Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signalling and airway inflammation.

RATIONALE: Respiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of interferon-stimulated genes (ISGs). How asthma-susceptibility genes modulate cellular response upon viral infection by fine-tuning ISG induction and subsequent airway inflammation in genetically susceptible asthma patients remains largely unknown. OBJECTIVES: To decipher the functions of gasdermin B (encoded by GSDMB) in respiratory virus-induced lung inflammation. METHODS: In two independent cohorts, we analysed expression correlation between GSDMB and ISG s. In human bronchial epithelial cell line or primary bronchial epithelial cells, we generated GSDMB-overexpressing and GSDMB-deficient cells. A series of quantitative PCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism of GSDMB for ISG induction. We also generated a novel transgenic mouse line with inducible expression of human unique GSDMB gene in airway epithelial cells and infected the mice with respiratory syncytial virus to determine the role of GSDMB in respiratory syncytial virus-induced lung inflammation in vivo. RESULTS: GSDMB is one of the most significant asthma-susceptibility genes at 17q21 and acts as a novel RNA sensor, promoting mitochondrial antiviral-signalling protein (MAVS)-TANK binding kinase 1 (TBK1) signalling and subsequent inflammation. In airway epithelium, GSDMB is induced by respiratory viral infections. Expression of GSDMB and ISGs significantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of human GSDMB in mouse airway epithelium led to enhanced ISGs induction and increased airway inflammation with mucus hypersecretion upon respiratory syncytial virus infection. CONCLUSIONS: GSDMB promotes ISGs expression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers.

Sepsis: Diagnosis and Management.

Guidelines published in 2016 provide a revised definition of sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection. The guidelines define septic shock as sepsis with circulatory, cellular, and metabolic dysfunction that is associated with a higher risk of mortality. The measurement of serum lactate has been incorporated into the latest septic shock definition. The guidelines recommend the Sequential Organ Failure Assessment (original and quick versions) as an important tool for early diagnosis. Respiratory, gastrointestinal, genitourinary, and skin and soft tissue infections are the most common sources of sepsis. Pneumonia is the most common cause of sepsis. Although many patients with sepsis have fever, the clinical manifestation can be subtle, particularly in older patients and those who are immunocompromised. Initial evaluation of patients with suspected sepsis includes basic laboratory tests, cultures, imaging studies as indicated, and sepsis biomarkers such as procalcitonin and lactate levels. Fluid resuscitation is the priority in early management, including administering an intravenous crystalloid at 30 mL per kg within the first three hours. Antimicrobial therapy should also be initiated early. Most research indicates that antimicrobial therapy should be started within three hours of presentation. The latest guidelines recommend starting antimicrobials within one hour, but this is controversial. Vasopressor therapy is indicated if hypotension persists despite fluid administration. Future trials of sepsis management are focusing on improving long-term rates of readmission and death, physical disability, cognitive impairment, and quality of life.

Diagnosis and management of inhalation injury: an updated review.

In this article we review recent advances made in the pathophysiology, diagnosis, and treatment of inhalation injury. Historically, the diagnosis of inhalation injury has relied on nonspecific clinical exam findings and bronchoscopic evidence. The development of a grading system and the use of modalities such as chest computed tomography may allow for a more nuanced evaluation of inhalation injury and enhanced ability to prognosticate. Supportive respiratory care remains essential in managing inhalation injury. Adjuncts still lacking definitive evidence of efficacy include bronchodilators, mucolytic agents, inhaled anticoagulants, nonconventional ventilator modes, prone positioning, and extracorporeal membrane oxygenation. Recent research focusing on molecular mechanisms involved in inhalation injury has increased the number of potential therapies.

Transcriptional and functional consequences of Oncostatin M signaling on young Dnmt3a-mutant hematopoietic stem cells.

