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Scientific Reports May 2024In our study, we aimed to evaluate the effect of high-dose intravenous anakinra treatment on the development of thrombotic events in severe and critical COVID-19... (Observational Study)
Observational Study
In our study, we aimed to evaluate the effect of high-dose intravenous anakinra treatment on the development of thrombotic events in severe and critical COVID-19 patients. This retrospective observational study was conducted at a tertiary referral center in Aksaray, Turkey. The study population consisted of two groups as follows; the patients receiving high-dose intravenous anakinra (anakinra group) added to background therapy and the patients treated with standard of care (SoC) as a historical control group. Age, gender, mcHIS scores, and comorbidities such as diabetes mellitus, hypertension, and coronary heart disease of the patients were determined as the variables to be matched. We included 114 patients in SoC and 139 patients in the Anakinra group in the study. Development of any thromboembolic event (5% vs 12.3%, p = 0.038; OR 4.3) and PTE (2.9% vs 9.6%, p = 0.023; OR 5.1) were lower in the Anakinra group than SoC. No patient experienced cerebrovascular accident and/or clinically evident deep venous thrombosis both in two arms. After 1:1 PS matching, 88 patients in SoC and 88 patients in the Anakinra group were matched and included in the analysis. In survival analysis, the development of any thromboembolic event, pulmonary thromboembolism, and acute coronary syndrome (ACS) were higher in SoC compared to Anakinra. Survival rate was also lower in patients with SoC arm than Anakinra in patients who had any thromboembolic event as well as ACS. In our study, the development of thrombosis was associated with hyperinflammation in patients with severe and critical COVID-19. Intravenous high-dose anakinra treatment decreases both venous and arterial events in patients with severe and critical COVID-19.
Topics: Humans; Male; Interleukin 1 Receptor Antagonist Protein; Female; Acute Coronary Syndrome; Middle Aged; Retrospective Studies; COVID-19; Venous Thrombosis; Propensity Score; Aged; COVID-19 Drug Treatment; SARS-CoV-2; Administration, Intravenous; Turkey
PubMed: 38811592
DOI: 10.1038/s41598-024-62079-y -
AJP Reports Apr 2024This study aims to elucidate the clinical manifestations, diagnostic challenges, and management strategies of adult-onset Still's disease (AOSD) during pregnancy,... (Review)
Review
This study aims to elucidate the clinical manifestations, diagnostic challenges, and management strategies of adult-onset Still's disease (AOSD) during pregnancy, leveraging a case series overview and a detailed case report from our center. A comprehensive review of 21 published case reports on AOSD diagnosed during pregnancy was conducted, alongside a detailed case report of a patient diagnosed and managed at our center. This study emphasizes the importance of recognizing AOSD in pregnant patients, outlines the therapeutic challenges encountered, and discusses the potential complications arising from the disease and its treatment. The onset of AOSD during pregnancy predominantly occurs in the first or second trimester, with a polycyclic disease course observed in most cases. Management primarily involves corticosteroids and immunosuppressive medications, balancing the disease control with potential pregnancy complications. The case report highlights the complex interplay between AOSD, hemophagocytic lymphohistiocytosis, and pregnancy, illustrating a multidisciplinary approach to management that ensured favorable maternal and fetal outcomes despite the significant challenges. AOSD presents unique diagnostic and therapeutic challenges during pregnancy, requiring careful consideration of maternal and fetal health. Early diagnosis, a multidisciplinary approach to care, and judicious use of immunosuppressive therapy are critical for managing AOSD flares and associated complications. Further research is necessary to optimize care for this rare condition in the context of pregnancy.
PubMed: 38799549
DOI: 10.1055/a-2318-0305 -
Journal of Cardiovascular Development... May 2024Kawasaki disease (KD) is a type of vasculitis in which giant coronary artery aneurysms (CAAs) can occur. There are no specific guidelines for managing giant CAAs that...
BACKGROUND
Kawasaki disease (KD) is a type of vasculitis in which giant coronary artery aneurysms (CAAs) can occur. There are no specific guidelines for managing giant CAAs that develop quickly and are at risk of rupture. Regarding cardiovascular drugs, only beta-blockers are formally recommended in the acute phase of KD.
CASE PRESENTATION
A 6-month-old male patient with multiresistant Kawasaki disease and giant CAAs that continued to enlarge after controlling systemic inflammation was examined. The patient required three doses of intravenous immunoglobulin, methylprednisolone pulses, and anakinra and infliximab to normalize systemic inflammation. Due to the rapid increment of aneurysms' dimensions and the risk of rupture, we introduced anticoagulant therapy and propranolol plus captopril, and titration doses were introduced according to a tolerated decrease in heart rate and arterial pressure. CAAs increment stabilized and slowly reduced their dimensions.
