Indicators of Clinical Trajectory in Patients With Cancer Who Receive Cardiopulmonary Resuscitation.

BACKGROUND: Patients with cancer who require cardiopulmonary resuscitation (CPR) historically have had low survival to hospital discharge; however, overall CPR outcomes and cancer survival have improved. Identifying patients with cancer who are unlikely to survive CPR could guide and improve end-of-life discussions prior to cardiac arrest. METHODS: Demographics, clinical variables, and outcomes including immediate and hospital survival for patients with cancer aged ≥18 years who required in-hospital CPR from 2012 to 2015 were collected. Indicators capturing the overall declining clinical and oncologic trajectory (ie, no further therapeutic options for cancer, recommendation for hospice, or recommendation for do not resuscitate) prior to CPR were determined a priori and manually identified. RESULTS: Of 854 patients with cancer who underwent CPR, the median age was 63 years and 43.6% were female; solid cancers accounted for 60.6% of diagnoses. A recursive partitioning model selected having any indicator of declining trajectory as the most predictive factor in hospital outcome. Of our study group, 249 (29%) patients were found to have at least one indicator identified prior to CPR and only 5 survived to discharge. Patients with an indicator were more likely to die in the hospital and none were alive at 6 months after discharge. These patients were younger (median age, 59 vs 64 years; P≤.001), had a higher incidence of metastatic disease (83.0% vs 62.9%; P<.001), and were more likely to undergo CPR in the ICU (55.8% vs 36.5%; P<.001) compared with those without an indicator. Of patients without an indicator, 145 (25%) were discharged alive and half received some form of cancer intervention after CPR. CONCLUSIONS: Providers can use easily identifiable indicators to ascertain which patients with cancer are at risk for death despite CPR and are unlikely to survive to discharge. These findings can guide discussions regarding utility of resuscitation and the lack of further cancer interventions even if CPR is successful.

Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study.

OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. DESIGN: Retrospective cohort study. SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected. RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.

Tocilizumab therapy in 5 solid and composite tissue transplant recipients with early ARDS due to SARS-CoV-2.

There are emerging data depicting the clinical presentation of coronavirus disease 19 (COVID-19) in solid organ transplant recipients but negligible data-driven guidance on clinical management. A biphasic course has been described in some infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), beginning with a flu-like illness followed by an intense inflammatory response characterized by elevated c-reactive protein (CRP), interleukin 6 (IL-6), and acute respiratory distress syndrome (ARDS) associated with high mortality. The exuberant and possibly dysregulated immune response has prompted interest in therapeutic agents that target the cytokines involved, particularly IL-6. Tocilizumab is an IL-6 receptor antagonist with a record of use for a variety of rheumatologic conditions and cytokine release syndrome due to chimeric antigen receptor T-cell therapy but experience in solid organ and composite tissue transplant recipients (SOT/CTTRs) with SARS-CoV-2-related ARDS has not been previously reported in detail. We present the clinical course of 5 SOT/CTTRs with SARS-CoV-2-related ARDS that received tocilizumab with favorable short-term outcomes in 4. Responses were characterized by reductions in CRP, discontinuation of vasopressors, improved oxygenation and respiratory mechanics, and variable duration of ventilator support. Four bacterial infections occurred within 2 weeks of tocilizumab administration. We discuss safety concerns and the need for randomized comparative trials to delineate tocilizumab's clinical utility in this population.

Characteristics and Outcomes of Ethics Consultations in an Oncologic Intensive Care Unit.

OBJECTIVE: To evaluate the frequency, characteristics, and outcomes of ethics consultations in critically ill patients with cancer. DESIGN, SETTING, AND METHODS: This is a retrospective analysis of all adult patients with cancer who were admitted to the intensive care unit (ICU) of a comprehensive cancer center and had an ethics consultation between September 2007 and December 2011. Demographic and clinical variables were abstracted along with the details and contexts of the ethics consultations. MAIN RESULTS: Ethics consultations were obtained on 53 patients (representing 1% of all ICU admissions). The majority (90%) of patients had advanced-stage malignancies, had received oncologic therapies within the past 12 months, and required mechanical ventilation and/or vasopressor therapy for respiratory failure and/or severe sepsis. Two-thirds of the patients lacked decision-making capacity and nearly all had surrogates. The most common reasons for ethics consultations were disagreements between the patients/surrogates and the ICU team regarding end-of-life care. After ethics consultations, the surrogates agreed with the recommendations made by the ICU team on the goals of care in 85% of patients. Moreover, ethics consultations facilitated the provision of palliative medicine and chaplaincy services to several patients who did not have these services offered to them prior to the ethics consultations. CONCLUSION: Our study showed that ethics consultations were helpful in resolving seemingly irreconcilable differences between the ICU team and the patients' surrogates in the majority of cases. Additionally, these consultations identified the need for an increased provision of palliative care and chaplaincy visits for patients and their surrogates at the end of life.

