Brain ; blood supply ; diagnostic imaging ; Brain Ischemia ; blood ; diagnosis ; diagnostic imaging ; Combined Modality Therapy ; methods ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; Stroke ; drug therapy ; physiopathology ; Tomography, X-Ray Computed

Cerebrovascular Circulation ; drug effects ; Computer Systems ; Fibrinolytic Agents ; administration & dosage ; pharmacology ; Humans ; Infarction, Middle Cerebral Artery ; drug therapy ; physiopathology ; Infusions, Intravenous ; Male ; Middle Aged ; Regional Blood Flow ; drug effects ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; administration & dosage ; pharmacology

<p>BACKGROUND AND AIMIntravenously-administered tissue plasminogen activator (IV-TPA) induces thrombolysis and remains the only FDA-approved therapy for acute ischaemic stroke. IV-TPA thrombolysis has been approved recently in Singapore for acute stroke. Continuous exposure of clot to 2-MHz pulsed-wave transcranial Doppler (TCD) ultrasound during IV-TPA infusion is known to augment thrombolysis. We aimed to determine the feasibility, safety and efficacy of ultrasound-assisted thrombolysis in acute ischaemic stroke in Singapore.p><p>SUBJECTS AND METHODSConsecutive patients with acute ischaemic stroke due to intracranial arterial-occlusions were treated with standard IV-tPA and continuously monitored with 2-MHz TCD according to the CLOTBUST-trial protocol. Arterial recanalisation was determined with Thrombolysis in Brain Ischemia (TIBI) flow-grading system. Safety and efficacy of ultrasoundassisted thrombolysis were assessed by rates of symptomatic intracranial haemorrhage (sICH) and functional recovery at 1 month, respectively.p><p>RESULTSFive consecutive patients (mean age 58 years, 3 men and 3 of Chinese ethnicity) were included. Mean time elapsed between symptom onset and presentation to emergency room was 98 minutes (range, 50 to 135 minutes) while the mean time interval between symptom onset to IV-TPA bolus was 144 minutes (range, 125 to 180 minutes). Partial or complete recanalisation with reduction in the stroke severity was noted in 4 out of the 5 patients during IV-TPA infusion (mean change in NIHSS = 4 points; range 2 to 8 points). None of our patients developed sICH while 4 patients demonstrated good functional outcome at 1 month.p><p>CONCLUSIONSOur preliminary study demonstrates the feasibility, safety and efficacy of ultrasound-assisted thrombolysis in acute ischaemic stroke in Singapore. Continuous TCD-monitoring during IV-TPA infusion provides real-time information, enhances thrombolysis and improves functional outcomes in acute ischaemic stroke.p>
Aged ; Brain Infarction ; diagnostic imaging ; Female ; Fibrinolytic Agents ; administration & dosage ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Thrombolytic Therapy ; methods ; Tissue Plasminogen Activator ; administration & dosage ; Ultrasonography, Interventional ; methods

INTRODUCTION: We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity. METHODS: We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded. RESULTS: 169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum. CONCLUSION Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.
Humans ; Asian People ; COVID-19/complications* ; Inflammation/complications* ; SARS-CoV-2 ; Thrombosis