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Frontiers in Immunology 2024The objective of this study was to investigate the risk of cardiovascular toxicities related to PD-1/PD-L1 inhibitors in solid tumors. (Meta-Analysis)
Meta-Analysis
PURPOSE
The objective of this study was to investigate the risk of cardiovascular toxicities related to PD-1/PD-L1 inhibitors in solid tumors.
METHODS
A literature search was performed following the participants, interventions, comparisons, outcomes, and study design (PICOS) principles, and the study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analysis was conducted using Review Manager version 5.4.
RESULTS
This meta-analysis included 69 randomized controlled trials (RCTs) divided into five groups based on the treatment regimens: PD-1/PD-L1 + chemotherapy versus chemotherapy, PD-1/PD-L1 versus chemotherapy, PD-1/PD-L1 versus placebo, PD-1/PD-L1 + CTLA-4 versus PD-1/PD-L1 and PD-1/PD-L1 + CTLA-4 versus chemotherapy. Compared to chemotherapy treatment alone, PD-1/PD-L1 +chemotherapy significantly increased the risk of hypertension [all-grade (OR = 1.27, 95% CI [1.05, 1.53], p = 0.01); grade 3-5 (OR = 1.36, 95% CI [1.04, 1.79], p = 0.03)], hypotension [all-grade (OR = 2.03, 95% CI [1.19, 3.45], p = 0.009); grade 3-5 (OR = 3.60, 95% CI [1.22, 10.60], p = 0.02)], arrhythmia [all-grade (OR = 1.53, 95% CI [1.02, 2.30], p = 0.04); grade 3-5 (OR = 2.91, 95% CI [1.33, 6.39], p = 0.008)] and myocarditis [all-grade (OR = 2.42, 95% CI [1.06, 5.54], p = 0.04)]. The risk of all-grade hypotension (OR = 2.87, 95% CI [1.26, 6.55], p = 0.01) and all-grade arrhythmia (OR = 2.03, 95% CI [1.13, 3.64], p = 0.02) significantly increased when treated with PD-1/PD-L1 inhibitors compared to the placebo. The risks of cardiovascular toxicities are significantly higher with PD-1+CTLA-4 compared to PD-1 alone (OR = 2.02, 95% CI [1.12, 3.66], p = 0.02).
CONCLUSION
PD-1/PD-L1 inhibitor leads to an increased risk of cardiovascular toxicities, especially hypertension, hypotension, arrhythmia, and myocarditis.
Topics: Humans; Arrhythmias, Cardiac; B7-H1 Antigen; CTLA-4 Antigen; Hypertension; Hypotension; Immune Checkpoint Inhibitors; Myocarditis; Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 38318172
DOI: 10.3389/fimmu.2024.1255825 -
International Journal of Molecular... Jan 2024The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the...
The number of children suffering from cardiovascular diseases (CVDs) is rising globally. Therefore, there is an urgent need to acquire a better understanding of the genetic factors and molecular mechanisms related to the pathogenesis of CVDs in order to develop new prevention and treatment strategies for the future. MicroRNAs (miRNAs) constitute a class of small non-coding RNA fragments that range from 17 to 25 nucleotides in length and play an essential role in regulating gene expression, controlling an abundance of biological aspects of cell life, such as proliferation, differentiation, and apoptosis, thus affecting immune response, stem cell growth, ageing and haematopoiesis. In recent years, the concept of miRNAs as diagnostic markers allowing discrimination between healthy individuals and those affected by CVDs entered the purview of academic debate. In this review, we aimed to systematise available information regarding miRNAs associated with arrhythmias, cardiomyopathies, myocarditis and congenital heart diseases in children. We focused on the targeted genes and metabolic pathways influenced by those particular miRNAs, and finally, tried to determine the future of miRNAs as novel biomarkers of CVD.
Topics: Child; Humans; Aging; Apoptosis; Cardiovascular Diseases; Cell Cycle; MicroRNAs
PubMed: 38256030
DOI: 10.3390/ijms25020956 -
Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409 -
Radiology Case Reports Mar 2024We present a case involving a young individual who developed acute myocarditis on the fourth day following administration of a COVID-19 mRNA vaccine. The patient's...
