REFERRAL BEHAVIOUR OF PRIMARY CARE DOCTORS TO RHEUMATOLOGY CLINIC IN MALAYSIA

BackgroundThe workload at rheumatology clinics have been growing relentlessly and an audit on new.referrals helps to identify referral behaviour of primary care doctors and improvement can be done by providing further training.ObjectivesTo audit on new referral cases to rheumatology clinic from 2020-2022 and to identify new cases with misdiagnosis for future training purpose.MethodsThis was a retrospective study. The medical records of all new referral to rheumatology clinic Hospital Sultan Ismail and Hospital Pakar Sultanah Fatimah from 1st January 2020 to 31th November 2022 were reviewed. The referral diagnosis and final diagnosis were identified and analysed.ResultsThere were total of 927 new cases referral throughout the 35 months during Covid-19pandemic. Majority of them were diagnosed to have rheumatoid arthritis (217/927)followed by systemic lupus erythematosus (190/927), psoriatic arthritis (147/927),gout (62/927), osteoarthritis (58/927), systemic sclerosis (25/927), ankylosing spondylitis (25/927), soft tissue rheumatism (24/927), Sjogren syndrome (24/927),mixed connective tissue disease (14/927), vasculitis (11/927), fibromyalgia (10/927),polymyositis (7/927) and miscellaneous (39/927).45 out of the new cases were diagnosed as unlikely rheumatic diseases. There were 29pending cases awaiting final diagnosis.212 of the referrals were identified as misdiagnosis with the highest as nodal osteoarthritis.(55/212) followed by unlikely rheumatic disease (43/212), soft tissue rheumatism (24/212),psoriatic arthritis (20/212), Sjogren syndrome (14/212), gout (8/212), rheumatoid arthritis (7/212), fibromyalgia (6/212), systemic lupus erythematosus (5/212), ankylosing spondylitis (4/212), mixed connective tissue disease (3/212), systemic sclerosis (2/212), polymyositis (2/212) and others (19/212): diffuse idiopathic skeletal hyperostosis, hypermobility syndrome, RS3PE syndrome, idiopathic uveitis, graft versus host disease, juvenile idiopathic arthritis, antiphospholipid syndrome, hypothyroidism, post streptococcal arthritis, prolapsed intervertebral disc, cerebrovascular disease, traumatic sternoclavicular joint subluxation, ledderhose disease, paraspinal muscle spasm and viral myalgia).ConclusionNodal osteoarthritis and soft tissue rheumatism can be great mimicker for inflammatory.arthritis and if wrongly diagnosed will lead to unnecessary anxiety or wrong treatment. More training is needed to improve clinical skills amongst primary care doctors.ReferencesNA.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

COVID-19 and stroke: A review.

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

Football, dementia, . . . and other stories

The increased risk of dementia didn't apply to goalkeepers, which is compatible with the hypothesis that repeated head impacts sustained when heading the ball are part of the cause (Lancet doi:10.1016/S2468-2667(23)00027-0). Mental illness and septic shock A nationwide study of 200 000 adults admitted to intensive care units in French hospitals with septic shock reveals that those with severe mental illness (schizophrenia, bipolar disorder, or major depressive disorder) have substantially lower case fatality, assessed at 30, 90, and 365 days after admission, than controls matched for age, sex, and social deprivation. For vascular dementia, the most consistent precursors were an abnormal electrocardiogram, cardiac dysrhythmias, cerebrovascular disease, non-epithelial skin cancer, depression, and hearing loss (Ann Neurol doi:10.1002/ana.26584).

2019-NCoV: What every neurologist should know?

The 2019 novel Corona Virus pandemic beginning from Wuhan, China primarily affects the respiratory tract but its has impacted clinical practice across a range of specialities including neurology. We review the bearing of the 2019 NCoV infection on neurological practice. Neurological manifestations are less common than respiratory manifestations, yet conspicuous, affecting nearly over a third of hospitalized individuals. These may be classified in to early – headache, dizziness, hyposmia and hypogeusia and late – encephalopathy. Rarely but surely, a very small proportion of infected individuals might present with stroke. Certain neurological conditions, including cerebrovascular disease in both China and Italy and dementia in Italy predispose to infection and more severe manifestations, requiring intensive care unit admission. There is no convincing evidence that the manifestations, course and outcome of various neurological disorders is impacted by 2019 nCoV infection. Concerns of an increased risk of febrile seizures offset by a reduced frequency of infection in the paediatric age group. Individuals with multiple sclerosis might potentially experience both true and pseudorelapses. Besides a direct effect, 2019 nCoV has tremendously affected neurological care by disrupting the continuity of care and the availability of neurological medicines worldwide. Neurologists should respond to this challenge by developing and sustaining innovative methods of providing care as well as alerting the society at large to adopt measures to contain the spread of 2019 nCoV.

