Use Of Immunomodulatory Therapies Research Articles

Use of bimekizumab to treat palmoplantar psoriasis in a patient receiving treatment for disseminated tuberculosis: A Case Report.

Due to their inherent role in immunomodulation, concerns have long existed about the use of biologic therapies in patients with active tuberculosis. Most guidelines currently list active tuberculosis as an absolute contraindication to the use of immunomodulatory therapies. Contrary to this, we present a case of a patient with active, disseminated tuberculosis, safely treated with the IL-17 inhibitor bimekizumab.

Impact of Non-steroidal Anti-inflammatory Drugs, Glucocorticoids, and Disease-Modifying Anti-Rheumatic Drugs on Cancer Response to Immune Checkpoint Inhibitor Therapy

Immune checkpoint inhibitor (ICI) therapy for advanced malignancies often leads to off-target adverse events. Rheumatic immune-related adverse events can often linger beyond the duration of ICI therapy and sometimes requires the use of immunomodulator therapy. A key question, therefore, is if the commonly used therapies affect cancer outcomes. In this review, the authors summarize the state of the data as it currently stands, taking into consideration the limitations of the various source studies. The most information is known about glucocorticoids, which appear to be harmful especially when used early and at high doses.

Biologically derived epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted swine hearts

There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.

Multi-System Inflammatory Syndrome in Neonates (MIS-N) - Clinical Profile and Outcomes - A Prospective Cohort Study

Aims: To analyze the clinical spectrum in Neonates with MIS-N based on the time of presentation and also to assess the use of immunomodulator therapy in MIS-N.
 Subjects and Methods: We studied 100 neonates delivered at BLDE (DU) Shri B M Patil Medical College Hospital admitted to Level III-A NICU from JULY 2020 to MAY 2021. 98 neonates had high titers of IG G antibodies and were negative for COVID Antigen. We categorized the cohorts into EARLY MIS-N (<72 hrs) and LATE MIS-N (>72 hrs).
 Results: 58 presented as EARLY MIS-N with Respiratory distress (RD) in 40 (70%), cardiac dysfunction 34 (60%), PPHN 12(20%), Fever 12(20%), seizures 12(20%), encephalopathy in 6(10%), sepsis-like features 6(10%), had elevated inflammatory markers like CRP (30%), D-Dimer (70%), Ferritin (30%), cardiac biomarkers like BNP (60%), LDH (30%) and ECHO showing LV dysfunction in 50%. LATE MIS-N presented mostly with fever 28(70%), sepsis-like features 24(60%), Respiratory Distress in 16(40%), cardiac dysfunction 12 (30%), hypoglycemia 4(10%), parotitis 4(10%), had significantly elevated inflammatory markers like CRP (70%), D-Dimer (50%), Ferritin (70%), cardiac biomarkers like BNP (40%), LDH (20%) and ECHO showing LV dysfunction in 20%, dilated coronaries in 20 %, PPHN in 10%. Oxygen and respiratory support requirements were higher in EARLY presenters and IVIG and steroid requirements were more in LATE presenters.
 Conclusion: We observed that maternal SARS-COV-2 antibodies transferred transplacentally and neonatal antibodies acquired after COVID-19 infection can cause MIS-N in neonates. Immunomodulator therapy is required in severe cases of MIS-N only.

Implantation Failure/ Reccurent miscarriages- TreatmentPOSTER 5Adalimumab for recurrent miscarriages and implantation failure

