scholarly journals Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics

2020 ◽  
Vol 222 (9) ◽  
pp. 1444-1451 ◽  
Author(s):  
Wenjun Wang ◽  
Xiaoqing Liu ◽  
Sipei Wu ◽  
Sibei Chen ◽  
Yimin Li ◽  
...  
Keyword(s):  
Critically Ill ◽  
Virus Disease ◽  
Pulmonary Inflammation ◽  
Case Series ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Disease Characteristics ◽  
Medical University ◽  
Termination Date

Abstract Corona virus disease 2019 (COVID-19) patients with severe immune abnormalities are at risk of cytokine release syndrome (CRS). The definition, prevention, and treatment of symptoms of CRS in critically ill patients with COVID-19 are important problems. We report a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome from The First Affiliated Hospital of Guangzhou Medical University in China from 26 January 2020 to 18 February 2020. The termination date of follow-up was 19 February 2020. Eight patients were determined to have characteristics of CRS, including pulmonary inflammation, fever, and dysfunction of nonpulmonary organs. An increase in interleukin-6 in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.

scholarly journals The definition and risks of Cytokine Release Syndrome-Like in 11 COVID-19-Infected Pneumonia critically ill patients: Disease Characteristics and Retrospective Analysis

2020 ◽  
Author(s):  
Wang Wenjun ◽  
Liu Xiaoqing ◽  
Wu Sipei ◽  
Lie Puyi ◽  
Huang Liyan ◽  
...  
Keyword(s):  
Nk Cells ◽  
Retrospective Analysis ◽  
Critically Ill ◽  
Immune Cells ◽  
Critically Ill Patients ◽  
Peripheral Blood ◽  
Pulmonary Inflammation ◽  
Clinical Treatment ◽  
Cytokine Release ◽  
Cytokine Release Syndrome

IMPORTANCECOVID-19-infected pneumonia patients with severe immune abnormalities and risk of cytokine release syndrome. The definition, prevention, and treatment of COVID-19-infected pneumonia in critically ill patients with cytokine release syndrome symptoms is an important problem.OBJECTIVETo define the cytokine release syndrome-like (CRSL) in COVID-19-infected pneumonia in critically ill patients and study the risk factors and therapeutic strategies.DESIGN, SETTING, AND PARTICIPANTSThis is a retrospective, single center case study of 11 COVID-19-infected pneumonia patients with acute respiratory distress syndrome (ARDS) from The First Affiliated Hospital of Guangzhou Medical University in China from January 26, 2020 to February 18, 2020. The follow-up termination date was February 19, 2020.EXPOSERESEleven COVID-19-infected pneumonia patients with ARDS in the ICU. Some of these patients also had cytokine release syndrome-like (CRSL). Immunologic detection, clinical characteristics, and clinical treatment analysis were carried out to define the CRSL in these COVID-19-infected pneumonia patients.MAIN OUTCOMES AND MEASURESClinical, radiological, immunology (including immune cell subsets and cytokines analysis), laboratory, and clinical treatment data were collected and analyzed. The critically ill patients with CRSL were defined. Prevention and control strategies were studied.RESULTSOf 11 critically ill patients in the ICU, the median age was 58 (Inter-Quartile Range{IQR}, 49–72; range, 26–72 years), and 10 (83.3%) were males. Ten (83.3%) patients had extensive pulmonary inflammation and ARDS (the median time from the first symptom to ARDS was 10.0 d), fever, and hypoxia; four (28.6%) patients experienced shock. The lymphocyte subpopulations including CD3 (CD3 + CD45+), CD4 (CD3 + CD4+), CD8 (CD3 + CD8+), NK (CD3-CD16 + CD56 +), Tregs (CD4 + CD25 + CD127 low), B lymphocyte (CD3-CD19 +) cells; and cytokines including IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ were detected at different time points. All of the patients had a decrease of CD3 (IQR,169–335; range, 50–635 cells/μL), CD4 (IQR,101–303; range, 27–350 cells/μL), CD8 (IQR, 33–141; range, 21–277 cells/μL); ten (90.9%) patients have a decrease in NK immune cells (IQR,8–72; range, 5–170 cells/μL); both of Tregs (IQR,3.3-7.8;rang,2.3-9.4%) and B immune cells (IQR,61-146; rang,44-222 cells/μL)were decreased in two (18.2%) patients. And nine patients were increase in CD4 / CD8 (IQR,3.3–7.8%; range, 2.3–9.7%). All patients had a significant increase of IL-6 (IQR,14.26-92.2; range, 4.58–1182.91ng/L). Eight (72.7%) patients were determined to have CRSL characteristics, including pulmonary inflammation, fever, a decrease of CD4, CD8, and NK cells; an increase of CD4/CD8, a significant increase of IL-6, and the dysfunction of non-pulmonary organs. The numbers of CD4, CD8, and NK cells and the level of IL-6 in peripheral blood were correlated with the area of pulmonary inflammation in CT images (P<0.05). Mechanical-ventilation used to increase blood oxygen concentration could increased the numbers of CD4 (after Vs before ventilation=259±53 VS 507±101; P=0.013, and CD8 (after Vs before ventilation=193±38 VS 279±63; P=0.048), while decreasing the level of IL-6 (after Vs before ventilation=223.2± 89.9 VS 26.8±10; P=0.041). The increased of IL-6 was occurred earlier than the decrease of CD4·, CD8 in the patients with rapidly worsened after ICU.CONCLUSIONS AND RELEVANCEIn this retrospective analysis of 11 critically ill pneumonia patients infected with COVID-19, we defined and identified eight patients (72.7%) with cytokine release syndrome-like (CRSL). We found that a large area of lung injury (≥50%) with an decrease of CD4, CD8 (Lower than 50% minimum normal range) and increase of IL-6 in peripheral blood was the highest risk factor of CRSL. IL-6 was a early indicators of CRSL in COVID-19-infected pneumonia. We also found that reduce injury to the lung is a useful method to prevent and improve COVID-19-infected pneumonia-related CRSL in critically ill pneumonia patients.

