Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase 2b multinational, randomised, double-blind, placebo-controlled ARROYO trial.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils. OBJECTIVES: To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment. METHODS: The 24-week, randomised, double-blind, placebo-controlled, phase 2b portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomised to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in ISS7 at Week 12. The key secondary endpoint was change from baseline in UAS7 at Week 12. Additional secondary endpoints included other metrics to assess CSU at Week 24; blood eosinophil levels; and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups. RESULTS: Of 155 patients, 59 were randomised to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% confidence interval -4.09 to 0.50) nor in change from baseline in UAS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.4016; benralizumab 60 mg vs. placebo, P = 0.0819). Depletion of blood eosinophil levels was observed at Week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab. CONCLUSIONS: Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.

Mechanistic insights into the electrolyte effects on the electrochemical nitrogen reduction reaction using copper hexacyanoferrate/f-MWCNT nano-composites.

Developing an efficient, selective, and stable electrocatalysis system for the electrocatalytic N2 reduction reaction (ENRR) is a promising strategy for the green and sustainable production of ammonia. The activity, selectivity, and stability of various electrocatalysts in different electrolyte solvents, mainly acidic and alkaline electrolytes, are commonly compared in the literature. However, a mechanistic insight into the effect of these electrolytes on ENRR activity is lacking. Herein we demonstrate that the acidity or alkalinity of the electrolyte is a key factor in determining the rate-limiting step and, by extension, the ENRR performance of an electrochemical setup for the electroproduction of ammonia. Our results from ex situ X-ray photoelectron, Raman, and FTIR spectroscopy analysis of the fresh and spent Cu-hexacyanoferrate Prussian blue analogue-decorated functionalized carbon nanotube (CuFe PBA/f-CNT) catalyst reveal that NH4+-species are more strongly adsorbed on the catalyst surface during the ENRR in acidic than in alkaline electrolytes. The results of our detailed rotating ring-disc electrode voltammetry studies suggest that the ENRR over CuFe PBA/f-CNT is mostly controlled by surface adsorption in an acidic electrolyte and by mass transport in an alkaline electrolyte. In situ Raman spectroscopy confirms this finding and shows that the leaching of Fe(CN)6 species from the CuFe PBA/f-CNT composite in an alkaline electrolyte greatly affects the ENRR performance. We believe that the work presented herein offers a new insight into the mechanistic aspects of the ENRR in different electrolyte systems and hence can prove very valuable for the development of effective ENRR electrode/electrolyte systems for practical applications.

Composed solutions of synchronized patterns in multiplex networks of Kuramoto oscillators.

Networks with different levels of interactions, including multilayer and multiplex networks, can display a rich diversity of dynamical behaviors and can be used to model and study a wide range of systems. Despite numerous efforts to investigate these networks, obtaining mathematical descriptions for the dynamics of multilayer and multiplex systems is still an open problem. Here, we combine ideas and concepts from linear algebra and graph theory with nonlinear dynamics to offer a novel approach to study multiplex networks of Kuramoto oscillators. Our approach allows us to study the dynamics of a large, multiplex network by decomposing it into two smaller systems: one representing the connection scheme within layers (intra-layer), and the other representing the connections between layers (inter-layer). Particularly, we use this approach to compose solutions for multiplex networks of Kuramoto oscillators. These solutions are given by a combination of solutions for the smaller systems given by the intra- and inter-layer systems, and in addition, our approach allows us to study the linear stability of these solutions.

Use of primary bariatric surgery among patients with obesity and diabetes. Insights from the Diabetes Collaborative Registry.

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m2), and depression (23% vs. 14%; p < 0.001 for all). Over a median (IQR) follow-up after surgery of 722 days (364-993), patients who underwent bariatric surgery had lost an average of 11.8 ± 18.5 kg (23% of excess body weight), 10.2% were on fewer glucose-lowering medications, and 8.4% were on fewer antihypertensives. Despite bariatric surgery being safer and more accessible over the past two decades, less than one in fifty eligible patients with diabetes receive this therapy.

Discrepancies Between the Management of Fever in Young Infants Admitted From Urban General Emergency Departments and Pediatric Emergency Departments.

