Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke.

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making. METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm3 and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma. RESULTS: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R2=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05). CONCLUSIONS: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.

Mobile Stroke Units: Current Evidence and Impact.

PURPOSE OF REVIEW: Several approaches have been developed to optimize prehospital systems for acute stroke given poor access and significant delays to timely treatment. Specially equipped ambulances that directly initiate treatment, known as Mobile Stroke Units (MSUs), have rapidly proliferated across the world. This review provides a comprehensive summary on the efficacy of MSUs in acute stroke, its various applications beyond thrombolysis, as well as the establishment, optimal setting and cost-effectiveness of incorporating an MSU into healthcare systems. RECENT FINDINGS: MSUs speed stroke treatment into the first "golden hour" when better outcomes from thrombolysis are achieved. While evidence for the positive impact of MSUs on outcomes was previously unavailable, two recent landmark controlled trials, B_PROUD and BEST-MSU, show that MSUs result in significantly lesser disability compared to conventional ambulance care. Emerging literature prove the significant impact of MSUs. Adaptability however remains limited by significant upfront financial investment, challenges with reimbursements and pending evidence on their cost-effectiveness.

Changes in treatment and outcomes after creation of a pulmonary embolism response team (PERT), a 10-year analysis.

Multidisciplinary pulmonary embolism response teams (PERTs) are being implemented to improve care of patients with life-threatening PE. We sought to determine how the creation of PERT affects treatment and outcomes of patients with serious PE. A pre- and post-intervention study was performed using an interrupted time series design, to compare patients with PE before (2006-2012) and after (2012-2016) implementation of PERT at a university hospital. T-tests, Chi square tests and logistic regression were used to compare outcomes, and multivariable regression were used to adjust for differences in PE severity. Two-sided p-value < 0.05 was considered significant. For the interrupted time-series analysis, data was divided into mutually exclusive 6-month time periods (11 pre- and 7 post-PERT). To examine changes in treatment and outcomes associated with PERT, slopes and change points were compared pre- and post-PERT. Two-hundred and twelve pre-PERT and 228 post-PERT patients were analyzed. Patient demographics were generally similar, though pre-PERT, PE were more likely to be low-risk (37% vs. 19%) while post-PERT, PE were more likely to be submassive (32% vs. 49%). More patients underwent catheter directed therapy (1% vs. 14%, p = < 0.0001) or any advanced therapy (19 [9%] vs. 44 [19%], p = 0.002) post PERT. Interrupted time series analysis demonstrated that this increase was sudden and coincident with implementation of PERT, and most noticeable among patients with submassive PE. There were no differences in major bleeding or mortality pre- and post-PERT. While the use of advanced therapies, particularly catheter-directed therapies, increased after creation of PERT, especially among patients with submassive PE, there was no apparent increase in bleeding.

Correction to: Changes in treatment and outcomes after creation of a pulmonary embolism response team (PERT), a 10-year analysis.

The original version of the article unfortunately contained an error in conflict of interest. This erratum is published with the correct conflict of interest.

Factors associated with clinical deterioration shortly after PE.

BACKGROUND: Several factors have been associated with mortality in the months after PE. Factors associated with short-term clinical deterioration or need for hospital-based intervention are less well known. METHODS: We prospectively enrolled consecutive emergency department patients with PE and recorded clinical, biomarker and radiographic data. We assessed hospitalised patients daily to identify clinical deterioration or need for hospital-based intervention for 5 days after PE. We captured postdischarge events via 5-day and 30-day interviews. We used univariate and multivariable models to assess associations with clinical deterioration, severe clinical deterioration and 30-day all-cause mortality. We also assessed the test characteristics of three published clinical decision rules. RESULTS: We enrolled 298 patients with PE: mean age 59 (SD±17) years; 152 (51%) male and 268 (90%) white race. 101 (34%) patients clinically deteriorated or required a hospital-based intervention within 5 days, and 197 (66%) did not. 27 (9%) patients suffered severe clinical deterioration and 12 died within 30 days. Factors independently associated with clinical deterioration were hypotension (p=0.001), hypoxia (p<0.001), coronary disease (p=0.004), residual deep vein thrombosis (p=0.006) and right heart strain on echocardiogram (p<0.001). In contrast, factors associated with 30-day all-cause mortality were active malignancy (p<0.001) and congestive heart failure (p=0.009). The sensitivity of clinical decision rules was moderate (39-80%) for 5-day clinical deterioration but higher (67-100%) for 30-day mortality. CONCLUSIONS: Most patients do not clinically deteriorate after PE diagnosis. Several factors are associated with short-term clinical deterioration, but these factors differ from those associated with 30-day mortality.

