Nanomolar concentrations of the photodynamic compound TLD-1433 effectively inactivate numerous human pathogenic viruses.

The anti-viral properties of a small (≈1 kDa), novel Ru(II) photo dynamic compound (PDC), referred to as TLD-1433 (Ruvidar™), are presented. TLD-1433 had previously been demonstrated to exert strong anti-bacterial and anti-cancer properties. We evaluated the capacity of TLD-1433 to inactivate several human pathogenic viruses. TLD-1433 that was not photo-activated was capable of effectively inactivating 50 % of influenza H1N1 virus (ID50) at a concentration of 117 nM. After photo-activation, the ID50 was reduced to <10 nM. The dose of photo-activated TLD-1433 needed to reduce H1N1 infectivity >99 % (ID99) was approximately 170 nM. Similarly, the ID99 of photo-activated TLD-1433 was determined to range from about 20 to 120 nM for other tested enveloped viruses; specifically, a human coronavirus, herpes simplex virus, the poxvirus Vaccinia virus, and Zika virus. TLD-1433 also inactivated two tested non-enveloped viruses; specifically, adenovirus type 5 and mammalian orthoreovirus, but at considerably higher concentrations. Analyses of TLD-1433-treated membranes suggested that lipid peroxidation was a major contributor to enveloped virus inactivation. TLD-1433-mediated virus inactivation was temperature-dependent, with approximately 10-fold more efficient virucidal activity when viruses were treated at 37 °C than when treated at room temperature (∼22 °C). The presence of fetal bovine serum and virus solution turbidity reduced TLD-1433-mediated virucidal efficiency. Immunoblots of TLD-1433-treated human coronavirus indicated the treated spike protein remained particle-associated.

Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets.

Lipid droplets (LDs), crucial regulators of lipid metabolism, accumulate during oocyte development. However, their roles in fertility remain largely unknown. During Drosophila oogenesis, LD accumulation coincides with the actin remodeling necessary for follicle development. Loss of the LD-associated Adipose Triglyceride Lipase (ATGL) disrupts both actin bundle formation and cortical actin integrity, an unusual phenotype also seen when the prostaglandin (PG) synthase Pxt is missing. Dominant genetic interactions and PG treatment of follicles indicate that ATGL acts upstream of Pxt to regulate actin remodeling. Our data suggest that ATGL releases arachidonic acid (AA) from LDs to serve as the substrate for PG synthesis. Lipidomic analysis detects AA-containing triglycerides in ovaries, and these are increased when ATGL is lost. High levels of exogenous AA block follicle development; this is enhanced by impairing LD formation and suppressed by reducing ATGL. Together, these data support the model that AA stored in LD triglycerides is released by ATGL to drive the production of PGs, which promote the actin remodeling necessary for follicle development. We speculate that this pathway is conserved across organisms to regulate oocyte development and promote fertility.

Absence of significant myocardial injury following elective direct current cardioversion for atrial fibrillation.

Background: Direct current (DC) cardioversion is used to terminate cardiac arrhythmias. Current guidelines list cardioversion as a cause of myocardial injury. Objective: This study determined whether external DC cardioversion results in myocardial injury measured by serial changes in high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI). Methods: This was a prospective study of patients undergoing elective external DC cardioversion for atrial fibrillation. hs-cTnT and hs-cTnI were measured precardioversion and at least 6 hours postcardioversion. Myocardial injury was present when there were significant changes in both hs-cTnT and hs-cTnI. Results: Ninety-eight subjects were analyzed. Median cumulative energy delivered was 121.9 (interquartile range [IQR] 102.2-302.7) J. Multiple cases 23 (23.5%) required 300 J or more. Maximum cumulative energy delivered was 2455.1 J. There were small significant changes in both hs-cTnT (median precardioversion 12 [IQR 7-19) ng/L], median postcardioversion 13 [IQR 8-21] ng/L; P < .001) and hs-cTnI (median precardioversion 5 [IQR 3-10) ng/L], median postcardioversion 7 [IQR 3.6-11) ng/L; P < .001). Results were similar in patients with high-energy shocks and did not vary based on precardioversion values. Only 2 (2%) cases met criteria for myocardial injury. Conclusion: DC cardioversion resulted in a small but statistically significant changes in hs-cTnT and hs-cTnI in 2% of patients studied irrespective of shock energy. Patients with marked troponin elevations after elective cardioversion should be assessed for other causes of myocardial injury. It should not be assumed the myocardial injury was from the cardioversion.

