Single-step Optimization in Triaging Large Vessel Occlusion Strokes: Identifying Factors to Improve Door-to-groin Time for Endovascular Therapy.

INTRODUCTION: Although acute stroke endovascular therapy (EVT) has dramatically improved outcomes in acute ischemic stroke (AIS) patients with large vessel occlusions (LVO), access to EVT-capable centers remains limited, particularly in rural areas. Therefore, it is essential to optimize triage systems for EVT-eligible patients. One strategy may be the use of a telestroke network that typically consists of multiple spoke sites that receive a consultation to determine appropriateness of patient transfer to an EVT-capable hub site. Standardization of AIS protocols may be necessary to achieve target door-to-groin (DTG) times of less than 60 minutes in EVT-eligible patients upon hub arrival. Specifically, the decision to obtain vascular imaging at the transferring hub site vs delaying until arrival at the hub is controversial. The purpose of this study was to identify factors associated with reduced DTG time in LVO-AIS patients. METHODS: We performed a retrospective chart review for all patients treated over a 3.5-year period at our home hub institution. Patients were classified as telestroke transfers, non-telestroke transfers, and direct-to-hub presentations. We recorded demographic information, DTG time, reperfusion status, length of stay (LOS), functional status at discharge, seven-day mortality, and the site where vascular imaging- computed tomography angiography (CTA)-was obtained. We performed binary logistic regression to identify factors associated with DTG <60 minutes. RESULTS: In the sample of EVT-eligible patients (n = 383), CTA was performed at the spoke site prior to transfer to the hub institution in 53% of cases. Further, 59% of telestroke transfer cases received a CTA prior to transfer compared to only 40% of non-telestroke transfers (59 vs 40%, P = 0.01). A Door-to-groin time <60 minutes was achieved in 67% of transfer patients who received pre-transfer CTA compared to only 22% of transfer patients who received CTA upon hub arrival and 17% of patients who presented directly to the hub. Ultimately, transfer patients who received CTA prior to transfer were 7.2 times more likely to have a DTG <60 minutes compared to those who did not (OR 7.2, 95% confidence interval 3.5-14.7; P < 0.001). CONCLUSION: Pre-transfer computed tomography angiography was the only significant predictor of achieving target door-to-groin times of less than 60 minutes. Because DTG time has been well established as a predictor of clinical outcomes, including pre-transfer CTA in a standardized acute ischemic stroke protocol may prove beneficial. Our findings also illustrate the need to optimize direct-to-hub stroke alerts and telestroke relationships to minimize workflow disruptions, which became more apparent during the pandemic.

Online interactive medical neuroimaging exercise to identify human brain structures.

A persisting need remains for developing methods for inspiring and teaching undergraduate medical students to quickly learn to identify the hundreds of human brain structures, tracts and spaces that are clinically relevant (viewed as three-dimensional volumes or two-dimensional neuroimages), and to accomplish this with the option of virtual on-line methods. This notably includes teaching the essentials of recommended diagnostic radiology to allow students to be familiar with patient neuroimages routinely acquired using magnetic resonance imaging (MRI) and computed tomography (CT). The present article includes a brief example video plus details a clinically oriented interactive neuroimaging exercise for first year medical students (MS1s) in small groups, conducted with instructors either in-person or as an entirely online virtual event. This "find-the-brain-structure" (FBS) event included teaching students to identify brain structures and other regions of interest in the central nervous system (and potentially in head and neck gross anatomy), which are traditionally taught using brain anatomy atlases and anatomical specimens. The interactive, small group exercise can be conducted in person or virtually on-line in as little as 30 min depending on the scope of objectives being covered. The learning exercise involves coordinated interaction between MS1s with one or several non-clinical faculty and may include one or several physicians (clinical faculty and/or qualified residents). It further allows for varying degrees of instructor interaction online and is easy to convey to instructors who do not have expertise in neuroimaging. Anonymous pre-event survey (n = 113, 100% response rate) versus post-event surveys (n = 92, 81% response rate) were attained from a cohort of MS1s in a neurobiology course. Results showed multiple statistically significant group-level shifts in response to several of the questions, showing an increase in MS1 confidence with reading MRI images (12% increase shift in mean, p < 0.001), confidence in their approaching physicians for medical training (9%, p < 0.01), and comfort levels in working online with virtual team-based peers and with team-based faculty (6%, p < 0.05). Qualitative student feedback revealed highly positive comments regarding the experience overall, encouraging this virtual medium as a desirable educational approach.