Age-associated clonal hematopoiesis (CH) occurs due to somatic mutations accrued in hematopoietic stem cells (HSCs) that confer a selective growth advantage in the context of aging. The mechanisms by which CH-mutant HSCs gain this advantage with aging are not comprehensively understood. Using unbiased transcriptomic approaches, we identified Oncostatin M (OSM) signaling as a candidate contributor to age-related Dnmt3a-mutant CH. We found that Dnmt3a-mutant HSCs from young adult mice (3-6 months old) subjected to acute OSM stimulation do not demonstrate altered proliferation, apoptosis, hematopoietic engraftment, or myeloid differentiation. Dnmt3a-mutant HSCs from young mice do transcriptionally upregulate an inflammatory cytokine network in response to acute in vitro OSM stimulation as evidenced by significant upregulation of the genes encoding IL-6, IL-1ß, and TNFα. OSM-stimulated Dnmt3a-mutant HSCs also demonstrate upregulation of the anti-inflammatory genes Socs3, Atf3, and Nr4a1. In the context of an aged bone marrow (BM) microenvironment, Dnmt3a-mutant HSCs upregulate proinflammatory genes but not the anti-inflammatory genes Socs3, Atf3, and Nr4a1. The results from our studies suggest that aging may exhaust the regulatory mechanisms that HSCs employ to resolve inflammatory states in response to factors such as OSM.

The Asthma Risk Gene, GSDMB, Promotes Mitochondrial DNA-induced ISGs Expression.

Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes inflammation, as frequently seen in asthmatic airways. However, whether the genetic determinant, Gasdermin B (GSDMB), the most replicated asthma risk gene, regulates this pathway remains unknown. We set out to determine whether and how GSDMB regulates mtDNA-activated cGAS-STING pathway and subsequent ISGs induction in human airway epithelial cells. Using qPCR, ELISA, native polyacrylamide gel electrophoresis, co-immunoprecipitation and immunofluorescence assays, we evaluated the regulation of GSDMB on cGAS-STING pathway in both BEAS-2B cells and primary normal human bronchial epithelial cells (nHBEs). mtDNA was extracted in plasma samples from human asthmatics and the correlation between mtDNA levels and eosinophil counts was analyzed. GSDMB is significantly associated with RANTES expression in asthmatic nasal epithelial brushing samples from the Genes-environments and Admixture in Latino Americans (GALA) II study. Over-expression of GSDMB promotes DNA-induced IFN and ISGs expression in bronchial epithelial BEAS-2B cells and nHBEs. Conversely, knockout of GSDMB led to weakened induction of interferon (IFNs) and ISGs in BEAS-2B cells. Mechanistically, GSDMB interacts with the C-terminus of STING, promoting the translocation of STING to Golgi, leading to the phosphorylation of IRF3 and induction of IFNs and ISGs. mtDNA copy number in serum from asthmatics was significantly correlated with blood eosinophil counts especially in male subjects. GSDMB promotes the activation of mtDNA and poly (dA:dT)-induced activation of cGAS-STING pathway in airway epithelial cells, leading to enhanced induction of ISGs.

Oncostatin M is a Master Regulator of an Inflammatory Network in Dnmt3a -Mutant Hematopoietic Stem Cells.

Age-associated clonal hematopoiesis (CH) occurs due to somatic mutations accrued in hematopoietic stem cells (HSCs) that confer a selective advantage in the context of aging. The mechanisms by which CH-mutant HSCs gain this advantage with aging are not comprehensively understood. Using unbiased transcriptomic approaches, we identify Oncostatin M (OSM) signaling as a candidate contributor to aging-driven Dnmt3a -mutant CH. We find that Dnmt3a -mutant HSCs from young mice do not functionally respond to acute OSM stimulation with respect to proliferation, apoptosis, hematopoietic engraftment, or myeloid differentiation. However, young Dnmt3a -mutant HSCs transcriptionally upregulate an inflammatory cytokine network in response to acute OSM stimulation including genes encoding IL-6, IL-1ß and TNFα. In addition, OSM-stimulated Dnmt3a -mutant HSCs upregulate the anti-inflammatory genes Socs3, Atf3 and Nr4a1 , creating a negative feedback loop limiting sustained activation of the inflammatory network. In the context of an aged bone marrow (BM) microenvironment with chronically elevated levels of OSM, Dnmt3a -mutant HSCs upregulate pro-inflammatory genes but do not upregulate Socs3, Atf3 and Nr4a1 . Together, our work suggests that chronic inflammation with aging exhausts the regulatory mechanisms in young CH-mutant HSCs that resolve inflammatory states, and that OSM is a master regulator of an inflammatory network that contributes to age-associated CH.

CRISPR interference interrogation of COPD GWAS genes reveals the functional significance of desmoplakin in iPSC-derived alveolar epithelial cells.

