Acute Coronary Syndrome during the Pandemic New Coronavirus Infection.

The experience of managing patients with COVID-19 around the world has shown that, although respiratory symptoms predominate during the manifestation of infection, then many patients can develop serious damage to the cardiovascular system. However, coronary artery disease (CHD) remains the leading cause of death worldwide. The purpose of the review is to clarify the possible pathogenetic links between COVID-19 and acute coronary syndrome (ACS), taking into account which will help to optimize the management of patients with comorbid pathology. Among the body's responses to SARS-CoV-2 infection, which increase the likelihood of developing ACS, the role of systemic inflammation, the quintessence of which is a "cytokine storm" that can destabilize an atherosclerotic plaque is discussed. Coagulopathy, typical for patients with Covid-19, is based on immunothrombosis, caused by a complex interaction between neutrophilic extracellular traps and von Willebrandt factor in conditions of systemic inflammation. The implementation of a modern strategy for managing patients with ACS, focused on the priority of percutaneous interventions (PCI), during a pandemic is experiencing great difficulties due to the formation of time delays before the start of invasive procedures due to the epidemiological situation. Despite this, the current European, American and Russian recommendations for the management of infected patients with ACS confirm the inviolability of the position of PCI as the first choice for treating patients with ACS and the undesirability of replacing invasive treatment with thrombolysis.Copyright © 2023 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

SINGLE CELL MULTIOMIC PROFILING OF DISRUPTED REGULATORY NETWORKS IN COVID19 ASSOCIATED MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN

BackgroundChildren infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually present minimal symptoms or are asymptomatic. Nevertheless, a subset of children 2-6 weeks after the initial SARS-CoV-2 infection develops a postinfectious SARS-CoV-2-related multisystem inflammatory syndrome in (MIS-C). Recently, transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation, however, the underlying pathophysiology of MIS-C is not fully understood [1].ObjectivesThe purpose of our project is to characterize the complexity of cell populations and capture cellular heterogeneity to uncover the regulatory networks and interactions that are disrupted during MIS-C flare with simultaneous profiling of gene expression and open chromatin regions from the same nuclei.MethodsSamples of peripheral blood mononuclear cells from patients with MIS-C diagnosed at the University Children's Hospital, University Medical Center Ljubljana, were collected during the initial presentation before any treatment and at 6-12 months in remission. The primary aim is to identify which regulatory networks are driving inflammation in MIS-C flare, for which we are performing single cell Multiome ATAC + Gene Expression Sequencing. To enable simultaneous profiling of epigenomic landscape and gene expression from the same nuclei, we are using Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kit from 10X Genomics.ResultsWe included 32 patients with MIS-C from whom we collected paired blood samples during the initial presentation before treatment and at 6-12 months in remission. In single cell multiomic experiment we included 10 patients with paired samples, with the most viable cell count prior cryopreservation. All samples that are included into multiomic single cell analysis have 75% - 99% viability prior cryopreservation. In the protocol the key is to remove remaining granulocytes causing high mitochondrial RNA burden and extensively optimize the dilution factor of lysis buffer and the length of cell lysis step in order to get intact nuclei with no significant blebbing. Afterward, the single cell ATAC libraries as well as single-cell gene expression libraries are constructed and sequenced. Data are undergoing pairwise analysis to compare the cell population heterogeneity, expression profile and open chromatin landscape in the time of the initial presentation of MIS-C and in the remission, with Cell ranger software as well as with R package scREG [2], and custom scripting. In the second step we will inspect if the resulting altered transcriptomic signature from single-cell experiment is present on larger cohort. In that regard, we will perform bulk transcriptomic profiling on all paired collected samples during the initial presentation of MIS-C before treatment and at 6-12 months in remission.ConclusionThe results of this project are expected to enlighten the underlying pathophysiology of MIS-C flare and thus support clinical decision on more targeted treatment. The identified disrupted networks during MIS-C flare could lead the way to establish an early diagnosis and improve long-term outcome, including prevention of myocardial and neuropsychological impairment. Moreover, a better understanding of the disrupted regulatory networks that are driving inflammation in MIS-C, could lead to new insights into diseases with similar clinical presentations as is Kawasaki Disease.References[1]Sacco, K., Castagnoli, R., Vakkilainen, S. et al. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nat Med 28, 1050–1062 (2022).[2]Duren, Z., Chang, F., Naqing, F. et al. Regulatory analysis of single cell multiome gene expression and chromatin accessibility data with scREG. Genome Biol 23, 114 (2022).AcknowledgementsThis research was supported by Slovenian research agency grant J3-3061 and Interreg ITA-SLO project Cattedra.Disclosure of InterestsNone Declared.