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications.

Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves good response, life-threatening toxicities have been reported. Mechanistically, can be divided into two categories: (1) toxicities related to T-cell activation and release of high levels of cytokines: or (2) toxicities resulting from interaction between CAR and CAR targeted antigen expressed on non-malignant cells (i.e., on-target, off-tumor effects). Variations in conditioning therapies, co-stimulatory domains, CAR T-cell dose and anti-cytokine administration, pose a challenge in distinguishing cytokine mediated related toxicities from on-target, off-tumor toxicities. Timing, frequency, severity, as well as optimal management of CAR T-cell-related toxicities vary significantly between products and are likely to change as newer therapies become available. Currently the FDA approved CARs are targeted towards the B-cell malignancies however the future holds promise of expanding the target to solid tumor malignancies. Further highlighting the importance of early recognition and intervention for early and late onset CAR-T related toxicity. This contemporary review aims to describe presentation, grading and management of commonly encountered toxicities, short- and long-term complications, discuss preventive strategies and resource utilization.

Risk factors associated with development of coinfection in critically Ill patients with COVID-19.

BACKGROUND: At outset of the coronavirus disease 2019 (COVID-19) pandemic, the significance of bacterial and fungal coinfections in individuals with COVID-19 was unknown. Initial reports indicated that the prevalence of coinfection in the general population was low, but there was uncertainty regarding the risk of coinfection in critically ill patients. METHODS: Nine hundred critically ill adult patients with COVID-19 infection were enrolled in this observational case-control study. Patients with a coinfection (case) and patients without a coinfection (control) were compared using univariate and multivariable analyses. A subgroup analysis was performed on patients with coinfection, dividing them into early (infection within 7 days) and late (infection after 7 days) infection groups. RESULTS: Two hundred and thirty-three patients (25.9%) had a bacterial or fungal coinfection. Vasopressor use (P<0.001) and severity of illness (higher Acute Physiology and Chronic Health Evaluation III score, P=0.009) were risk factors for the development of a coinfection. Patients with coinfection had higher mortality and length of stay. Vasopressor and corticosteroid use and central line and foley catheter placement were risk factors for late infection (>7 days). There were high rates of drug-resistant infections. CONCLUSIONS: Critically ill patients with COVID-19 are at risk for both community-acquired and hospital-acquired infections throughout their hospitalization for COVID-19. It is important to consider the development of a coinfection in clinically worsening critically ill patients with COVID-19 and consider the likelihood of drug-resistance when choosing an empiric regimen.

Toxicities Associated with Immunotherapy and Approach to Cardiotoxicity with Novel Cancer Therapies.

In recent years, major advances in oncology especially the advent of targeted agents and immunotherapies (immune checkpoint inhibitors [ICIs] and chimeric antigen receptor [CAR] T-cell therapy) have led to improved quality of life and survival rates in patients with cancer. This article focuses on the clinical features, and grading and management of toxicities associated with ICIs and CAR T-cell therapy. In addition, because cardiotoxicity is one of the most harmful effects of anticancer therapeutics, we describe the risk factors and mechanisms of cardiovascular injury associated with newer agents, screening technologies for at-risk patients, and preventive and treatment strategies.

A High Neutrophil-Lymphocyte Ratio Is Associated With Increased Morbidity and Mortality in Patients With Coronavirus Disease 2019.