IntroductionRecurrent miscarriages and implantation failures are a frequent and still unresolved clinical situation, without any recommended therapies. In euploid implantation, the impact of dys-immune reaction such as allograft rejection could raise the use of immunomodulatory therapies. TNFa antagonists were recently reported in small case series and here we present a multicenter retrospective cohort study. Patients and MethodsPatients referred to our center for unexplained miscarriages and or implantation failure and which were refractory to previous various immunomodulatory therapies (HBPM, steroids, hydroxychloroquine) received adalimumab at 40 mg every 2 weeks a month before implantation and until 9 weeks of gestation. The primary objective was the number of pregnancies with alive baby and the safety was the second objective. ResultsA total of 42 patients with implantation failure and /or recurrent miscarriage (previous number of failures 9 [4-19], received adalimumab alone or associated with other immunomodulatory therapies. Among them, 27 were pregnant and were analyzed for the efficacy of adalimumab. Among these 27 patients, 16 women (59%) experienced a pregnancy with alive baby and 11 (41%) experienced recurrent miscarriages. The number of previous failures was not significantly different between the women with recurrent miscarriages and others (11 [4-19] vs 9 [4-15]. The number of associated immunosuppressive therapies was not significantly different between women with and without recurrent failures: low molecular weight heparin in 1 and 5 cases, steroids in 5 and 12 cases, hydroxychloroquine in 2 and 6 cases, respectively. There was no case with malformation or teratogenicity in both groups and no cases of maternal serious side effect. ConclusionIn a recurrent miscarriages and implantation failures women with particular high rates of failures, adalimumab seems to allow a good rate of alive babies with a good maternal and fetal tolerance.

Pulse Dose Methylprednisolone Therapy in a Cohort of Very Severe COVID-19 Patients in a Resource-limited Setting in Myanmar: A Case Series of 13 Patients

Aims: Coronavirus disease 2019 (COVID-19) has very high mortality in severe forms of disease, where immunopathology plays an important role. Use of immunomodulating therapies including 6 to 12 mg of dexamethasone is well established. Higher doses of corticosteroids were used with reported success in some settings. This study aims to explore the role of pulse dose methylprednisolone therapy in very severe COVID-19 patients in preventing the need for ICU care and death in resource-limited setting.
 Study Design: Retrospective case series study.
 Place and Duration of Study: Oak-ta-chat-thal-ta-pwint COVID-19 treatment center in Yangon, Myanmar between September 2021 to December 2021.
 Methodology: This study included 13 confirmed COVID-19 patients with severe to critical illness, who were treated with pulse dose methylprednisolone therapy. We reviewed the patients’ demographics, comorbidities, and disease severity before starting pulse dose methylprednisolone therapy and changes in oxygen requirement, chest X-ray scores, inflammatory markers, development of significant clinical events, and 28 days mortality after therapy.
 Results: Before pulse dose methylprednisolone therapy, all 13 patients had very severe disease (mean SPO2/FiO2 = 173 mmHg, mean SPO2 = 88.54%, mean CRP = 115 mg/L, mean ferritin = 1,295.5 ng/mL and mean Brixia Score = 6.54). They received 3-7 days (mean = 5.5 days) of pulse dose methylprednisolone. Ten patients (76%) survived in a setting with limited ICU care. High ferritin was a significant predictor of mortality. Improvement in oxygen requirement was noticeable after 1-11 days (mean = 5.6 days). Hyperglycemia was common and confirmed bacterial infection was found in 3 patients, but all patients received empirical antibiotics therapy.
 Conclusion: Pulse-dose methylprednisolone therapy may be an effective salvage therapy in a carefully selected subset of very severe COVID-19 patients. It might be a feasible alternative to other more expensive immunomodulating agents and organ support treatments in a resource-limited setting.

P-503 Immunological therapies in women undergoing assisted conception: a systematic review and meta-analysis