Incidence of Atrial Fibrillation in Large Vessel Occlusion and Large Embolic Stroke of Undetermined Source.

INTRODUCTION: Large vessel occlusion (LVO) stroke is a common presentation of acute ischemic stroke and is often unknown or cryptogenic in etiology. There is a strong association between atrial fibrillation (AF) and cryptogenic LVO stroke, making it a unique stroke subgroup. Therefore, we propose that any LVO stroke meeting the criteria for an embolic stroke of an undetermined source (ESUS) be classified as large ESUS (LESUS). The purpose of this retrospective cohort study was to report the etiology of anterior LVO strokes that underwent endovascular thrombectomy. METHODS: This was a single-center retrospective cohort study characterizing the etiology of acute anterior circulation LVO strokes that received emergent endovascular thrombectomy from 2011 to 2018. Patients with LESUS designation at hospital discharge were changed to cardioembolic etiology if AF was discovered during the two-year follow-up period.  Results: Overall, 155 (45%) of 307 patients in the study were found to have AF. New onset AF was discovered in 12 (23%) of 53 LESUS patients after hospitalization. Furthermore, eight (35%) of 23 LESUS patients who received extended cardiac monitoring were found to have AF. CONCLUSION: Nearly half the patients with LVO stroke who received endovascular thrombectomy were found to have AF. With the use of extended cardiac monitoring devices after hospitalization, AF is frequently discovered in patients with LESUS and may change the secondary stroke prevention strategy.

Neutrophil lymphocyte ratio (NLR) and systemic immune inflammatory index (SII) for the differential diagnosis of CT-negative mild acute ischemic stroke and transient ischemic attack.

Background: A number of acute ischemic stroke (AIS) cases may be misdiagnosed as transient ischemic attack (TIA), due to no infarct on initial computed tomography scan and/or mild deficits upon presentation. Several studies have found that the neutrophil-lymphocyte ratio (NLR) is an accurate differential diagnostic biomarker for AIS versus TIA; however, no study has evaluated the use of the NLR in differentiating CT negative AIS from TIA. Furthermore, the systemic immune-inflammation index (SII) is a relatively novel immune biomarker that has been shown to be positively correlated with AIS severity, poor functional outcomes and mortality. The purpose of this study is to determine if NLR or SII can be used as a diagnostic biomarker for the differential diagnosis of mild AIS with a negative CT upon admission and TIA. Methods: We performed a retrospective medical record review of patients diagnosed with either AIS or TIA. We collected peripheral white blood cell counts within 24 h of symptom onset and calculated the NLR and SII. Logistic regression was utilized to determine if NLR or SII are significant predictors of CT negative mild AIS. Results: CT negative mild AIS patients were 2 times as likely to have an NLR ≥ 2.71 compared to TIA patients, and CT negative mild AIS patients were 2.1 times as likely to have an SII ≥ 595 compared to TIA patients. Conclusion: NLR and SII are easily obtained biomarkers that can be used in early clinical decision making in cases of mild AIS with negative CT scan upon admission.

A Case for the Non-Neurologist Telestroke Provider.