CONCLUSIONS
The authors describe an atypical case of multiresistant KD with giant rapidly increasing CAAs even after controlling systemic inflammation. The introduction of a beta-blocker and an angiotensin-converting enzyme (ACE) inhibitor was demonstrated to be useful for stabilizing giant CAAs growth and reducing the potential risk of rupture.
PubMed: 38786971
DOI: 10.3390/jcdd11050149 -
Frontiers in Immunology 2024Corticosteroid therapy is the mainstay of immune effector cell-associated neurotoxicity syndrome (ICANS) management, although its use has been associated with worse...
Corticosteroid therapy is the mainstay of immune effector cell-associated neurotoxicity syndrome (ICANS) management, although its use has been associated with worse overall survival (OS) and progression-free survival (PFS) after chimeric antigen receptor T-cell (CAR-T cell) therapy. Many options are being investigated for prophylaxis and management. Accumulating evidence supports the use of intrathecal (IT) chemotherapy for the management of high-grade ICANS. Here, we describe a case of a patient with stage IV Primary mediastinal B-cell lymphoma (PMBCL) successfully treated with IT methotrexate, cytarabine, and dexamethasone as first-line therapy for CD19 CAR-T cell-associated grade IV ICANS. The stable and rapid resolution of ICANS to grade 0 allowed us to discontinue systemic corticosteroid use, avoiding CAR-T cells ablation and ensuring preservation of CAR-T cell function. The described patient achieved a complete radiologic and clinical response to CD19 CAR-T cell therapy and remains disease-free after 9 months. This case demonstrates a promising example of how IT chemotherapy could be used as first-line treatment for the management of high-grade ICANS.
Topics: Humans; Dexamethasone; Injections, Spinal; Methotrexate; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Male; Neurotoxicity Syndromes; Middle Aged; Treatment Outcome; Immunotherapy, Adoptive; Lymphoma, B-Cell; Female
PubMed: 38765003
DOI: 10.3389/fimmu.2024.1380451 -
Mediterranean Journal of Rheumatology Mar 2024Calcium pyrophosphate deposition (CPPD) arthritis is the second most common type of crystal-induced arthritis after gout. Acute flares are commonly treated with...
Calcium pyrophosphate deposition (CPPD) arthritis is the second most common type of crystal-induced arthritis after gout. Acute flares are commonly treated with non-steroidal anti-inflammatory drugs, intra-articular or short-term systemic glucocorticoids or colchicine. However, since there is no pharmacological treatment to reduce CPPD crystal burden, relapsing or chronic CPPD arthritis may be challenging to treat, particularly in patients with end-stage renal disease who are at risk for toxicity of the above medications. Since IL-1β appears to be driving CPPD arthritis, we treated two patients with chronic CPPD arthritis and end-stage renal disease on haemodialysis with the IL-1β receptor antagonist anakinra. In both patients, arthritis resolved quickly, while continuation of anakinra maintained remission and allowed complete glucocorticoid withdrawal. Therefore, anakinra may be a safe and effective option both for short and long-term treatment of CPPD arthritis in patients on chronic renal replacement therapy.
PubMed: 38756932
DOI: 10.31138/mjr.261123.afr -
Frontiers in Pediatrics 2024Chronic infantile neurological cutaneous articular (CINCA) syndrome is an autoinflammatory disease encompassed in the group of cryopyrin-associated periodic syndromes...
Case Report: Efficacy, safety, and favorable long-term outcome of early treatment with IL-1 inhibitors in a patient with chronic infantile neurological cutaneous articular (CINCA) syndrome caused by NLRP3 mosaicism.
Chronic infantile neurological cutaneous articular (CINCA) syndrome is an autoinflammatory disease encompassed in the group of cryopyrin-associated periodic syndromes (CAPS). Patients suffering from CINCA have an elevated risk of developing chronic sequelae, including deforming arthropathy, chronic meningitis, neurodevelopmental delay, and neurosensorial hearing loss. The diagnosis of CINCA presents several difficulties, as the clinical phenotype could be difficult to recognize, and almost half of the patients have negative genetic testing. In this paper, we describe the case of a patient presenting with the typical phenotype of neonatal-onset CINCA who resulted negative for NLRP3 mutations. Based on the clinical judgment, the patient underwent treatment with anti-interleukin-1 (IL-1) agents (anakinra and, later, canakinumab) resulting in a complete clinical and laboratory response that allowed confirmation of the diagnosis. Additional genetic investigations performed after the introduction of anti-IL-1 therapy revealed a pathogenic mosaicism in the NLRP3 gene. After a 12-year follow-up, the patient has not experienced chronic complications. Although genetics is rapidly progressing, this case highlights the importance of early diagnosis of CINCA patients when the clinical and laboratory picture is highly suggestive in order to start the appropriate anti-cytokine treatment even in the absence of a genetic confirmation.