Football, dementia, . . . and other stories

The increased risk of dementia didn't apply to goalkeepers, which is compatible with the hypothesis that repeated head impacts sustained when heading the ball are part of the cause (Lancet doi:10.1016/S2468-2667(23)00027-0). Mental illness and septic shock A nationwide study of 200 000 adults admitted to intensive care units in French hospitals with septic shock reveals that those with severe mental illness (schizophrenia, bipolar disorder, or major depressive disorder) have substantially lower case fatality, assessed at 30, 90, and 365 days after admission, than controls matched for age, sex, and social deprivation. For vascular dementia, the most consistent precursors were an abnormal electrocardiogram, cardiac dysrhythmias, cerebrovascular disease, non-epithelial skin cancer, depression, and hearing loss (Ann Neurol doi:10.1002/ana.26584).

Early arrival did not ensure the early acquisition of intravenous thrombosis for acute ischemic stroke during the COVID-19 pandemic.

BACKGROUND: Intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) is a time-dependent treatment with a narrow therapeutic time window, in which the time delay could result from the deadline effect. METHODS: One hospital-based cohort was recruited to detect the factors contributing to the deadline effect, where patients with the deadline effect were defined as those who were presented with the onset-to-door time (ODT) in the first 50%, while the door-to-needle time (DNT) was in the last quartile. DNT (in-hospital delay) was further subdivided into several time intervals [door-to-examination time (DET), door-to-imaging time (DIT), door-to-laboratory time (DLT), and decision-making time (DMT) of the patients or their proxies. RESULTS: A total of 186 IVT cases were enrolled, of which 17.2% (32/186) suffered a delay of the deadline effect. The median age was 66 years, and 35.5% were female. Baseline characteristics were similar between the two groups (all p > .05). For the comparisons of the time intervals, DIT (26 versus 15 min, p = .001) was significantly longer in the group with deadline effect, while the differences of DET, DLT, DMT, and ONT did not reach statistical significance (all p > .05). Upon multivariable adjustment in the binary logistic regression model, longer DIT [odds ratio (OR), 1.076; 95% confidence interval (CI), 1.036-1.118; p < .001], and history of coronary heart disease (OR, 3.898; 95%CI, 1.415-10.735; p = .008) were independently associated with deadline effect in the binary logistic regression model, while admitted in the working day (OR, 0.674; 95%CI, 0.096-0.907; p = .033), and having medical insurance (OR, 0.350; 95% CI, 0.132-0.931; p = .035) were negatively associated with the deadline effect. CONCLUSIONS: A speed-safety tradeoff phenomenon from the deadline effect was observed in 17.2% of IVT cases during the COVID-19 pandemic, where longer DIT contributed a lot to this time delay. Patients without medical insurance, or admitted in official holidays were more likely to experience a delay of the deadline effect.

Recent advances in Chinese patent medicines entering the international market.

As an indispensable part of Traditional Chinese medicine (TCM), Chinese patent medicines have played an important role in preventing and treating diseases in China. Since they are easy to use, easy to store, and cost-effective, Chinese patent medicines have been generally accepted and widely used in Chinese clinical practice as a vital medical resource. In recent years, as TCM has developed and it has been accepted around the world, many Chinese patent medicine companies have gained international market access and successfully registered several Chinese patent medicines as over-the-counter (OTC) or prescription drugs in regions and countries that primarily use Western medicine such as the EU, Russia, Canada, Singapore, and Vietnam. Moreover, several Chinese patent medicines have been obtained the US Food and Drug Administration (FDA) approval conducting phase II or III clinical trials in the US. The current work has focused on several Chinese patent medicines that have been successfully registered or that have been submitted for registration abroad. Summarized here are recent advances in the efficacy and molecular mechanisms of these Chinese patent medicines to treat respiratory infectious diseases (Lianhua Qingwen capsules, Jinhua Qinggan granules, and Shufeng Jiedu Capsules), cardiovascular and cerebrovascular diseases (Compound Danshen Dripping Pills, Huatuo Zaizao pills, and Tongxinluo Capsules), cancers (a Kanglaite injection and a Shenqi Fuzheng Injection), and gynecological diseases (Guizhi Fuling Capsules). The hope is that this review will contribute to a better understanding of Chinese patent medicines by people around the world.