Genome-wide association studies (GWAS) have identified dozens of loci associated with chronic obstructive pulmonary disease (COPD) susceptibility; however, the function of associated genes in the cell type(s) affected in disease remains poorly understood, partly due to a lack of cell models that recapitulate human alveolar biology. Here, we apply CRISPR interference to interrogate the function of nine genes implicated in COPD by GWAS in induced pluripotent stem cell-derived type 2 alveolar epithelial cells (iAT2s). We find that multiple genes implicated by GWAS affect iAT2 function, including differentiation potential, maturation, and/or proliferation. Detailed characterization of the GWAS gene DSP demonstrates that it regulates iAT2 cell-cell junctions, proliferation, mitochondrial function, and response to cigarette smoke-induced injury. Our approach thus elucidates the biological function, as well as disease-relevant consequences of dysfunction, of genes implicated in COPD by GWAS in type 2 alveolar epithelial cells.

Casualty Evacuation (CASEVAC) Platform Review and Case Series of US Military Enroute Critical Care Team With Contract Personnel Recovery Services in an Austere Environment.

In a rapidly changing operational environment, in which there has been an emphasis on prolonged field care and limited evacuation platforms, military providers must practice to the full scope of their training to maximize outcomes. In addition to pushing military providers further into combat zones, the Department of Defense has relied on contracted personnel to help treat and evacuate servicemembers. This article is a retrospective review on the interoperability of the expeditionary resuscitative surgical team (ERST) and a contracted personnel recovery (CPR) team in a far-forward austere environment and will discuss actual patient transport case reviews that used multiple evacuation platforms across thousands of miles of terrain. To effectively incorporate CPR personnel into a military transport team model, we recommend including cross-training on equipment and formularies, familiarization with CPR evacuation platforms, and mass casualty (MASCAL) exercises that incorporate the different platforms available.

A Non-Comparative Prospective Pilot Study of Ketamine for Sedation in Adult Septic Shock.

Introduction: Sedation and analgesia in the intensive care unit (ICU) for patients with sepsis can be challenging. Opioids and benzodiazepines can lower blood pressure and decrease respiratory drive. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that provides both amnesia and analgesia without depressing respiratory drive or blood pressure. The purpose of this pilot study was to assess the effect of ketamine on the vasopressor requirement in adult patients with septic shock requiring mechanical ventilation. Materials and Methods: We conducted a two-phase study in a multi-disciplinary adult ICU at a tertiary medical center. The first phase was a retrospective chart review of patients admitted with septic shock between July 2010 and July 2011; 29 patients were identified for a historical control group. The second phase was a prospective, non-randomized, open-label pilot study. Patients were eligible for inclusion if they were 18-89 yr of age with a diagnosis of septic shock, who also required mechanical ventilation for at least 24 h, concomitant sedation, and vasopressor therapy. Pregnant patients, patients in the peri-operative timeframe, and patients with acute coronary syndrome were excluded. Patients enrolled in the phase two pilot study received ketamine as the primary sedative. Ketamine was administered as a 1-2 mg/kg IV bolus, then as a continuous infusion starting at 5 mcg/kg/min, titrated 2 mcg/kg/min every 30 min as needed to obtain a Richmond Agitation Sedation Scale (RASS) goal of -1 to -2. If continuous sedation was still required after 48 h, patients were transitioned off ketamine and sedative strategy reverted to usual ICU sedation protocol. The primary outcome was the dose of vasopressor required at 24, 48, 72 and 96 h after enrollment. Secondary outcomes included cumulative ketamine dose, additional sedative and analgesics used, cumulative sedative and analgesic dosing at all time periods, corticosteroid use, days of mechanical ventilation, ICU LOS, hospital LOS, and mortality. Contiguous data were analyzed with unpaired t-tests and categorical data were analyzed with two-tailed, Fisher's exact test. This study was approved by our Institutional Review Board. Results: From January 2012 to April 2015, a total of 17 patients were enrolled. Patient characteristics were similar in the control and study group. Ketamine was discontinued in one patient due to agitation at 36 h. There was a trend towards decreased norepinephrine and vasopressin use in the study group at all time periods. Regarding secondary outcomes, the study group received less additional analgesia with fentanyl at 24 and 48 h (p < 0.001), and less additional sedation with lorazepam, midazolam or dexmedetomidine at 24 h (p = 0.015). Conclusion: This pilot study demonstrated a trend towards decreased vasopressor dose, and decreased benzodiazepine and opiate use when ketamine is used as the sole sedative. The limitations to our study include a small sample size and those inherent in using a retrospective control group. Our findings should be further explored in a large, randomized prospective study.

Inhalation Injury and Toxic Industrial Chemical Exposure.