Young Female With Hypereosinophilia, Rash, and Gait Disturbance: A Case Report.

Eosinophilia is known to be associated with a multitude of co-morbidities. However, unexplained eosinophilia poses a diagnostic challenge, and the methods used to investigate unexplained eosinophilia vary from region to region. In this case report, we describe a unique case of a young female presenting with marked eosinophilia to a tertiary hospital in the northeastern United States. Our patient presented with a few weeks of lower extremity rash, gait instability, and new onset marked eosinophilia. We further report the investigations undertaken during the hospitalization to highlight the broad differential diagnoses. Later, we provide a consolidated diagnosis of eosinophilic granulomatosis with polyangiitis (EPGA) based on the clinical context. Our patient was eventually started on a high-dose steroid taper. In the following weeks, while we noted gait improvement, we observed biomarker (eosinophilia) relapse after steroid taper. Depending on symptom progression, we planned for future remission induction with immunomodulatory agents. The report further discusses the pleomorphic presentation of EPGA cases, the natural course of disease, and currently available prognostic indices.

Sensitivity of erythrocyte sedimentation rate and C-reactive protein for the exclusion of septic arthritis in emergency department patients.

BACKGROUND: Previous studies in post-operative orthopedic and pediatric patients suggest that erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) testing may be helpful in ruling out septic arthritis. However, these tests have not been evaluated in a population of adult Emergency Department (ED) patients. STUDY OBJECTIVE: Determine the sensitivity of ESR and CRP in patients with septic arthritis. METHODS: Retrospective analysis of ED patients with septic arthritis from 2003 to 2008. Eligible patients had an International Classification of Diseases-Ninth Revision diagnosis of pyogenic arthritis (711.0x) plus: positive synovial fluid culture, positive synovial Gram stain, or operative irrigation. Patients were excluded if no ESR or CRP was performed within 24 h. Sensitivity of ESR and CRP at various cutoffs was calculated with 95% confidence intervals (CI). RESULTS: We identified 167 patients with septic arthritis. We included 143 (86%) who had ESR (n=140, 84%) or CRP (n=96, 57%) performed. Mean age was 49 (± 22) years, and 85 (59%) were male. Race was: 125 (87%) white, 4 (3%) black, and 12 (8%) Hispanic. Thirty-five (24%) had infection of prosthetic joints. Synovial cultures were positive in 102 (71%). Sensitivity of ESR was: 98% (95% CI 94-100%) using a cutoff of ≥10 mm/h (n=134) and 94% (95% CI 88-97%) using a cutoff of ≥15 mm/h (n=131). The sensitivity of CRP was 92% (95% CI 84-96%) using a cutoff of ≥20 mg/L (n=88). CONCLUSION: ESR and CRP have sensitivities of >90% for septic arthritis, but only when low thresholds are used. Further study is required to determine the clinical usefulness of ESR and CRP testing.

Mapping gene and gene pathways associated with coronary artery disease: a CARDIoGRAM exome and multi-ancestry UK biobank analysis.

Coronary artery disease (CAD) genome-wide association studies typically focus on single nucleotide variants (SNVs), and many potentially associated SNVs fail to reach the GWAS significance threshold. We performed gene and pathway-based association (GBA) tests on publicly available Coronary ARtery DIsease Genome wide Replication and Meta-analysis consortium Exome (n = 120,575) and multi ancestry pan UK Biobank study (n = 442,574) summary data using versatile gene-based association study (VEGAS2) and Multi-marker analysis of genomic annotation (MAGMA) to identify novel genes and pathways associated with CAD. We included only exonic SNVs and excluded regulatory regions. VEGAS2 and MAGMA ranked genes and pathways based on aggregated SNV test statistics. We used Bonferroni corrected gene and pathway significance threshold at 3.0 × 10-6 and 1.0 × 10-5, respectively. We also report the top one percent of ranked genes and pathways. We identified 17 top enriched genes with four genes (PCSK9, FAM177, LPL, ARGEF26), reaching statistical significance (p ≤ 3.0 × 10-6) using both GBA tests in two GWAS studies. In addition, our analyses identified ten genes (DUSP13, KCNJ11, CD300LF/RAB37, SLCO1B1, LRRFIP1, QSER1, UBR2, MOB3C, MST1R, and ABCC8) with previously unreported associations with CAD, although none of the single SNV associations within the genes were genome-wide significant. Among the top 1% non-lipid pathways, we detected pathways regulating coagulation, inflammation, neuronal aging, and wound healing.