Acute Coronary Syndrome during the Pandemic New Coronavirus Infection.

The experience of managing patients with COVID-19 around the world has shown that, although respiratory symptoms predominate during the manifestation of infection, then many patients can develop serious damage to the cardiovascular system. However, coronary artery disease (CHD) remains the leading cause of death worldwide. The purpose of the review is to clarify the possible pathogenetic links between COVID-19 and acute coronary syndrome (ACS), taking into account which will help to optimize the management of patients with comorbid pathology. Among the body's responses to SARS-CoV-2 infection, which increase the likelihood of developing ACS, the role of systemic inflammation, the quintessence of which is a "cytokine storm" that can destabilize an atherosclerotic plaque is discussed. Coagulopathy, typical for patients with Covid-19, is based on immunothrombosis, caused by a complex interaction between neutrophilic extracellular traps and von Willebrandt factor in conditions of systemic inflammation. The implementation of a modern strategy for managing patients with ACS, focused on the priority of percutaneous interventions (PCI), during a pandemic is experiencing great difficulties due to the formation of time delays before the start of invasive procedures due to the epidemiological situation. Despite this, the current European, American and Russian recommendations for the management of infected patients with ACS confirm the inviolability of the position of PCI as the first choice for treating patients with ACS and the undesirability of replacing invasive treatment with thrombolysis.Copyright © 2023 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.

Successful Systemic Lysis Therapy of a Floating Carotid Thrombus in an Acute Stroke Patient with Known Immune Thrombocytopenia (ITP) on Ongoing Eltrombopag Therapy and Acute COVID-19 Infection: a Case Report.

Patients with immune thrombocytopenia (ITP) under eltrombopag therapy are vulnerable to thrombotic disbalance, both due to the disease itself and therapy-related hypercoagulability. Vascular events such as the development of a free-floating carotid thrombus are known rare complications of acute COVID-19 infections due to endothelial inflammation and presumptive underlying hypercoagulable state. In patients at risk, the onset of new focal neurological symptoms should prompt immediate angiographic diagnostics and, if necessary, appropriate treatment. Here, we report a case of a 38-year-old female with a medical history of ITP and the presence of COVID-19 infection presenting an acute sensorimotor hemiparesis of the right side while on eltrombopag therapy. Initial CT angiography revealed a free-floating thrombus in the left common carotid artery. Upon admission, the patient's platelet count was significantly elevated at 896 × 109/l. After systemic lysis therapy, the thrombus was fully dissolved. Follow-up diffusion-weighted imaging revealed multilocular cortical infarction of the left MCA territory. The patient soon recovered and was discharged with residual mild sensorimotor deficits in the right arm. Eltrombopag was paused at admission, and the patient's platelet count was quickly returning to normal. She was discharged with a daily intake of acetylsalicylic acid, a reduced daily dose of eltrombopag, and weekly monitoring of her platelet count for the next three months. This unique case highlights the need for caution in patients at vascular risk who contract COVID-19 and discusses thrombocytic derailment under thrombopoietin receptor agonist therapy in the context of an acute COVID-19 infection.

Rapid SARS-CoV-2 testing with duplexed recombinase polymerase amplification and a bacteriophage internal control

OBJECTIVES/GOALS: Current COVID-19 rapid molecular tests require cartridge-reader detection, expensive circuitry, and complex microfluidics making the most accurate tests unavailable to the masses. Here we present a rapid molecular diagnostic leveraging isothermal amplification and paper-based microfluidics for a low-cost ultra-sensitive COVID-19 assay. METHODS/STUDY POPULATION: We designed a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of SARS-CoV-2 and bacteriophage MS2 RNA. RT-RPA is a sequence specific, ultrasensitive, rapid isothermal DNA amplification technique that is well suited to home based testing due to its rapid assay time, robustness, ease of use, and readout options. RT-RPA reagents are added to a tube and incubated at 39°C in a fluorometer. Realtime fluorometer data gives results in under 15 minutes. This assay also provides visual detection via lateral flow readout with results in 23 minutes. RESULTS/ANTICIPATED RESULTS: We have developed a rapid multiplexed nucleic acid amplification assay with an internal process control for SARS-CoV-2 using single-pot RT-RPA. We screened 21 primer combinations to select primers that demonstrated excellent performance and target specificity against common respiratory viruses. We demonstrate the ability to multiplex SARS-CoV-2 and MS2 detection, utilizing MS2 as an internal process control for lysis, reverse transcription, amplification, and readout. We show duplexed detection using both fluorescence readout and visual readout using lateral flow strips. Duplexed fluorescence detection shows a limit of detection of 25 copies per reaction. Duplexed lateral flow readout shows a limit of detection of 50 copies per reaction DISCUSSION/SIGNIFICANCE: We developed a duplexed RT-RPA assay for SARS-CoV-2 with fluorescence or lateral flow readout. Our assay does not re-quire expensive reader, circuity, or fluid handling. The low material cost, temperature, and robustness make it ideal for a more accurate home-based COVID-19 diagnostic.