Visualizing Lipid Droplets in Drosophila Oogenesis.

Lipid droplets (LDs) are fat storage organelles highly abundant in oocytes and eggs of many vertebrates and invertebrates. They have roles both during oogenesis and in provisioning the developing embryo. In Drosophila, large numbers of LDs are generated in nurse cells during mid-oogenesis and then transferred to oocytes. Their number and spatial distribution changes developmentally and in response to various experimental manipulations. This chapter demonstrates how to visualize LDs in Drosophila follicles, both in fixed tissues and living samples. For fixed samples, the protocol explains how to prepare female flies, dissect ovaries, isolate follicles, fix, apply stains, mount the tissue, and perform imaging. For live samples, the protocol shows how to dissect ovaries, apply a fluorescent LD dye, and culture follicles such that they remain alive and healthy during imaging. Finally, a method is provided that employs in vivo centrifugation to assess colocalization of markers with LDs.

A Phase 1b Clinical Study of Intravesical Photodynamic Therapy in Patients with Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer.

Background: A phase 1b study of photosensitizer TLD-1433-mediated photodynamic therapy (PDT) was performed in bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. Objective: The primary objectives were safety and tolerability of PDT, with secondary objectives of (1) pharmacokinetic (PK) properties of TLD-1433 and (2) efficacy, as evaluated by recurrence-free survival and complete response (CR) at 90 and 180 d for patients treated at the maximum recommended starting dose (0.35 mg/cm2 bladder surface area) and the therapeutic dose (0.70 mg/cm2). Design setting and participants: Six BCG-unresponsive patients were enrolled in an open-label, single-arm, dose-escalating study of PDT. TLD-1433 was instilled intravesically for 60 min preoperatively. PDT was performed under general anesthesia using intravesically delivered irradiation of the bladder wall with green light (520 nm) to a dose of 90 J/cm2. Outcome measurements and statistical analysis: Patients were followed by standard cystoscopy and cytology for up to 18 mo to assess time to recurrence. Results and limitations: PDT was well tolerated by all patients. All patients experienced at least one grade ≤2 adverse event (AE). There were no patient deaths or light sensitivity reactions. The most common AE was moderate bladder irritability, which resolved within the first weeks after treatment. AEs were independent of the TLD-1433 dose. TLD-1433 was cleared in the urine and from the plasma within 24 and 72 h, respectively. Of three patients treated at the therapeutic dose, two achieved a CR at 180 d, which was durable at 18 mo. The other patient was diagnosed with metastatic disease at 138 d. Conclusions: PDT with TLD-1433 appears safe for the treatment of BCG-unresponsive NMIBC. Early efficacy signals from full-dose photosensitizer are encouraging and warrant phase 2 trial investigation. The safety and PK results obtained support the potential for administration of consecutive PDT treatments as required. Patient summary: Photodynamic therapy with TLD-1433 appears to be safe and effective for the treatment of bacillus Calmette-Guérin (BCG)-unresponsive bladder cancer.

From Dynamics to Novelty: An Agent-Based Model of the Economic System.

The modern economy is both a complex self-organizing system and an innovative, evolving one. Contemporary theory, however, treats it essentially as a static equilibrium system. Here we propose a formal framework to capture its complex, evolving nature. We develop an agent-based model of an economic system in which firms interact with each other and with consumers through market transactions. Production functions are represented by a pair of von Neumann technology matrices, and firms implement production plans taking into account current price levels for their inputs and output. Prices are determined by the relation between aggregate demand and supply. In the absence of exogenous perturbations the system fluctuates around its equilibrium state. New firms are introduced when profits are above normal, and are ultimately eliminated when losses persist. The varying number of firms represents a recurrent perturbation. The system thus exhibits dynamics at two levels: the dynamics of prices and output, and the dynamics of system size. The model aims to be realistic in its fundamental structure, but is kept simple in order to be computationally efficient. The ultimate aim is to use it as a platform for modeling the structural evolution of an economic system. Currently the model includes one form of structural evolution, the ability to generate new technologies and new products.