Introduction: Telestroke networks have effectively increased the number of ischemic stroke patients who have access to acute stroke therapy. However, the availability of a dedicated group of stroke subspecialists is not always feasible. We hypothesize that rates of tPA recommendation, sensitivity of final diagnosis, and post-tPA hemorrhagic complications do not differ significantly between neurologists and an emergency-medicine physician during telestroke consultations. Methods: Retrospective review of all telestroke consults performed at a comprehensive stroke center over 1 year. Statistical analysis: Chi squared test. Results: Three hundred and three consults were performed among 6 spoke sites. 16% (48/303) were completed by the emergency medicine physician; 25% (76/303) were performed by non-stroke-trained neurologists, and 59% (179/303) were completed by a board-certified Vascular Neurologist. Overall rate of tPA recommendation was 40% (104/255), 38% (18/48), 41% (73/179), and 41% (31/76) among the all neurology-trained, emergency medicine-trained, stroke neurology-trained and other neurology- trained provider groups, respectively (p = 0.427). Sensitivity of final stroke diagnosis was 77% (14/18) and 72% (75/104) in the emergency-medicine trained and neurology-trained provider groups (p = 0.777) No symptomatic hemorrhagic complications following the administration of tPA via telestroke consultation occurred in any group over this time period. One asymptomatic intracerebral hemorrhage was observed (0.96% or 1/104) in the neurology-trained provider group. Discussion/Conclusion: Our results did not illustrate any statistically significant difference between care provided by an emergency medicine-trained physician and neurologists during telestroke consultation. While our study is limited by its relatively low numbers, it suggests that identifying a non-neurologist provider who has requisite clinical experience with acute stroke patients can safely and appropriately provide telestroke consultation. The lack of formerly trained neurologists, therefore, may not need to serve as an impediment to building an effective telestroke network. Future efforts should be focused on illuminating all strategies that facilitate sustainable telestroke implementation.

Leukocyte Biomarkers for the Differential Diagnosis of Mild Acute Ischemic Stroke, Transient Ischemic Attack, and Stroke Mimic.

Introduction The differential diagnosis of transient ischemic attack (TIA) versus mild acute ischemic stroke (AIS) during the initial presentation to the emergency department is often difficult, as the diagnosis of both TIA and AIS relies on the presence of focal neurologic signs. As such, roughly 50% of patients with transient or mild neurologic deficits have an uncertain diagnosis prior to neuroimaging. Biomarkers, particularly leukocyte biomarkers, may be used by clinicians to diagnose mild AIS prior to neuroimaging, and this study is the first to describe the use of leukocyte biomarkers for the differentiation of mild AIS, TIA, and stroke mimic. Methods We performed a retrospective chart review of patients discharged from a local hospital with a discharge diagnosis of either TIA or AIS. Past medical history and complete blood cell count with differential upon admission were collected for all subjects. Statistical analyses were performed to compare immune cell parameters between the two groups. For all comparisons, logistic regression analysis was used to assess the effect of confounding variables, such as age, gender, and medical history for each study variable. Results Of all the immune parameters assessed in this study, the neutrophil percentage was the only significant biomarker that significantly differed between study groups. After adjustment for confounding variables using stepwise logistic regression, mild AIS patients were 5.3 times more likely than TIA cases to have a neutrophil percentage above the normal range. Conclusion Our results suggest that clinicians may utilize neutrophil percentage as an additional piece of information that may aid in their diagnosis of mild AIS versus TIA.

Lateral Heterotaxy Syndrome in a Newborn Caucasian Male.

Heterotaxy syndrome is a varied spectrum of rearrangements of thoracic and abdominal organs that present many unique complications. Among all congenital deformities, heterotaxy syndrome is rare although this is likely an underestimate without routine imaging due to the benign nature of some defects. Numerous genes have been identified that play a role in its pathogenesis, and it has been hypothesized that heterotaxy syndrome is a consequence of both genetic and environmental impacts on the body axis. This case report also demonstrates the fundamental role of cardiac catheterization and imaging in further specifying the subtype of heterotaxy. Furthermore, it highlights the inconsistency of laterality with functional asplenia, visceral situs ambiguus, double-outlet right ventricle, and a left-sided inferior vena cava apart from other anomalies in a newborn male.

Utilization of a Parental Approach to Informed Consent in Intravenous Tissue Plasminogen Activator Administration Decision-Making: Patient Preference and Ethical Considerations.

