Unaffected ex vivo clotting cascade by experimental hemostatic nanoparticles when introduced in the presence of recombinant tissue plasminogen activator.

CONTEXT: Hemostatic nanoparticles (hNPs) have shown efficacy in decreasing intracerebral hemorrhage (ICH) in animal models and are suggested to be of use to counter tissue plasminogen activator (tPA)-induced acute ICH. AIMS: The objective of this study was to test the ability of an hNP preparation to alter the clotting properties of blood exposed to tPA ex vivo. MATERIALS AND METHODS: Fresh blood samples were obtained from normal male Sprague-Dawley rats (~300 g; n = 6) and prepared for coagulation assays by thromboelastography (TEG) methods. Samples were untreated, exposed to tPA, or exposed to tPA and then to hNP. TEG parameters included reaction time (R, time in minutes elapsed from test initiation to initial fibrin formation), coagulation time (K, time in minutes from R until initial clot formation), angle (α, a measure in degrees of the rate of clot formation), maximum amplitude (MA, the point when the clot reaches its MA in mm), lysis at 30 min after MA (LY30, %), and clot strength (G, dynes/cm2), an index of clot strength. STATISTICAL ANALYSIS USED: Kruskal-Wallis test was employed to compare TEG parameters measured for untreated control samples versus those exposed to tPA and to compare tPA-exposed samples to samples treated with tPA + hNPs. Significances were inferred at P ≤ 0.05. RESULTS: Compared to untreated samples, tPA-treated samples showed a trend toward decreased angle and G suggesting potentially clot formation rate and clot strength. The addition of hNP did not affect any of these or other measured indices. CONCLUSIONS: The data demonstrated no hemostatic effects when the hNP was used in the presence of tPA. The lack of change in any of the TEG parameters measured in the present study may indicate limitations of the hNPs to reverse the thrombolytic cascade initiated by tPA.

Classification and Prediction of Post-Trauma Outcomes Related to PTSD Using Circadian Rhythm Changes Measured via Wrist-Worn Research Watch in a Large Longitudinal Cohort.

Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. APPROACH: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. RESULTS: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. SIGNIFICANCE: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.

Challenge of intravascular volume assessment in acute ischemic stroke.

INTRODUCTION: Retrospective data indicates that dehydration in acute ischemic stroke patients may be common, even though these patients frequently have elevated blood pressure. We sought to evaluate clinical and laboratory measures of intravascular volume status compared to more objective measures using ultrasound measurements of the inferior vena cava (IVC). METHODS: This was a prospective observation study of acute ischemic stroke patients in the emergency department. Patients with NIH stroke scale ≥4 within 12 h of symptom onset were included. A trained ultrasonographer performed bi-dimensional imaging of the IVC with passive respiration to determine the percent inspiratory collapse and maximum diameter. We defined low intravascular volume as >50% IVC collapse and a maximal diameter < 2.1 cm. Analysis was limited to patients with confirmed ischemic stroke. RESULTS: There were 42 patients, of whom 31 had confirmed acute ischemic stroke. The mean age was 65 ±â€¯15 years, 52% were female, and 71% were hypertensive. The median NIH stroke scale score was 7 (IQR 5-15). Based on IVC ultrasound, low intravascular volume was present in 63% (95% CI 44-80%) of patients. A higher proportion of hypertensive patients had low intrasvascular volume (72% vs. 33%). There was poor correlation between IVC assessment of intrasvascular volume and blinded clinician assessment or laboratory markers of dehydration. CONCLUSION: The majority of ED acute ischemic stroke patients in this sample were hypertensive and demonstrated low intravascular volume based on IVC ultrasound.

Clinical practice guideline: sudden hearing loss.