Characterization of Streptomyces nymphaeiformis sp. nov., and its taxonomic relatedness to other polyhydroxybutyrate-degrading streptomycetes.

A polyhydroxybutyrate (PHB)-degrading actinomycete, strain SFB5AT, was identified as a species of Streptomyces based on its membrane fatty acid profile and the presence of ll-diaminopimelic acid in the cell wall. It formed sporulating mycelia on most agar media, but flat or wrinkled, moist colonies on trypticase soy agar. Spores were smooth, cylindrical, and borne on long, straight to flexuous chains. It produced a light brown diffusible pigment, but not melanin. Comparison of genomic digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values indicated that strain SFB5AT was related to Streptomyces litmocidini JCM 4394T, Streptomyces vietnamensis GIMV4.0001T, Streptomyces nashvillensis JCM 4498T and Streptomyces tanashiensis JCM 4086T, plus 11 other species. However, the dDDH and ANI values were well below the species differentiation thresholds of <70 and <95 %, respectively; also, multilocus sequence analysis distances exceeded the species threshold of 0.007. Moreover, strain SFB5AT differed from the other species in pigmentation and its ability to catabolize arabinose. Strain SFB5AT and 11 of its 15 closest relatives degraded PHB and have genes for extracellular, short-chain-length denatured polyhydroxyalkanoate depolymerases. These enzymes from strain SFB5AT and its closest relatives had a type 1 catalytic domain structure, while those from other relatives had a type 2 structure, which differs from type one in the position of a consensus histidine in the active site. Thus, phenotypic and genotypic differences suggest that strain SFB5AT represents a new species of Streptomyces, for which we propose the name Streptomyces nymphaeiformis sp. nov. The type strain is SFB5AT (=NRRL B-65520T=DSM 112030T).

Sequestration to lipid droplets promotes histone availability by preventing turnover of excess histones.

Because both dearth and overabundance of histones result in cellular defects, histone synthesis and demand are typically tightly coupled. In Drosophila embryos, histones H2B, H2A and H2Av accumulate on lipid droplets (LDs), which are cytoplasmic fat storage organelles. Without LD binding, maternally provided H2B, H2A and H2Av are absent; however, how LDs ensure histone storage is unclear. Using quantitative imaging, we uncover when during oogenesis these histones accumulate, and which step of accumulation is LD dependent. LDs originate in nurse cells (NCs) and are transported to the oocyte. Although H2Av accumulates on LDs in NCs, the majority of the final H2Av pool is synthesized in oocytes. LDs promote intercellular transport of the histone anchor Jabba and thus its presence in the ooplasm. Ooplasmic Jabba then prevents H2Av degradation, safeguarding the H2Av stockpile. Our findings provide insight into the mechanism for establishing histone stores during Drosophila oogenesis and shed light on the function of LDs as protein-sequestration sites.

Epidemiology of in-hospital cardiac arrest complicating non-ST-segment elevation myocardial infarction receiving early coronary angiography.

In the period between 2000 and 2014, 584,704 admissions with non-ST-segment elevation myocardial infarction that received early coronary angiography (day zero) were identified from the National Inpatient Sample. In-hospital cardiac arrest was noted in 4349 (0.8%), of which ~47% were from ventricular arrhythmias and ~90% of occurred within ≤4 days. Non-ST-segment elevation myocardial infarction admissions with in-hospital cardiac arrest had higher in-hospital mortality compared to those without (61% vs. 1.6%) with an unchanged temporal trend of in-hospital cardiac arrest rates (adjusted odds ratio 1.29 [95% confidence interval 0.73-2.28]) in 2014 compared to 2000).

Reduced Size Profile of Amniotic Membrane Particles Decreases Osteoarthritis Therapeutic Efficacy.