Toxic industrial chemicals include chlorine, phosgene, hydrogen sulfide, and ammonia have variable effects on the respiratory tract, and maybe seen alone or in combination, secondary to inhalation injury. Other considerations include the effects of cyanide, carbon monoxide, and fire suppressants. This Clinical Practice Guideline (CPG) will provide the reader with a brief overview of these important topics and general management strategies for each as well as for inhalation injury. Chlorine, phosgene, hydrogen sulfide, and ammonia are either of intermediate or high water solubility leading to immediate reactions with mucous membranes of the face, throat, and lungs and rapid symptoms onset after exposure. The exception to rapid symptom onset is phosgene which may take up to a day to develop severe acute respiratory distress syndrome. Management of these patients includes early airway management, lung-protective ventilator strategies, aggressive pulmonary toilet, and avoidance of volume overload.

Burn Casualty Care in the Deployed Setting.

Management of wartime burn casualties can be very challenging. Burns frequently occur in the setting of other blunt and penetrating injuries. This clinical practice guideline provides a manual for burn injury assessment, resuscitation, wound care, and specific scenarios including chemical and electrical injuries in the deployed or austere setting. The clinical practice guideline also reviews considerations for the definitive care of local national patients, including pediatric patients, who are unable to be evacuated from theater. Medical providers are encouraged to contact the US Army Institute of Surgical Research (USAISR) Burn Center when caring for a burn casualty in the deployed setting.

The bee sting that was not: an unusual case of hymenoptera anaphylaxis averted in a patient treated with omalizumab for asthma.

This paper presents a case of hymenoptera venom anaphylaxis averted by omalizumab, a monoclonal antibody to IgE antibody. This case suggests a novel and unintentional effect of this therapy. Currently omalizumab is only FDA approved for the treatment of moderate-persistent allergic asthma. However case reports, such as ours have illustrated omalizumab's efficacy in the treatment of a myriad immunologic and allergic diseases. These outcomes have broadened the understanding of omalizumab's complex mechanism of action.

Analysis of an electromagnetic tube placement device versus a self-advancing nasal jejunal device for postpyloric feeding tube placement.

BACKGROUND: Initiation of enteral feeding is an important part of the best practice model for critically ill patients. Although nasogastric feeding is appropriate for the majority of patients requiring short-term nutrition support, certain patients benefit greatly from postpyloric feeding. OBJECTIVE: To determine which of 2 specialized enteral tube systems achieved postpyloric placement on initial insertion attempt most efficiently. DESIGN: Retrospective study comparing the Tiger 2 tube (T2T) and Cortrak Enteral Access System (C-EAS). SETTING: Academic medical center, mixed intensive care unit (ICU). PATIENTS: All patients admitted to the ICU between 2009 and 2013 who had either a C-EAS or T2T placed. MEASUREMENTS: Success rate for postpyloric placement, congruency of real-time tube placement with x-ray confirmation for C-EAS, and complication rates. RESULTS: Seventy-one T2T and 74 C-EAS patients were included. The T2T was postpyloric 62% (44/71) of attempted placements. C-EAS was postpyloric 43% (32/74) of attempted placements (P = 0.03). C-EAS tracings accurately reflected chest x-ray findings 83% and 82% for postpyloric and non-postpyloric insertion, respectively. During the entire study period, no adverse events were recorded. CONCLUSION: Our institution evaluated 2 different systems designed to ensure postpyloric placement of a small bore feeding tube. No literature exists directly comparing the 2 systems. Our retrospective review, although limited, showed that the T2T was more effective at postpyloric placement on first attempt. Although 1 benefit of the C-EAS system may be real-time visualization, our practice showed this system to be user dependent, which likely led to less success with postpyloric placement.

Coronary artery aneurysms in acute coronary syndrome: case series, review, and proposed management strategy.

Coronary artery aneurysm (CAA) is an uncommon clinical finding, with an incidence varying from 1.5%-4.9% in adults, and is usually considered a variant of coronary artery disease (CAD). CAA identified in the context of acute coronary syndrome (ACS) represents a unique management challenge, particularly if the morphology of the CAA is suspected to have provoked the acute clinical syndrome. CAA is associated with thrombus formation due to abnormal laminar flow, as well as abnormal platelet and endothelial-derived pathophysiologic factors within the CAA. Once formed, mural thrombus may potentiate the deposition of additional thrombus within aneurysmal segments. Percutaneous revascularization of CAA has been associated with complications including distal embolization of thrombus, no-reflow phenomenon, stent malapposition, dissection, and rupture. Presently, there are no formal guidelines to direct the management of CAA in patients presenting with ACS; controversies exist whether conservative, surgical, or catheter-based management should be pursued. In this manuscript, we present an extensive review of the existing literature and associated clinical guidelines, and propose a management algorithm for patients with this complex clinical scenario. Armed with this perspective, therapeutic decisions may be tailored to synthesize patient factors and preferences, individualized clinical assessment, and existing American Heart Association/American College of Cardiology guidelines for management of ACS.

