Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for type 2 diabetes and metabolic syndrome. However, accurately differentiating nonalcoholic steatohepatitis (NASH) from hepatosteatosis remains a clinical challenge. We identified a critical transition stage (termed pre-NASH) during the progression from hepatosteatosis to NASH in a mouse model of high fat-induced NAFLD, using lipidomics and a mathematical model termed dynamic network biomarkers (DNB). Different from the conventional biomarker approach based on the abundance of molecular expressions, the DNB model exploits collective fluctuations and correlations of different metabolites at a network level. We found that the correlations between the blood and liver lipid species drastically decreased after the transition from steatosis to NASH, which may account for the current difficulty in differentiating NASH from steatosis based on blood lipids. Furthermore, most DNB members in the blood circulation, especially for triacylglycerol (TAG), are also identified in the liver during the disease progression, suggesting a potential clinical application of DNB to diagnose NASH based on blood lipids. We further identified metabolic pathways responsible for this transition. Our study suggests that the transition from steatosis to NASH is not smooth and the existence of pre-NASH may be partially responsible for the current clinical limitations to diagnose NASH. If validated in humans, our study will open a new avenue to reliably diagnose pre-NASH and achieve early intervention of NAFLD.

Introduction: Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide and is caused by infection from the severe acute respiratory syndrome coronavirus-2 pathogen. While COVID-19 most commonly affects the respiratory system, multiple neurological complications have been associated with this pathogen. We report a case of Wernicke encephalopathy in a young girl with poor oral intake secondary to anosmia and dysgeusia after a COVID-19 infection. Case Report: After a recent infection of COVID-19, a 15-year-old girl developed an overwhelming noxious metallic tase resulting in a 30 lb weight loss from being unable to tolerate oral foods. She presented to the hospital 3 months later with bilateral horizontal conjugate gaze palsies, up beating vertical nystagmus, difficulty with limb coordination and gait ataxia. She was found to have a thiamine level of 51 nmol/L (reference range: 70 to 180 nmol/L) and her brain magnetic resonance imaging showed fluid-attenuated inversion recovery and diffusion-weighted imaging changes in the periaqueductal gray and dorsomedial thalami suggestive of Wernicke encephalopathy. She was started on parenteral thiamine replacement and had significant neurological improvement. Conclusions: As this pandemic continues to progress, more long-term neurological sequelae from COVID-19 such as Wernicke encephalopathy can be expected. Strong clinical suspicion for these complications is needed to allow for earlier diagnosis and faster treatment initiation.

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Introduction: Ticagrelor with aspirin has been recently shown to reduce the risk of stroke or death compared to aspirin alone in patients with high risk TIAs and mild strokes. However, this benefit is offset by increased risk of severe bleeding. We sought to evaluate the safety of ticagrelor in patients with moderate to severe ischemic stroke. Methods: This was a retrospective cohort study of adults discharged on ticagrelor after presenting with acute ischemic stroke and NIHSS > 5 from January 2016 to December 2019 at a large, urban, academic comprehensive stroke center. Patients were excluded if they underwent carotid or intracranial angioplasty and/or stenting, or carotid endarterectomy during admission. Baseline clinical characteristics, imaging, and outcomes were reviewed. Data was organized into continuous and categorical variables. Results: Sixty-one patients met inclusion and exclusion criteria. Median age was 61 (IQR, 52-68) years; 33 (54%) were men, and 33 (54%) were African American. Median NIHSS was 11 (IQR, 8-15). Fourteen (23%) patients received IV Alteplase and 35 (57%) patients underwent mechanical thrombectomy. Five (8%) patients received both IV Alteplase and mechanical thrombectomy. Median ticagrelor start date was hospital day 1 (IQR, 0-3). Large artery atherosclerosis was presumed etiology in 53 (87%) patients. No patients experienced neurologic worsening, recurrent stroke, sICH, or major bleeding during inpatient stay. Sixty (98%) patients were on aspirin and ticagrelor at discharge. Follow-up information was available for 53 (87%) patients for a median duration of 3 (IQR, 2-6) months. Following discharge, 3 (5%) patients experienced recurrent ischemic stroke despite being compliant. One (2%) patient experienced major bleeding—gastrointestinal hemorrhage requiring transfusion—two months after hospital discharge. Conclusions: This study highlights the potential expanding role for ticagrelor in secondary stroke prevention in patients with moderate to severe stroke. Early ticagrelor use did not result in sICH during inpatient stay—and only 1 major bleeding event on follow-up—in our cohort. While further research in this area is needed, these findings present an exciting opportunity for future prospective studies.

Introduction Carotid Web (CaW) is an increasingly recognized etiology of ischemic stroke, and has been shown to be amenable to endovascular stenting. The technical complexity of stenting for CaW may be lower than for carotid atherosclerotic disease (CAD). We aimed to assess procedural characteristics of stenting for CaW as compared to CAD. Methods We retrospectively analyzed a cohort of consecutive patients at a single comprehensive stroke center from 2014 to 2021, who had undergone elective endovascular stent placement for symptomatic CAD or CaW. Results In total, 118 patients underwent elective stent placement following ischemic stroke/transient ischemic attack; 88 patients had CAD and 30 patients had CaW. CAD patients were older (63.2 vs 51.2 years, p < 0.001), less likely to be female (28.4% vs 73.3%, p < 0.001), and more likely to have pre-existing vascular risk factors. Procedure time (73.0 vs 57.5 min, p = 0.007), radiation exposure (1482 vs 1125 milliGray, p = 0.03), filter time (24 vs 14 min, p = 0.04), and use of pre-stent (68.2% vs 0%, p < 0.001) and post-stent (34.1% vs 3.3%, p < 0.001) balloon angioplasty were higher in CAD cases. There was no significant difference between groups in the rate of periprocedural complications such as hypotension, use of vasopressors, or bradycardia. Recurrent stroke/TIA was reported in five CAD patients and 0 CaW patients by the end of the follow-up period (8.3% vs 0%, p = 0.12). In-stent restenosis was detected in seven CAD patients and 0 CaW patients (10.1% vs 0%, p = 0.09) at a median follow-up of 4 vs 16 months ( p = 0.01), respectively. Periprocedural intracranial hemorrhage was not observed in either group. Conclusion Stenting for CaW was found to be technically simpler than CAD and not to confer increased risk of baroreceptor dysregulation. Intimal hyperplasia was uncommon in CaW cases.