Clinical factors associated with massive pulmonary embolism and PE-related adverse clinical events.

BACKGROUND: Clinicians evaluating acute PE patients often have to identify risks for massive PE, a measure of hemodynamic instability and its consequence, massive PE related adverse clinical events (PEACE). We investigated the association of these risk factors with massive PE and PEACE in a consecutive PE cohort (n = 364). METHODS: Massive PE was defined as an acute central clot (proximal to the lobar artery) in a patient with right heart strain and systolic blood pressure ≤ 90 mg. PEACE was defined as any massive PE who died or required one or more of the following: ACLS, assisted ventilation, vasopressor use, thrombolytic therapy, or invasive thrombectomy, within seven days of PE diagnosis. Univariate and multivariate analysis assessing associations between the risk factors (age, gender, comorbidities, PE provoking risks, and whether the PE was felt to be idiopathic) and massive PE or PEACE were performed. Significance was determined at p < 0.05. RESULTS: Thirteen percent (n = 48) of patients presented with massive PE, and 9% (n = 32) had PEACE. In the final multivariate model, recent invasive procedure (RR = 7.4, p = 0.007), recent hospitalization (RR = 7.3, p = 0.002), and idiopathic PE (RR = 6.5, p = 0.003) were associated with massive PE. Only idiopathic PE (RR = 5.7, p = 0.005) was significantly associated with PEACE. No comorbidities or other PE provoking risks were associated with massive PE or PEACE. CONCLUSIONS: As a take-home message, recent invasive procedure, recent hospitalization, and idiopathic PE were associated with massive PE, and only idiopathic PE was associated with PEACE. Simultaneously, comorbidities like age or chronic cardiopulmonary disease seem not to be associated with massive PE or PEACE.

A Case of Guillain-Barré Syndrome Associated With COVID-19.

A novel member of human RNA coronavirus, which is an enveloped betacoronavirus, has been termed severe acute respiratory syndrome coronavirus-2 (SARS COV-2). The illness caused by SARS COV-2 is referred to as the coronavirus disease 2019 (COVID-19). It is a highly contagious disease that has resulted in a global pandemic. The clinical spectrum of COVID-19 ranges from asymptomatic illness to acute respiratory distress syndrome, septic shock, multi-organ dysfunction, and death. The most common symptoms include fever, fatigue, dry cough, dyspnea, and diarrhea. Neurological manifestations have also been reported. However, the data on the association of Guillain-Barré syndrome (GBS) with COVID-19 are scarce. We report a rare case of a COVID-19-positive 36-year-old immunocompromised male who presented with clinical features of GBS. His clinical examination showed generalized weakness and hyporeflexia. The cerebrospinal fluid (CSF) analysis showed albuminocytological dissociation. Intravenous immunoglobulin (IVIG) was administered based on the high clinical suspicion of GBS. The patient's neurological condition worsened with progression to bulbar weakness and ultimately neuromuscular respiratory failure requiring mechanical ventilation. His nerve conduction studies were consistent with demyelinating polyneuropathy. He received five plasma exchange treatments and was successfully weaned from mechanical ventilation. A brain and cervical spine magnetic resonance imaging was obtained to rule out other causes, which was normal. COVID-19 is believed to cause a dysregulated immune system, which likely plays an important role in the neuropathogenesis of GBS.

Electrophysiology of Olfactory and Optic Nerve in Outpatient and Intraoperative Settings.

Evoked potentials are time-locked electrophysiologic potentials recorded in response to standardized stimuli using scalp electrodes. These responses provide good temporal resolution and have been used in various clinical and intraoperative settings. Olfactory evoked potentials (OEPs) may be used as an adjunct tool in identifying patients of Parkinson disease and Alzheimer dementia. In clinical practice, visual evoked potentials (VEPs) are particularly useful in identifying subclinical cases of optic neuritis and in treatment surveillance. In recent times, pattern electroretinograms and photopic negative response have been gaining attention in identifying glaucoma suspects. During surgical manipulation, there is a risk of damage to optic or olfactory nerve. Intraoperative neurophysiologic monitoring can provide information regarding the integrity of olfactory or visual pathway. OEPs and VEPs, however, show high degree of variability and are not reliable tools because the responses are extremely susceptible to volatile anesthetic agents. Newer techniques that could possibly circumvent these drawbacks have been developed but are not used extensively. In this article, we briefly review the available techniques to obtain OEPs and VEPs, diagnostic applications, the utility of intraoperative monitoring, the limitations of the current techniques, and the future directions for research.