In-hospital outcomes of ST elevation myocardial infarction in post-COVID-19 patients.

Aim. To study clinical and anamnestic data, as well as inhospital outcomes in patients with ST elevation myocardial infarction (STEMI) with prior coronavirus disease 2019 (COVID-19) compared with previously uninfected STEMI patients. Material and methods. This prospective study included 181 patients treated for STEMI. The patients were divided into 2 groups, depending on the anti-SARS-CoV-2 IgG titer as follows: the main group included 62 seropositive patients, while the control group - 119 seronegative patients without prior COVID-19. Anamnesis, clinical and paraclinical examination, including electrocardiography, echocardiography, coronary angiography, were performed. Mortality and incidence of STEMI complications at the hospital stage were analyzed. Results. The mean age of the patients was 62,6+/-12,3 years. The vast majority were men (69,1% (n=125)). The median time from the onset of COVID-19 manifestations to STEMI was 60,00 [45,00;83,00] days. According to, the patients of both groups were comparable the severity of circulatory failure (p>0,05). Coronary angiography found that in patients of the main group, Thrombolysis In Myocardial Infarction (TIMI) score of 0-1 in the infarct-related artery was recorded much less frequently (62,9% (n=39) vs, 77,3% (n=92), p=0,0397). Patients of the main group demonstrated a lower concentration of leukocytes (9,30*109/l [7,80;11,40] vs 10,70*109/l [8,40;14,00], p=0,0065), higher levels of C-reactive protein (21,5 mg/L [9,1;55,8] vs 10,2 mg/L [5,1;20,5], p=0,0002) and troponin I (9,6 ng/mL [2,2;26,0] vs 7,6 ng/mL [2,2;11,5], p=0,0486). Lethal outcome was recorded in 6,5% (n=4) of cases in the main group and 8,4% (n=10) in the control group (p=0,6409). Both groups were comparable in terms of the incidence of complications (recurrent myocardial infarction, ventricular fibrillation, complete atrioventricular block, stroke, gastrointestinal bleeding) during hospitalization (p>0,05). Conclusion. Patients with STEMI after COVID-19, despite a more burdened history and higher levels of C-reactive protein and troponin I, compared with STEMI patients without COVID-19, did not differ significantly in clinical status, morbidity, and inhospital mortality.Copyright © 2023, Silicea-Poligraf. All rights reserved.

Acute STEMI : Before and During the COVID-19 Pandemic Single Center Study

Background: During COVID-19 pandemic, the pattern of hospital admissions for acute ST-elevation myocardial infarction (STEMI) has been changing, and increased mortality and morbidity is being noted in these patients. Patient may present with acute myocardial infarction, myocarditis simulating a presentation like STEMI, coronary spasm, myocardial injury not fulfilling the criteria of type 1 & type 2 acute MI and cardiomyopathy. In this study we have tried to determine some important differences among the patients presented with STEMI during The COVID-19 pandemic versus non-COVID-19 era. Method(s): This prospective observational study was carried out in National Heart Foundation Hospital & Research Institute from 8thMarch,2019 to 7th March, 2021. Total 2531 patients were included. The study populations were divided into two groups. Group I: Acute STEMI patients presenting during pre COVID period (n=1385). Group II: Acute STEMI patients presenting during COVID period (n=1146). COVID period was calculated from 8th march, 2020 onward as first case of COVID -19 was detected on that day in Bangladesh. All patients presented with Acute STEMI was included in the study however NSTEMI-ACS, Unstable angina were excluded from the study. Result(s): Male was predominant in both groups. Regarding risk factors Hypertension, Obesity and family H/O of CAD was statistically significant (p<0.05). Acute STEMI patients presented lately during COVID-19 period probably due to lock down& lack of transport facility. Regarding coronary artery disease severity, vessel score was more during COVID period. SV-CAD were more during pre COVID period while DV-CAD & TV-CAD were more during COVID period. Gensini score was also calculated among the study populations, it was 57.21+/-28.42 and 63.16+/- 40.43respectively in group I and group I, which was statistically significant. Regarding treatment options of the patients, primary PCI was less during COVID period, however medical management, elective PCI and Thrombolysis were more during COVID era. Regarding in hospital outcome, acute LVF, cardiogenic shock were more during COVID period which were also statistically significant. [Formula presented] [Formula presented] Conclusion(s): During COVID -19, STEMI patients presented lately in comparison to pre COVID period. Coronary artery Disease were more severe during COVID period as evaluated by Vessel Score & Gensini Score. During COVID -19 period majority of patients got medical management& routine PCI were done more in comparison to primary PCI. In Hospital outcome of STEMI was worse during COVID-19 period in terms of acute LVF & cardiogenic shock. [Formula presented] [Formula presented] [Formula presented]Copyright © 2023