Myelopathy Due to CAR-T Related Neurotoxicity Treated with Siltuximab

2021 ◽  
pp. 10.1212/CPJ.0000000000001078
Author(s):  
Yasmin Aghajan ◽  
Alison Yu ◽  
Caron A. Jacobson ◽  
Austin I. Kim ◽  
Leslie Kean ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Hematologic Malignancy ◽  
Case Series ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Car T ◽  
Large Case Series ◽  
Large Case

Chimeric antigen receptor T (CART) cell therapy is highly effective for relapsed/refractory hematologic malignancy [1,2]; however, cytokine release syndrome (CRS) and neurotoxicity are observed in up to 77% of patients [3]. In large case series, the most common presentations of neurotoxicity were encephalopathy (57%), headache (42%), tremor (38%) and aphasia (35%). CART mediated spinal cord toxicity is not well characterized. Structural neurologic damage (stroke and intracranial hemorrhage) was only observed in 1-2% and seizures were seen in 1%-8% of cases [3, 4]. Neuroimaging findings in patients with neurotoxicity are rare and not specific.

scholarly journals Hemophagocytic Lymphohistiocytosis in Adults (aHLH): Results from the German HLH Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2523-2523 ◽  
Author(s):  
Sebastian Birndt ◽  
Thomas Schenk ◽  
Frank M. Brunkhorst ◽  
Georg Maschmeyer ◽  
Frank Rothmann ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Case Series ◽  
B Cell Lymphoma ◽  
Compound Heterozygous ◽  
Cytokine Release ◽  
Laboratory Findings

