Latha G. Stead

Matrix Metalloproteinase-9 as a Marker for Acute Ischemic Stroke: A Systematic Review

Matrix metalloproteinase-9 (MMP-9) is a possible marker for acute ischemic stroke (AIS). In animal models of cerebral ischemia, MMP expression was significantly increased and was related to blood-brain barrier disruption, vasogenic edema formation, and hemorrhagic transformation. The definition of the exact role of MMPs after ischemic stroke will have important diagnostic implications for stroke and for the development of therapeutic strategies aimed at modulating MMPs. The objectives of the present study were to determine (1) whether MMP-9 is a possible marker for AIS; (2) whether MMP-9 levels correlate with infarct volume, stroke severity, or functional outcome; and (3) whether MMP-9 levels correlate with the development of hemorrhagic transformation after tissue plasminogen activator (t-PA) administration. The literature was searched using MEDLINE and EMBASE with no year restriction. All relevant reports were included. A total of 22 studies (3,289 patients) satisfied the inclusion criteria. Our review revealed that higher MMP-9 values were significantly correlated with larger infarct volume, severity of stroke, and worse functional outcome. There were significant differences in MMP-9 levels between patients with AIS and healthy control subjects. Moreover, MMP-9 was a predictor of the development of intracerebral hemorrhage in patients treated with thrombolytic therapy. MMP-9 level was significantly increased after stroke onset, with the level correlating with infarct volume, stroke severity, and functional outcome. MMP-9 is a possible marker for ongoing brain ischemia, as well as a predictor of hemorrhage in patients treated with t-PA.

Management of Acute Ischemic Stroke

The treatment of acute ischemic stroke has evolved from observation and the passage of time dictating outcome to an approach that emphasizes time from ictus, rapid response, and a dedicated treatment team. We review the treatment of acute ischemic stroke from the prehospital setting, to the emergency department, to the inpatient hospital setting. We discuss the importance of prehospital assessment and treatment, including the use of elements of the neurologic examination, recognition of symptoms that can mimic those of acute ischemic stroke, and rapid transport of patients who are potential candidates for thrombolytic therapy to hospitals with that capability. Coordinated management of acute ischemic stroke in the emergency department is critical as well, beginning with non-contrast-enhanced computed tomography of the brain. The advantages of a multidisciplinary dedicated stroke team are discussed, as are thrombolytic therapy and other inpatient treatment options. Finally, we cover evolving management strategies, treatments, and tools that could improve patient outcomes.

Effect of anticoagulant and antiplatelet therapy in patients with spontaneous intra-cerebral hemorrhage: Does medication use predict worse outcome?

OBJECTIVES To assess the impact of anticoagulants and antiplatelet agents on the severity and outcome of spontaneous non-traumatic intra-cerebral hemorrhage (ICH). To evaluate associations between reversal of anticoagulation and mortality/morbidity in these patients. METHODS Data was collected on a consecutive cohort of adults presenting with ICH to an academic Emergency Department over a 3-year period starting January 2006. RESULTS The final cohort of 245 patients consisted of 125 females (51.1%). The median age of the cohort was 73 years [inter-quartile (IQR) range of 59-82 years]. Antiplatelet (AP) use was seen in 32.6%, 18.4% were using anticoagulant (AC) and 8.9% patients were on both drugs (AC+AP). Patients on AC had significantly higher INR (median 2.3) and aPTT (median 31 s) when compared to patients not on AP/AC (median INR 1.0, median aPTT 24s; p<0.001). Similarly patients on AC+AP also had higher INR (median 1.9) and aPTT (median 30s) when compared to those not on AC/AP (p<0.001). Hemorrhage volumes were significantly higher for patients on AC alone (median 64.7 cm(3)) when compared to those not on either AC/AP (median 27.2 cm(3); p=0.05). The same was not found for patients using AP (median volume 20.5 cm(3); p=0.813), or both AC+AP (median volume 27.7 cm(3); p=0.619). Patients on AC were 1.43 times higher at risk to have intra-ventricular extension of hemorrhage (IVE) as compared to patients not on AC/AP (95% CI 1.04-1.98; p=0.035). There was no relationship between the use of AC/AP/AC+AP and functional outcome of patients. Patients on AC were 1.74 times more likely to die within 7 days (95% CI 1.0-3.03; p=0.05). No relationship was found between use of AP or AC+AP use and mortality. Of the 82 patients with INR>1.0, 52 patients were given reversal (minimum INR 1.4, median 2.3). Therapy was heterogeneous, with fresh frozen plasma (FFP) being the most commonly used agent (86.5% patients, median dose 4U). Vitamin K, activated factor VIIa and platelets were the other agents used. Post reversal, INR normalized within 24h (median 1.2, IQR 1.1-1.3). There was no association between reversal and volume of hemorrhage, IVE, early mortality (death<7 days) or functional outcome. CONCLUSIONS Anticoagulated patients were at 1.7 times higher risk of early mortality after ICH. Reversal of INR to normal did not influence mortality or functional outcome.