OBJECTIVES: The neutrophil-lymphocyte ratio is an inexpensive and simple inflammatory marker. A higher ratio, indicative of an acute hyperinflammatory response or diminished overall physiologic health status, has been associated with poor prognoses. This study aimed to evaluate the prognostic potential of admission neutrophil-lymphocyte ratio in patients admitted to the medical ICU with coronavirus disease 2019. DESIGN: Retrospective review of prospectively collected data. SETTING: Medical ICU from a large medical center. PATIENTS: 2,071 consecutive patients admitted to the medical ICU with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 between March 15, 2020, and December 30, 2020, were grouped by neutrophil-lymphocyte ratio above or below the median (7.45) at the time of hospital admission. INTERVENTIONS: Complete blood count with differential at the time of hospital admission. MEASUREMENTS AND MAIN RESULTS: A neutrophil-lymphocyte ratio above 7.45 at the time of hospital admission was associated with increased need for mechanical ventilation (45.8% vs 38.0%, p < 0.0001), vasopressor therapy (55.6% vs 48.2%, p = 0.001), and decreased survival through 180 days (54.8% vs 67.0%, p < 0.0001). Patients with a high neutrophil-lymphocyte ratio exhibited a 1.32 (95% CI, 1.14-1.54) times greater risk of mortality than those with a low neutrophil-lymphocyte ratio. CONCLUSIONS: The neutrophil-lymphocyte ratio at the time of hospital admission is an independent risk factor for morbidity and mortality. This prognostic indicator may assist clinicians appropriately identify patients at heightened risk for a severe disease course and tailor treatment accordingly.

Tocilizumab in Coronavirus Disease 2019-Related Critical Illness: A Propensity Matched Analysis.

The primary objective was to evaluate ICU mortality at 28 days in patients with severe hypoxemic respiratory failure due to coronavirus disease 2019 infection who received tocilizumab. The secondary objectives were to evaluate ICU-, hospital-, mechanical ventilation-, and vasopressor-free days at day 28 and development of secondary infections. DESIGN: Retrospective, observational, multicenter, cohort study between March 15, 2020, and May 31, 2020. Using propensity score matching based on ICU admission source, C-reactive protein, Sequential Organ Failure Assessment score, vasopressor use, age, race, weight, and mechanical ventilation, patients who received tocilizumab were matched to patients who did not receive tocilizumab. SETTING: Ten hospitals within the Cleveland Clinic Enterprise. PATIENTS: Adult patients admitted to a medical, surgical, neurosciences, or mixed ICU with severe acute respiratory syndrome coronavirus 2 infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred forty-four patients were included: 342 patients (77%) did not receive tocilizumab and 102 patients (23%) received tocilizumab. Of those, 82 patients in each arm were matched. Before matching, patients who received tocilizumab had higher Sequential Organ Failure Assessment scores (6.1 ± 3.4 vs 4.7 ± 3.6), higher C-reactive protein (21.0 ± 10.2 vs 13.7 ± 9.6 mg/dL), higher frequency of intubation, vasopressor requirement, and paralytics. After matching, characteristics were more balanced and over 85% of patients required mechanical ventilation. ICU mortality was lower in tocilizumab group (23.2% vs 37.8%; risk difference, -15%; 95% CI, -29% to -1%), with more ICU-, hospital-, and vasoactive-free days at day 28 compared with those who did not receive tocilizumab. There was no difference in mechanical ventilation-free days at day 28 or development of secondary infections. CONCLUSIONS: Tocilizumab use was associated with a significant decrease in ICU mortality in critically ill coronavirus disease 2019 patients with severe hypoxemic respiratory failure. Future randomized controlled trials limited to tocilizumab administration in critically ill coronavirus disease 2019 patients, with severe hypoxemic respiratory failure, are needed to support these findings.

Critically ill patients with severe immune checkpoint inhibitor related neurotoxicity: A multi-center case series.

PURPOSE: Serious immune checkpoint inhibitor (ICI)-related neurotoxicity is rare. There is limited data on the specifics of care and outcomes of patients with severe neurological immune related adverse events (NirAEs) admitted to the Intensive Care Unit (ICU). MATERIALS AND METHODS: Retrospective study of patients with severe NirAEs admitted to the ICU at 3 academic centers between January 2016 and December 2018. Clinical data collected included ICI exposure, type of NirAE (central [CNS] or peripheral nervous system [PNS) disorders), and patient outcomes including neurological recovery and mortality. RESULTS: Seventeen patients developed severe NirAEs. Eight patients presented with PNS disorders; 6 with myasthenia gravis (MG), 1 had a combination of MG and polyneuropathy and 1 had Guillain-Barre syndrome. Nine patients had CNS disorders (6 seizures and 5 had concomitant encephalopathy. During ICU admission, 65% of patients required mechanical ventilation, 35% vasopressors, and 18% renal replacement therapy. The median ICU and hospital length of stay were 7 (2-36) and 18 (4-80) days, respectively. Hospital mortality was 29%. At hospital discharge, 18% of patients made a full neurologic recovery, 41% partial recovery, and 12% did not recover. CONCLUSION: Severe NirAEs while uncommon, can be serious or even life-threatening if not diagnosed and treated early.