INTRODUCTION/OBJECTIVE: Most pediatric emergency visits occur in general emergency departments (GED). Our study aims to assess whether medical decision making regarding the management of febrile infants differs in GEDs from pediatric EDs (PED) and deviates from pediatric expert consensus. METHODS: We conducted a retrospective chart review on patients younger than 60 days with fever admitted from 13 GEDs versus 1 PED to a children's hospital over a 3-year period. Adherence to consensus guidelines was measured by frequency of performing critical components of initial management, including blood culture, urine culture, attempted lumbar puncture, and antibiotic administration (<29 days old), or complete blood count and/or C-reactive protein, blood culture, and urine culture (29-60 days old). Additional outcomes included lumbar puncture, collecting urine specimens via catheterization, and timing of antibiotics. RESULTS: A total of 176 patient charts were included. Sixty-four (36%) patients were younger than 29 days, and 112 (64%) were 29 to 60 days old. Eighty-eight (50%) patients were admitted from GEDs.In infants younger than 29 days managed in the GEDs (n = 32), 65.6% (n = 21) of patients underwent all 4 critical items compared with 96.9% (n = 31, P = 0.003) in the PED. In infants 29 to 60 days old managed in GEDs (n = 56), 64.3% (n = 36) patients underwent all 3 critical items compared with 91.1% (n = 51, P < 0.001) in the PED. CONCLUSIONS: This retrospective study suggests that providers managing young infants with fever in 13 GEDs differ significantly from providers in the PED examined and literature consensus. Inconsistent testing and treatment practices may put young infants at risk for undetected bacterial infection.

Responses of three urban U.S. Children's Hospitals to COVID-19: Seattle, New York and New Orleans.

Since January 2020, there has been a worldwide pandemic of COVID-19, caused by a novel coronavirus-severe acute respiratory syndrome coronavirus 2. The United States has been particularly affected, with the largest number of confirmed cases in a single country in the world. Healthcare systems for adults as well as children have dealt with challenges. This article will reflect on the experiences of selected children's hospitals in Seattle, New York City, and New Orleans, three of the "hotspots" in the US and share common aspects and lessons learned from these experiences. This article discusses testing and cohorting of patients, personal protective equipment utilization, limiting workplace exposure, and information sharing.

Nanofluidic microsystem for sustained intraocular delivery of therapeutics.

Globally, 145.2 million people suffer from moderate to severe vision impairment or blindness due to preventable or treatable causes. However, patient adherence to topical or intravitreal treatment is a leading cause of poor outcomes. To address this issue, we designed an intraocularly implantable device called the nanofluidic Vitreal System for Therapeutic Administration (nViSTA) for continuous and controlled drug release based on a nanochannel membrane that obviates the need for pumps or actuation. In vitro release analysis demonstrated that our device achieves sustained release of bimatoprost (BIM) and dexamethasone (DEX) at concentrations within clinically relevant therapeutic window. In this proof of concept study, we constructed an anatomically similar in silico human eye model to simulate DEX release from our implant and gain insight into intraocular pharmacokinetics profile. Overall, our drug-agnostic intraocular implant represents a potentially viable platform for long-term treatment of various chronic ophthalmologic diseases, including diabetic macular edema and uveitis.

Efficacy of sustained delivery of GC-1 from a Nanofluidic system in a spontaneously obese non-human primate: a case study.

With nearly 40% of U.S. adults obese, and childhood and adolescent rates rising, obesity and associated comorbidities are serious public health concerns with massive societal costs. Often, lifestyle interventions do not offer sufficient weight loss to improve health, requiring surgery and medications as adjunct management strategies. Here, we present a 4-month case study in which the sustained, low-dose, and constant administration of the thyroid receptor ß selective agonist GC-1 (sobetirome) from a novel nanochannel membrane implant was assessed in an obese, pre-diabetic rhesus macaque. Dramatic loss of white adipose tissue in the abdomen from 36 to 18% was observed via magnetic resonance imaging in conjunction with normalized serum insulin and glycemia, with no signs of cardiotoxicity shown. The non-human primate study highlights sustained low-dose delivery of GC-1 from our minimally invasive subcutaneous implant as a valuable approach to induce weight loss and manage obesity and comorbidities, including type 2 diabetes.