Pharmacoinvasive Therapy in Treating Acute STEMI Patients in COVID-19 Era-Thrombolysis by Tenecteplase (TNK) / Streptokinase (STK) Followed by Rescue PCI of the Culprit Vessel

Background: Treating acute STEMI patients by primary PCI has dramatically fallen globally in covid era as there is chances of potential threat of spreading Covid among the non-Covid patient. Thereby, thrombolysis of acute STEMI patient either by Streptokinase (STK) or Tenecteplase (TNK) in grey zone till Covid RT PCR report to come, was the mode of treatment of acute myocardial infarction patient in our hospital. Post thrombolysis, Covid positive cases were managed conservatively in a Covid dedicated unit. Covid negative cases were treated by rescue PCI of the culprit lesion. Exact data on benefit of thrombolysis either by TNK or STK of STEMI patients in Covid era, is not well addressed in our patient population. Thereby, we have carried out this prospective observational study to see the outcomes of thrombolysis and subsequent intervention. Method(s): STEMI Patient who represented to our ER with chest pain and ECG and hs-TROP-I evidenced acute ST segment elevated myocardial infarction (STEMI), were enrolled in the study. Total 139 patients enrolled (Male:120, Female :19);average age for Male: 54yrs., female was: 56yrs. All patients were admitted in the grey zone of CCU where thrombolysis done either by TNK or STK. Positive for COVID-19, were patients excluded from intervention and managed conservatively in Covid-19 dedicated ward. Covid Negative patients were kept transferred to CCU green zone. Result(s): COVID-19 test was carried out on all studied patients. Among them, Covid-19 positive were 7.9% (11) patients and managed conservatively in dedicated Covid ward, Covid-19 negative were 92.1% (128). Primary PCI was performed in 5.03% (7). Rest was managed by Pharmacoinvasive therapy either by TNK or STK. Thrombolysis by Tenecteplase in 64% (89), Streptokinase in 17.9% (25) patient, 12.9% (18) patient did not receive any thrombolysis due to late presentation and primary PCI done in 5.4% (7). On average 2.1 days after Fibrinolysis, elective PCI carried out. Data analysis from 48 patients;chest pain duration (3.71 +/-2.8 hr., Chest pain to contact time 3.3+/-2.8hr., Chest pain to needle time 7.2 +/-12.7hr., thrombolysis to balloon time 117.5+/-314.8hr., as many of the patient develop LVF post thrombolysis. More than 50% stenosis resolution observed in 41.6% (20) patients, chest pain resolution with one hour of thrombolysis observed in 43.8% (21) patients and development of LVF in 20.8% (10) patients. Door to needle time was 30 min. At presentation of STEMI;Ant Wall MI 46.8% (65), Inferior Wall MI 52.5% (73) and high Lateral 0.7% (1). Average Serum hs Trop-I was 16656 for male and 12109 for female. LVEF were 41% for male and 48% for female. HbA1C were in Male 8.34%: Female 8.05%, SBP for Male 120mmHg: Female 128 mmHg. Total, 88 stents were deployed in 83 territories. CABG recommended for 5.03% (7) patients, PCI in 58.3% (81), remaining were kept on medical management. Stented territory was LAD 45.7% (37) and RCA 39.5% (32) and LCX 14.8% (12). Common stent used;Everolimus 61.4% (54), Sirolimus 25% (22), Progenitor cell with sirolimus 2.3%(2) and Zotarolimus 11.4% (10) Conclusion(s): In the era of COVID-19, in this prospective cohort study, on acute STEMI patient management, we found that Pharmaco therapy by Tenecteplase and Streptokinase, reduced patient symptom and ST resolution partially. Therefore, coronary angiogram and subsequent Rescue PCI by Drug Eluting Stents (DES) are key goals of complete revascularization.Copyright © 2023

Comparison of acute ischemic stroke care quality before and during the COVID-19 pandemic in a private tertiary hospital in metro Manila, Philippines

