Chunyan Cai

Thrombelastography Detects Possible Coagulation Disturbance in Patients With Intracerebral Hemorrhage With Hematoma Enlargement

Background and Purpose— Intracerebral hemorrhage (ICH) has high morbidity, and hematoma enlargement (HE) causes worse outcome. Thrombelastography (TEG) measures the dynamics of clot formation and dissolution, and might be useful for assessing bleeding risk. We used TEG to detect changes in clotting in patients with and without HE after ICH. Methods— This prospective study included 64 patients with spontaneous ICH admitted from 2009 to 2013. TEG was performed within 6 hours of symptom onset and after 36 hours. Brain imaging was obtained at baseline and at 36±12 hours, and HE was defined as total volume increase >6 cc or >33%. TEG was also obtained from 57 controls. Results— Compared with controls, patients with ICH demonstrated faster and stronger clot formation; shorter R and delta (P<0.0001) at baseline; and higher MA and G (P<0.0001) at 36 hours; 11 patients had HE. After controlling for potential confounders, baseline K and delta were longer in HE+ compared with HE− patients, indicating that HE+ patients had slower clot formation (P<0.05). TEG was not different between HE+ and HE− patients at 36 hours. Conclusions— TEG may detect important coagulation changes in patients with ICH. Clotting may be faster and stronger in immediate response to ICH, and a less robust response may be associated with HE. These findings deserve further investigation.

Neutrophil transfer of miR-223 to lung epithelial cells dampens acute lung injury in mice

Intercellular transfer of miR-223 from neutrophils to alveolar epithelial cells reduces lung inflammation in a mouse model of ventilator-induced lung injury or pulmonary bacterial infection. Starting an intercellular conversation In a new study, Neudecker et al. show that transfer of microRNA-223 (miR-223) from neutrophils to lung alveoli helps to dampen lung inflammation and promotes the resolution of ventilator-induced lung injury in mice. The authors suggest that neutrophils secrete microRNAs in microvesicles that are then taken up by alveolar epithelial cells. They show that miR-223–deficient mice are prone to lung injury, whereas overexpression of miR-223 is protective. Intercellular transfer of microRNAs can mediate communication between critical effector cells. We hypothesized that transfer of neutrophil-derived microRNAs to pulmonary epithelial cells could alter mucosal gene expression during acute lung injury. Pulmonary-epithelial microRNA profiling during coculture of alveolar epithelial cells with polymorphonuclear neutrophils (PMNs) revealed a selective increase in lung epithelial cell expression of microRNA-223 (miR-223). Analysis of PMN-derived supernatants showed activation-dependent release of miR-223 and subsequent transfer to alveolar epithelial cells during coculture in vitro or after ventilator-induced acute lung injury in mice. Genetic studies indicated that miR-223 deficiency was associated with severe lung inflammation, whereas pulmonary overexpression of miR-223 in mice resulted in protection during acute lung injury induced by mechanical ventilation or by infection with Staphylococcus aureus. Studies of putative miR-223 gene targets implicated repression of poly(adenosine diphosphate–ribose) polymerase–1 (PARP-1) in the miR-223–dependent attenuation of lung inflammation. Together, these findings suggest that intercellular transfer of miR-223 from neutrophils to pulmonary epithelial cells may dampen acute lung injury through repression of PARP-1.

Difficult mask ventilation in general surgical population: observation of risk factors and predictors.

Background: There are few predictors of difficult mask ventilation and a simple, objective, predictive system to identify patients at risk of difficult mask ventilation does not currently exist. We present a retrospective - subgroup analysis aimed at identifying predictive factors for difficult mask ventilation (DMV) in patients undergoing pre-operative airway assessment before elective surgery at a major teaching hospital. Methods: Data for this retrospective analysis were derived from a database of airway assessments, management plans, and outcomes that were collected prospectively from August 2008 to May 2010 at a Level 1 academic trauma center. Patients were stratified into two groups based on the difficulty of mask ventilation and the cohorts were analyzed using univariate analysis and stepwise selection method. Results: A total of 1399 pre-operative assessments were completed with documentation stating that mask ventilation was attempted. Of those 1399, 124 (8.9%) patients were found to be difficult to mask ventilate. A comparison of patients with and without difficult mask ventilation identified seven risk factors for DMV: age, body mass index (BMI), neck circumference, history of difficult intubation, presence of facial hair, perceived short neck and obstructive sleep apnea. Although seven risk factors were identified, no individual subject had more than four risk factors. Conclusion: The results of this study confirm that in a real world clinical setting, the incidence of DMV is not negligible and suggest the use of a simple bedside predictive score to improve the accuracy of DMV prediction, thereby improving patient safety. Further prospective studies to validate this score would be useful.