OBJECTIVE: While administration of intravenous tissue plasminogen activator (IV-tPA) is the standard of care in acute ischemic stroke and has been shown to have statistically significant benefit, there can also be potentially life-threatening complications; however, there is no standard informed consent approach. The purpose of this study was to present a parental, technical, and general model of informed consent for IV-TPA and to determine which approach was preferred. METHODS: Survey respondents were asked to hypothetically decide whether or not to provide consent for their family member to receive IV-tPA. Respondents were presented with 3 informed consent models: one emphasizing parental qualities, one emphasizing statistical data, and one representing a general consent statement. After being presented each model, the respondents had to select their preferred consent model, as well as rate their level of agreeability toward their family member receiving the medication following each approach. RESULTS: The results of 184 surveys showed respondents were equally as likely to give consent for their family member to receive IV-TPA following all three approaches; however, respondents were significantly more likely to prefer the parental approach compared to a technical or general approach. CONCLUSION: Our results indicate that while paternalism is generally discouraged in the medical community, some degree of parental language may be preferred by patients in tough decision-making situations toward consent to receive medical interventions.

Temporal dynamics of peripheral neutrophil and lymphocytes following acute ischemic stroke.

BACKGROUND: The immune response to acute ischemic stroke (AIS) is implicated in diagnosis, prognosis, and intervention; however, the temporal dynamics of leukocytes following AIS are poorly understood. The purpose of this study was to characterize peripheral leukocyte dynamics following AIS among individuals with poor and favorable outcomes. METHODS: A retrospective chart review was conducted among patients with a diagnosis of AIS who were treated at a comprehensive stroke center across a 3-year timeframe. Groups were defined according to stroke outcomes. Patients with poor outcomes were distinguished from those with favorable outcomes by discharge National Institute of Health Stroke Score, infarct size, and Modified Rankin Scale. Leukocyte counts were compared among controls and AIS outcome groups. RESULTS: The neutrophil-lymphocyte ratio (NLR) calculated at 48-72 h post-AIS was identified as the strongest predictor of outcome. NLR was significantly higher in the poor outcome group (8.68 ± 0.93) compared with both the favorable outcome (4.5 ± 0.51, p = 0.009) and control group (4.33 ± 0.66, p < 0.001). Patients with a 48-72 h NLR ≥ 4.58 were 5.58 times more likely to have a poor outcome than AIS patients with an NLR < 4.58. CONCLUSIONS: The results of this study improve the understanding of the immune response in AIS. Low neutrophil count relative to high lymphocyte count at 48-72 h post-AIS should be considered a predictor of a favorable stroke outcome. Conversely, high neutrophil count relative to low lymphocyte count at 48-72 h post-AIS should be considered a predictor of a poor stroke outcome.

Paraneoplastic Opsoclonus Myoclonus in a Patient with Pancreatic Adenocarcinoma.

Opsoclonus myoclonus syndrome (OMS) is an extremely rare neurological syndrome typically affecting as few as 1 in 10,000,000 people annually. OMS is characterized by the presence of involuntary, saccadic eye movements, as well as ataxia, including gait incoordination, rigidity, and tremor. The origin of OMS is unclear, but a significant percentage of OMS cases are indicative of an underlying malignancy, most commonly neuroblastoma and small cell lung cancer. Here we describe an adult patient with OMS, who was ultimately diagnosed with a small ductal adenocarcinoma of the pancreas. To our knowledge, this is the third published report of an association between OMS and pancreatic malignancy, and the only case where the pancreatic malignancy was detected prior to metastasis or autopsy at death. This case report highlights the importance of careful, aggressive malignancy screening with OMS, as the pancreatic duct cut-off sign may be overlooked if pancreatic malignancy is not suspected.

Utilization of a Role-Based Head Covering System to Decrease Misidentification in the Operating Room.