Abstract Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome caused by excessive immune activation leading to a life-threatening pro-inflammatory cytokine storm. HLH is not an entity of its own, but a clinical syndrome triggered by various conditions like infections, malignancy or autoimmune disorders. HLH pathogenesis is complex and still not fully understood. Contributing factors include immunosuppression (chemotherapy, long-term immunosuppressive therapy), cytokine release from tumor cells, imbalance between infected and immune effector cells as well as genetic predisposition. Despite improved HLH-specific therapy (adapted components from the pediatric HLH-1994 protocol), prognosis is still poor among adult HLH patients. Due to the lack of data on adult HLH in Germany, a national multicenter registry (http://www.hlh-registry.org/) was initiated. Methods: Patients (pts) with proven or suspected HLH were registered by 35 institutions across Germany from August 2010 to July 2016. Both HLH-2004 diagnostic criteria and the HScore (www.saintantoine.aphp.fr/score/) were used to confirm HLH diagnosis. To characterize adult HLH patients, data referring to underlying disease, treatment, outcome, clinical manifestations and laboratory findings were recorded. Where available, patient samples were tested for mutations of the perforin gene PRF1 by standard Sanger sequencing. Results: A total of 125 pts (48 female) were enrolled in our registry, of whom 105 pts either fulfilled diagnostic criteria according to HLH-2004 diagnostic guidelines (n=96) or met at least 4 out of 8 criteria and reached HLH-probability of over 90 % in the HScore (n=9). Among these 105 pts, n=38 (36 %) were female and n=67 (64 %) male. Median age at diagnosis was 49 years (range 17 - 81). Trigger diseases were in line with the literature, with infections (n=34) and malignancy (n=40) being most frequent (Table 1). Patients show a wide spectrum of underlying conditions, i.e. allogeneic stem cell transplantation (alloSCT) or HLH-mimicking diseases due to cytokine release in response to blinatumomab therapy. Late onset hereditary HLH was found in 3 pts (XLP-1 and -2 respectively in EBV-coinfected pts, one pt with perforin mutation - see below). 22 of 105 patients (21 %) were tested for PRF1 mutations. A compound heterozygous PRF1 A91V/Q405X mutation was identified in one pt presenting with NK/T-cell lymphoma. Heterozygous PRF1 A91V mutations were found in 2 pts with B-cell lymphoma and HLH following alloSCT respectively, in one case with available buccal swab DNA to prove germline origin of the mutation. Table 2 summarizes clinical and laboratory findings in the cohort. A median ferritin value of 32,000 µg/L underlines the importance to evaluate pts with highly elevated ferritin with respect to potential HLH diagnosis. Apart from fever and splenomegaly, clinical presentation frequently comprised hepatomegaly, liver failure, hyperbilirubinemia, renal failure, lung involvement like ARDS, or bleeding. Treatment included steroids in the vast majority of pts (n=89), often combined with i.v. immunoglobulins (n=47) and etoposide (n=49). After a median follow up time of 164 days, 48/97 pts (49.5 %) were alive, 8 pts were lost to follow up. Survival analysis revealed median overall survival of 454 days (Figure 1a). Comparing malignancy-associated HLH and HLH after alloSCT with infection- and autoimmune-associated HLH or HLH due to unknown triggers, survival was significantly poorer in the malignancy/alloSCT group (Figure 1b). Conclusions: HLH trigger conditions in adult patients in Germany are in accordance with published case series. Outcome in adult HLH is still poor, with malignancy-associated and HLH after alloSCT showing the worst prognosis. Diagnostic vigilance and early treatment is a prerequisite for improving outcome of adult HLH. In particular, high ferritin values should raise suspicion of HLH. Disclosures Hochhaus: Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding.

Nevus Lipomatosus Superficialis Unseen or Unrecognized: A Report of Eight Cases

2013 ◽  
Vol 17 (5) ◽  
pp. 335-339 ◽  
Author(s):  
Muthu Sendhil Kumaran ◽  
Tarun Narang ◽  
Sunil Dogra ◽  
Uma Nahar Saikia ◽  
Amarinder Jit Kanwar
Keyword(s):  
Treatment Outcome ◽  
Health Care Providers ◽  
Case Reports ◽  
Case Series ◽  
Care Providers ◽  
Reticular Dermis ◽  
Disease Characteristics ◽  
Long Term Follow Up

Background: Nevus lipomatosus superficialis (NLS) is a unique developmental anomaly or nevoid form of lipoma characterized by the ectopic presence of mature adipocytes in reticular dermis. The condition is rare; apart frrom isolated case reports, there are no large case series dealing with the clinicoepidemiologic characteristics and posttreatment long-term follow-up in patients with NLS and little published information on treatment outcome. Objective: To study the clinicoepidemiologic characteristics and long-term posttreatment follow-up in patients with NLS. Methods: This was an 11-year retrospective study analyzing disease characteristics and treatment outcome in eight patients with NLS. Results: There were eight (six males, two females) patients with NLS, of whom three were children. The classic variant of NLS was the predominant presentation. One patient demonstrated a combination of both classic and solitary variants. Most patients, especially those with solitary variants, were commonly misdiagnosed before presenting to us. Four patients, including two with the solitary variant, one each with the classic and the combined type, underwent surgical resection without any recurrence over 8 years of follow-up. Conclusions: The rare nature of the disorder, which is commonly misdiagnosed, and the absence of long-term follow-up data prompted us to share our experience about NLS to increase its awareness among health care providers.

scholarly journals The Use of CytoSorb Therapy in Critically Ill COVID-19 Patients: Review of the Rationale and Current Clinical Experiences

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Juan Carlos Ruiz-Rodríguez ◽  
Zsolt Molnar ◽  
Efthymios N. Deliargyris ◽  
Ricard Ferrer
Keyword(s):  
Critically Ill ◽  
Host Response ◽  
Blood Purification ◽  
Vital Organ ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Clinical Experiences ◽  
Health Crisis ◽  
Considerable Evidence ◽  
Beneficial Effects