Agathisflavone isolated from Anacardium occidentale suppresses SIRT1-mediated neuroinflammation in BV2 microglia and neurotoxicity in APPSwe-transfected SH-SY5Y cells.

Agathisflavone is a bioactive compound in Anacardium occidentale. In this study, we investigated inhibition neuroinflammation in BV2 microglia by agathisflavone. Neuroprotective activity of the compound was investigated in differentiated SH-SY5Y cells. Experiments in lipopolysaccharide (LPS)-activated BV2 microglia showed that pretreatment with agathisflavone (5-20 µM) produced significant reduction in the release of tumour necrosis factor-α, interleukin-6, interleukin-1ß, NO, and PGE2 from the cells. Immunoblotting experiments also revealed that agathisflavone reduced levels of iNOS and COX-2 protein. Further studies revealed that agathisflavone reduced neuroinflammation by targeting critical steps in NF-κB signalling in BV2 microglia. Treatment of SH-SY5Y cells with conditioned medium from LPS-activated BV2 microglia produced a significant reduction in neuronal viability. However, conditioned medium from BV2 cells that were stimulated with LPS in the presence of agathisflavone did not induce neurotoxicity. Agathisflavone also produced neuroprotection in APPSwe plasmid-transfected SH-SY5Y neurons. The compound further attenuated LPS-induced and APPSwe plasmid-induced reduction in SIRT1 in BV2 microglia and SH-SY5Y, respectively. In the presence of EX527, agathisflavone lost its anti-inflammatory and neuroprotective activities. Our results suggest that agathisflavone inhibits neuroinflammation in BV2 microglia by targeting NF-κB signalling pathway. The compound also reduces neurotoxicity through mechanisms that are possibly linked to SIRT1 in the microglia and neurons.

A pharmacokinetic study of GC-1 delivery using a nanochannel membrane device.

This study demonstrated a nanochannel membrane device (NMD) for controlled and sustained release of GC-1 in rats, in the context of the treatment of metabolic syndrome. Release profiles were established in vitro both with and without 5% labrasol for over 2 months. In vivo pharmacokinetic evaluation showed effective GC-1 plasma concentrations, which resulted in significant reductions in body weight after just one week of treatment when compared to the NMD releasing vehicle only (PBS). We also provided evidence that rats treated with NMD-GC-1 present sub-active thyroids and clear differences in the morphology of the epithelium and follicles as compared to the controls, while the heart showed changes in weight. Moreover, body temperatures remained stable throughout treatment, and glucose, pancreatic islet size, and liver histology appeared similar between the treated and control groups. Prolonged constant administration of GC-1 from the NMD proved to be a valid strategy to facilitate weight loss.

Diagnosis and management of dementia in family practice.

BACKGROUND: Improving quality of care for people with dementia is a high priority. Considerable resources have been invested in financial incentives, guideline development, public awareness and educational programmes to promote earlier diagnosis and better management. OBJECTIVES: Evaluating family physicians' concordance with guidelines on diagnosis and management of people with dementia, from first documentation of symptoms to formal diagnosis. METHOD: Analysis of medical records of 136 people with dementia recruited by 19 family practices in NW London and surrounding counties. RESULTS: Practices invited 763 people with dementia to participate, 167 (22%) agreed. Complete records were available for 136 (18%). The majority of records included reference to recommended blood tests, informant history and caregiver concerns. Presence or absence of symptoms of depression, psychosis, other behavioural and psychological symptoms of dementia, and cognitive function tests were documented in 30%-40% of records. Documentation of discussions about signs and symptoms of dementia, treatment options, care, support, financial, legal and advocacy advice were uncommon. Comparison of these findings from a similar study in 2000-2002 suggests improvements in concordance with blood tests, recording informant history, presence or absence of depression or psychosis symptoms. There was no difference in documenting cognitive function tests. Immediate referral to specialists was more common in the recent study. CONCLUSION: Five years after UK dementia guidelines and immediately after the launch of the dementia strategy, family physicians appeared concordant with clinical guidelines for dementia diagnosis (other than cognitive function tests), and referred most patients immediately. However, records did not suggest systematic dementia management.