Abstract Study question What is the effectiveness and safety of immunological therapies in women undergoing assisted conception? Summary answer The evidence on the overall effectiveness and safety of immunomodulators was scarce and uncertain, although some drugs may lead to improved outcomes in selected women. What is known already Embryo implantation is a pre-requisite for pregnancy success. It requires a state of immune tolerance within the maternal endometrium permitting the attachment and subsequent invasion into the decidua of the semi-allogenic blastocyst. Mechanistic data suggesting that heightened immune responses may impair implantation have led to the widespread use of immunomodulatory therapies in clinical practice. These include drugs such as aspirin, heparin, corticosteroids, intralipid and intravenous immunoglobulin (IVIG). However, despite the common use of immunomodulatory drugs in women having in vitro fertilisation (IVF), there is no consensus on their effectiveness and safety, owing to a paucity of well-designed interventional studies. Study design, size, duration We searched MEDLINE, EMBASE, PubMed and CENTRAL until September 2022. We selected randomised controlled trials (RCTs) investigating immunological therapies in women undergoing IVF, including aspirin, heparin, corticosteroids, granulocyte-colony stimulating factor (G-CSF), intralipid, intravenous immunoglobulin (IVIG), tumour necrosis factor-alpha inhibitors and peripheral blood mononuclear cells (PBMCs), evaluated alone or in combination, versus no intervention, placebo or any other immunomodulator(s). The primary outcomes were the rates of live birth or ongoing pregnancy (LBR/OPR) and miscarriage per participant. Participants/materials, setting, methods Two reviewers independently selected studies and extracted data. We conducted pairwise meta-analyses according to participants’ phenotypes as reported by the trialists, including: good prognosis, previous implantation failure, autoimmunity, high inflammation, thin endometrium, and low ovarian reserve. Using the Cochrane-RoB-1 tool, we restricted our primary analyses to RCTs at low risk of selection and other biases. We presented effect estimates as risk ratio (RR) with 95% confidence interval (CI) and considered I2>50% as representing substantial heterogeneity. Main results and the role of chance Our searches identified 14,893 records. We included a total of 84 studies in the qualitative synthesis, of which 43 contributed to the meta-analyses, evaluating in total 7,301 participants and 12 treatment comparisons. The primary analysis showed that aspirin resulted in little to no difference in LBR (RR 0.97, 95% CI 0.94-1.23; n = 688 women; moderate-certainty evidence) and MR (RR 1.20, 95% CI 0.73-1.99; n = 988 women; low-certainty evidence) compared with placebo. The data did not identify a difference in LBR/OPR in women using subcutaneous heparin (RR 1.30, 95% CI 0.80-2.12; n = 150 women; very low-certainty evidence) or IVIG (RR 1.28, 95% CI 0.32-5.16; n = 51 women; very low-certainty evidence) versus placebo. For the remaining interventions, the primary analysis was uncertain of an effect or insufficient for quantitative synthesis. However, the sensitivity analysis including all studies, irrespective of risk of bias, showed that corticosteroids may improve LBR in women with thyroid autoimmunity (RR 2.33, 95% CI 1.04-5.25; n = 60 women; very low-certainty evidence); intrauterine G-CSF may improve LBR in women with a thin endometrium (RR 2.57, 95% CI 1.24-5.29; n = 304 women; very low-certainty evidence); and intrauterine PBMCs may improve LBR in women with previous implantation failure (RR 2.03, 95% CI 1.33-3.10; n = 312 women; very low-certainty evidence). Limitations, reasons for caution For most of the interventions under study, the evidence was of low or very-low certainty, owing to limitations in study design, imprecision, indirectness and inconsistency. Further, very few studies reported on adverse events, highlighting a worrying lack of data on the safety of immunological therapies for women undergoing assisted conception. Wider implications of the findings A scarcity of well-designed RCTs limits the evidence on immunomodulators in women undergoing IVF. However, we identified positive signals for some therapies in specific conditions (e.g. corticosteroids for thyroid autoimmunity, intrauterine G-CSF for thin endometrium, and PBMCs in women with previous implantation failure). This merits further investigation in high-quality trials. Trial registration number PROSPERO registration number CRD42021294031

COVID-19 outcomes in patients with psoriasis and psoriatic arthritis: A prospective cohort study

To the Editor: Few studies have directly investigated the effects of psoriatic disease and the use of immunomodulatory therapies on COVID-19 outcomes. Here, we report the COVID-19 outcomes of patients with psoriatic disease from a multidisciplinary, prospective, cohort study, namely, Web-based Assessment of Autoimmune, Immune-Mediated, and Rheumatic Patients during the COVID-19 Pandemic.1