Non-clinical safety evaluation of prophylactic mRNA vaccine:general principles and concerns

Messenger RNA（mRNA） vaccine, with antigen-encoded mRNA packaged in delivery vehicles, performs its functions via antigen translation and specific immune response. mRNA vaccines have proven their protective effects and safety in the ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）. The World Health Organization issued guidelines specifically for prophylactic mRNA vaccines in 2021, which provide important guidance for non-clinical research on mRNA vaccines. Furthermore, some unusual adverse reactions, such as cerebrovascular disease, embolic stroke, transient cerebral ischemia, deep vein thrombosis, myocarditis（pericarditis） and allergic reactions, have been also found in clinical trials and applications of mRNA vaccines, which deserves attention in non-clinical studies.

Effects of COVID-19 on Synaptic and Neuronal Degeneration.

Neurons are the basic building blocks of the human body's neurological system. Atrophy is defined by the disintegration of the connections between cells that enable them to communicate. Peripheral neuropathy and demyelinating disorders, as well as cerebrovascular illnesses and central nervous system (CNS) inflammatory diseases, have all been linked to brain damage, including Parkinson's disease (PD). It turns out that these diseases have a direct impact on brain atrophy. However, it may take some time after the onset of one of these diseases for this atrophy to be clearly diagnosed. With the emergence of the Coronavirus disease 2019 (COVID-19) pandemic, there were several clinical observations of COVID-19 patients. Among those observations is that the virus can cause any of the diseases that can lead to brain atrophy. Here we shed light on the research that tracked the relationship of these diseases to the COVID-19 virus. The importance of this review is that it is the first to link the relationship between the Coronavirus and diseases that cause brain atrophy. It also indicates the indirect role of the virus in dystrophy.

Should I Wear a Mask in School?

Furthermore, we are only beginning to appreciate the severity of post-acute sequelae of COVID-19 (PASC, post-COVID or long-COVID) that can affect many body systems and cause neurological (brain fog, headache, anosmia), respiratory (fatigue), gastrointestinal, metabolic (diabetes), and cardiovascular symptoms (e.g., cerebrovascular disorders, dysrhythmias, inflammatory heart disease;Xie et al. 2022). New variants may continue to become more resistant to vaccines and even more transmissible, and some carriers do not display symptoms. [...]masking (CDC 2022) will be an important part of my "personal protection plan" for the foreseeable future. [...]I include discussions of COVID-19 and prevention practices in my teaching and with middle school teachers in our professional development programs (Folk, van Garderen, and Lannin 2018).

COVID-19 Outcomes in Patients Who Started GLP1-RAs during Hospitalization

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been hypothesized to exert beneficial effects on COVID-19 outcomes due to their anti-inflammatory properties. In our COVID-19 ward, patients admitted for severe interstitial bilateral pneumonia due to SARS-COV2 infection and having type 2 diabetes (T2D) or in-hospital hyperglycemia (IHH) were treated with GLP-1 RAs in addition to standard therapy according to usual care. Aim of the present study was to evaluate if GLP-1 RAs therapy was related with outcomes. A retrospective analysis was performed to assess if the GLP1-RAs were associated with a lower risk of a composite outcome (death or admission to intensive care unit) . During the COVID-19 pandemics, 135 patients were admitted (61.5% men, age 66.3±13.7 years, 49.6% with T2D and 50.4% with IHH) , of whom 23.1% initiated GLP1-RA during the hospitalization (39.1% of patients with T2D and 7.6% of patients with IHH) . Almost all patients were treated with once-weekly subcutaneous semaglutide, while dulaglutide was administered in 2 cases. Overall, 26.3% of patients not treated vs. 7.1% of patients treated with GLP1-RAs reached the composite outcome (p=0.03) . At multivariate analysis adjusted for age, gender, T2D, history of cardio/cerebrovascular disease, hypertension, pulmonary disease, and dementia, the use of GLP-1 RAs was associated with a reduced risk of composite outcome of 80% (OR 0.20;95% confidence intervals 0.04-0.95) . Dementia resulted the only other independent correlate of the outcome. These preliminary results suggest that the addition of GLP1-RAs to standard care during hospitalization for SARS-CoV2 infection could play a role in improving clinical outcomes in patients with COVID-19 and T2D or IHH: at the best of our knowledge this is the first study showing such an effect when GLP1-RAs were started during hospitalization.