Tuning the d-Band Center in Prussian Blue Analogues via Modulated Carbon and Nitrogen Coordinated Metals for Boosted Bi-Functional Oxygen Electrocatalytic Activity.

The d-band center is a promising descriptor to understand trends in electrocatalysis extensively studied in transition metal oxides but largely unexplored in metal organic frameworks (MOFs). Herein, we present our systematic study aimed at developing a mini-volcano plot demonstrating dependence of bifunctional oxygen electrocatalytic activity of Prussian blue analogues (PBAs) on their d-band center. Our results from ex-situ core level and valence band XPS, Raman, and FTIR spectroscopy suggest that the tuning of the d-band center via modulated N and C-coordinated metal centers dictates their electrocatalytic OER and ORR activities. Among PBAs, the CoCo PBA exhibits highest activity due to its optimal position of d-band center and abundant Co3+ active sites. Moreover, M-Co PBAs showcased superior performance compared to M-Fe PBAs, attributed to facile formation of surface-active sites, i.e., metal oxy(hydroxide). The study advances the understanding of the influence of metal center tuning in PBAs on the intermediate energies and catalytic activity.

Catalytic reduction of oxygen to water by non-heme iron complexes: exploring the effect of the secondary coordination sphere proton exchanging site.

In this study, we prepared non-heme FeIII complexes (1, 2, and 3) of an N4 donor set of ligands (H2L, Me2L, and BPh2L). 1 is supported by a monoanionic bispyridine-dioxime ligand (HL). In 2 and 3, the primary coordination sphere of Fe remained similar to that in 1, except that the oxime protons of the ligand were replaced with two methyl groups and a bridging -BPh2 moiety, respectively. X-ray structures of the FeII complexes (1a and 3a) revealed similar Fe-N distances; however, they were slightly elongated in 2a. The FeIII/FeII potential of 1, 2, and 3 appeared at -0.31 V, -0.25 V, and 0.07 V vs. Fc+/Fc, respectively, implying that HL and Me2L have comparable donor properties. However, BPh2L is more electron deficient than HL or Me2L. 1 showed electrocatalytic oxygen reduction reaction (ORR) activity in acetonitrile in the presence of trifluoroacetic acid (TFAH) as the proton source at Ecat/2 = -0.45 V and revealed selective 4e-/4H+ reduction of O2 to H2O. 1 showed an effective overpotential (ηeff) of 0.98 V and turnover frequency (TOFmax) of 1.02 × 103 s-1. Kinetic studies revealed a kcat of 2.7 × 107 M-2 s-1. Strikingly, 2 and 3 remained inactive for electrocatalytic ORR, which established the essential role of the oxime scaffolds in the electrocatalytic ORR of 1. Furthermore, a chemical ORR of 1 has been investigated using decamethylferrocene as the electron source. For 1, a similar rate equation was noted to that of the electrocatalytic pathway. A kcat of 6.07 × 104 M-2 s-1 was found chemically. Complex 2, however, underwent a very slow chemical ORR. Complex 3 chemically enhances the 4e-/4H+ reduction of O2 and exhibits a TOF of 0.24 s-1 and a kcat value of 2.47 × 102 M-1 s-1. Based on the experimental observations, we demonstrate that the oxime backbone of the ligand in 1 works as a proton exchanging site in the 4e-/4H+ reduction of O2. The study describes how the ORR is affected by the tuning of the ligand scaffold in a family of non-heme Fe complexes.

Impact of a Coordinated Sepsis Response on Time to Treatment in a Pediatric Emergency Department.