Endometriosis and autoimmunity

Endometriosis is an inflammatory oestrogen-dependent chronic disease and is mainly expressed by pain and increased infertility. Several studies showed an increased prevalence of autoimmune systemic diseases and various autoantibodies in endometriosis. The association of these autoimmune markers and diseases could raise the fact that endometriosis is an authentic autoimmune or inflammatory disease and thus could argue for the use of immunomodulatory therapies. Usually, it is considered that the autoantibodies did not directly act in endometrium implants growth, and could be rather implicated in endometriosis-related infertility. The use of immunomodulatory strategies could be an important alternative or additional strategy to the use of hormones and surgery but need prospective well-designed trials.

Impact of the COVID-19 pandemic on uveitis patient care

BackgroundThe COVID-19 pandemic has significantly changed practice of medicine and patient care worldwide. The impact of the pandemic on patients with uveitis is unknown. We developed the COVID-19 Practice Patterns...

Merkel Cell Carcinoma: Evaluation of the Clinico-Pathological Characteristics, Treatment Strategies and Prognostic Factors in a Monocentric Retrospective Series (n=143)

BackgroundMerkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC.MethodsA retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens.Results143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor.ConclusionsAutoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. The relevance of a multidisciplinary approach to the patient with MCC is confirmed, with the aim of assessing the risks and benefits related to the use of immunomodulating therapy in the individual patient.

2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19

ObjectivesTo update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.MethodsAccording to the EULAR standardised operating procedures, a systematic literature review up to 14 July...

S2409 Histoplasmosis Presenting as New-Onset Ascites in a Crohn’s Disease Patient on Adalimumab

Introduction: Histoplasma capsulatum is the most frequently diagnosed endemic mycosis in the United States. The majority of cases are self-limiting but infections in immunocompromised patients may result in severe pulmonary or disseminated disease. We report a rare case of disseminated histoplasmosis presenting as new- onset ascites due to granulomatous hepatitis in a patient with perianal Crohn’s Disease on Adalimumab. Case description/methods: A 39-year-old white female with perianal but no intraluminal Crohn’s Disease currently on adalimumab and azathioprine presented with cyclical fevers and rapid onset ascites. In the preceding weeks she was noted to have uptrending alkaline phosphatase (600s) with isoenzymes consistent with liver etiology, GGT 162, mildly elevated AST (53) with normal ALT and total bilirubin. Further workup included positive anti-smooth muscle (1:160) and F-actin antibodies. Anti-nuclear and anti-mitochondrial antibodies both returned negative. MRCP demonstrated a circumferential 1.9 x 1.3cm peribiliary mass with segmental biliary duct dilation. Paracentesis with peritoneal fluid analysis demonstrated a low serum-ascites albumin gradient, lymphocytic predominance, and negative cytology, acid-fast stain, tuberculosis PCR, and adenosine deaminase. Transjugular liver biopsy revealed multiple non-necrotizing granulomas surrounded by chronic inflammation, consisting predominantly of lymphocytes and eosinophils. Grocott’s methenamine sliver stain was positive for narrow-based budding yeast, with morphology suggestive of Histoplasma species. Additionally, a quantitative serum Histoplasmosis antigen returned positive at 2.53 ng/ml. Following these findings, a course of IV Amphotericin B was started with eventual transition to PO Itraconazole for 1 year. Discussion: Histoplasmosis capsulatum is a dimorphic fungus that is endemic to the United States, specifically the Ohio and Mississippi River valleys. The majority of infections are subclinical, but when diagnosed are primarily in immunocompromised patients. A high degree of clinical suspicion is required to facilitate early treatment and prevent poor outcomes. Pulmonary histoplasmosis is by far the most common clinical presentation. Progressive disseminated disease is rare, but may involve the liver, skin, adrenals, gastrointestinal tract, central nervous system, and bone marrow. With the use of immunomodulating therapies on the rise, it is important to consider opportunistic infections in patients with atypical presentations.Figure 1.: A: H&E staining at 200x magnification of liver biopsy demonstrating non-caseating granulomas. B: Liver biopsy shows narrow-based budding yeast with positive silver stain suggestive of Histoplasma.