PubMed: 38720945
DOI: 10.3389/fped.2024.1379616 -
Nature Communications May 2024The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and...
The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.
Topics: Lyme Disease; Humans; Quantitative Trait Loci; Cytokines; Male; Female; Interleukin-10; Adult; Genome-Wide Association Study; Middle Aged; Interleukin 1 Receptor Antagonist Protein; Borrelia burgdorferi; Anti-Bacterial Agents; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Aged
PubMed: 38714679
DOI: 10.1038/s41467-024-47505-z -
The Journal of Allergy and Clinical... Aug 2024A patient presented with overlapping clinical and laboratory features of 2 rare autoinflammatory diseases, NLRP1-associated autoinflammation with arthritis and...
A patient presented with overlapping clinical and laboratory features of 2 rare autoinflammatory diseases, NLRP1-associated autoinflammation with arthritis and dyskeratosis and familial multiple self-healing palmoplantar carcinoma. Her severe inflammatory attack was treated with the IL-1 receptor-α inhibitor anakinra along with the Janus kinase inhibitor ruxolitinib. Three years into the treatment, the patient's inflammatory symptoms are completely in remission.
PubMed: 38706460
DOI: 10.1016/j.jacig.2024.100251 -
Italian Journal of Pediatrics May 2024Multisystem inflammatory syndrome in children (MIS-C) shows a significant overlap of symptoms with other hyper-inflammatory diseases such as Kawasaki disease (KD), but...
Cardiovascular involvement in children with COVID-19 temporally related multisystem inflammatory syndrome (MIS-C): can cardiac magnetic resonance arrive to the heart of the problem?
BACKGROUND
Multisystem inflammatory syndrome in children (MIS-C) shows a significant overlap of symptoms with other hyper-inflammatory diseases such as Kawasaki disease (KD), but the real difference of the two conditions is still matter of debate. Coronary artery lesions (CAL) are the most relevant complication in KD. Nonetheless, CAL, myocarditis, pericarditis, arrhythmia are the main cardiovascular complications in MIS-C. A close clinical assessment is mandatory, both at the diagnosis and during the follow-up, by ECG and echocardiography. Cardiac magnetic resonance (MRI) adds important data to ultrasound findings. However, cardiac MRI studies in MIS-C are limited to a small number of cohorts.
METHODS
We enrolled 20 children (age:1-16 years; 11 F; 9 M) with cardiac involvement secondary to MIS-C, all evaluated by cardiac MRI.
RESULTS
8 children showed pathological cardiac MRI: 2 showed pericardial effusion; 2 showed myocardial oedema; 1 showed aortic insufficiency; 3 showed delayed enhancement (one for acute myocarditis with oedema; 2 for myocardial fibrosis). Delayed enhancement was reduced significantly 5.6-9 months after the first MRI evaluation. 25% of patients with pathological MRI had CAL associated with valvular insufficiency of 2 valves. 17% of patients with normal MRI had CAL, associated with valvular insufficiency of 1 valve in 1 patient. The correlations between haematological, clinical, cardiologic parameters, treatment, did not reach the statistical significance. 4 patients were treated with anakinra. Among those, 2 patients showed a normal cardiac MRI. Cardiac lesions resolved in all the patients during the follow-up. Some patients with pathological cardiac MRI could not underwent a control with MRI, for the low compliance. However, echocardiography and ECG, documented the resolution of the pathological data in these cases.
CONCLUSIONS
A higher risk of CAL was documented in patients with an association of other cardiac lesions. Cardiac MRI is difficult to perform routinely; however, it is useful for evaluating the acute myocardial damage and the outcome of patients with MIS-C.
Topics: Humans; Systemic Inflammatory Response Syndrome; COVID-19; Child; Male; Female; Adolescent; Child, Preschool; Infant; Magnetic Resonance Imaging; Echocardiography; SARS-CoV-2; Magnetic Resonance Imaging, Cine
PubMed: 38702753
DOI: 10.1186/s13052-024-01658-1 -
Medicine May 2024The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab,... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis.
METHODS
Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value.
RESULTS
We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously.
CONCLUSIONS
Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.
Topics: Arthritis, Juvenile; Humans; Network Meta-Analysis; Antirheumatic Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Adalimumab; Antibodies, Monoclonal, Humanized; Interleukin 1 Receptor Antagonist Protein; Bayes Theorem
PubMed: 38701278
DOI: 10.1097/MD.0000000000038002