Background: The Coronavirus Disease 2019 (COVID-19) pandemic had disrupted established medical care systems worldwide, especially for highly time-sensitive acute conditions such as stroke. Strategies to maintain the quality of stroke care during the COVID-19 outbreak are crucial to prevent indirect mortality and disability due to suboptimal care. Objective: We conducted a single center analysis to compare the time-based measures for acute ischemic stroke care quality before and during the COVID-19 pandemic. Methods: A retrospective study was done utilizing the Registry of Stroke Care Quality (RES-Q) database. All acute ischemic stroke patients who presented within 4.5 hours of symptom onset in Makati Medical Center were included. Patient characteristics, treatment received, in-hospital time-based measures of stroke care quality and clinical outcomes were compared between the two periods-pre-COVID-19 and COVID-19. Results: There were 151 patients during the pre-COVID-19 period and 108 patients during the COVID-19 period who presented to the hospital with acute ischemic strokes within 4.5 hours of symptom onset. There was significantly higher NIHSS scores on admission and MRS scores on discharge during the COVID-19 period. There was no significant difference in the door-to-scan time, door-to-needle time and door-to-groin time between the two periods. Conclusion: There is no significant change in the acute ischemic stroke care quality on the basis of in-hospital time-based measures: door-to-scan time, door-to-needle time, and door-to-groin time, between the pre-COVID-19 and COVID-19 periods. Further studies on pre-hospital challenges are recommended to identify specific targets for improvements in stroke care during pandemics. © 2023, ASEAN Neurological Association. All rights reserved.

Massive polyuria associated with severe COVID-19-related pneumonia complicated by pulmonary embolism

Coronavirus disease 2019 (COVID-19) predominantly manifests with signs of respiratory system injury;however, multi-systemic manifestations may occur. Renal pathology develops in up to 80% of patients with COVID-19. The aim of the study was to describe the case of isolated massive polyuria of unknown etiology in the patient with severe COVID-19-related pneumonia complicated by pulmonary embolism (PE). A 54-year-old male with bilateral pneumonia, related to COVID-19, developed PE. The next day after successful thrombolysis with alteplase (90 mg) the diuresis of the patient began to increase and fluctuated between 5000 mL and 8000 mL. The diuresis returned to normal ranges two weeks after PE episode. The rise of the diuresis was not accompanied by electrolyte disorders and elevation of serum creatinine. Changes in the urine tests were minimal, only once the urine protein was detected (0.25 g/L). The highest urine excretion was observed in evening hours (16.00-24.00). Chest CT on the day 14 after the patient's admission revealed 90% of lung tissue injury, cranial CT showed no brain abnormalities, including hypothalamus and pituitary gland. The patient's condition met neither diagnostic criteria of acute kidney injury, nor acute interstitial nephritis, nor pituitary gland damage. The course of the polyuria in the presented case was benign (self-limiting, no blood electrolyte abnormalities, compensated by oral rehydration only). Polyuria in patients with COVID-19 may not be a life-threatening condition that does not require active treatment.Copyright © 2021 EDIZIONI MINERVA MEDICA.

Stroke Simulation Improves Medical Student Confidence in Recognition and Management of Acute Stroke and TIA

Introduction: By the time of graduation medical students need to be equipped to recognise and manage acute stroke and TIA (Transient Ischemic Attack). Despite inclusion of acute stroke and TIA in our local curriculum less than 10% of students (2/30) reported directly observing stroke thrombolysis. Due to COVID restrictions no student was able to attend TIA clinic. To improve students practical understanding of assessment and management of acute stroke and TIA a simulation-based teaching session was designed. Method(s): The simulation session consisted of a hyperacute stroke assessment (2 scenarios) and management simulation and a simulated TIA clinic (3 scenarios). Students were asked to complete a pre-course and postcourse questionnaire regarding their confidence in 8 domains, on a continuous scale 0 to 5. Result(s): There were 23 participants over 2 sessions. 18/23 completed the pre-course questionnaire and 16/23 the post-course questionnaire. The mean confidence reported by students increased in all domains: recognition of acute stroke from 3.3 to 4.8;identifying candidates for thrombolysis, 3.1 to 4.6;discussing thrombolysis with a patient or carer, 2.3 to 4.1;knowing when to call for senior support, 3.1 to 4.3;asking for a patient to be transferred to facilitate acute stroke care, 2.2 to 4.2;recognising a TIA, 2.8 to 4.9;requesting investigations for TIA, 2.5 to 4.6;and discussing anticoagulation with a patient from 2.9 to 4.4. Conclusion(s): Improvements in confidence of medical students in assessing and managing acute stroke (including thrombolysis) and TIA can be achieved through a stroke medicine themed simulation session.