OBJECTIVES: In a typical operating room (OR), there are many individuals who present all dressed in similar attire, making it extremely difficult to distinguish a person's role in the OR. Misidentification of an individual in the OR can make effective communication difficult, which could adversely impact patient safety. Furthermore, an inability to identify graduate medical students or distinguish students from OR faculty may hinder student learning opportunities within the OR. The purpose of this study was to determine whether implementation of a role-based, colored head covering requirement would improve identification in the OR and ultimately patient safety. METHODS: Operating room faculty and graduate medical students completed a four-question survey to assess opinions on misidentification in the OR, 1 month before and 2 months after a role-based head covering requirement was instituted in the OR. We analyzed the data from a total of 28 preintervention responses. RESULTS: Before intervention, students and OR faculty reported that it was difficult to distinguish students from OR faculty in the OR. After intervention, there was a significant decrease in the proportion of respondents who felt that it was difficult to distinguish students in training from trained OR personnel from 79% to 42% (P = 0.007) CONCLUSIONS: Implementation of a role-based head covering system in the OR significantly increased the ability to determine a person's role in the OR. This study provides evocative support for a simple, inexpensive solution able to improve patient safety and learning opportunities for graduate medical students.

Outcomes in an Interdisciplinary Diabetes Clinic in Rural Primary Care.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of an interdisciplinary diabetes team model of care in assisting patients to achieve improved glucose control in a primary care rural setting. METHODS: A family medicine clinic at a rural university medical center developed an interdisciplinary diabetes team clinic composed of a certified diabetes educator/dietitian, a case manager, a pharmacist, nursing staff, a family medicine resident, a psychologist, and a board-certified family medicine attending physician. Patients were referred if their hemoglobin A1c (HbA1c) was ≥9% (75 mmol/mol); patients were seen for an initial consultation and for additional visits as needed. RESULTS: A total of 94 patients attended an initial visit and at least 1 follow-up within 6 months. Mean age was 57 ± 13 years, and 54% were female. Median time from the initial intensive diabetes clinic visit to a follow-up visit was 2.8 months. There was a significant reduction in median HbA1c percentage from 10.25% (88.5 mmol/mol) ± 1.4% (range 73-104 mmol/mol) at the initial intensive diabetes clinic visit to 8.7% (72 mmol/mol) ± 1.8% (range 52-92 mmol/mol) at a 1- to 6-month follow-up (z = -7.161, P < 0.001) and a significant difference between baseline HbA1c (10.25% [88.5 mmol/mol] ± 1.4% [range 73-104 mmol/mol]) and latest HBA1c (1-18 months later) 8.4% (68 mmol/mol) ± 2.2% (range 44-92 mmol/mol; z = -7.022, P < 0.001). Overall, 86% of patients had a lower HbA1c at follow-up, and 33% had an HbA1c <8% (64 mmol/mol). There were no differences in patients' blood pressure, immunization rates, or lipid values between baseline and follow-up visits (P > 0.05). CONCLUSIONS: An interdisciplinary team approach to glycemic control can achieve significant reductions in HbA1c in the rural primary care setting.

A randomized control trial using intraoperative dexmedetomidine during Roux-en-Y gastric bypass surgery to reduce postoperative pain and narcotic use.