Electrophysiology of Extraocular Cranial Nerves: Oculomotor, Trochlear, and Abducens Nerve.

The utility of extraocular cranial nerve electrophysiologic recordings lies primarily in the operating room during skull base surgeries. Surgical manipulation during skull base surgeries poses a risk of injury to multiple cranial nerves, including those innervating extraocular muscles. Because tumors distort normal anatomic relationships, it becomes particularly challenging to identify cranial nerve structures. Studies have reported the benefits of using intraoperative spontaneous electromyographic recordings and compound muscle action potentials evoked by electrical stimulation in preventing postoperative neurologic deficits. Apart from surgical applications, electromyography of extraocular muscles has also been used to guide botulinum toxin injections in patients with strabismus and as an adjuvant diagnostic test in myasthenia gravis. In this article, we briefly review the rationale, current available techniques to monitor extraocular cranial nerves, technical difficulties, clinical and surgical applications, as well as future directions for research.

Assessment of Right Ventricular Strain by Computed Tomography Versus Echocardiography in Acute Pulmonary Embolism.

BACKGROUND: Right ventricular strain (RVS) identifies patients at risk of hemodynamic deterioration from pulmonary embolism (PE). Our hypothesis was that chest computed tomography (CT) can provide information about RVS analogous to transthoracic echocardiography (TTE) and that RVS on CT is associated with adverse outcomes after PE. METHODS: Consecutive emergency department patients with acute PE were prospectively enrolled and clinical, biomarker, and imaging data were recorded. CTs were overread by two radiologists. We compared diagnoses of RVS on CT (defined as right ventricle:left ventricle ratio ≥ 0.9 or interventricular septal bowing) to echocardiography (defined as right ventricular hypokinesis, right ventricular dilatation, or interventricular septal bowing). We calculated the test characteristics (with 95% confidence interval) of CT and TTE for a composite outcome of severe clinical deterioration, thrombolysis/thrombectomy, or death within 5 days. RESULTS: A total of 298 patients were enrolled; 274 had CT and 118 had formal TTE. Of the 104 patients who had both CT and TTE, the mean (±SD) age was 58 (±17) years; 50 (48%) were female and 88 (85%) were Caucasian. Forty-two (40%) had RVS by TTE and 75 (72%) had RVS by CT. CT and TTE agreed on the presence or absence of RVS in 61 (59%) cases (κ = 0.24). Using TTE as criterion standard, the test characteristics of CT for RVS were as follows: sensitivity = 88%, specificity = 39%, positive predictive value = 49%, and negative predictive value = 83%. Fourteen (13%) patients experienced severe clinical deterioration or required hospital-based intervention within 5 days. This occurred in 30% of patients with RVS on both TTE and CT, 20% of patients with RVS on TTE alone, 3% of patients with RVS on CT alone, and 4% of patients without RVS on either modality. CONCLUSIONS: In acute PE, CT is highly sensitive but only moderately specific for RVS compared to TTE. RVS on both CT and TTE predicts more events than either modality alone. TTE confers additional positive prognostic value compared to CT in predicting post-PE clinical deterioration.

Sjogren-Larsson syndrome: A rare neurocutaneous disorder.

Sjogren-Larsson syndrome is an autosomal recessive disorder characterized by defective activity of fatty aldehyde dehydrogenase. It presents as a triad of congenital ichthyosis, spastic diplegia, and mental retardation. The pathology behind this syndrome is the failure of degradation of fatty aldehydes. This case is presented for its rarity.

Relation Among Clot Burden, Right-Sided Heart Strain, and Adverse Events After Acute Pulmonary Embolism.