We present a case involving a young individual who developed acute myocarditis on the fourth day following administration of a COVID-19 mRNA vaccine. The patient's condition was managed conservatively, resulting in a favorable outcome. This paper extensively discusses the pathogenesis, clinical manifestations, imaging characteristics of COVID-19 mRNA vaccine-related myocarditis and includes a comprehensive review of pertinent literature. Additionally, a systematic review of COVID-19 mRNA vaccine-related myocarditis, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) principles, is presented. Healthcare professionals should maintain a clinical suspicion for COVID-19 mRNA vaccine-related myocarditis when encountering patients with confirmed myocarditis who have received recent COVID-19 mRNA vaccination, after ruling out other potential causes. The diagnosis of acute myocarditis primarily relies on adherence to the Lake Louise Criteria (LLC) for cardiac magnetic resonance (CMR). Nevertheless, specific CMR features or distinctive patterns indicative of COVID-19 mRNA vaccine-related myocarditis are currently undefined. Among patients with vaccine-related myocarditis, common CMR findings encompass subepicardial late gadolinium enhancement and T2-based myocardial edema, although these findings lack specificity and may resemble other medical conditions. Supportive care involving a short-term regimen of NSAIDs, colchicine, and steroids represents the cornerstone of treatment for this variant of myocarditis, which tends to be self-limiting with favorable short-term prognoses. Timely diagnosis is paramount for optimizing patient care.
PubMed: 38226053
DOI: 10.1016/j.radcr.2023.11.070 -
Multidisciplinary Respiratory Medicine Jan 2023In the beginning of the SARS-CoV-2 pandemic, health care professionals dealing with COVID-19 had to rely exclusively on general supportive measures since specific...
BACKGROUND
In the beginning of the SARS-CoV-2 pandemic, health care professionals dealing with COVID-19 had to rely exclusively on general supportive measures since specific treatments were unknown. The subsequent waves could be faced with new diagnostic and therapeutic tools (., anti-viral medications and vaccines). We performed a meta-analysis and systematic review to compare clinical endpoints between the first and subsequent waves.
METHODS
Three databases were assessed. The primary outcome was in-hospital mortality. The secondary outcomes were intensive care unit (ICU) mortality, ICU length of stay (LOS), acute renal failure, extracorporeal membrane oxygenation (ECMO) implantation, mechanical ventilation time, hospital LOS, systemic thromboembolism, myocarditis and ventilator associated pneumonia.
RESULTS
A total of 25 studies with 126,153 patients were included. There was no significant difference for the primary endpoint (OR=0.94, 95% CI 0.83-1.07, p=0.35). The first wave group presented higher rates of ICU LOS (SMD= 0.23, 95% CI 0.11-0.35, p<0.01), acute renal failure (OR=1.71, 95% CI 1.36-2.15, p<0.01) and ECMO implantation (OR=1.64, 95% CI 1.06-2.52, p=0.03). The other endpoints did not show significant differences.
CONCLUSIONS
The analysis suggests that the first wave group, when compared with the subsequent waves group, presented higher rates of ICU LOS, acute renal failure and ECMO implantation, without significant difference in in-hospital or ICU mortality, mechanical ventilation time, hospital LOS, systemic thromboembolism, myocarditis or ventilator- associated pneumonia.
PubMed: 38155706
DOI: 10.4081/mrm.2023.933 -
International Journal of Cardiology.... Dec 2023Myocarditis secondary to Coronavirus Disease 2019 (COVID-19) vaccination has been reported in the literature.
BACKGROUND
Myocarditis secondary to Coronavirus Disease 2019 (COVID-19) vaccination has been reported in the literature.
OBJECTIVE
This study aimed to characterize the reported cases of myocarditis after COVID-19 vaccination based on age, gender, doses, and vaccine type from published literature and the EudraVigilance database.
METHODS
We performed an analysis in the EudraVigilance database (until December 18, 2021) and a systematic review of published literature for reported cases of suspected myocarditis and pericarditis (until 30th June 2022) after the COVID-19 vaccination.
RESULTS
EudraVigilance database analysis revealed 16,514 reported cases of myocarditis or pericarditis due to the vaccination with COVID-19 vaccines. The cases of myo- or pericarditis were reported predominantly in the age group of 18-64 (n = 12,214), and in males with a male-to-female (M: F) ratio of 1.7:1. The mortality among myocarditis patients was low, with 128 deaths (2 cases per 10.000.000 administered doses) being reported. For the systematic review, 72 studies with 1026 cases of myocarditis due to the vaccination with COVID-19 vaccines were included. The analysis of published cases has revealed that the male gender was primarily affected with myocarditis post-COVID-vaccination. The median (IQR) age of the myocarditis cases was 24.6 [19.5-34.6] years, according to the systematic review of the literature. Myocarditis cases were most frequently published after the vaccination with m-RNA vaccines and after the second vaccination dose. The overall mortality of published cases was low (n = 5).