Visual representation of National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network criteria for anaphylaxis

We present a user-friendly visual representation of The National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network criteria so as to enhance recognition of anaphylaxis and active teaching and learning.

Emergency department over-crowding: a global perspective

Emergency department (ED) over-crowding has been a topic of intense interest over the past few years, with the Institute of Medicine report “Emergency Care at a Crossroads” published in 2006 [1], followed by the American College of Emergency Physicians task force report on boarding (2008) and, most recently, the United States Government Accountability Office (GAO) Report to the Chairman [2], Committee on Finance, U.S. Senate published in April 2009. Similarly, the Canadian Association of Emergency Physicians and the Australasian College for Emergency Medicine have also recognized the primary problem of over-crowding in the ED [3, 4]. The adverse effects of the global problem of ED over-crowding are well known. Crowding negatively impacts all stakeholders: patients, physicians, and the hospital. Most important is patient safety, with decreased quality of care and an increase in medical errors in overcrowded EDs. Further, patients have a poor experience, which leads them to leave without being seen, and they are less likely to return to the ED in the future. Physicians and other providers experience decreased job satisfaction, resulting in decreased productivity and increased staff turnover. For the hospital, ED over-crowding results in lost revenue from multiple sources. Revenue is lost from patients who leave without being seen, from emergency medical service (EMS) diversion secondary to dissatisfaction among both patients and EMS crews, and from shifting of the market share to competitors. Consider the real mortality risk associated with ED over-crowding. A study of over 55,000 ED patients demonstrated a higher mortality rate among patients boarded in the ED than in those moved to an inpatient hallway bed (p < 0.05). Furthermore, the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) notes that 50% of sentinel events occur in the ED and of these one third are due to over-crowding. Hospitals and EDs react in a crisis. Institutions, stressed by overcrowding, often engage in short-term fixes which do not address the underlying issues, and ultimately only exacerbate the problem. For example, increased staffing and expansion of the ED do not necessarily produce gains. Rather, redesigning for optimization of the system by which patients are processed is the key. The secret to success is not to allocate more, but to strategically re-allocate resources. In 2001, a survey of 575 ED directors reported overcrowding in 94% of academic EDs and 91% of private hospital EDs [5]. In this time of economic downturn, the issue of ED over-crowding becomes even more poignant as a global issue. This issue of International Journal of Emergency Medicine features two studies that highlight the problem of ED over-crowding. In their 7-year longitudinal study, Graham et al. [6] report on the trends in Prince of Wales Hospital, a busy (>155,000 patient visits per year) tertiary referral facility with 1,400 beds which serves as the primary teaching hospital of the Chinese University of Hong Kong. The authors note that while the SARS epidemic and the introduction of co-pay in the ED resulted in an overall net decrease of ED volumes, the concurrent increase in patients brought in via ambulance plus reduction of medical and nursing staff resulted in increased waiting times. The over-crowding problem is compounded by the marked increase in the medical admission rate, which correlates with the 12% increase in the geriatric population visits. The second study, by Kulstad and Kelley [7], entitled “Over-crowding is associated with delays in percutaneous coronary intervention for acute myocardial infarction” uses the EDWIN score as a marker of ED over-crowding and its association with ultimate delays in patients receiving percutaneous intervention for acute myocardial infarction. The EDWIN score is the sum of the number of patients in the ED multiplied by their acuity, divided by the number of attending physicians working in the ED, multiplied by the number of inpatient boarders. The authors report a decreased likelihood of timely treatment for acute MI during times of over-crowding in their emergency department. These studies underscore the very real and detrimental effects of ED over-crowding. The most important root cause of ED over-crowding is the inability to transfer emergency patients to inpatient beds and the resultant boarding of admitted patients in the ED. Solutions to decrease boarding in the ED include moving boarders into inpatient hallways at the front end, and increasing the rate of discharges by noon at the back end. Movement of patients to inpatient hallways, while known to be safer for patients, still often results in push-back from the inpatient services. One commonly cited reason is patient dissatisfaction. As the science of ED over-crowding evolves, studies addressing this very issue have also been performed. A study of 445 patients reports an overall preference of 87% for inpatient hallway beds. Reasons cited for this preference included better privacy, staff availability, safety, rest, quiet, and treatment [8]. Movement of patients to hallway beds and boosting discharges before noon are sometimes thought of as the “external factor,” as they involve practice outside of the ED, namely inpatient floors. There are of course a number of measures that can be undertaken to increase throughput in the ED that can be considered “internal factors.” These include streamlined and simplified triage, point-of-care laboratory testing for diagnostics that are a bottleneck to the next step, and care pathways, to name a few. The first step of solving any problem, acknowledging it, is well past. We know that patient volumes of EDs are going to increase at an exponential rate, as suggested by the CDC in 2005 [9], Our objectives should be to enable efficient care to everyone at all times. We have potential allies in technology, streamlined business management strategies, including Lean for process evolution and Six Sigma, and collaborative alliances between hospitals to develop creative solutions to the problem of ED over-crowding. In today’s evolving healthcare scenario, EDs are not only a point of care for the acutely ill, but also have a role as a safety net to provide healthcare to people regardless of their insurance status or ability to pay, as dictated by laws like the Emergency Medical Treatment and Labor Act (EMTALA) in the US. It is of paramount importance that a serious and unified approach to ED over-crowding be taken, at all levels. This would represent a major step towards establishing a culture of patient safety and satisfaction in the ED.