Computed tomography pulmonary angiogram (CTPA) provides a volumetric assessment of clot burden in acute pulmonary embolism (PE). However, it is unclear if clot burden is associated with right-sided heart strain (RHS) or adverse clinical events (ACE). We prospectively enrolled Emergency Department patients with PE (in CTPA) from 2008 to 2011. We assigned 1 to 9 points as clot burden score, based on whether emboli were saddle, central, lobar, segmental, and subsegmental. We evaluated a novel score (the "CT-PASS") based on the sum (in millimeters) of the largest filling defects in the right and left pulmonary vasculature. Our primary outcome was RHS, defined by imaging (echocardiography or CTPA) or cardiac biomarkers. Our secondary outcomes included 5-day ACE. We included 271 patients (50% women), with a mean age of 59 ± 17 years. Based on CTPA, 131 patients (48%) had central PE (clot burden score ≥5 points). The median CT-PASS was 9.1 mm (interquartile range 4.9 to 16.4). In univariate analysis, higher clot burden (highest quartile CT-PASS) was associated with RHS (p = 0.003). In multivariate analysis, after adjusting for RHS, age, and gender, central PE (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.10 to 7.81) and CT-PASS >20 mm (OR 3.54, 95% CI 1.39 to 8.97) were significantly associated with ACE. However, this association of central PE with ACE was not statistically significant after excluding patients with shock index >1 (OR 2.56, 95% CI 0.62 to 10.64). In conclusion, highest quartile CT-PASS was associated with RHS and central PE and ACE, but this association was not statistically significant in hemodynamically stable PE [corrected].

A rare case of glycine encephalopathy unveiled by valproate therapy.

Glycine encephalopathy (GE) or nonketotic hyperglycinemia is an autosomal recessive disorder due to a primary defect in glycine cleavage enzyme system. It is characterized by elevated levels of glycine in plasma and cerebrospinal fluid usually presenting with seizures, hypotonia, and developmental delay. In our case, paradoxical increase in seizure frequency on starting sodium valproate led us to diagnose GE.

Association between electrocardiographic findings, right heart strain, and short-term adverse clinical events in patients with acute pulmonary embolism.

BACKGROUND: Electrocardiographic (ECG) changes may be seen with pulmonary emboli (PE). Whether ECG is associated with short-term adverse clinical events after PE is less well established. HYPOTHESIS: ECG findings are associated with short-term clinical deterioration after PE. METHODS: Consecutive adult PE patients were enrolled in an academic emergency department from 2008 to 2011. The primary outcome was right heart strain (RHS) on echocardiogram or CT pulmonary angiography, or TnT ≥0.1 ng/mL. We derived an ECG (TwiST) score that is associated with RHS and short-term adverse clinical events. RESULTS: We enrolled 298 patients with PE. On multivariate analysis, T-wave inversion in leads V(1) through V(3) (OR: 4.7, 95% confidence interval [CI]: 1.7-13.2), S wave in lead I (OR: 2.0, 95% CI: 1.1-3.5), and tachycardia (OR: 2.5, 95% CI: 1.3-4.8) were associated with RHS. A TwiST score ≤2 (n = 210, 72%) was 84% (95% CI: 77%-90%) sensitive for the absence of RHS, whereas a TwiST score ≥5 (n = 47, 16%) was 93% (95% CI: 88%-97%) specific for the presence of RHS. CONCLUSIONS: A simple ECG (TwiST) score can identify patients likely or not likely to have RHS with >80% specificity and sensitivity and may assist in identifying patients with acute PE at risk for adverse clinical events before pursuing other advanced imaging tests.

A comparison of patients diagnosed with pulmonary embolism who are ≥65 years with patients <65 years.

Recent studies have highlighted differences in how older patients respond to high-risk pulmonary embolism (PE) and treatment. However, guidelines for PE risk stratification and treatment are not based on age, and data are lacking for older patients. We characterized the impact of age on clinical features, risk stratification, treatment, and outcomes in a sample of patients with PE in the emergency department. We performed an observational cohort study of 547 consecutive patients with PE in the emergency department from 2005 to 2011 in an urban tertiary hospital. We used bivariate proportions and multivariable logistic regression to compare clinical presentation, risk category, treatment, and outcomes in patients ≥65 years with those <65 years. The mean age was 58 ± 17 years, 276 (50%) were women, and 210 (38%) were ≥65 years. PE was more severe in patients ≥65 years (massive 14% vs 5%, submassive 48% vs 25%, and low risk 38% vs 70%, p <0.0001), with submassive PE being the most common presentation in patients ≥65 years. However, subanalysis removing natriuretic peptides from the definition of submassive PE negated this finding. Treatment with parenteral anticoagulation (88% vs 90%, p = 0.32), thrombolytic therapy (5% vs 4%, p = 0.87), and inferior vena cava filter (4% vs 4%, p = 0.73) were similar among age groups. Patients ≥65 years had higher 30-day mortality (11% vs 3%, p <0.001). In conclusion, patients ≥65 years present with more severe PE and have higher mortality, although treatment patterns were similar to younger patients. Age-specific guideline definitions of submassive PE may better identify high-risk patients.