CT-reconstructed three-dimensional printed models of the right subclavian artery and aorta define age-related changes and facilitate benchtop catheter testing.

BACKGROUND: Severe tortuosity of the right subclavian artery (RSCA) encountered during transradial cardiac catheterization can lead to longer procedures, increased fluoroscopy time, inability to engage the coronary artery ostia, and potentially procedural failure. Increasing age is strongly correlated with subclavian tortuosity; however, the magnitude and direction of age-related changes in aortic and subclavian artery anatomy have not been defined. METHODS: Chest computed tomography (CT) angiograms of 14 patients (6 age <45 years and 8 age ≥75 years) were evaluated for RSCA tortuosity. Measurements were taken along the midline of the vessel and compared to the straight distance traveled (index of tortuosity = straight distance/midline length). One normal and one tortuous subclavian were selected for three-dimensional printing and various catheters were benchtop tested on both models. RESULTS: The older group had longer (11.95 cm vs 9.6 cm; P<.01) and more tortuous subclavian arteries (lower index of tortuosity, 0.65 vs 0.76; P<.01) with more posterior unfolding (distance to most posterior aspect, 3.74 ± 0.77 cm vs 1.76 ± 0.58 cm; P<.001). Engagement of the coronary arteries of the normal model was significantly easier, with successful engagement of one or both coronaries with every catheter (n=7). Only 2 of 7 catheters (Radial Brachial and Extra Backup 3.0) were able to engage the coronary arteries in the tortuous model. CONCLUSION: Age is associated with elongation, tortuosity, and posterior unfolding of the RSCA. Three-dimensional printing of normal and tortuous arteries is feasible and shows potential to test differences between catheters.

Aortic stiffness is associated with left ventricular diastolic dysfunction in systemic lupus erythematosus: a controlled transesophageal echocardiographic study.

BACKGROUND: Aortic stiffness and left ventricular (LV) diastolic dysfunction are common and associated with increased morbidity and mortality in systemic lupus erythematosus (SLE). HYPOTHESIS: In SLE, aortic stiffness and LV diastolic dysfunction may be associated. METHODS: This 6-year-duration, cross-sectional, and controlled study was conducted in 76 SLE patients (69 women; mean age, 37 ± 12 years) and 26 age- and sex-matched healthy controls. All subjects underwent clinical and laboratory evaluations and transesophageal echocardiography (TEE) to assess LV diastolic function and stiffness of the descending thoracic aorta using the pressure-strain elastic modulus (PSEM). To validate results using PSEM, aortic strain, stiffness, and distensibility were assessed. RESULTS: Patients as compared with controls had higher PSEM (8.14 ± 4.25 vs 5.97 ± 2.31 U, P < 0.001) and had lower mitral inflow E/A and septal and lateral mitral annulus tissue Doppler E'/A' velocity ratios, longer isovolumic relaxation time, lower septal and lateral mitral annulus E' velocities, and higher mitral E/septal E' and mitral E/lateral E' velocity ratios (all P ≤ 0.03), all indicative of LV diastolic dysfunction. In patients, PSEM was correlated with parameters of LV diastolic dysfunction (all P < 0.05), was independently negatively associated with E/A and E'/A' ratios and E' velocities, and was positively associated with E/E' ratios (P ≤ 0.02 for each parameter and P < 0.001 for all parameters as a profile). Aortic strain, stiffness, and distensibility were also worse in patients than in controls (all P < 0.05) and were correlated with parameters of LV diastolic dysfunction (all P ≤ 0.03). CONCLUSIONS: Aortic stiffness is independently associated with LV diastolic dysfunction in young adult patients with SLE.

High femoral artery bifurcation predicts contralateral high bifurcation: implications for complex percutaneous cardiovascular procedures requiring large caliber and/or dual access.