Acute ischemic stroke due to floating thrombus of ascending aorta: An acute and subacute complication of SARS-CoV-2 infection

Objective: To describe ischemic stroke due to floating thrombus of ascending aorta occurring as acute and subacute complication of SARS-CoV-2 infection. Material(s) and Method(s): consecutive identification in clinical practice of ischemic strokes secondary to aortic arch thrombosis and history of acute or recent Covid-19 infection. Result(s): two patients had ischemic stroke with evidence of aortic arch thrombosis. The first case had concomitant acute Covid-19 infection, the second had recent Covid-19 infection. Both patients underwent intravenous thrombolysis, and subsequent anticoagulation. One patient died due to cerebral hemorrhage. Discussion and Conclusion(s): aortic arch thrombosis can be an incidental finding in acute ischemic stroke in patients with concomitant and recent COVID-19 disease. However, the infection may lead to thrombosis in non-atherosclerotic vessels and to cerebral embolism. Our findings support active radiological search for aortic thrombosis during acute stroke in patients with acute or recent COVID-19 disease.Copyright © 2022

Impact of the COVID-19 Epidemic on Stroke Care and Potential Solutions

Background and Purpose: When the coronavirus disease 2019 (COVID-19) outbreak became paramount, medical care for other devastating diseases was negatively impacted. In this study, we investigated the impact of the COVID-19 outbreak on stroke care across China. Method(s): Data from the Big Data Observatory Platform for Stroke of China consisting of 280 hospitals across China demonstrated a significant drop in the number of cases of thrombolysis and thrombectomy. We designed a survey to investigate the major changes during the COVID-19 outbreak and potential causes of these changes. The survey was distributed to the leaders of stroke centers in these 280 hospitals. Result(s): From the data of Big Data Observatory Platform for Stroke of China, the total number of thrombolysis and thrombectomy cases dropped 26.7% (P<0.0001) and 25.3% (P<0.0001), respectively, in February 2020 as compared with February 2019. We retrieved 227 valid complete datasets from the 280 stroke centers. Nearly 50% of these hospitals were designated hospitals for COVID-19. The capacity for stroke care was reduced in the majority of the hospitals. Most of the stroke centers stopped or reduced their efforts in stroke education for the public. Hospital admissions related to stroke dropped =40%;thrombolysis and thrombectomy cases dropped =25%, which is similar to the results from the Big Data Observatory Platform for Stroke of China as compared with the same period in 2019. Many factors contributed to the reduced admissions and prehospital delays;lack of stroke knowledge and proper transportation were significant limiting factors. Patients not coming to the hospital for fear of virus infection was also a likely key factor. Conclusion(s): The COVID-19 outbreak impacted stroke care significantly in China, including prehospital and in-hospital care, resulting in a significant drop in admissions, thrombolysis, and thrombectomy. Although many factors contributed, patients not coming to the hospital was probably the major limiting factor. Recommendations based on the data are provided.Copyright © 2020 Authors. All rights reserved.

A case of disseminated intravascular coagulation following tumour lysis syndrome due to small cell carcinoma of the lung.

A 64-year-old man was diagnosed with small cell lung cancer (SCLC) with multiple bone and liver metastases and bone marrow metastases. Spontaneous tumour lysis syndrome (TLS) was observed before starting chemotherapy with carboplatin, etoposide, and atezolizumab. The tumour further collapsed, and the patient developed disseminated intravascular coagulation (DIC) on day 4 of chemotherapy. The patient was successfully treated with intravenous hydration and rasburicase for TLS and subcutaneous unfractionated heparin for DIC. A large amount of tissue factor may be released in TLS, which could induce DIC. However, to the best of our knowledge, this is the first report of DIC following TLS in a case of SCLC. DIC following TLS in SCLC is a rare but life-threatening oncologic complication. Therefore, clinicians should be aware of this possibility when treating patients with advanced SCLC.

Controlled release nanomedicine (CRNM) of aspirin using "biomimetic niosomal nanoparticles (BNNs)”for Covid-19 and cardiovascular treatment: DOE based optimization

Biomimetic strategies can be adopted to improve biopharmaceutical aspects. Subsequently, Biomimetic reconstitutable pegylated amphiphilic lipid nanocarriers have high translational potential for systemic controlled drug delivery;however, such an improvised system for systemic aspirin delivery exploring nanotechnology is not available. Systemic administration of aspirin and its controlled delivery can significantly control blood clotting events, leading to stroke, which has immediate applications in cardiovascular diseases and Covid-19. In this work, we are developing aspirin sustained release pegylated amphiphilic self-assembling nanoparticles to develop reconstitutable aspirin injections by solvent-based co-precipitation method with phase inversion technique that leads to novel "biomimetic niosomal nanoparticles (BNNs).” DOE led optimization is done to develop Design of space for optimized particles. Upon reconstitution of solid powder, the particle size was 144.8 ± 12.90 nm with a surface charge of -29.2 ± 2.24 mV. The entrapment efficiency was found to be 49 ± 0.15%, wherein 96.99 ± 1.57% of the drug was released in 24hr showing super case II transport-based drug release mechanism. The formulation has the least hemolysis while showing significant suppression of platelet aggregation. MTT assay does not show any significant cytotoxicity. This is a potential nanoparticle that can be explored for developing aspirin injection, which is not available.