CONCLUSION
Myocarditis is a rare serious adverse event associated with a COVID-19 vaccination. With early recognition and management, the prognosis of COVID-19 vaccine-induced myocarditis is favorable.
PubMed: 38143781
DOI: 10.1016/j.ijcha.2023.101280 -
Annals of Medicine and Surgery (2012) Dec 2023Coronavirus disease 2019 (COVID-19) can present with significant cardiac dysfunction, including cardiogenic shock. Mechanical circulatory support with an Impella device... (Review)
Review
BACKGROUND
Coronavirus disease 2019 (COVID-19) can present with significant cardiac dysfunction, including cardiogenic shock. Mechanical circulatory support with an Impella device may be utilized in these patients to support and offload native right ventricle (RV) and left ventricle (LV) functions. This systematic review aims to describe clinical indications, management, laboratory data, and outcomes in patients with severe cardiogenic shock from COVID-19 treated with an Impella device.
METHODS
A PRISMA-directed systematic review was performed and prospectively registered in PROSPERO. The databases accessed included PubMed/MEDLINE, Scopus, and ScienceDirect. Quality and risk of bias assessments were completed using the Joanna Briggs Institute (JBI) checklist for case reports.
RESULTS
A total of 16 records were included in the qualitative synthesis; 8/16 (50%) of the patients were men. The average age was 39 years (SD: 14.7). The biventricular Impella (BiPella) approach was recorded in 3/16 (18.75%) patients. A total of 4/16 (25%) individuals required renal replacement therapy (RRT). Single-device usage was observed in three cases: 2/16 Impella CP (12.5%) and 1/16 Impella RP (6.25%). Treatment of COVID-19 myocarditis included a wide range of antivirals and immunomodulators; 8/16 (50%) cases needed ECMO (extracorporeal membrane oxygenation) support. Overall, only 2/16 (11.7%) individuals died.
CONCLUSIONS
Sixteen reported individuals have received an Impella implanted with a mortality rate of 11.7%. Concurrent use of RRT and ECMO implantation was often observed. Overall, the Impella device is an effective and safe strategy in the management of COVID-19-related cardiogenic shock. Future studies should include long-term results.
PubMed: 38098597
DOI: 10.1097/MS9.0000000000001425 -
Revista Da Sociedade Brasileira de... 2023The increase in inflammatory markers associated with persistent chronic fibrosing myocarditis, a characteristic of chronic Chagas disease, can result in a reduction in...
The increase in inflammatory markers associated with persistent chronic fibrosing myocarditis, a characteristic of chronic Chagas disease, can result in a reduction in inspiratory muscle strength (IMS) in Chagas cardiomyopathy (CC). However, literature in this field is still scarce. This review aimed to map and summarize the evidence regarding IMS in patients with CC. The inclusion criteria included reports with adult participants with a CC diagnosis, with or without heart failure (HF). The core concept examined was the maximum inspiratory pressure evaluated in the untrained and trained groups in the pre-training period. The context was open, including but not limited to hospitals and health centers. Two authors independently identified eligible studies and extracted the data. Descriptive synthesis was used as the primary strategy for analyzing the results. Nine studies (five clinical trials, three cross-sectional, and one cohort) were included. The CC classification differed among the studies, with no mention of HF in five and no CC staging specification in six. IMS was assessed using a manovacuometer, and only six studies analyzed and interpreted the data concerning the predicted values. The CC population with HF appeared to have impaired IMS. All studies involved only Brazilian volunteers. In conclusion, randomized clinical trials evaluating IMS and the effects of inspiratory muscle training need to be conducted to better understand the prevalence and risk of inspiratory muscle weakness in the CC population, as well as the effects of training. Such studies should be conducted at different stages of CC in different populations and countries.
Topics: Adult; Humans; Chagas Cardiomyopathy; Cross-Sectional Studies; Muscle Strength; Chronic Disease; Brazil; Respiratory Muscles
PubMed: 38088665
DOI: 10.1590/0037-8682-0389-2023 -
Neurology(R) Neuroimmunology &... Jan 2024We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE).
BACKGROUND AND OBJECTIVES
We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE).