Surge capacity and capability of intensive care units across a large healthcare system: An operational blueprint for regional integration.

OBJECTIVE: Many hospitals were unprepared for the surge of patients associated with the spread of coronavirus disease 2019 (COVID-19) pandemic. We describe the processes to develop and implement a surge plan framework for resource allocation, staffing, and standardized management in response to the COVID-19 pandemic across a large integrated regional healthcare system. SETTING: A large academic medical center in the Cleveland metropolitan area, with a network of 10 regional hospitals throughout Northeastern Ohio with a daily capacity of more than 500 intensive care unit (ICU) beds. RESULTS: At the beginning of the pandemic, an equitable delivery of healthcare services across the healthcare system was developed. This distribution of resources was implemented with the potential needs and resources of the individual ICUs in mind, and epidemiologic predictions of virus transmissibility. We describe the processes to develop and implement a surge plan framework for resource allocation, staffing, and standardized management in response to the COVID-19 pandemic across a large integrated regional healthcare system. We also describe an additional level of surge capacity, which is available to well-integrated institutions called "extension of capacity." This refers to the ability to immediately have access to the beds and resources within a hospital system with minimal administrative burden. CONCLUSIONS: Large integrated hospital systems may have an advantage over individual hospitals because they can shift supplies among regional partners, which may lead to faster mobilization of resources, rather than depending on local and national governments. The pandemic response of our healthcare system highlights these benefits.

Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: In patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. We aimed to evaluate whether mavrilimumab, a monoclonal antibody to the GM-CSF receptor, would improve outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. METHODS: This investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals in the USA. Inclusion required hospitalisation, COVID-19 pneumonia, hypoxaemia, and a C-reactive protein concentration of more than 5 mg/dL. Patients were excluded if they required mechanical ventilation. Patients were randomly assigned (1:1) centrally, with stratification by hospital site, to receive mavrilimumab 6 mg/kg as a single intravenous infusion, or placebo. Participants and all clinical and research personnel were masked to treatment assignment. The primary endpoint was the proportion of patients alive and off supplemental oxygen therapy at day 14. The primary outcome and safety were analysed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04399980, NCT04463004, and NCT04492514. FINDINGS: Between May 28 and Sept 15, 2020, 40 patients were enrolled and randomly assigned to mavrilimumab (n=21) or placebo (n=19). A trial of 60 patients was planned, but given slow enrolment, the study was stopped early to inform the natural history and potential treatment effect. At day 14, 12 (57%) patients in the mavrilimumab group were alive and off supplemental oxygen therapy compared with nine (47%) patients in the placebo group (odds ratio 1·48 [95% CI 0·43-5·16]; p=0·76). There were no treatment-related deaths, and adverse events were similar between groups. INTERPRETATION: There was no significant difference in the proportion of patients alive and off oxygen therapy at day 14, although benefit or harm of mavrilimumab therapy in this patient population remains possible given the wide confidence intervals, and larger trials should be completed. FUNDING: Kiniksa Pharmaceuticals.

Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation.

Aims: In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1ß, in patients with COVID-19, myocardial injury, and heightened inflammation. Methods and results: This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo [recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46-2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23-1.64]. At Day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups. Conclusion: There was no difference in time to clinical improvement at Day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at Day 28.

Ethical considerations during the COVID-19 pandemic.

The care of patients during the COVID-19 pandemic has added many layers of complexity to ethical issues. Our response emphasizes the importance of having an ethically sound framework to inform our decisions, requiring caregivers to consider what is ethically optimal and feasible for the patient. It is increasingly important to understand the ethical principles and to appropriately apply them to both patient management decisions and guide scarce resource allocation. If we are to be prepared to face the many challenges of this pandemic, we must prioritize the ethical demands to our treatment and management concerns.

Addressing caregiver moral distress during the COVID-19 pandemic.

Moral distress is the psychological distress that is experienced in relation to a morally challenging situation or event. Although it was first observed within nursing, caregivers across all disciplines-including physicians, respiratory therapists, social workers and chaplains-experience moral distress. In this consult, we discuss 5 types of moral distress using examples of changes to clinical practice that have occurred due to COVID-19. We also provide suggestions for responding to moral distress and outline the resources available at Cleveland Clinic.

Practical aspects of targeting IL-6 in COVID-19 disease.