Efficacy Validation of SARS-CoV-2-Inactivation and Viral Genome Stability in Saliva by a Guanidine Hydrochloride and Surfactant-Based Virus Lysis/Transport Buffer.

To enhance biosafety and reliability in SARS-CoV-2 molecular diagnosis, virus lysis/transport buffers should inactivate the virus and preserve viral RNA under various conditions. Herein, we evaluated the SARS-CoV-2-inactivating activity of guanidine hydrochloride (GuHCl)- and surfactant (hexadecyltrimethylammonium chloride (Hexa-DTMC))-based buffer, Prep Buffer A, (Precision System Science Co., Ltd., Matsudo, Japan) and its efficacy in maintaining the stability of viral RNA at different temperatures using the traditional real-time one-step RT-PCR and geneLEAD VIII sample-to-result platform. Although Prep Buffer A successfully inactivated SARS-CoV-2 in solutions with high and low organic substance loading, there was considerable viral genome degradation at 35 °C compared with that at 4 °C. The individual roles of GuHCl and Hexa-DTMC in virus inactivation and virus genome stability at 35 °C were clarified. Hexa-DTMC alone (0.384%), but not 1.5 M GuHCl alone, exhibited considerable virucidal activity, suggesting that it was essential for potently inactivating SARS-CoV-2 using Prep Buffer A. GuHCl and Hexa-DTMC individually reduced the viral copy numbers to the same degree as Prep Buffer A. Although both components inhibited RNase activity, Hexa-DTMC, but not GuHCl, directly destroyed naked viral RNA. Our findings suggest that samples collected in Prep Buffer A should be stored at 4 °C when RT-PCR will not be performed for several days.

Catastrophic Antiphospholipid Syndrome Presenting as Diffuse Peripheral and Central Thromboses

