Cerebral Venous Sinus Thrombosis in the COVID-19 Pandemic.

BACKGROUND: Recent studies have noted concern for increased thromboembolic events in the setting of Coronavirus Disease 2019 (COVID-19). Cerebral venous sinus thrombosis (CVST) is a form of thromboembolism that has been observed as a neuro-ophthalmologic complication of COVID-19. METHODS: Review of the scientific literature. RESULTS: In this article, we report an overview of CVST epidemiology, clinical presentation, diagnostics, disease pathophysiology, and management in the setting of COVID-19. CONCLUSION: CVST is an uncommon thromboembolic event with variable phenotypes and multiple etiologies. Neurologic complications can be severe, including significant visual deficits and death. Current observations suggest that the risk of CVST may be profoundly impacted by this novel COVID-19 pandemic, thus prompting increased attention to disease presentation, pathogenesis, and management.

Aneurysmal Subarachnoid Hemorrhage and Cardiac Related Fatality: Who Dies and Why?

Medical complications are a notable source of in-hospital death following aneurysmal subarachnoid hemorrhage (aSAH). However, there is a paucity of literature examining medical complications on a national scale. This study uses a national dataset to analyze the incidence rates, case fatality rates, and risk factors for in-hospital complications and mortality following aSAH. We found that the most common complications in aSAH patients (N = 170, 869) were hydrocephalus (29.3%) and hyponatremia (17.3%). Cardiac arrest was the most common cardiac complication (3.2%) and was associated with the highest case fatality rate overall (82%). Patients with cardiac arrest also had the highest odds of in-hospital mortality [odds ratio (OR), 22.92; 95% confidence interval (CI), 19.24-27.30; P < 0.0001], followed by patients with cardiogenic shock (OR, 2.96; 95% CI, 2.146-4.07; P < 0.0001). Advanced age and National Inpatient Sample-SAH Severity Score were found to be associated with an increased risk of in-hospital mortality (OR, 1.03; 95% CI, 1.03-1.03; P < 0.0001 and OR, 1.70; 95% CI, 1.65-1.75; P < 0.0001, respectively). Renal and cardiac complications are significant factors to consider in aSAH management, with cardiac arrest being the strongest indicator of case fatality and in-hospital mortality. Further research is needed to characterize factors that have contributed to the decreasing trend in case fatality rates identified for certain complications.

The critically ill brain after cardiac arrest.

Cardiac arrest can cause hypoxic-anoxic ischemic brain injury due to signaling cascades that lead to damaged cell membranes and vital cellular organelles, resulting in cell death in the setting of low or no oxygen. Some brain areas are more prone to damage than others, so patients with hypoxic-anoxic ischemic brain injury present with several outcomes, including reduced level of consciousness or alertness, memory deficits, uncoordinated movements, and seizures. Some patients may have mild deficits, while others may have such severe injury that it can progress to brain death. High-quality cardiopulmonary resuscitation is a proven technique to improve outcome after cardiac arrest, although morbidity and mortality remain high. Induced hypothermia, which involves artificially cooling the body immediately after cardiac arrest, may reduce injury to the brain and improve morbidity and mortality. Neuroprognostication after cardiac arrest is challenging and requires a multimodal approach involving clinical neurologic examinations, brain imaging, electrical studies to assess brain activity, and biomarkers to predict outcome.

Echocardiographic Algorithm for Post-Myocardial Infarction LV Thrombus: A Gatekeeper for Thrombus Evaluation by Delayed Enhancement CMR.