Coexistence of SARS-CoV-2 and cerebrovascular diseases: does COVID-19 positivity trigger cerebrovascular pathologies?

The objectives of this study were to determine the prevalence of cerebrovascular diseases caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and to assess the pharmacological agents used in such cases as reported in the literature. Patient files were retrospectively scanned to determine the prevalence of neurological symptoms of the central nervous system (headache, dizziness, lack of smell and taste, numbness in arms and legs, change in consciousness, muscle weakness, loss of urine and stool control) and cerebrovascular diseases (ischemic cerebrovascular diseases, cerebral venous sinus thrombosis, intracerebral hemorrhage, subarachnoid/subdural hemorrhage) in 2019 novel coronavirus (2019-nCoV) disease (COVID-19) cases (n = 20,099). The diagnostic laboratory, radiology examinations and treatments applied to these cases were recorded. The data from studies presenting cerebrovascular diseases associated with SARS-Cov-2, which constituted 0.035% of all cases, were systematically evaluated from electronic databases. During the treatment of cerebrovascular diseases, it was discovered that high doses of enoxaparin sodium anti-Xa are combined with apixaban or acetylsalicylic acid or clopidogrel or piracetam, and mannitol, in addition to SARS-CoV-2 treatment modalities. While neurological symptoms of the central nervous system are uncommon in cases of SARS-CoV-2 infection, cerebrovascular diseases are far less common, according to the findings of this study. Acute cerebral ischemia was discovered to be the most common cerebrovascular disease associated with SARS-CoV-2. The mortality rate increases with the association between SARS-CoV-2 and cerebrovascular disease.

Neurological manifestations in patients with COVID‐19: A systematic review and meta‐analysis

IntroductionThe intensification of coronavirus disease 2019 (COVID‐19) complications, severe symptoms, and high mortality rate has led researchers to focus on this significant issue. While respiratory and cardiac complications have been described as high‐risk manifestations in patients with COVID‐19, neurological complications can also enhance mortality. This study aimed to evaluate the prevalence of neurological complications arises from SARS‐CoV‐2 and assess the mortality rate from neurological complications.Material and MethodsLiterature review was conducted by searching in PubMed/Medline, Web of Sciences, and Embase. After performing search strategies with relevant terms, a number of articles were excluded, including review articles, systematic review or meta‐analysis, duplicate publication of same researchers, congress s, animal studies, case reports, case series, and articles reporting a history of neurological features prior to COVID‐19 infection. After retrieving the data, statistical analysis was performed using the STATA Version 14 software.ResultsFrom 4455 retrieved publications, 20 articles were selected for further analysis. Among 18,258 included patients, 2791 showed neurological symptoms, which were classified into different groups. Headache, confusion, and fatigue were reported as the most non‐specific neurological features in confirmed COVID‐19 patients. Psychiatric symptoms, CNS disorders, cerebrovascular disorders, CNS inflammatory disorders, PNS disorders, neuromuscular disorders, etc., were defined as specific neurological manifestations. The pooled prevalence of neurological manifestations and mortality rate of COVID‐19 patients with neurological features were estimated to be 23.0% (95% CI: 17.8–29.2) and 29.1% (95% CI: 20.3–39.8), respectively.ConclusionNeurological manifestations may commonly happen in patients with COVID‐19. This study reported a high prevalence of neurological complications and mortality rates in COVID‐19 patients. Therefore, patients with COVID‐19 who indicated neurological symptoms should be taken seriously and should receive early treatment to prevent undesirable events.

Progress of thrombus formation and research on the structure-activity relationship for antithrombotic drugs.

Many populations suffer from thrombotic disorders such as stroke, myocardial infarction, unstable angina and thromboembolic disease. Thrombus is one of the major threatening factors to human health and the prevalence of cardio-cerebrovascular diseases induced by thrombus is growing worldwide, even some persons got rare and severe blood clots after receiving the AstraZeneca COVID vaccine unexpectedly. In terms of mechanism of thrombosis, antithrombotic drugs have been divided into three categories including anticoagulants, platelet inhibitors and fibrinolytics. Nowadays, a large number of new compounds possessing antithrombotic activities are emerging in an effort to remove the inevitable drawbacks of previously approved drugs such as the high risk of bleeding, a slow onset of action and a narrow therapeutic window. In this review, we describe the causes and mechanisms of thrombus formation firstly, and then summarize these reported active compounds as potential antithrombotic candidates based on their respective mechanism, hoping to promote the development of more effective bioactive molecules for treating thrombotic disorders.