Interleukin 6 (IL-6) took center stage as a therapeutic target, given its role in the cytokine storm phase of COVID-19. While IL-6 inhibitors have been widely used to treat a variety of immune-mediated disease states, they have not been used often in the intensive care setting, and new data question their efficacy. This brief review provides practical information on their administration and safety.

Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies.

COVID-19 is a clinical syndrome ranging from mild symptoms to severe pneumonia that often leads to respiratory failure, need for mechanical ventilation, and death. Most of the lung damage is driven by a surge in inflammatory cytokines [interleukin-6, interferon-γ, and granulocyte-monocyte stimulating factor (GM-CSF)]. Blunting this hyperinflammation with immunomodulation may lead to clinical improvement. GM-CSF is produced by many cells, including macrophages and T-cells. GM-CSF-derived signals are involved in differentiation of macrophages, including alveolar macrophages (AMs). In animal models of respiratory infections, the intranasal administration of GM-CSF increased the proliferation of AMs and improved outcomes. Increased levels of GM-CSF have been recently described in patients with COVID-19 compared to healthy controls. While GM-CSF might be beneficial in some circumstances as an appropriate response, in this case the inflammatory response is maladaptive by virtue of being later and disproportionate. The inhibition of GM-CSF signaling may be beneficial in improving the hyperinflammation-related lung damage in the most severe cases of COVID-19. This blockade can be achieved through antagonism of the GM-CSF receptor or the direct binding of circulating GM-CSF. Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. Prospective, randomized, placebo-controlled trials are ongoing. Anti-GM-CSF monoclonal antibodies, TJ003234 and gimsilumab, will be tested in clinical trials in patients with COVID-19, while lenzilumab received FDA approval for compassionate use. These trials will help inform whether blunting the inflammatory signaling provided by the GM-CSF axis in COVID-19 is beneficial.

Canakinumab to reduce deterioration of cardiac and respiratory function in SARS-CoV-2 associated myocardial injury with heightened inflammation (canakinumab in Covid-19 cardiac injury: The three C study).

BACKGROUND: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation. HYPOTHESIS: The primary hypothesis is that canakiumab will shorten time to recovery. METHODS: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin and C-reactive protein (CRP). The primary endpoint is defined as the time in days from randomization to either an improvement of two points on a seven category ordinal scale or discharge from the hospital, whichever occurs first up to 14 days postrandomization. The secondary endpoint is mortality at day 28. A total of 45 patients will be enrolled with an anticipated 5 month follow up period. RESULTS: Baseline characteristics for the first 20 randomized patients reveal a predominantly male (75%), elderly population (median 67 years) with a high prevalence of hypertension (80%) and hyperlipidemia (75%). CRPs have been markedly elevated (median 16.2 mg/dL) with modest elevations in high-sensitivity troponin T (median 21 ng/L), in keeping with the concept of enrolling patients with early myocardial injury. CONCLUSIONS: The three C study will provide insights regarding whether IL-1ß inhibition may improve outcomes in patients with SARS-CoV2 associated myocardial injury and increased inflammation.

The chimeric antigen receptor-intensive care unit (CAR-ICU) initiative: Surveying intensive care unit practices in the management of CAR T-cell associated toxicities.

PURPOSE: A task force of experts from 11 United States (US) centers, sought to describe practices for managing chimeric antigen receptor (CAR) T-cell toxicity in the intensive care unit (ICU). MATERIALS AND METHODS: Between June-July 2019, a survey was electronically distributed to 11 centers. The survey addressed: CAR products, toxicities, targeted treatments, management practices and interventions in the ICU. RESULTS: Most centers (82%) had experience with commercial and non-FDA approved CAR products. Criteria for ICU admission varied between centers for patients with Cytokine Release Syndrome (CRS) but were similar for Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Practices for vasopressor support, neurotoxicity and electroencephalogram monitoring, use of prophylactic anti-epileptic drugs and tocilizumab were comparable. In contrast, fluid resuscitation, respiratory support, methods of surveillance and management of cerebral edema, use of corticosteroid and other anti-cytokine therapies varied between centers. CONCLUSIONS: This survey identified areas of investigation that could improve outcomes in CAR T-cell recipients such as fluid and vasopressor selection in CRS, management of respiratory failure, and less common complications such as hemophagocytic lymphohistiocytosis, infections and stroke. The variability in specific treatments for CAR T-cell toxicities, needs to be considered when designing future outcome studies of critically ill CAR T-cell patients.