Tocilizumab for the Critically Ill With Severe COVID-19: A Community Hospital Case Series.

OBJECTIVE: To evaluate the use of tocilizumab in a community hospital setting for critically ill patients with severe COVID-19. DESIGN: A retrospective case series. SETTING: Five community hospitals within 1 urban health system. PATIENTS: Adult patients whom received tocilizumab between March 27th, 2020 to April 30th, 2020 for severe COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixteen patients in total were evaluated from the 5 community hospitals. The mean (± SD) age of the patients was 53.9 ± 9.2 years, 56% were men, and the most common comorbidities present on admission were hypertension (31%) and diabetes mellitus (25%). All patients received at least 1 other treatment modality for COVID-19 (steroids, hydroxychloroquine, or convaslescent plasma). Additionally, all patients on admission to intensive care units had severe COVID-19 with 56% requiring mechanical ventilation with a pre-tocilizumab median (IQR) Pao2: Fio2 of 84 (69 - 108.6), 19% requiring vasopressor support, and inflammatory markers (CRP, LDH, ferritin, and IL-6) were elevated. The median (IQR) tocilizumab dose was 400 mg (400-600) which correlated with a weight-based mean (± SD) dose of 5.4 mg/kg ± 1.3. Of the 16 patients that received tocilizumab, 8 (50%) were discharged home, 7 (44%) died, and 1 (6%) was still hospitalized at the end of data collection. Patients who died were more likely to be older 62 ± 2 years, female (57%), had a higher rate of mechanical ventilation (86%) and vasopressors (43%) use at baseline, and had a higher median (IQR) IL-6 level prior to tocilizumab administration 550 pg/mL (IQR 83-1924). There were no reported adverse drug reactions reported after the administration of tocilizumab for any patient. CONCLUSIONS: Our findings do not support the effectiveness of tocilizumab in treatment of severe COVID-19 infection in critically ill patients.

Sensitizing the interdisciplinary team to desensitizations: An alemtuzumab case report.

INTRODUCTION: We describe a case of alemtuzumab (Campath®) hypersensitivity requiring desensitization within the medical intensive care unit (MICU) in a patient with T-cell prolymphocytic leukemia. CASE REPORT: We adopted a desensitization protocol from Gutierrez-Fernandez et al., which included three aliquots (0.15 mg intravenously (IV), 1.5 mg IV, and 28.5 mg IV) given approximately 1 h apart on day 1 followed by a full 30 mg dose IV on day 3. Unlike prior attempts to administer alemtuzumab to this patient, she tolerated the medication well and did not require any rescue medications. MANAGEMENT AND OUTCOME: Successful plan development required a significant amount of strategic communication between hematology/oncology and MICU-related physicians, pharmacists, and nurses to ensure a safe and effective desensitization. The first step of planning required creation of a desensitization order set with directions for medication preparation and administration, premedications, and available medications in the event of an adverse reaction or anaphylaxis. Anaphylactoid-related medications were prepared at bedside and ready for administration prior to beginning the desensitization. Alemtuzumab was compounded in a chemotherapy-certified hood and verified by at least two chemotherapy-certified pharmacists. Foreword planning was also necessary to ensure multiple people were available or present at bedside for the desensitization, including a chemotherapy-certified nurse, a second chemotherapy-certified nurse for verification, a critical care-certified pharmacist, a pulmonary/critical care attending physician, and hematology attending physician. DISCUSSION: This case exemplifies the importance of clear and coordinated communication between different healthcare fields to safely and effectively complete extensive protocols such as desensitization strategies.

Interplay of personal, pet, and environmental colonization in households affected by community-associated methicillin-resistant Staphylococcus aureus.