A Population-Based Registry Analysis on Hospitalized COVID-19 Patients with Previous Cardiovascular Disease: Clinical Profile, Treatment, and Predictors of Death.

A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI.

Influenza vaccination uptake among high-risk target groups and health care workers in Spain and change from 2017 to 2020.

OBJECTIVE: Using the 2020 European Health Survey for Spain (EHSS2020), which ran from July 2019 to July 2020, we aimed to describe influenza vaccination uptake among the following target groups; individuals aged ≥65 years, health care workers (HCWs), and persons with high-risk chronic medical conditions. We analyzed changes in uptake since the previous Spanish National Health Interview Survey conducted in 2017 and identified variables associated with vaccine uptake. METHODS: We performed a cross-sectional study. The primary study variable was the self-reported uptake of influenza vaccine in the previous year. We analyzed sex, age, country of birth, and being an HCW. We identified participants with self-reported respiratory diseases, cardiovascular disease, diabetes, cancer, and cerebrovascular diseases. Multivariable logistic regression was applied to assess changes over time and to identify variables associated with vaccination in target groups. RESULTS: Uptake was 19.2% in 22,072 participants aged ≥15 years. Uptake was 54.4% for those aged ≥65 years, 41.6% for those with a high-risk medical condition, and 26.53% among HCWs. Uptake by disease was 52.1% for cerebrovascular diseases, 51.3% for cardiovascular diseases, 48.3% for diabetes, 46.1% for cancer, and 36.2% for respiratory diseases. No significant improvement has been observed since 2017 in any target group, except for participants with cancer, whose uptake increased from 33.2% to 46.1%(p < 0.001). The variables that significantly increased the probability of reporting vaccine uptake were female sex, age ≥35 years, being born in Spain, self-reported respiratory or cardiovascular diseases, diabetes, cancer, and being a HCW. CONCLUSIONS: Influenza vaccination uptake among target groups in Spain is below desirable levels and has not improved significantly since 2017. Older age, female sex, and being born in Spain are positive predictors of vaccine uptake. The COVID-19 pandemic highlights the urgent need to implement new strategies to increase influenza vaccine uptake.

[Diagnostic and treatment recommendations from the FACME ad-hoc expert working group on the management of cerebral venous sinus thrombosis associated with COVID-19 vaccination]. / Recomendaciones diagnóstico-terapéuticas del grupo de trabajo de expertos de FACME ad-hoc sobre el manejo de la trombosis venosa cerebral relacionada con la vacunación frente a COVID-19.

INTRODUCTION: Cases of cerebral venous sinus thrombosis have been reported in individuals vaccinated against COVID-19 with non-replicating adenoviral vector vaccines. We issue our recommendations on the diagnosis and management of patients presenting this complication. METHOD: The multidisciplinary working group, led by the Spanish Federation of Medical and Scientific Associations and including representatives of several scientific societies, reviewed the available evidence from the literature and reports of the European Medicines Agency. We establish a definition for suspected cases and issue diagnostic and treatment recommendations regarding vaccine-induced immune thrombotic thrombocytopaenia. RESULTS: We define suspected cases as those cases of cerebral venous sinus thrombosis occurring between 3 and 21 days after the administration of non-replicating adenoviral vector vaccines, in patients with a platelet count below 150,000/µL or presenting a decrease of 50% with respect to the previous value. Findings suggestive of vaccine-induced immune thrombotic thrombocytopaenia include the presence of antibodies to platelet factor 4, D-dimer levels 4 times greater than the upper limit of normal, and unexplained thrombosis. The recommended treatment includes intravenous administration of non-specific human immunoglobulin or alternatively plasmapheresis, avoiding the use of heparin, instead employing argatroban, bivalirudin, fondaparinux, rivaroxaban, or apixaban for anticoagulation, and avoiding platelet transfusion. CONCLUSIONS: Non-replicating adenoviral vector vaccines may be associated with cerebral venous sinus thrombosis with thrombocytopaenia; it is important to treat the dysimmune phenomenon and the cerebral venous sinus thrombosis.