Case report - Introduction: Catastrophic Antiphospholipid Syndrome (cAPS) is the most severe form of antiphospholipid syndrome with a high mortality;it is characterised by multiorgan involvement that develops within a short time frame and usually consists of microvascular thrombosis. We present the case of a 50-year-old lady with recurrent microvascular and macrovascular thromboses who was initially treated with endovascular stents and amputation progressing to require immunosuppression and anticoagulation, to include steroids, rituximab, intravenous immunoglobulin and plasma exchange. Case report - Case description: A 50-year-old lady presented to the Emergency Department with bilateral leg and abdominal pain. Her comorbidities included type two diabetes, psoriasis, three miscarriages, borderline personality disorder and a heavy smoking history. Clinical examination revealed pulse deficits in the distal lower limbs with gangrene evidence of ischaemia on her toe digits. CT angiogram demonstrated complete thrombus of the Infrarenal abdominal aorta extending to the common iliac and external iliac arteries bilaterally. Thrombolysis ensued and an aortic stent was inserted with symptom relief. Two weeks later readmission occurred with bilateral leg pain;Ultrasound Doppler revealed a tight stenosis at the distal aortic region. Initial management consisted of Intravenous heparin but worsening ischaemia resulted in insertion of kissing stents at the aortic bifurcation. The patient's pain settled with no residual arterial compromise. One month later the patient was re-admitted with bilateral leg pain and necrotic right toes;this led to a right forefoot amputation. A triphasic bilateral finger colour change was noted with ischaemic pain and livedo reticularis on lower limbs, with a decision to institute Iloprost and methylprednisolone ensued. Antiphospholipid antibodies returned showing triple positivity. Management subsequently included addition of IV rituximab, plasma exchange, IVIG and sildenafil. Two months later the patient was re-admitted with complete lower limb paralysis due to a complete thrombus of the aortic bi-iliac stent;thrombolysis ensued with good result. A further admission 1- month later occurred due to sepsis and an infected necrotic left forefoot resulting in an above knee amputation. No further endovascular stenting was advised to risk of embolic seeding following medical management. Case report - Discussion: We have described a case of cAPS on a previously asymptomatic female patient who presented with diffuse peripheral and central thromboses. Our patient suffered from intraabdominal organ infarction and subsequent acute kidney injury, recurrent arterial and venous occlusion over a period of 12 months and previous pulmonary emboli. Livedo reticularis and gangrene were visible cutaneous manifestations of this disorder on our patient. cAPS accounts for less than 1% of APS and has a high mortality of 50% which means early and frequent discussion with specialist centres is important. In addition to the clinical features described in our patient, laboratory features included moderate thrombocytopaenia and evidence of haemolysis (raised bilirubin and LDH). The cAPS registry demonstrates that the majority of patients are female (72%) with a mean age of 37 years, 46% have primary APS, 40% suffer from SLE and 9% from other autoimmune diseases. This patient does not have a secondary autoimmune condition. The most common clinical features to present before cAPS develops include foetal loss, previous DVT or thrombocytopaenia, two of which our patient demonstrated. The prognosis and clinical features of cAPS have been shown to depend on the extent of thrombosis, organs affected and the presence of a systemic immune response from affected tissues. Treatment options available for cAPS consist of multiorgan support, anticoagulation and immunosuppression, in the form of glucocorticoids, rituximab, IV Immunoglobulin and plasma exchange. Our patient required all of these due to accelerating thrombosis as determined b new gangrene, ongoing livedo reticularis rash and thrombocytopenia. Case report - Key learning points: Our case demonstrates the importance of keeping a high index of suspicion for cAPS as up to 46% will have this as their first presenting feature of APS - including our patient. On her admission to hospital particular attention was paid to clinical examination which suggested Raynauds and a skin rash consistent with livedo reticularis - this prompted a rheumatology consult, serology testing, starting Iloprost and tertiary centre transfer. The diagnosis was secure with high titre of IgG anticardiolipin antibody, anti Beta-2 glycoprotein 1 antibodies and Lupus Anticoagulant detected- all on two occasions more than 12 weeks apart. Patients may present to surgical specialties in view of peripheral vascular symptoms and signs. It would be appropriate to identify patients with APS early to prevent multiple surgeries or considerations for endovascular stents, as they are frequently not successful. This case highlights the need for discussion and education within the multidisciplinary setting for patients with APS, including surgical teams. Finally, the risk of immunosuppression for patients who have received rituximab can persist for up to 12 months following treatment and this lady also had the co-morbidity of diabetes. This patient's risk stratification was high in view of COVID-19 and she was advised to shield until government guidelines ended last year. Currently she is doing well without new symptoms and she will be reviewed at 6 months following rituximab, in the Autumn of 2021.

A Case Report on Superior Mesenteric Artery Thrombosis in a Covid-19 Patient

INTRODUCTION: This case report discussed and reviewed an atypical presentation of COVID 19 involving superior mesenteric artery thrombosis with associated ischemic colitis. Thrombosis had been reported in up to 50 percent of patients with severe COVID -19. The pathophysiology of thrombosis in COVID 19 infection may include increasing blood viscosity and endothelial damage. DESCRIPTION: Case: A 59-year-old male with GERD, hiatal hernia, and diverticulitis was presented with ten days history of abdominal pain and vomiting, which later became coffee ground in nature. He was diagnosed with COVID 19 seven days before his presentation. Lab work showed hypokalemia with lactic acidosis, polycythemia, leukocytosis, thrombocytosis, and elevated D dimer. Esophagogastroduodenoscopy demonstrated actively bleeding Mallory Weiss tear successfully treated with bipolar circumactive probe cautery (BICAP). The patient's abdominal pain worsened, and a repeat CTA abdomen revealed a superior mesenteric artery thrombosis with thickening of the distal small bowel and ascending colon. Vascular surgery was consulted, and performed catheter-assisted tPA thrombolysis to the SMA. Atrial fibrillation, diverticulitis, and other possible causes were eliminated as etiologies. DISCUSSION: Acute mesenteric ischemia is a rare abdominal emergency. Due to rapid deterioration, early diagnosis and treatment are momentous for management. Severe abdominal pain and hematemesis are the keys to starting the evaluation. Initial investigation should include basic labs with a coagulation profile;the most common abnormalities are polycythemia, metabolic acidosis, lactic acidosis, and leukocytosis. CTA provides exquisite detail of the vascular anatomy and beneficial information regarding other bowel pathologies. After diagnosis, definitive management with fluid resuscitation, antibiotics, and IV high dose unfractionated heparin, if not contraindicated, should be initiated immediately. Recently, catheter-directed procedures for intravascular thrombectomy have been used with tPA. CONCLUSION(S): In our case, we attempted to emphasize the importance of a high index of suspicion with proper history, physical examination, and appropriate imaging for proper diagnosis and management of this life-threatening incident.