OBJECTIVE: We sought to determine the prevalence, molecular epidemiology, and factors associated with Staphylococcus aureus environmental surface and pet colonization in households of children with community-associated methicillin-resistant S. aureus (CA-MRSA) infection. METHODS: Between 2012 and 2015, 150 children with CA-MRSA infections and their household contacts and pets were enrolled in this cross-sectional study in metropolitan Saint Louis, MO. Cultures to detect S. aureus were collected from 3 anatomic sites of household members, 2 dog/cat sites, and 21 environmental surfaces in each household. Molecular epidemiology of S. aureus isolates was determined via repetitive-sequence PCR. Generalized linear models were developed to identify factors associated with S. aureus/MRSA household contamination. RESULTS: MRSA was recovered from environmental surfaces in 69 (46%) households (median 2 surfaces [range 1-18]). The enrollment infecting strain type was the most common strain recovered from the environment in most (64%) households. In generalized linear models, factors associated with a higher proportion of MRSA-contaminated environmental surfaces were household member MRSA colonization burden, MRSA as the dominant S. aureus strain colonizing household members, more strain types per household member, index case African-American race, and renting (vs. owning) the home. Of 132 pets, 14% were colonized with MRSA. Pets whose primary caretaker was MRSA-colonized were more likely to be MRSA-colonized than pets whose primary caretaker was not MRSA-colonized (50% vs. 4%, p < 0.001). CONCLUSIONS: Household environments and pet dogs and cats serve as reservoirs of MRSA. Household member MRSA colonization burden predicts environmental MRSA contamination. Longitudinal studies will inform the directionality of household transmission.

Multivalent Binding of a Ligand-Coated Particle: Role of Shape, Size, and Ligand Heterogeneity.

We utilize a multiscale modeling framework to study the effect of shape, size, and ligand composition on the efficacy of binding of a ligand-coated particle to a substrate functionalized with the target receptors. First, we show how molecular dynamics along with steered molecular dynamics calculations can be used to accurately parameterize the molecular-binding free energy and the effective spring constant for a receptor-ligand pair. We demonstrate this for two ligands that bind to the α5ß1-domain of integrin. Next, we show how these effective potentials can be used to build computational models at the meso- and continuum-scales. These models incorporate the molecular nature of the receptor-ligand interactions and yet provide an inexpensive route to study the multivalent interaction of receptors and ligands through the construction of Bell potentials customized to the molecular identities. We quantify the binding efficacy of the ligand-coated-particle in terms of its multivalency, binding free-energy landscape, and the losses in the configurational entropies. We show that 1) the binding avidity for particle sizes less than 350 nm is set by the competition between the enthalpic and entropic contributions, whereas that for sizes above 350 nm is dominated by the enthalpy of binding; 2) anisotropic particles display higher levels of multivalent binding compared to those of spherical particles; and 3) variations in ligand composition can alter binding avidity without altering the average multivalency. The methods and results presented here have wide applications in the rational design of functionalized carriers and also in understanding cell adhesion.

A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock.

OBJECTIVE: To review and summarize data on angiotensin II (AT-II), approved by the Food and Drug Administration (FDA) in December 2017 to increase blood pressure in adults with septic or other distributive shock. DATA SOURCES: A PubMed/MEDLINE search was conducted using the following terms: (angiotensin ii OR angiotensin 2) AND (shock) from 1966 to February 2018. STUDY SELECTION AND DATA EXTRACTION: A total of 691 citations were reviewed with only relevant clinical data extracted. DATA SYNTHESIS: AT-II is a peptide hormone with a multitude of physiological effects-namely, vasoconstriction of venous and arterial smooth muscle. The priority approval granted by the FDA was secondary to a phase 3 study of patients receiving at least 0.2 µg/kg/min of norepinephrine or equivalent for vasodilatory shock. Compared with placebo, AT-II had a significantly higher rate of response, defined as a mean arterial pressure of 75 mm Hg or an increase of 10 mm Hg. No significant difference was found in death by day 28. CONCLUSIONS: AT-II is a newly available vasoactive agent with a novel mechanism for the treatment of distributive shock. Further research is needed to define its exact role in therapy of shock states, identify patients most likely to benefit, and further study its safety profile in critical illness.