Diagnostic and treatment recommendations from the FACME ad-hoc expert working group on the management of cerebral venous sinus thrombosis associated with COVID-19 vaccination.

INTRODUCTION: Cases of cerebral venous sinus thrombosis have been reported in individuals vaccinated against COVID-19 with non-replicating adenoviral vector vaccines. We issue our recommendations on the diagnosis and management of patients presenting this complication. METHODS: The multidisciplinary working group, led by the Spanish Federation of Medical and Scientific Associations (FACME) and including representatives of several scientific societies, reviewed the available evidence from the literature and reports of the European Medicines Agency. We establish a definition for suspected cases and issue diagnostic and treatment recommendations regarding vaccine-induced immune thrombotic thrombocytopaenia. RESULTS: We define suspected cases as those cases of cerebral venous sinus thrombosis occurring between 3 and 21 days after the administration of non-replicating adenoviral vector vaccines, in patients with a platelet count below 150 000/µL or presenting a decrease of 50% with respect to the previous value. Findings suggestive of vaccine-induced immune thrombotic thrombocytopaenia include the presence of antibodies to platelet factor 4, D-dimer levels 4 times greater than the upper limit of normal, and unexplained thrombosis. The recommended treatment includes intravenous administration of non-specific human immunoglobulin or alternatively plasmapheresis, avoiding the use of heparin, instead employing argatroban, bivalirudin, fondaparinux, rivaroxaban, or apixaban for anticoagulation, and avoiding platelet transfusion. CONCLUSIONS: Non-replicating adenoviral vector vaccines may be associated with cerebral venous sinus thrombosis with thrombocytopaenia; it is important to treat the dysimmune phenomenon and the cerebral venous sinus thrombosis.

Renin-Angiotensin System in Central Nervous System Diseases and its Interaction with COVID-19.

BACKGROUND: The Renin-Angiotensin System (RAS) comprises a complex molecular cascade with two counter-regulatory axes, the classical and the alternative. Angiotensin II and Angiotensin-(1-7), the main peptides of the RAS, exert opposite effects in multiple organs and systems, including the cardiovascular, renal, pulmonary, and immune systems. Strong evidence supports the hypothesis of a local RAS in the Central Nervous System (CNS) and its modulatory roles in neuroendocrinology and neurotransmission. OBJECTIVE: In this narrative review, we provide a comprehensive approach to experimental and clinical data regarding RAS molecule expression and their possible roles in the physiology and physiopathology of CNS diseases. METHODS: This non-systematic review summarizes evidence on RAS implications in CNS diseases and their possible relationships with COVID-19. RESULTS: We divided the possible RAS mechanisms in distinct conditions during the lifespan, approaching from congenital infections to neurodegenerative alterations, passing through mood disorders and cerebrovascular diseases. We also gathered current evidence about the possible effects of RAS in Covid-19, particularly in cases with neurological manifestations. CONCLUSION: Although there are limitations and controversies, the analysis of RAS mechanisms in the CNS certainly represents an interesting field of research. However, further investigation is necessary to support the noteworthy interactions and provide a better comprehension of the cross-talk between RAS and the CNS. Investigations in this research field may shed light on the novel therapeutic targets.

Crosstalk Between Covid-19 and Associated Neurological Disorders: A Review.

COVID-19 is a global pandemic, primarily affecting the pulmonary system but its effects on other systems are not certain. Coronavirus, the causative organism, binds with angiotensinconverting enzyme 2 (ACE2) receptors in the lungs and produces pneumonia-like symptoms. Other than lungs, ACE2 receptors are also seen in the endothelium of blood vessels. Therefore, viruses can bind to the ACE2 that is present in the endothelium of brain blood vessels and thus can invade BBB, leading to neuronal damage. It is also believed that olfactory cells rich in ACE2 receptors may act as the main route of viral spread into various parts of the brain. The reported neurological effects of SARS-CoV-2 include cerebrovascular diseases, ageusia and anosmia, Guillain Barre Syndrome, and viral encephalitis. The extent of neurological involvement in SARS-CoV-2 infection warrants the necessity of further research to systematically classify neurological complications associated with SARS-CoV-2 infection, its diagnosis, and treatment. As ACE2 receptors are present in various other organs, it is obligatory to study the effect of coronavirus on other organs also. Since the long-lasting effects of the COVID-19 are unclear, more studies should be conducted to confirm the effect of the virus on the central nervous system. This review highlights the reported neurological manifestations of SARS-CoV-2 and its mechanism.