Immunomodulatory therapies for the treatment of SARS-CoV-2 infection: an update of the systematic literature review to inform EULAR points to consider

ObjectiveTo update the EULAR 2020 systematic literature review (SLR) on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection.MethodsAs part of a EULAR taskforce, a systematic literature search update was...

Differences in Inflammatory Marker Kinetics between the First and Second Wave of COVID-19 Patients Admitted to the ICU: A Retrospective, Single-Center Study.

Background: We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients. Methods: In a single-center retrospective observational study, ICU patients were enrolled during the first and second waves of the COVID-19 pandemic. Data were collected on patient demographics, comorbidities, laboratory results, management strategies, and complications during the ICU stay. The inflammatory response was evaluated using WBC count, CRP, PCT, and Ferritin levels on the day of admission until Day 28, respectively. Organ dysfunction was measured by the SOFA score. Results: 65 patients were admitted during the first and 113 patients during the second wave. WBC and ferritin levels were higher in the second wave. CRP and PCT showed markedly different longitudinal kinetics up until day 28 of ICU stay between the first and second wave, with significantly lower levels in the second wave. Steroid and immunomodulatory therapy use was significantly greater in the second wave. Mortality was similar in both waves. Conclusions: We found that there was a significantly reduced inflammatory response in the second wave, which is likely to be attributable to the more widespread use of immunomodulatory therapies.

Herpes zoster and Janus kinase inhibition in rheumatology and gastroenterology patients: managing risk and vaccination

Patients with chronic inflammatory diseases, such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis (UC), have an increased risk of herpes zoster (HZ) infection, compared with the general population. This risk is further increased by the use of immunomodulatory therapies, with a higher incidence of HZ reported in patients receiving Janus kinase (JAK) inhibitors, compared with those receiving other immunomodulatory or biological therapies. Tofacitinib is an oral JAK inhibitor for the treatment of RA, PsA and UC. In this narrative review, we discuss the effects of tofacitinib and other JAK inhibitors on HZ risk in patients with RA, PsA and UC, and strategies for risk management. We also discuss current UK guidelines for HZ vaccination in healthy individuals and patients with chronic inflammatory diseases, consider selected international guidelines, and review current HZ vaccination strategies.

Acute exudative polymorphous vitelliform maculopathy during pembrolizumab treatment for metastatic melanoma: a case report

BackgroundThe use of immunomodulating therapy to treat various cancers has been on the rise and these immune checkpoint inhibitors are known to cause ocular side effects. In this article a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) is reported which developed during a first line treatment with pembrolizumab.Case presentationA 54-year-old woman was referred because of blurry vision in both eyes with a yellow spot in the central visual field of the left eye. These symptoms started after four treatments with pembrolizumab (a monoclonal antibody against the programmed cell death receptor-1) for a metastatic recurrent vaginal mucosal melanoma. Her best corrected visual acuity was 10/10 in both eyes with a correction of + 2.00 bilaterally. There were no inflammatory findings in the anterior segment or the vitreous. Fundoscopy revealed an attenuation of the foveal reflex with subtle yellow-white subretinal macular deposits (vitelliform lesions) in both eyes. Fluorescein angiography did not show staining or leakage in the mid-phase, neither a late staining. Spectral-domain optical coherence tomography of the macula illustrated bilateral neurosensory retinal detachment with a thick, highly reflective band at the outer photoreceptor segment. En face structural OCT at the level of the photoreceptors showed focal areas of increased signal corresponding to hyperreflective vitelliform material. The treatment with pembrolizumab was ceased immediately. During the following visits we slowly saw an improvement of the neurosensory retinal detachment. After almost four months a total resolution of the subretinal fluid was visualized in both eyes without the use of additional treatment, though the vitelliform deposits persisted.ConclusionsThe development of AEPVM in melanoma patients could be triggered by treatment with Pembrolizumab. Pembrolizumab has the potential to disturb indirectly the retinal pigment epithelium homeostasis with accumulation of lipofuscin deposits and subretinal fluid, both signs of AEPVM.