Osteoarthritis (OA) is a widespread disease that continues to lack approved and efficacious treatments that modify disease progression. Micronized dehydrated human amnion/chorion membrane (µ-dHACM) has been shown to be effective in reducing OA progression, but many of the engineering design parameters have not been explored. The objectives of this study were to characterize the particle size distributions of two µ-dHACM formulations and to investigate the influence of these distributions on the in vivo therapeutic efficacy of µ-dHACM. Male Lewis rats underwent medial meniscus transection (MMT) or sham surgery, and intra-articular injections of saline, µ-dHACM, or reduced particle size µ-dHACM (RPS µ-dHACM) were administered at 24 hours postsurgery (n = 9 per treatment group). After 3 weeks, the animals were euthanized, and left legs harvested for equilibrium partitioning of an ionic contrast agent microcomputed tomography and histological analysis. µ-dHACM and RPS µ-dHACM particles were fluorescently tagged and particle clearance was tracked in vivo for up to 42 days postsurgery. Protein elution from both formulations was quantified in vitro. Treatment with µ-HACM, but not RPS µ-dHACM, reduced lesion volume in the MMT model 3 weeks postsurgery. In contrast, RPS µ-dHACM increased cartilage surface roughness and osteophyte cartilage thickness and volume compared to saline treatment. There was no difference of in vivo fluorescently tagged particle clearance between the two µ-dHACM sizes. RPS µ-dHACM showed significantly greater protein elution in vitro over 21 days. Overall, delivery of RPS µ-dHACM did result in an increase of in vivo joint degeneration and in vitro protein elution compared to µ-dHACM, but did not result in differences in joint clearance in vivo. These results suggest that particle size and factor elution may be tailorable factors that are important to optimize for particulate amniotic membrane treatment to be an effective therapy for OA. Impact Statement Osteoarthritis (OA) is a widespread disease that continues to lack treatments that modify the progression of the disease. Micronized dehydrated human amnion/chorion membrane (µ-dHACM) has been shown to be effective in reducing OA progression, but many of the engineering design parameters have not been explored. This work investigates the effects of particle size profile of the µ-dHACM particles and lays out the methods used in these studies. The results of this work will guide engineers in designing µ-dHACM treatments specifically and disease-modifying OA therapeutics generally, and it demonstrates the utility of novel therapeutic evaluation methods such as contrast-enhanced microcomputed tomography.

Early vs. delayed in-hospital cardiac arrest complicating ST-elevation myocardial infarction receiving primary percutaneous coronary intervention.

BACKGROUND: There are limited data on the timing and outcomes of in-hospital cardiac arrest (IHCA) in patients with ST-elevation myocardial infarction (STEMI) receiving primary percutaneous coronary intervention (pPCI). This study sought to examine the in-hospital mortality, temporal trends and resource utilization in early vs. delayed IHCA in STEMI. METHODS: Retrospective cohort study from the National Inpatient Sample of all STEMI admissions during 2000-2014 receiving pPCI on hospital day zero. Admissions transferred from other hospitals, with do-not-resuscitate status, without information on IHCA timing, and receiving surgical revascularization were excluded. IHCA was classified as early (hospital day zero) and delayed (on/after hospital day 1). The primary outcome was in-hospital mortality and secondary outcomes included prevalence, temporal trends, and resource utilization. RESULTS: During this 15-year period, 19,185 admissions met the inclusion criteria, with 15,404 (80%) experiencing an early IHCA. The cohort with delayed IHCA was on average older, female, with higher comorbidity, and greater prevalence of non-shockable rhythms and acute organ failure. There was a temporal increase in early IHCA (adjusted odds ratio [aOR] 1.67 [95% confidence interval {CI} 1.35-2.08]) and a decrease in delayed IHCA (aOR 0.60 [95% CI 0.48-0.74]) in 2014 compared to 2000. Compared to the early IHCA cohort, the delayed IHCA cohort had higher in-hospital mortality (aOR 5.35 [95% CI 4.83-5.94]), higher hospitalization costs ($115,165 ± 109,848 vs. 139,038 ± 142,745) and less frequent discharges to home (74% vs. 52%). CONCLUSIONS: Delayed IHCA (on or after hospital day 1) was associated with higher in-hospital mortality and resource utilization compared to early IHCA.

Metal-based photosensitizers for photodynamic therapy: the future of multimodal oncology?

Photodynamic therapy (PDT) is an approved medical technique to treat certain forms of cancer. It has been used to complement traditional anticancer modalities such as surgery, chemotherapy or radiotherapy, and in certain cases, to replace these treatments. One critical parameter of PDT is the photosensitizer (PS); historically, a purely organic macrocyclic tetrapyrrole-based structure. This short review surveys two recent clinical examples of metal complexes, namely TOOKAD®-Soluble and TLD-1433, which have ideal photophysical properties to act as PDT PSs. We highlight the important role played by the metal ions in the PS for PDT activity.