The COVID-19 pandemic has led to the biggest global health crisis of our lifetime. There is accumulating evidence that a substantial number of critically ill COVID-19 patients exhibit a dysregulated host response manifesting as cytokine storm or cytokine release syndrome, which in turn contributes to the high observed rates of mortality. Just as in other hyperinflammatory conditions, extracorporeal cytokine removal may have potential beneficial effects in this subgroup of COVID-19 patients. The CytoSorb blood purification device is the most extensively investigated cytokine removal platform with considerable evidence suggesting that early intervention can provide rapid hemodynamic stabilization and improvement in vital organ functions. The purpose of this review is to provide an overview of the pathophysiological background of hyperinflammation in COVID-19 and to summarize the currently available evidence on the effects of hemoadsorption in these patients.

scholarly journals Cytokine Release Syndrome-Associated Encephalopathy in Patients with COVID-19

2020 ◽  
Author(s):  
Peggy Perrin ◽  
Nicolas Collongues ◽  
Seyyid Baloglu ◽  
Dimitri Bedo ◽  
Xavier Bassand ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Severe Disease ◽  
Brain Mri ◽  
Case Series ◽  
Neurological Manifestations ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Mri Findings ◽  
Depth Analysis

Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making &ndash; especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted &ndash; resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.

SPEARHEAD-1: A phase 2 trial of afamitresgene autoleucel (Formerly ADP-A2M4) in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11504-11504
Author(s):  
Sandra P. D'Angelo ◽  
Brian Andrew Van Tine ◽  
Steven Attia ◽  
Jean-Yves Blay ◽  
Sandra J. Strauss ◽  
...  
Keyword(s):  
T Cells ◽  
Synovial Sarcoma ◽  
Phase 1 ◽  
Low Grade ◽  
Phase 2 ◽  
Round Cell ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Wide Range

11504 Background: This phase 2, open-label trial (SPEARHEAD-1; NCT04044768) is designed to evaluate the efficacy, safety, and tolerability of afamitresgene autoleucel in 45 patients (pts) with advanced/metastatic synovial sarcoma or Myxoid/Round Cell Liposarcoma (MRCLS). Methods: Eligible pts are HLA-A*02 positive with MAGE-A4-expressing tumors. Pts undergo leukapheresis for collection of autologous T-cells for processing and manufacture into afamitresgene autoleucel cells. Pts were treated with afamitresgene autoleucel doses between 1–10 × 109 transduced T-cells after receiving lymphodepleting chemotherapy. The primary endpoint is overall response rate per RECIST v1.1 by independent review. An independent Data Safety Monitoring Board reviews ongoing safety and benefit: risk during the interventional phase. Results: As of Feb 4, 2021, 32 pts received afamitresgene autoleucel. Of these pts, 59% were male, 87.5% had synovial sarcoma, the median age was 43 yrs (range: 24–73), and they had a median of 3 prior systemic lines of therapy. The MAGE-A4 antigen expression level (histoscore) ranged from 112–300, and the transduced cell dose ranged from 2.7–9.9 x 109. At the data cutoff, 25 pts were evaluable for preliminary efficacy (23 with synovial sarcoma and 2 with MRCLS) and 7 pts (5 with synovial sarcoma and 2 with MRCLS) had insufficient follow-up (<8 weeks follow-up and/or awaiting first scan). Of the 25 evaluable pts, the investigator-assessed responses were: complete response (2 pts), partial response (8 pts), stable disease (11 pts), and progressive disease (4 pts). All responses were confirmed. Nine of the 10 responders had ongoing response at the data cutoff and 3 responders had MAGE-A4 antigen histoscores <200. The most common AEs of any grade (>30% pts) were neutropenia, lymphopenia, nausea, cytokine release syndrome, leukopenia, fatigue, pyrexia, and anemia. Cytokine release syndrome of any grade occurred in 19/32 pts; 95% of those events were ≤Grade 2. No immune effector cell-associated neurotoxicity syndrome (ICANS) has been reported to date. Cytopenia (≥G3) at 4 wks post-infusion was observed in 6 pts (anemia 3 pts, neutropenia 2 pts, and thrombocytopenia 1 pt). Conclusion: These preliminary data demonstrate afamitresgene autoleucel is efficacious and well tolerated in heavily pre-treated pts. Objective responses are reported across a wide range of MAGE-A4 antigen levels and deep responses have been observed. Initial durability data is encouraging. Preliminary response data in SPEARHEAD-1 is comparable to the findings of the prior Phase 1 trial [1]. To date, the safety profile of afamitresgene autoleucel has been favorable, with mainly low-grade cytokine release syndrome and tolerable/reversible hematologic toxicities. [1]. Van Tine BA, et al. CTOS; November 18-21, 2020; Virtual. Clinical trial information: NCT04044768.

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