BACKGROUND: Dexmedetomidine (DMET), a selective a2-adrenergic agonist, is an opioid-sparing adjuvant sedative that avoids respiratory depression and has been shown to be beneficial in bariatric surgery patients. Although benefit has been shown, prior studies have not evaluated the pain control effects of a single intraoperative bolus. OBJECTIVES: To evaluate the postoperative effects of a single intraoperative dose of DMET. SETTINGS: University Hospital, United States. METHODS: This is a prospective, randomized, double-blinded study registered with clinicaltrials.gov (#NCT02604940). Patients undergoing laparoscopic Roux-en-Y gastric bypass surgery were randomized and given either a placebo or an intraoperative DMET bolus, where 1 mg/kg was delivered over 10 minutes at the time of surgical closure. Measured outcomes included the following: postoperative pain scores, patient-controlled analgesia (PCA) opioid consumption, PCA demand bolus attempts, duration of postanesthesia care unit (PACU) stay, and vital signs. Descriptive statistics were recorded as frequencies and compared using Χ2 analysis, and a Welch's 2-sample t test was used to compare continuous variables. RESULTS: Forty-six participants undergoing laparoscopic Roux-en-Y gastric bypass surgery were randomized into placebo (n = 20) or DMET (n = 26) groups. There were no statistical differences in age (45.1 versus 43.2 yr, P = .522), sex (80% versus 81% female, P = .948), and body mass index (46.1 versus 45.6 kg/m2, P = .818) between the 2 groups. There were no statistically significant differences in vital signs (heart rate, blood pressure, oxygen saturation, and respiration rate) between DMET and placebo groups in the preoperative and intraoperative period. During the initial 4 hours in the PACU postoperatively, mean heart rate (70 ± 12 versus 86 ± 14, P < .001), systolic blood pressure (107 ± 17 versus 148 ± 16, P < .001), and diastolic blood pressure (56 ± 15 versus 79 ± 13, P < .001) were significantly lower in the DMET-treated group compared with placebo. During the initial 4 hours in the PACU, mean self-reported pain scores were significantly lower in the DMET-treated group (3.6 ± 2.8) compared with the placebo group (6.7 ± 3; P = .005). The lower pain scores occurred with no significant difference in the mean opioid dosage received in the PACU between DMET-treated (2.66 ± 2.02 mg) and placebo (3.7 ± 2.3 mg; P = .09) groups. Also, there was no statistically significant difference in the total number of PCA attempts for opioids between the DMET-treated and placebo groups (P = .49). CONCLUSIONS: A single bolus of DMET (1 mg/kg delivered over 10 min) administered at the time of surgical closure did not reduce immediate PACU usage of opioids but significantly reduced reported pain scores and caused a significant decrease in the number of attempts made by patients; this is a trend of decreased attempts over time (P = .04) in the DMET group. The trend of the mean total medication used over time indicates that there is neither an increasing nor decreasing trend for the DMET group, but there is an increasing trend in the total used over time for the placebo group. There was no statistically or clinically significant bradycardia, hypotension, hypoxia, respiratory depression intraoperative duration, or PACU stay. Reduced single bolus dosing of DMET required for analgesia in bariatric surgery patients is optimal from physiologic, level of care, and cost perspectives.

Leukocyte Dynamics Influence Reference Gene Stability in Whole Blood: Data-Driven qRT-PCR Normalization Is a Robust Alternative for Measurement of Transcriptional Biomarkers.

BACKGROUND: The use of reference genes for normalization of whole blood qRT-PCR data may be problematic in conditions such as stroke which induce alterations in white blood cell differential. In this study, we assessed the influence of stroke on the stability of commonly employed reference genes, and we evaluated data-driven normalization as an alternative. METHODS: Peripheral whole blood was sampled from 33 stroke patients and 29 controls, and qRT-PCR was used to measure the expression levels of 10 target genes whose transcripts are known stroke biomarkers. Target gene expression levels were normalized via those of 2 frequently cited reference genes (ACTB and B2M) as well as with the NORMA-Gene data-driven normalization algorithm. RESULTS: Whole blood expression levels of reference genes were significantly altered in stroke patients relative to controls. In comparison to normalization via reference genes, NORMA-Gene produced more robust target gene expression data in terms of differential expression dynamics, variance properties, and diagnostic performance. CONCLUSIONS: Our findings suggest that whole blood expression levels of commonly used reference genes may be sensitive to changes in white blood cell differential, and that data-driven qRT-PCR normalization approaches offer a powerful alternative.

Circulating extracellular DNA levels are acutely elevated in ischaemic stroke and associated with innate immune system activation.