Recent advances in technology have led to an increase in the use of bilateral femoral artery access and the requirement for large-bore access. Optimal access is in the common femoral artery (CFA), rather than higher (in the external iliac artery) or lower (in one of the branches of the CFA). However, there is a paucity of data in the literature about the relationship between bifurcation level of one CFA and the contralateral CFA. To define the prevalence of high bifurcation of the CFA and the relationship between bifurcation level on both sides, we performed a retrospective analysis of all patients with bilateral femoral angiography. From 4880 femoral angiograms performed at UCSF cardiac catheterization laboratory between 2005-2013, a total of 273 patients had bilateral femoral angiograms. The prevalence of low/normal, high, and very-high femoral bifurcations was 70%, 26%, and 4%, respectively, with no difference between sides. A high or very-high bifurcation significantly increased the likelihood of a high bifurcation on the contralateral side (odds ratio >3.0). Multivariable logistic regression analysis revealed age, gender, self-reported race, height, weight, and body mass index were not predictive of high or very-high bifurcations on either side. In conclusion, high femoral artery bifurcations are common and increase the likelihood of a high bifurcation of the contralateral femoral artery.

Tacrolimus-associated thrombotic microangiopathy in a lung transplant recipient.

A 25-year-old woman with a history of bilateral lung transplant secondary to cystic fibrosis presented with non-specific abdominal complaints and was found to have acute kidney injury, thrombocytopaenia and laboratory findings consistent with a microangiopathic haemolytic anaemia. Her thrombotic microangiopathy (TMA) was attributed to tacrolimus, which was discontinued and replaced with cyclosporine with resolution of her TMA and no subsequent complications. This is the fifth reported case of TMA associated with tacrolimus use in a lung transplant patient, and the third to be successfully managed with cyclosporine substitution. Clinicians must be aware of this uncommon, but likely under-reported complication of tacrolimus therapy in lung transplant recipients. Cyclosporine replacement may be used as a successful therapy to treat tacrolimus-associated TMA without increasing the risk of acute rejection that may be associated with other treatment strategies.

The effects of intra-arterial vasodilators on radial artery size and spasm: implications for contemporary use of trans-radial access for coronary angiography and percutaneous coronary intervention.

BACKGROUND: Transradial access (TRA) offers advantages including decreased vascular complications, reduced length of hospital stay, and reduced cost. The size of the radial artery (RA) limits the equipment that can be used via TRA. Intra-arterial (IA) vasodilators prevent and treat RA spasm, yet are not uniformly used in TRA and their effect on the absolute size of the RA remains unknown. METHODS AND MATERIALS: 121 patients undergoing TRA for cardiac catheterization were included. 78 patients underwent RA angiography prior to administration of IA vasodilators ('no vasodilator' group), 43 patients underwent radial angiography after administration of an IA verapamil and nitroglycerin cocktail ('vasodilator' group). Quantitative angiography was used to compare the RA diameters. RESULTS: Clinical characteristics were similar between the groups, except that patients in the 'no vasodilator' cohort were taller (1.67 ± 0.1 m vs. 1.73 ± 0.1 m, p=0.002), and heavier (84.9 ± 18.2 kg vs. 75 ± 17.1 kg, p=0.003). In the 'vasodilator' group the proximal RA diameter was larger (2.29 ± 0.47 mm vs. 2.09 ± 0.41 mm, p=0.02) as was the narrowest segment (1.83 ± 0.56 mm vs 1.39 ± 0.43, p<0.0001) compared to the 'no vasodilator' group. At the RA origin, 79.4% of those in the 'vasodilator' group were larger than a 6 Fr guide catheter, compared to 51.4% in the 'no vasodilator' group (p=0.004). At the narrowest segment a higher percentage of RAs in the 'vasodilator' group were larger than a 5 Fr guide catheter (65.1% vs 26.9%, p<0.001) and a 6 Fr catheter (34.9% vs 10.3%, p=0.001). CONCLUSION: IA vasodilators increase pre-procedural RA diameter in patients undergoing cardiac catheterization via TRA. This increase in diameter has important implications for procedural planning. SUMMARY FOR TABLE OF CONTENTS: Boyer et al. performed a blinded controlled clinical trial investigating the effects of intra-arterial vasodilators on radial artery size and spasm during cardiac catheterization. The study demonstrates that intra-arterial vasodilators significantly increased the radial artery size throughout the entire course of the vessel and significantly decreased the amount of radial artery spasm. The authors conclude that these findings support the use of intra-arterial vasodilators during cardiac catheterization and have important implications for emerging technologies such as larger bore sheathless radial procedures.