BACKGROUND: Sepsis is responsible for 75 000 pediatric hospitalizations annually, with an associated mortality rate estimated between 11% and 19%. Evidence supports the use of timely fluid resuscitation and antibiotics to decrease morbidity and mortality. Our emergency department did not meet the timeliness goals for fluid and antibiotic administration suggested by the 2012 Surviving Sepsis Campaign. METHODS: In November 2018, we implemented a sepsis response team utilizing a scripted communication tool and a dedicated sepsis supply cart to address timeliness barriers. Performance was evaluated using statistical process control charts. We conducted observations to evaluate adherence to the new process. Our aim was to meet the Surviving Sepsis Campaign's timeliness goals for first fluid and antibiotic administration (20 and 60 minutes, respectively) within 8 months of our intervention. RESULTS: We observed sustained decreases in mean time to fluids. We also observed a shift in the proportion of patients receiving fluids within 20 minutes. No shifts were observed for timely antibiotic administration. CONCLUSIONS: The implementation of a dedicated emergency department sepsis response team with designated roles and responsibilities, directed communication, and easily accessible supplies can lead to improvements in the timeliness of fluid administration in the pediatric population.

A novel cobalt(ii) acetate complex bearing lutidine ligand: a promising electrocatalyst for oxygen evolution reaction.

Developing cost-effective electrocatalysts using earth-abundant metal as an alternative to expensive precious metal catalyst remains a key challenge for researchers. Several strategies are being researched/tested for making low-cost transition metal complexes with controlled electron-density and coordination flexibility around the metal center to enhance their catalytic activity. Herein, we report a novel lutidine coordinated cobalt(ii) acetate complex [(3,5-lutidine)2Co(OAc)2(H2O)2] (1) as a promising electrocatalyst for oxygen evolution reaction (OER). Complex 1 was characterized by FT-IR, elemental analysis, and single crystal X-ray diffraction data. The structure optimization of complex 1 was also done using DFT calculation and the obtained geometrical parameters were found to be in good agreement with the parameters obtained from the solid state structure obtained through single crystal X-ray diffraction data. Further, the molecular electrostatic potential (MEP) maps analysis of complex 1 observed electron rich centers that were found to be in agreement with the solid-state structure. It was understood that the coordination of lutidine as a Lewis base and acetate moiety as a flexible ligand will provide more coordination flexibility around the metal center to facilitate the catalytic reaction. Further, the electron rich centers around metal center will also support the enhancement of their catalytic activity. Complex 1 shows impressive OER activity, even better than the state-of-the-art IrO2 catalyst, in terms of turnover frequency (TOF: 0.05) and onset potential (1.50 V vs. RHE). The TOF for complex 1 is two and half times higher, while the onset potential is ca. 20 mV lower, than the benchmark IrO2 catalyst studied under identical conditions.

An Innovative Polymeric Platform for Controlled and Localized Drug Delivery.

Precision medicine aims to optimize pharmacological treatments by considering patients' genetic, phenotypic, and environmental factors, enabling dosages personalized to the individual. To address challenges associated with oral and injectable administration approaches, implantable drug delivery systems have been developed. These systems overcome issues like patient adherence, bioavailability, and first-pass metabolism. Utilizing new combinations of biodegradable polymers, the proposed solution, a Polymeric Controlled Release System (PCRS), allows minimally invasive placement and controlled drug administration over several weeks. This study's objective was to show that the PCRS exhibits a linear biphasic controlled release profile, which would indicate potential as an effective treatment vehicle for cervical malignancies. An injection mold technique was developed for batch manufacturing of devices, and in vitro experiments demonstrated that the device's geometry and surface area could be varied to achieve various drug release profiles. This study's results motivate additional development of the PCRS to treat cervical cancer, as well as other malignancies, such as lung, testicular, and ovarian cancers.

Characteristics, treatment patterns, health care resource utilization and costs in patients with bullous pemphigoid: A retrospective analysis of US health insurance claims data.

Background: Real-world data describing the impact of incident bullous pemphigoid (BP) on patients and health care resource utilization (HCRU) are limited. Objective: To examine characteristics, treatment patterns, HCRU, and costs for incident BP. Methods: Retrospective analysis of 2015 to 2019 US health insurance claims for patients ≥18 years with an incident BP diagnosis. Patients with BP were matched to those without on demographic and clinical characteristics. Statistics were descriptive. Results: The mean Charlson Comorbidity Index score was higher for patients with BP (n = 1108) than without (n = 4621) at baseline (mean [SD]: 3.3 [2.7] vs 2.8 [2.4]) and during follow-up (5.0 [4.9] vs 3.7 [3.0]). Hypertension, diabetes, skin ulcers, chronic pulmonary disease, dyslipidemia, sleep disorders, and congestive heart failure were higher with BP. Most patients with BP received antibiotics (>80%) and/or corticosteroids (>90%). Hospitalizations were more common (44.0% vs 17.1%) and monthly all-cause health care costs more than double ($3214 vs $1353) in patients with BP than without. Limitations: Diagnoses were based on billing codes. HCRU claims data may not reflect the true number of encounters. Conclusion: Incident BP is associated with considerable morbidity, HCRU, and costs. More effective, targeted treatments are needed to improve quality of life, while minimizing exposure to systemic corticosteroids.