METHODS
Systematic review of English language publications in PubMed and reference lists between January 1, 2020, and June 30, 2023, in accordance with PRISMA guidelines. Patients with SARS-CoV-2 infection who fulfilled diagnostic criteria for sporadic and genetic ANE were included.
RESULTS
From 899 articles, 20 cases (17 single case reports and 3 additional cases) were curated for review (50% female; 8 were children). Associated COVID-19 illnesses were febrile upper respiratory tract infections in children while adults had pneumonia (45.6%) and myocarditis (8.2%). Children had early neurologic deterioration (median day 2 in children vs day 4 in adults), seizures (5 (62.5%) children vs 3 of 9 (33.3%) adults), and motor abnormalities (6 of 7 (85.7%) children vs 3 of 7 (42.9%) adults). Eight of 12 (66.7%) adults and 4 (50.0%) children had high-risk ANE scores. Five (62.5%) children and 12 (66.7%) adults had brain lesions bilaterally and symmetrically in the putamina, external capsules, insula cortex, or medial temporal lobes, in addition to typical thalamic lesions of ANE. Hypotension was only seen in adults (30%). Hematologic derangements were common: lymphopenia (66.7%), coagulopathy (60.0%), or elevated D-dimers (100%), C-reactive protein (91.7%), and ferritin (62.5%). A pathogenic heterozygous c/.1754 C>T variant in was present in 2 children: one known to have this before SARS-CoV-2 infection, and a patient tested because the SARS-CoV-2 infection was the second encephalopathic illness. Three other children with no prior encephalopathy or family history of encephalopathy were negative for this variant. Fifteen (75%) received immunotherapy (with IV methylprednisolone, immunoglobulins, tocilizumab, or plasma exchange): 6 (40.0%) with monotherapy and 9 (60.0%) had combination therapy. Deaths were in 8 of 17 with data (47.1%): a 2-month-old male infant and 7 adults (87.5%) of median age 56 years (33-70 years), 4 of whom did not receive immunotherapy.
DISCUSSION
Children and adults with SARS-CoV-2 ANE have similar clinical features and neuroimaging characteristics. Mortality is high, predominantly in patients not receiving immunotherapy and at the extremes of age.
Topics: Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Brain Diseases; COVID-19; Methylprednisolone; SARS-CoV-2; Seizures; Aged
PubMed: 38086061
DOI: 10.1212/NXI.0000000000200186 -
Journal of the American Heart... Dec 2023Veno-arterial extracorporeal membrane oxygenation serves as a crucial mechanical circulatory support for pediatric patients with severe heart diseases, but the mortality... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Veno-arterial extracorporeal membrane oxygenation serves as a crucial mechanical circulatory support for pediatric patients with severe heart diseases, but the mortality rate remains high. The objective of this study was to assess the short-term mortality in these patients.
METHODS AND RESULTS
We systematically searched PubMed, Embase, and Cochrane Library for observational studies that evaluated the short-term mortality of pediatric patients undergoing veno-arterial extracorporeal membrane oxygenation. To estimate short-term mortality, we used random-effects meta-analysis. Furthermore, we conducted meta-regression and binomial regression analyses to investigate the risk factors associated with the outcome of interest. We systematically reviewed 28 eligible references encompassing a total of 1736 patients. The pooled analysis demonstrated a short-term mortality (defined as in-hospital or 30-day mortality) of 45.6% (95% CI, 38.7%-52.4%). We found a significant difference (<0.001) in mortality rates between acute fulminant myocarditis and congenital heart disease, with acute fulminant myocarditis exhibiting a lower mortality rate. Our findings revealed a negative correlation between older age and weight and short-term mortality in patients undergoing veno-arterial extracorporeal membrane oxygenation. Male sex, bleeding, renal damage, and central cannulation were associated with an increased risk of short-term mortality.
CONCLUSIONS
The short-term mortality among pediatric patients undergoing veno-arterial extracorporeal membrane oxygenation for severe heart diseases was 45.6%. Patients with acute fulminant myocarditis exhibited more favorable survival rates compared with those with congenital heart disease. Several risk factors, including male sex, bleeding, renal damage, and central cannulation contributed to an increased risk of short-term mortality. Conversely, older age and greater weight appeared to be protective factors.
Topics: Humans; Male; Child; Extracorporeal Membrane Oxygenation; Myocarditis; Heart Defects, Congenital; Hemorrhage; Survival Rate; Retrospective Studies
PubMed: 38063152
DOI: 10.1161/JAHA.123.029571