Risk Factors for COVID-19 and Rheumatic Disease Flare in a US Cohort of Latino Patients.

ObjectiveLatino patients are overrepresented among cases of coronavirus disease 2019 (COVID‐19) and are at an increased risk of severe disease. Prevalence of COVID‐19 in Latinos with rheumatic diseases is poorly reported. This study was undertaken to characterize COVID‐19 clinical features and outcomes in Latino patients with rheumatic diseases.MethodsWe conducted a retrospective study of Latino patients with rheumatic diseases from an existing observational cohort in the Washington, DC area. Patients seen between April 1, 2020 and October 15, 2020 were analyzed in this study. We reviewed demographic characteristics, body mass index (BMI), comorbidities, and use of immunomodulatory therapies. An exploratory classification and regression tree (CART) analysis along with logistic regression analyses were performed to identify risk factors for COVID‐19 and rheumatic disease flare.ResultsOf 178 Latino patients with rheumatic diseases, 32 (18%) were identified as having COVID‐19, and the incidence rate of infection was found to be 3‐fold higher than in the general Latino population. No patients required intensive care unit–level care. A CART analysis and multivariable logistic regression analysis identified a BMI of >30.35 as a risk factor for COVID‐19 (odds ratio [OR] 3.37 [95% confidence interval (95% CI) 1.5–7.7]; P = 0.004). COVID‐19 positivity was a risk factor for rheumatic disease flare (OR 4.57 [95% CI 1.2–17.4]; P = 0.02).ConclusionOur findings indicate that Latino patients with rheumatic diseases have a higher rate of COVID‐19 compared with the general Latino population. Obesity is a risk factor for COVID‐19, and COVID‐19 is a risk factor for rheumatic disease flare. Latino patients with risk factors should be closely followed up, especially post–COVID‐19 in anticipation of disease flare.

Cytokine adsorption during ECMO for COVID-19-related ARDS

A syndrome of dysregulated systemic immune overactivation has been described in patients with COVID-19. Initially a cytokine storm paradigm1 was proposed, however subsequently, it has been shown that systemic concentrations of inflammatory cytokines, although elevated in patients with severe COVID-19, are not as high as has been reported in patients with other causes of the acute respiratory distress syndrome (ARDS).2 Despite this, data to support the use of immunomodulatory therapies, such as corticosteroids3 and interleukin-6 (IL-6) receptor antagonists,4 in patients critically ill with COVID-19 have emerged.

Post-ischemic Myocardial Inflammatory Response: A Complex and Dynamic Process Susceptible to Immunomodulatory Therapies.

Following acute occlusion of a coronary artery causing myocardial ischemia and implementing first-line treatment involving rapid reperfusion, a dynamic and balanced inflammatory response is initiated to repair and remove damaged cells. Paradoxically, restoration of myocardial blood flow exacerbates cell damage as a result of myocardial ischemia–reperfusion (MI-R) injury, which eventually provokes accelerated apoptosis. In the end, the infarct size still corresponds to the subsequent risk of developing heart failure. Therefore, true understanding of the mechanisms regarding MI-R injury, and its contribution to cell damage and cell death, are of the utmost importance in the search for successful therapeutic interventions to finally prevent the onset of heart failure. This review focuses on the role of innate immunity, chemokines, cytokines, and inflammatory cells in all three overlapping phases following experimental, mainly murine, MI-R injury known as the inflammatory, reparative, and maturation phase. It provides a complete state-of-the-art overview including most current research of all post-ischemic processes and phases and additionally summarizes the use of immunomodulatory therapies translated into clinical practice.