra, as a promising treatment modality for IRP in cases resistant to conventional treatment.

16.
Acta Chir Belg ; 124(2): 107-113, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37232347

RESUMO

BACKGROUND: Constrictive pericarditis (CP) is a pericardial disease characterized by the pericardium becoming calcified or fibrotic as a result of chronic inflammation, which impairs diastolic filling by compressing the cardiac chambers. Pericardiectomy is a promising surgical option for treating CP. In this study, we reviewed over 10 years of preoperative, perioperative, and short-term postoperative follow-ups of patients who underwent pericardiectomy for constrictive pericarditis at our clinic. METHODS: Between January 2012 and May 2022, 44 patients were diagnosed with constrictive pericarditis. Twenty-six patients underwent pericardiectomy for CP. Median sternotomy is the surgical approach of choice because it provides easy access for complete pericardiectomy. RESULTS: The patient median age was 56 (min: 32, max: 71), and 22 out of 26 patients (84.6%) were male. Twenty-one patients (80.8%) complained of dyspnea, which was the most common reason for admission. Twenty-four patients (92.3%) were scheduled for elective surgery. Cardiopulmonary bypass (CPB) was used during the procedure in six patients (23%). The duration of intensive care stay was two days (min: 1, max: 11), and the total hospitalization was six days (min: 4, max: 21). No in-hospital mortality was observed. CONCLUSION: The median sternotomy approach provides a critical advantage in terms of performing a complete pericardiectomy. Although CP is a chronic condition, early diagnosis and planning of pericardiectomy before irreversible deterioration of cardiac function leads to a notable reduction in mortality and morbidity.


Assuntos
Pericardite Constritiva , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Pericardite Constritiva/diagnóstico , Pericardite Constritiva/cirurgia , Pericardiectomia/métodos , Doença Crônica , Período Pós-Operatório , Ponte Cardiopulmonar , Estudos Retrospectivos
17.
Medicina (Kaunas) ; 60(2)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38399529

RESUMO

Diseases of the pericardium encompass a spectrum of conditions, including acute and recurrent pericarditis, where inflammation plays a pivotal role in the pathogenesis and clinical manifestations. Anti-inflammatory therapy indeed forms the cornerstone of treating these conditions: NSAIDs, colchicine, and corticosteroids (as a second-line treatment) are recommended by current guidelines. However, these medications come with several contraindications and are not devoid of adverse effects. In recent years, there has been an increased focus on the role of the inflammasome and potential therapeutic targets. Recurrent pericarditis also shares numerous characteristics with other autoinflammatory diseases, in which interleukin-1 antagonists have already been employed with good efficacy and safety. The objective of this review is to summarize the available studies on the use of anti-IL-1 drugs both in acute and recurrent pericarditis.


Assuntos
Interleucina-1 , Pericardite , Humanos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Corticosteroides/uso terapêutico , Pericardite/tratamento farmacológico , Pericardite/etiologia , Recidiva
18.
Artigo em Inglês | MEDLINE | ID: mdl-38888706

RESUMO

A 27-year-old male died suddenly due to cardiac tamponade arising from pericarditis complicating autoimmune polyglandular syndrome (APS) type 2. He had a history of primary Addison disease and autoimmune hypothyroidism which were corroborated at autopsy. In addition a florid fibrinous pericarditis was associated with 287 g of turbid fluid in the pericardial sac. Although pericarditis with tamponade is a potential complication of APS, it has rarely if ever, been reported as a cause of sudden death. Lethal mechanisms may involve both compressive and restrictive effects.

19.
Medicina (Kaunas) ; 60(2)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38399513

RESUMO

Patient prognoses have been significantly enhanced by immune checkpoint inhibitors (ICIs), altering the standard of care in cancer treatment. These novel antibodies have become a mainstay of care for metastatic non-small-cell lung cancer (mNSCLC) patients. Several types of adverse events related to ICIs have been identified and documented as a result of the launch of these innovative medicines. We present here a 74-year-old female patient with a stage IV lung adenocarcinoma, treated with nivolumab plus ipilimumab, who developed perimyocarditis two weeks after receiving the third cycle of immune checkpoint inhibitor therapy. The patient was diagnosed using troponin levels, computed tomography (CT) angiography, and echocardiography. After hospitalization, her cardiac condition was successfully resolved with corticosteroids, colchicine, and symptomatic treatment. To the best of our knowledge, this is one of the rarest cases to be reported of perimyocarditis as a toxicity of immunotherapy in a patient treated for adenocarcinoma of the lung.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Nivolumabe/efeitos adversos , Inibidores de Checkpoint Imunológico , Ipilimumab/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico
20.
Circulation ; 145(1): 61-78, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34965168

RESUMO

Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Colchicina/uso terapêutico , Supressores da Gota/uso terapêutico , Colchicina/farmacologia , Supressores da Gota/farmacologia , Humanos
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