Direct Current Cardioversion of Atrial Arrhythmias in Adults With Cardiac Amyloidosis.

BACKGROUND: Arrhythmias, conduction abnormalities, and intracardiac thrombus are common in patients with cardiac amyloidosis (CA). Outcomes of direct-current cardioversion (DCCV) for atrial arrhythmias in patients with CA are unknown. OBJECTIVES: This study sought to examine DCCV procedural outcomes in patients with CA. METHODS: Patients with CA scheduled for DCCV for atrial arrhythmias from January 2000 through December 2012 were identified and matched 2:1 with control patients by age, sex, type of atrial arrhythmia, and date of DCCV. RESULTS: CA patients (n = 58, mean age 69 ± 9 years, 81% male) were included. CA patients had a significantly higher cardioversion cancellation rate (28% vs. 7%; p < 0.001) compared with control patients, mainly due to intracardiac thrombus identified on transesophageal echocardiogram (13 of 16 [81%] vs. 2 of 8 [25%]; p = 0.02); 4 of 13 of the CA patients (31%) with intracardiac thrombus on transesophageal echocardiogram received adequate anticoagulation ≥3 weeks and another 2 of 13 (15%) had arrhythmia duration <48 h. DCCV success rate (90% vs. 94%; p = 0.4) was not different. Procedural complications were more frequent in CA versus control patients (6 of 42 [14%] vs. 2 of 106 [2%]; p = 0.007); complications in CA included ventricular arrhythmias in 2 and severe bradyarrhythmias requiring pacemaker implantation in 2. The only complication in the control group was self-limited bradyarrhythmias. CONCLUSIONS: Patients with CA undergoing DCCV had a significantly high cancellation rate mainly due to a high incidence of intracardiac thrombus even among patients who received adequate anticoagulation. Although the success rate of restoring sinus rhythm was high, tachyarrhythmias and bradyarrhythmias complicating DCCV were significantly more frequent in CA patients compared with control patients.

Echocardiographic left ventricular diastolic dysfunction predicts hospital mortality after out-of-hospital cardiac arrest.

PURPOSE: To determine whether systolic or diastolic dysfunction on transthoracic echocardiogram (TTE) predicts mortality after out-of-hospital cardiac arrest (OHCA). METHODS: Retrospective cohort study of 173 OHCA subjects undergoing targeted temperature management who underwent TTE during hospitalization. Univariate analysis and multivariate logistic regression were used to determine associations between TTE measurements of systolic and diastolic function and systemic hemodynamics with all-cause mortality. RESULTS: Mean age was 61.6 ±â€¯12.4 years (72.7% male) and initial rhythm was shockable in 89%. Hospital mortality was 30.6%. Mean LVEF was 40% and was not different in hospital survivors (p = 0.81). TTE parameters reflecting systolic function and systemic hemodynamics did not predict hospital mortality. Medial mitral E/e' ratio was associated with hospital mortality, with an optimal cut-off > 13 (p = 0.002). After multivariate adjustment, medial mitral E/e' ratio remained predictive of hospital mortality (OR 1.11, 95% CI 1.03-1.20, p = 0.004). Subjects with a medial mitral E/e' ratio > 13 had higher mortality during long-term follow-up (p < 0.001 by log-rank). CONCLUSIONS: Diastolic dysfunction (higher medial mitral E/e' ratio) on TTE independently predicted mortality after OHCA; systolic dysfunction and TTE hemodynamic parameters did not. This reflects a novel use of Doppler TTE to predict outcomes after OHCA.

Changes in left ventricular systolic and diastolic function on serial echocardiography after out-of-hospital cardiac arrest.