Insulin for Glycemic Control in Acute Ischemic Stroke

Hyperglycemia predicts increased stroke mortality independently of age, stroke severity, or stroke type. The next step is to ascertain whether treating hyperglycemia reduces mortality and improves functional outcome. The objective of this review was to determine whether maintaining serum glucose within a specific normal range (4–7.5 mmol/L or 72–135 mg/dL) in the first 24 hours of acute ischemic stroke influences outcome. We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, Science Citation Index, Web of Science, ongoing trials registers, and SCOPUS. Eligible studies were randomized controlled trials comparing intensively monitored insulin therapy versus usual care in adult patients with acute ischemic stroke. We obtained a total of 191 …

Acute deep vein thrombus due to May-Thurner syndrome.

A 63-year-old white woman with a history of hypertension, hyperlipidemia, hypothyroidism, and transient ischemic attack, on Premarin, presented with a 2-week history of worsening edema and pain on the left side of the lower extremity associated with purplish discoloration and decreased temperature after a prolonged car travel. Physical examination revealed 2+ edema from the midthigh to the toes associated with purpuric discoloration. All arterial pulses were 4+. Ultrasound examination demonstrated an acute deep vein thrombus extending from the external iliac veins down throughout the visualized veins of the left calf. The patient was started on intravenous heparin and underwent venogram with subsequent thrombolysis. After 48 hours of alteplase infusion, balloon angioplasty was performed and 2 stents were placed in the left common and external iliac veins. Premarin was discontinued and she remains on oral anticoagulation with Coumadin. The patient did well clinically and a second ultrasound showed interval improvement. There is significant family history but no personal history of thrombotic events; however, thrombophilia evaluation is unremarkable.

Dobutamine-induced complete heart block.

Dobutamine is commonly administered as a pharmacologic stressor in patients with limitations precluding exercise testing. The case report presented is one of transient complete heart block resulting from dobutamine sestamibi stress testing. Shortly after initiating the dobutamine infusion, the patient became pale and presyncopal, with hypotension and a heart rate of 50 beats per minute. Subsequently, third-degree heart block developed which lasted transiently and resolved. Subsequent cardiac evaluation of the patient revealed no cardiac etiology for her symptoms. Though bradycardia is infrequently noted in patients receiving dobutamine during stress electrocardiogram, complete heart block is a possibility during dobutamine-induced stress echocardiography and must be recognized as a potential risk.

The Triglyceride Paradox in Stroke Survivors: A Prospective Study

Objective. The purpose of our study was to understand the association between serum triglycerides and outcomes in acute ischemic stroke (AIS) patients. Methods. A cohort of all adult patients presenting to the Emergency Department (ED) with an AIS from March 2004 to December 2005 were selected. The lipid profile levels were measured within 24 hours of stroke onset. Demographics, admission stroke severity (NIHSS), functional outcome at discharge (modified Rankin Scale (mRS)), and mortality at 3 months were recorded. Results. The final cohort consisted of 334 subjects. A lower level of triglycerides at presentation was found to be significantly associated with worse National Institutes of Health Stroke Scale (NIHSS) (P = 0.004), worse mRS (P = 0.02), and death at 3 months (P = 0.0035). After adjusting for age and gender and NIHSS, the association between triglyceride and mortality at 3 months was not significant (P = 0.26). Conclusion. Lower triglyceride levels seem to be associated with a worse prognosis in AIS.