OBJECTIVE: The objective of this work was to assess the ability of peripheral blood cell-free DNA (cfDNA) levels to identify ischaemic stroke early in the acute phase of care, as well as to examine the relationship between peripheral blood cfDNA levels and stroke-induced innate immune system activation. METHODS: Upon emergency department admission, peripheral blood samples were obtained from 43 patients experiencing acute ischaemic stroke and 20 patients identified as stroke mimics. Plasma cfDNA levels were measured using quantitative polymerase chain reaction (qPCR), infarct volume and NIH stroke scale (NIHSS) were used to assess injury severity, and peripheral blood neutrophil count was used as a measure of innate immune system status. RESULTS: Peripheral blood cfDNA levels were significantly elevated in patients suffering stroke relative to those diagnosed as stroke mimics, and could differentiate between groups with 86% (95% CI = 72-95%) sensitivity and 75% (95% CI = 51-91%) specificity. Furthermore, cfDNA levels displayed significant positive associations between both infarct volume and peripheral blood neutrophil count within the stroke group. CONCLUSIONS: These findings suggest that assessment of peripheral blood cfDNA levels may be useful for the identification of ischaemic stroke in the acute care setting, and provide associative evidence that cfDNA is a potential activator of the peripheral innate immune system in response to cerebral ischaemia.

Evaluation of inflammatory cell biomarkers in chronic venous insufficiency.

Objective Inflammation has been implicated as a factor that may contribute to chronic venous insufficiency. The purpose of this study is to compare readily available inflammatory cell biomarkers, with an emphasis on neutrophil count, lymphocyte count, and neutrophil lymphocyte ratio, in patients with chronic venous insufficiency. We hypothesized that circulating leukocyte counts would be higher in the peripheral blood of patients with severe compared to mild chronic venous insufficiency. Methods We performed a retrospective medical record review of patients discharged from Ruby Memorial Hospital (Morgantown, WV, USA) with a primary diagnosis of chronic venous insufficiency. Patients were organized into two groups-mild and severe chronic venous insufficiency-based on the Clinical, Etiologic, Anatomic, and Pathophysiological classification system, and inflammatory cell counts were compared between groups. Results We observed a significantly higher neutrophil count ( p = .002) and neutrophil-lymphocyte ratio ( p = .005) in patients with severe chronic venous insufficiency compared to mild. Further, the neutrophil-lymphocyte ratio may be a useful predictor of chronic venous insufficiency severity. Conclusions We reported significant differences in inflammatory cell biomarkers between mild and severe chronic venous insufficiency, as well as provided support for the use of the neutrophil-lymphocyte ratio as a predictor of chronic venous insufficiency severity. These results may provide clinicians with additional insight to manage chronic venous insufficiency in patients and provide a framework for the development of novel treatment options targeting the immune system in chronic venous insufficiency.

Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post-stroke blood brain barrier disruption.

Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging. Early heightened expression levels of AKAP7, a gene encoding a protein kinase A-binding scaffolding molecule, were significantly associated with BBB disruption 24 hours post-hospital admission. We then determined that AKAP7 is predominantly expressed by lymphocytes in peripheral blood, and strongly co-expressed with ITGA3, a gene encoding the adhesion molecule integrin alpha 3. Subsequent in vitro experiments revealed that heightened expression of AKAP7 and ITGA3 in primary human lymphocytes is associated with a highly adherent phenotype. Collectively, our results suggest that AKAP7 expression levels may have clinical utility as a prognostic biomarker for post-stroke BBB complications, and are likely elevated early in patients who later develop post-stroke BBB disruption due to the presence of an invasive lymphocyte population in the peripheral blood.

Immune biomarkers for the diagnosis of mild traumatic brain injury.

BACKGROUND: In 2010, there were approximately 2.2 million emergency room visits associated with traumatic brain injury (TBI), with 80 percent diagnosed as mild TBI or concussion. In addition, there are a large number of TBIs, especially mild TBIs, which go either unreported by patients or initially undiagnosed by clinicians. Our team has previously identified a panel of immune-related genes that can diagnose ischemic stroke at triage, and due to shared pathophysiological mechanisms of TBI and stroke, we hypothesized that this panel of genes may also be utilized for the diagnosis of TBI. OBJECTIVES: The primary aims of this pilot study were to: (1) characterize changes in a panel of immune-related genes in TBI; (2) identify immune-related biomarkers that may be used to diagnose TBI and (3) describe the peripheral immune response following TBI. METHODS: Blood was drawn from TBI patients no later than 24 h of injury onset and matched control subjects. Real-time PCR was used to measure gene expression, and a white blood cell differential was performed to obtain neutrophil and lymphocyte percentages. RESULTS: Relative mRNA expression of ARG1, LY96, MMP9, s100a12 was significantly increased and CCR7 was significantly decreased in peripheral blood of TBI patients within 24 hours of injury compared to control subjects. We also observed a different pattern of leukocyte dynamics following TBI between mild and severe TBI. CONCLUSIONS: We have described a panel of immune-related genes that can accurately predict/diagnose TBI with higher sensitivity and specificity of other biomarkers to date.