Effect of Intrinsic and Extrinsic Factors on Global and Regional Cortical Thickness

Global and regional cortical thicknesses based on T1-weighted magnetic resonance images acquired at 1.5 T and 3 T were measured on a relatively large cohort of 295 subjects using FreeSurfer software. Multivariate regression analysis was performed using Pillais trace test to determine significant differences in cortical thicknesses measured at these two field strengths. Our results indicate that global cortical thickness is not affected by the field strength or gender. In contrast, the regional cortical thickness was observed to be field dependent. Specifically, the cortical thickness in regions such as parahippocampal, superior temporal, precentral and posterior cingulate is thicker at 3 T than at 1.5 T. In contrast regions such as cuneus and pericalcarine showed higher cortical thickness at 1.5 T than at 3 T. These differences appear to be age-dependent. The differences in regional cortical thickness between field strengths were similar in both genders. Further, male vs. female differences in regional cortical thickness were observed only at 1.5 T and not at 3 T. Our results indicate that magnetic field strength has a significant effect on the estimation of regional, but not global, cortical thickness. In addition, the pulse sequence, scanner type, and spatial resolution do not appear to have significant effect on the measured cortical thickness.

A call for formal telemedicine training during stroke fellowship

During the 20 years since US Food and Drug Administration approval of IV tissue plasminogen activator for acute ischemic stroke, vascular neurology consultation via telemedicine has contributed to an increased frequency of IV tissue plasminogen activator administration and broadened geographic access to the drug. Nevertheless, a growing demand for acute stroke coverage persists, with the greatest disparity found in rural communities underserved by neurologists. To provide efficient and consistent acute care, formal training in telemedicine during neurovascular fellowship is warranted. Herein, we describe our experiences incorporating telestroke into the vascular neurology fellowship curriculum and propose recommendations on integrating formal telemedicine training into the Accreditation Council for Graduate Medical Education vascular neurology fellowship.

Lactobacillus reuteri for Infants with Colic: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Objective To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables. Study design We performed a controlled, double‐blinded, phase 1 safety and tolerability trial in healthy breast‐fed infants with colic, aged 3 weeks to 3 months, randomly assigned to L reuteri strain DSM 17938 (5 × 108 colony‐forming units daily) or placebo for 42 days and followed for 134 days. Results Of 117 screened infants, 20 were randomized to L reuteri strain DSM 17938 or placebo (sunflower oil) (in a 2:1 ratio) with 80% retention. Eleven of the 20 (55%) presented with low absolute neutrophil counts (<1500/mm3), which resolved in all subjects by day 176. L reuteri strain DSM 17938 produced no severe adverse events and did not significantly change crying time, plasma bicarbonate, or inflammatory biomarkers. Fecal calprotectin decreased rapidly in both groups. In the infants with dominant fecal gram negatives (Klebsiella, Proteus, and Veillonella), resolution of colic was associated with marked decreases in these organisms. Conclusions Daily administration of L reuteri strain DSM 17938 appears to be safe in newborn infants with colic, including those with neutropenia, which frequently coexists. A placebo response of 66% suggests that many infants with colic will have resolution within 3 weeks. Trial registration ClinicalTrials.gov: NCT01849991.

Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke)

Background and Purpose— We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to recombinant tissue-type plasminogen activator (r-tPA)–treated ischemic stroke patients. Methods— Patients treated with standard-dose r-tPA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100 &mgr;g/kg bolus) followed by infusion of either 1 (low dose) or 3 &mgr;g/kg per minute (high dose) for 48 hours. Safety was incidence of symptomatic intracerebral hemorrhage. Probability of clinical benefit (modified Rankin Scale score 0–1 at 90 days) was estimated using a conservative Bayesian Poisson model (neutral prior probability centered at relative risk, 1.0 and 95% prior intervals, 0.33–3.0). Results— Ninety patients were randomized: 29 to r-tPA alone, 30 to r-tPA+low-dose argatroban, and 31 to r-tPA+high-dose argatroban. Rates of symptomatic intracerebral hemorrhage were similar among control, low-dose, and high-dose arms: 3/29 (10%), 4/30 (13%), and 2/31 (7%), respectively. At 90 days, 6 (21%) r-tPA alone, 9 (30%) low-dose, and 10 (32%) high-dose patients were with modified Rankin Scale score 0 to 1. The relative risks (95% credible interval) for modified Rankin Scale score 0 to 1 with low, high, and either low or high dose argatroban were 1.17 (0.57–2.37), 1.27 (0.63–2.53), and 1.34 (0.68–2.76), respectively. The probability that adjunctive argatroban was superior to r-tPA alone was 67%, 74%, and 79% for low, high, and low or high dose, respectively. Conclusions— In patients treated with r-tPA, adjunctive argatroban was not associated with increased risk of symptomatic intracerebral hemorrhage and provides evidence that a definitive effectiveness trial is indicated. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01464788.

Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial

BACKGROUND We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of Argatroban in Combination with Recombinant Tissue Plasminogen Activator for Acute Stroke (ARTSS-2). METHODS ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of Argatroban injection (low, high) in combination with recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as hemorrhage after thrombolysis (HAT) score and presence of distal internal carotid artery occlusion (DICAO). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 patients enrolled in ARTSS-2, we evaluated performance of our randomization program using chi-square tests of homogeneity or extended Fishers exact test. We also designed a four-step partly Bayesian safety stopping rule for low and high dose Argatroban arms. RESULTS Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), HAT score (0-2 vs. 3-5, P=1.0), and DICAO (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose Argatroban were not crossed. Despite challenges, data quality was assured. CONCLUSIONS We recommend adaptive designs for randomization and Bayesian safety stopping rules for multisite Phase I/II RCTs for maintaining additional flexibility. Efficient data coordination could lead to improved data quality.

CT characteristics of traumatic sacral fractures in association with pelvic ring injuries: correlation using the Young-Burgess classification system

PurposeThe purpose of the study is to determine the incidence of sacral fracture patterns on CT imaging of pelvic trauma patients with correlation with mechanism of injury and pelvic ring injury pattern using the Young-Burgess classification system.Materials and methodsThis is a retrospective review of all pelvic CTs with pelvic fractures performed at our level 1 trauma center during a 4-year period from July 2010 to June 2014.ResultsSacral fractures were very common in pelvic trauma patients, being present in 60% of patients presenting to our institution with pelvic fractures. Longitudinal fractures were almost always associated with additional pelvic ring injuries. Denis zone 1 fractures had the highest association with lateral compression pelvic ring injuries. Denis zone 2 and 3 fractures were seen with increased frequency in AP compression and vertical shear injuries. A third of transverse sacral fractures occurred in isolation, with isolated transverse sacral fractures typically occurring in the low (S3–S5) sacrum. Almost half of combined transverse and longitudinal sacral fractures occurred without an additional pelvic fracture present. Sacral avulsions almost always occurred as part of a pelvic ring fracture pattern, most commonly in AP compression injuries. Coccyx fractures frequently occurred in isolation, but were commonly seen in vertical shear injuries when associated with a pelvic ring injury pattern.ConclusionAvulsion fractures and longitudinal fractures of the sacrum are almost always associated with anterior pelvic ring injury. Conversely, transverse fractures of the lower sacrum and combined longitudinal and transverse sacral fractures are prone to occur in isolation.

CT incidence of Morel-Lavallee lesions in patients with pelvic fractures: a 4-year experience at a level 1 trauma center

The aim of this study is to determine the incidence and location of Morel-Lavallee lesions (MLLs) on pelvic CTs performed in evaluation of pelvic fractures and determine if correlation exists between MLLs and mechanism of injury or pelvic ring injury pattern. A retrospective review was performed of pelvic CTs on 1493 consecutive patients presenting with pelvic fractures at our level 1 trauma center. MLLs occurred in 182 of 1493 patients presenting with pelvic fractures. Statistical significance in MLL incidence was found across mechanism of injuries with MLLs being seen most frequently in MCC/ATV accidents and crush injuries. A little over half of MLLs occurred over the lateral thigh with almost all other MLLs occurring over the posterior (flank or lumbar) region. MLLs were much more common in vertical shear and spinopelvic dissociation pelvic ring fracture patterns compared to lateral compression and AP compression patterns. In lateral compression injuries, MLLs most commonly occurred over the thigh. In all other pelvic ring injury patterns, MLLs were predominately posterior. MLL’s are not as rare as previously believed. The lateral thigh and lumbar/flank regions should be closely inspected on pelvic trauma patients to identify MLLs, particularly in patients with a spinopelvic dissociation injury pattern.