Effects of Longitudinal Coaching on Relationships and Feedback Processes in Pediatric Subspecialty Fellowships-An Interpretive Description Study.

Background: Coaching in graduate medical education provides a facilitative approach to feedback as well as opportunities for residents and fellows to engage with feedback and develop individualized improvement goals. Objective: To explore the roles and actions of successful coaches in longitudinal coaching relationships and how they enable feedback processes. Methods: Using interpretive description methodology, we performed semi-structured interviews with pediatrics fellows (n=11), faculty coaches (n=9), and program directors (n=2) from 2 pediatric subspecialty fellowship training programs at Ann and Robert H. Lurie Children's Hospital of Chicago. Both training programs had previously implemented longitudinal clinical coaching programs. Interview questions aimed to explore the roles and impacts of coaches within a longitudinal coaching program. Interviews took place in 2019 and 2020. Results: We identified 4 major actions to the coaching role in longitudinal coaching relationships: (1) establish the coach-fellow relationship; (2) prepare for the coaching conversation; (3) facilitate feedback dialogue; and (4) serve as the go-to person to raise uncomfortable issues. Additionally, nearly all participants expressed support for a longitudinal coaching program to support fellows' growth and development of personalized learning goals. Conclusions: By fulfilling these 4 key aspects to the coaching role, coaches in longitudinal relationships with coachees enable feedback processes.

Use of argatroban as a procedural and bridging anticoagulant in a patient undergoing carotid endarterectomy with concomitant atrial fibrillation.

OBJECTIVE: To describe the use of argatroban as a procedural and bridging anticoagulant in a patient with a previous history of heparin allergy and atrial fibrillation undergoing carotid endarterectomy. CASE SUMMARY: A 78-year-old female with a history of heparin-induced thrombocytopenia (HIT) and multiple medical comorbidities, including atrial fibrillation requiring chronic anticoagulation with warfarin, was found to have greater than 70% stenosis of her left carotid artery by standard duplex imaging. Her warfarin therapy was discontinued as an outpatient approximately 48 hours prior to an elective left carotid endarterectomy and she was started on argatroban 2 µg/kg/min for bridging therapy. The endarterectomy was successfully performed while the patient was maintained on a continuous argatroban infusion. The dose was adjusted by 0.25-µg/kg/min intervals to achieve and maintain an activated clotting time of greater than 200 seconds during the procedure. Her postoperative course was unremarkable and she was transitioned back to warfarin and subsequently discharged home. DISCUSSION: HIT poses a challenge for patients in need of vascular surgery. Optimally, one would postpone any surgical intervention until the heparin antibodies are cleared from circulation, which on average takes about 100 days. In theory, it is safe to reexpose these patients to heparin products upon clearance of the antibody; however, there is scant literature available to show its safety. Current guidelines recommend limiting heparin exposure in any patients with a history of HIT, but the optimal alternative anticoagulant in this setting is unclear. There are several direct thrombin inhibitors available, but argatroban seemed to be a logical choice for our patient, especially in the setting of renal insufficiency, given its favorable pharmacokinetics and ease of monitoring with readily available coagulation tests. To our knowledge, this is the second reported case of the systemic use of argatroban in carotid endarterectomy in a patient with a previous history of HIT. CONCLUSIONS: Argatroban may be an effective anticoagulant during carotid endarterectomy in patients with underlying chronic renal disease and a history of HIT. Additional research is needed to determine the ideal anticoagulant in vascular surgery when heparin cannot be utilized.