AIM: Reversible myocardial dysfunction is common after out-of-hospital cardiac arrest (OHCA). The aim of this study was to determine if changes on serial transthoracic echocardiography (TTE) can predict long-term mortality in OHCA subjects. METHODS: This is a single-center historical cohort study of OHCA subjects undergoing targeted temperature management who received >1 TTE during hospitalization. Two-dimensional and Doppler parameters of systolic and diastolic function were compared between paired TTE. Univariate analysis was used to determine associations between TTE parameters and all-cause mortality. RESULTS: Fifty-nine patients were included; mean age was 59.4 ±â€¯11.2 years (75% male). Initial rhythm was shockable in 90%. Initial TTE was done a median of 10.4 h after admission and repeat TTE was done 5.7 ±â€¯4.1 days later. Between TTE studies, there were significant increases in left ventricular ejection fraction (LVEF, from 32% to 43%), cardiac output, stroke volume, and other Doppler-derived hemodynamic parameters, while systemic vascular resistance decreased (all p < 0.001). Systolic function and hemodynamic parameters on initial TTE were not associated with follow-up mortality. Patients who died during follow-up (n = 16, 27%) had smaller increases in LVEF and cardiac output-derived hemodynamic parameters than long-term survivors (p < 0.05). CONCLUSIONS: Significant changes in systolic function and hemodynamic parameters occur on serial Doppler TTE after OHCA, consistent with reversible post-arrest myocardial dysfunction. The magnitude of those changes is greater in long-term survivors, emphasizing that the degree of recovery from post-arrest myocardial dysfunction may be more important than its initial severity.

Improving trend in ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest in Rochester, Minnesota: A 26-year observational study from 1991 to 2016.

BACKGROUND: Mortality from out-of-hospital cardiac arrest (OHCA) is characterized by substantial regional variation. The Institute of Medicine (IOM) recently recommended enhancing the capabilities of EMS systems to improve outcome. In this study, we analyzed the trend in outcome from ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) OHCA in Rochester, MN. Survival from these forms of arrest is commonly employed as a benchmark of Emergency Medical Services (EMS) system performance. METHODS: Using a population-based Utstein-style registry in Rochester, MN where a first responder early defibrillation system is utilized, we evaluated outcome from all EMS-treated VF/pVT arrests and the subgroup of bystander-witnessed VF/pVT from 1991 to 2016. Outcome measurement was neurologically intact survival to discharge, defined as Cerebral Performance Category (CPC) 1 or 2. We divided the 26-year study into three periods: 1991-1997, 1998-2008, and 2009-2016, based on initiation of the first responder system of police officers in 1991 and fire-rescue personnel in 1998, and the latter period for comparison with our previous report in 2009. RESULTS: We observed 355 all VF/pVT arrests and 292 bystander-witnessed VF/pVT arrests between 1991 and 2016. In 2009-2016, neurologically intact survival to discharge from overall VF/pVT and bystander-witnessed VF/pVT increased to 53.7% and 65.2%, respectively, compared with 39.5% and 43.4% in 1991-1997. Using multivariable analysis, survival significantly increased in 2009-2016 among all VF/pVT arrests (adjusted OR, 3.10; 95% CI, 1.54-6.40) and bystander-witnessed VF/pVT (adjusted OR, 4.28; 95% CI, 2.01-9.50), compared with those in 1991-1997. CONCLUSIONS: We observed a significant improving secular trend in neurologically intact survival from VF/pVT cardiac arrests with a relatively high recent survival rate in this EMS System.

Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A Two-Center Study.

OBJECTIVE: The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors. DESIGN: Cohort study (April 2009 to March 2016). SETTING: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN). PATIENTS: Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries. INTERVENTIONS: All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations. MEASUREMENTS AND MAIN RESULTS: We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9-84.4%) and motor response (80.1%; 95% CI, 75.6-84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8-91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for early electroencephalography reactivity (86.6%; 95% CI, 82.6-90.0). Early highly malignant electroencephalography had an false positive rate of 1.5% with accuracy of 85.7% (95% CI, 81.7-89.2%). CONCLUSIONS: This study provides class III evidence that electroencephalography reactivity predicts both poor and good outcomes, and motor reaction good outcome after cardiac arrest. Electroencephalography reactivity seems to be the best discriminator between good and poor outcomes. Standardized electroencephalography interpretation seems to predict both conditions during and after targeted temperature management.

Indicators of Subarachnoid Hemorrhage as a Cause of Sudden Cardiac Arrest.

Subarachnoid hemorrhage (SAH) may present with cardiac arrest (SAH-CA). We report a case of SAH-CA to assist providers in distinguishing SAH as an etiology of cardiac arrest despite electrocardiogram findings that may be suggestive of a cardiac etiology. SAH-CA is associated with high rates of return of spontaneous circulation, but overall poor outcome. An initially non-shockable cardiac rhythm and the absence of brain stem reflexes are important clues in indentifying SAH-CA.