Rates of Nonsteroidal Anti-Inflammatory Drug Use in Patients with Established Cardiovascular Disease: A Retrospective, Cross-Sectional Study from NHANES 2009-2010.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, inflammation, and fever in the USA. Unfortunately, NSAIDs have been associated with an increased risk of adverse cardiovascular events, especially among NSAID users with established cardiovascular disease (CVD). In 2005, the Food and Drug Administration (FDA) released an initial warning regarding NSAID use and CVD risk, and recently, in July 2015, released an updated statement strengthening this initial warning. The purpose of this study is to evaluate the rates of NSAID use among patients with CVD following the 2005 FDA warning regarding NSAID use and increased CVD risk. METHODS: This was a retrospective, cross-sectional study of participants from the National Health and Nutrition Examination Survey, 2009-2010. Participants' CVD status was determined by self-reported diagnosis. Current use of over the counter (OTC) NSAIDs was defined by self-reported use of ibuprofen or naproxen, and we identified the current use of prescription NSAIDs in the database of prescription medication. RESULTS: Respondents with CVD were 2.1 times more likely to use OTC NSAIDs or prescription NSAIDs than respondents without CVD. Among CVD patients, respondents with angina and myocardial infarction were 60% more likely to use any form of NSAID, and respondents with congestive heart failure were less likely to use any form of NSAID than those with other forms of CVD. CONCLUSIONS: Our results indicate that there is still a large proportion of CVD patients using NSAIDs. It is now crucial to determine the reasons why prescribers are still prescribing NSAIDs despite the FDA warning.

Using Gene Expression Analysis to Examine Changes in Loneliness, Depression and Systemic Inflammation in Lonely Chronically Ill Older Adults.

PURPOSE: The purpose of this study was to evaluate the effectiveness of LISTEN (Loneliness Intervention) on loneliness, depression, physical health, systemic inflammation, and genomic expression in a sample of lonely, chronically ill, older adults. METHODS: This was a prospective, longitudinal randomized trial of LISTEN, a novel intervention based on theories of narrative and cognitive restructuring to target specific aspects of loneliness. Twenty-three older, lonely, chronically ill adults were recruited from a family medicine clinic in West Virginia. Participants were randomized to two groups, 13 in LISTEN group (Loneliness Intervention) and 10 in attention control (healthy aging education). Participants attended an enrollment session where they completed consent, survey data (including sociodemographics and chronic illness diagnoses), baseline physical measures, and blood sampling for gene expression analysis. After completing the 5 weekly sessions, all participants attended a 12 week post data collection meeting (17 weeks post-baseline) for survey completion, physical measures and blood sampling. RESULTS: The results of this study show that the LISTEN intervention improves measures of physical and psychosocial health. Specifically, subjects enrolled in LISTEN showed reductions in systolic blood pressure, as well as decreased feelings of loneliness and depression. These changes may be due, in part, to a reduction in systemic inflammation, as measured by interleukin-2. CONCLUSION: This study provides support for the use of LISTEN in reducing loneliness in chronically ill, older adults. Further, while some of our results are inconclusive, it provides rationale to expand our study population to evaluate the relationship between loneliness and systemic inflammation. In the future, enhancing knowledge about the relationships among loneliness, chronic illness, systemic inflammation, and gene expression of these particular targets, and how these relationships may change over time with intervention will inform translation of findings to clinical settings.