OBJECTIVES: The goal of this study was to determine the prevalence of post-myocardial infarction (MI) left ventricular (LV) thrombus in the current era and to develop an effective algorithm (predicated on echocardiography [echo]) to discern patients warranting further testing for thrombus via delayed enhancement (DE) cardiac magnetic resonance (CMR). BACKGROUND: LV thrombus affects post-MI management. DE-CMR provides thrombus tissue characterization and is a well-validated but an impractical screening modality for all patients after an MI. METHODS: A same-day echo and CMR were performed according to a tailored protocol, which entailed uniform echo contrast (irrespective of image quality) and dedicated DE-CMR for thrombus tissue characterization. RESULTS: A total of 201 patients were studied; 8% had thrombus according to DE-CMR. All thrombi were apically located; 94% of thrombi occurred in the context of a left anterior descending (LAD) infarct-related artery. Although patients with thrombus had more prolonged chest pain and larger MI (p ≤ 0.01), only 18% had aneurysm on echo (cine-CMR 24%). Noncontrast (35%) and contrast (64%) echo yielded limited sensitivity for thrombus on DE-CMR. Thrombus was associated with stepwise increments in basal → apical contractile dysfunction on echo and quantitative cine-CMR; the echo-measured apical wall motion score was higher among patients with thrombus (p < 0.001) and paralleled cine-CMR decrements in apical ejection fraction and peak ejection rates (both p < 0.005). Thrombus-associated decrements in apical contractile dysfunction were significant even among patients with LAD infarction (p < 0.05). The echo-based apical wall motion score improved overall performance (area under the curve 0.89 ± 0.44) for thrombus compared with ejection fraction (area under the curve 0.80 ± 0.61; p = 0.01). Apical wall motion partitions would have enabled all patients with LV thrombus to be appropriately referred for DE-CMR testing (100% sensitivity and negative predictive value), while avoiding further testing in more than one-half (56% to 63%) of patients. CONCLUSIONS: LV thrombus remains common, especially after LAD MI, and can occur even in the absence of aneurysm. Although DE-CMR yielded improved overall thrombus detection, apical wall motion on a noncontrast echocardiogram can be an effective stratification tool to identify patients in whom DE-CMR thrombus assessment is most warranted. (Diagnostic Utility of Contrast Echocardiography for Detection of LV Thrombi Post ST Elevation Myocardial Infarction; NCT00539045).

Association of Right Ventricular Pressure and Volume Overload with Non-Ischemic Septal Fibrosis on Cardiac Magnetic Resonance.

BACKGROUND: Non-ischemic fibrosis (NIF) on cardiac magnetic resonance (CMR) has been linked to poor prognosis, but its association with adverse right ventricular (RV) remodeling is unknown. This study examined a broad cohort of patients with RV dysfunction, so as to identify relationships between NIF and RV remodeling indices, including RV pressure load, volume and wall stress. METHODS AND RESULTS: The population comprised patients with RV dysfunction (EF<50%) undergoing CMR and transthoracic echo within a 14 day (5 ± 3) interval. Cardiac structure, function, and NIF were assessed on CMR. Pulmonary artery systolic pressure (PASP) was measured on echo. 118 patients with RV dysfunction were studied, among whom 47% had NIF. Patients with NIF had lower RVEF (34 ± 10 vs. 39 ± 9%; p = 0.01) but similar LVEF (40 ± 21 vs. 39 ± 18%; p = 0.7) and LV volumes (p = NS). RV wall stress was higher with NIF (17 ± 7 vs. 12 ± 6 kPa; p < 0.001) corresponding to increased RV end-systolic volume (143 ± 79 vs. 110 ± 36 ml; p = 0.006), myocardial mass (60 ± 21 vs. 53 ± 17 gm; p = 0.04), and PASP (52 ± 18 vs. 41 ± 18 mmHg; p = 0.001). NIF was associated with increased wall stress among subgroups with isolated RV (p = 0.005) and both RV and LV dysfunction (p = 0.003). In multivariable analysis, NIF was independently associated with RV volume (OR = 1.17 per 10 ml, [CI 1.04-1.32]; p = 0.01) and PASP (OR = 1.43 per 10 mmHg, [1.14-1.81]; p = 0.002) but not RV mass (OR = 0.91 per 10 gm, [0.69-1.20]; p = 0.5) [model χ2 = 21; p<0.001]. NIF prevalence was higher in relation to PA pressure and RV dilation and was > 6-fold more common in the highest, vs. the lowest, common tertile of PASP and RV size (p<0.001). CONCLUSION: Among wall stress components, NIF was independently associated with RV chamber dilation and afterload, supporting the concept that NIF is linked to adverse RV chamber remodeling.

Secretome identification of immune cell factors mediating metastatic cell homing.

Metastatic cell homing is a complex process mediated in part by diffusible factors secreted from immune cells found at a pre-metastatic niche. We report on connecting secretomics and TRanscriptional Activity CEll aRray (TRACER) data to identify functional paracrine interactions between immune cells and metastatic cells as novel mediators of homing. Metastatic breast cancer mouse models were used to generate a diseased splenocyte conditioned media (D-SCM) containing immune cell secreted factors. MDA-MB-231 metastatic cell activity including cell invasion, migration, transendothelial migration, and proliferation were increased in D-SCM relative to control media. Our D-SCM secretome analysis yielded 144 secreted factor candidates that contribute to increased metastatic cell activity. The functional mediators of homing were identified using MetaCore software to determine interactions between the immune cell secretome and the TRACER-identified active transcription factors within metastatic cells. Among the 5 candidate homing factors identified, haptoglobin was selected and validated in vitro and in vivo as a key mediator of homing. Our studies demonstrate a novel systems biology approach to identify functional signaling factors associated with a cellular phenotype, which provides an enabling tool that complements large-scale protein identification provided by proteomics.