OBJECTIVE: Sudden hearing loss (SHL) is a frightening symptom that often prompts an urgent or emergent visit to a physician. This guideline provides evidence-based recommendations for the diagnosis, management, and follow-up of patients who present with SHL. The guideline primarily focuses on sudden sensorineural hearing loss (SSNHL) in adult patients (aged 18 and older). Prompt recognition and management of SSNHL may improve hearing recovery and patient quality of life (QOL). Sudden sensorineural hearing loss affects 5 to 20 per 100,000 population, with about 4000 new cases per year in the United States. This guideline is intended for all clinicians who diagnose or manage adult patients who present with SHL. PURPOSE: The purpose of this guideline is to provide clinicians with evidence-based recommendations in evaluating patients with SHL, with particular emphasis on managing SSNHL. The panel recognized that patients enter the health care system with SHL as a nonspecific, primary complaint. Therefore, the initial recommendations of the guideline deal with efficiently distinguishing SSNHL from other causes of SHL at the time of presentation. By focusing on opportunities for quality improvement, the guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients. RESULTS: The panel made strong recommendations that clinicians should (1) distinguish sensorineural hearing loss from conductive hearing loss in a patient presenting with SHL; (2) educate patients with idiopathic sudden sensorineural hearing loss (ISSNHL) about the natural history of the condition, the benefits and risks of medical interventions, and the limitations of existing evidence regarding efficacy; and (3) counsel patients with incomplete recovery of hearing about the possible benefits of amplification and hearing-assistive technology and other supportive measures. The panel made recommendations that clinicians should (1) assess patients with presumptive SSNHL for bilateral SHL, recurrent episodes of SHL, or focal neurologic findings; (2) diagnose presumptive ISSNHL if audiometry confirms a 30-dB hearing loss at 3 consecutive frequencies and an underlying condition cannot be identified by history and physical examination; (3) evaluate patients with ISSNHL for retrocochlear pathology by obtaining magnetic resonance imaging, auditory brainstem response, or audiometric follow-up; (4) offer intratympanic steroid perfusion when patients have incomplete recovery from ISSNHL after failure of initial management; and (5) obtain follow-up audiometric evaluation within 6 months of diagnosis for patients with ISSNHL. The panel offered as options that clinicians may offer (1) corticosteroids as initial therapy to patients with ISSNHL and (2) hyperbaric oxygen therapy within 3 months of diagnosis of ISSNHL. The panel made a recommendation against clinicians routinely prescribing antivirals, thrombolytics, vasodilators, vasoactive substances, or antioxidants to patients with ISSNHL. The panel made strong recommendations against clinicians (1) ordering computerized tomography of the head/brain in the initial evaluation of a patient with presumptive SSNHL and (2) obtaining routine laboratory tests in patients with ISSNHL.

Sildenafil treatment of subacute ischemic stroke: a safety study at 25-mg daily for 2 weeks.

BACKGROUND: In several animal studies of young and aged rats with ischemic stroke, treatment with sildenafil improved functional outcomes compared with placebo. We conducted a safety study of sildenafil (25 mg daily for 2 weeks) shortly after ischemic stroke onset. METHODS: We recruited patients aged 18 to 80 years with ischemic stroke, National Institutes of Health stroke scale (NIHSS) score 2 to 21, between days 2 and 9 after symptom onset. Patients were treated with sildenafil for 2 weeks (25 mg daily). The primary outcome measure was the adverse occurrence of any of the following during the treatment period: stroke worsening, new stroke, myocardial infarction, vision loss, hearing loss, or death from any cause. Secondary outcome measures were NIHSS score, Barthel indices, and modified Rankin score at 90 days. RESULTS: Twelve patients were recruited. Mean age was 57 years, 5 were female, and median NIHSS score at entry was 9.5 (range 2-20). The primary outcome measure occurred in one patient (sudden death). Another patient committed suicide 2 months after study entry (and 6 weeks after treatment with sildenafil had been completed). Among the 10 survivors, at 90 days, median NIHSS score was 2 (range 0-12), median Barthel index was 95 (range 15-100), and median modified Rankin score was 1.5 (range 0-5). CONCLUSIONS: Sildenafil (25 mg daily for 2 weeks) appeared to be safe in this group of patients with mild to moderately severe stroke. Further studies of higher doses will be tested.

Transient ischemic attack: definitions and clinical presentations.

The definition of transient ischemic attack has changed from a focal, neurologic event that lasts less than 24 hours to one that typically lasts less than 1 hour and is not associated with changes on neuroimaging. Transient ischemic attacks, using the older definition, carry a 10% risk of stroke within 90 days and are therefore considered a serious condition meriting urgent attention. The manifestations of transient ischemic attacks are varied and include events that involve the anterior and posterior cerebral circulations. Correct diagnosis depends on an accurate medical history and physical examination, combined with the appropriate neuroimaging. It is uncommon that syndromes such as syncope, isolated dizziness, drop attacks, or global amnesia are caused by cerebral ischemia or transient ischemic attack. With the careful evaluation of symptoms according to this definition of transient ischemic attack, a clinician can determine whether a transient ischemic attack has occurred and thus propose treatment that may decrease the likelihood of a subsequent stroke.

Centenarian stroke treated with tissue-type plasminogen activator.

BACKGROUND: Elderly patients with acute ischemic stroke often do worse than younger counterparts independent of thrombolytic therapy. Further, tissue-type plasminogen activator, (t-PA) is frequently withheld from the very old. This may be the result of comorbid conditions prohibiting its use or possibly the fear of causing more harm than good. We present a case of a 100-year-old woman who was treated with t-PA for acute ischemic stroke with rapid resolution of symptoms. CASE DESCRIPTION: A 100-year-old woman presented to the emergency department with slurred speech, right hemiparesis and right hemisensory loss. Computed tomography revealed neither hemorrhage nor early ischemic changes. Intravenous t-PA was administered at 0.9 mg/kg 3 min prior to the 3-hour limit. She improved rapidly (NIHSS from 12 on admission to 4 at 1 month) and was discharged to the care of her family after 4 hospital days. CONCLUSION: Intravenous thrombolysis may be beneficial in the very elderly and should be considered in any eligible elderly patients with acute ischemic stroke, with a risk/benefit analysis individualized to each case.