Intracerebral Hemorrhage associated COVID-19 patient with normal coagulation profile after ECMO treatment: A case report".

Background: Coronavirus disease 2019 (COVID-19) is a novel coronavirus-caused infectious acute respiratory disease that can progress to severe acute respiratory distress syndrome (ARDS). For severe cases, extracorporeal membrane oxygenation (ECMO) is an excellent treatment option. ECMO had a number of side effects, including bleeding. Intracerebral hemorrhage can occur in COVID patients due to a variety of mechanisms, including covid's effect on ACE-2 receptors and subsequent hypertension, coagulopathy, DIC, or medication, such as anticoagulant use. Case: We present a case of a 53-year-old male COVID-19 patient who developed multiple, massive, severe intracerebral hemorrhages (ICH) despite a normal coagulation profile after ECMO treatment. Conclusion: COVID-19 can progress to severe acute respiratory distress syndrome (ARDS), necessitating the use of extracorporeal membrane oxygenation (ECMO). Although ICH is not a common complication in patients with COVID-19 disease, it is unknown why this patient had a lower threshold of ICH despite having a normal coagulation profile.

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.

Intracranial Hemorrhage After Pfizer-BioNTech (BNT162b2) mRNA COVID-19 Vaccination: A Case Report.

The Coronavirus 2019 (COVID-19) pandemic has affected over 700 million people worldwide and caused nearly 7 million deaths. Vaccines currently developed or in development are the most effective tools for curbing the pandemic and mitigating its impacts. In Turkey, inoculation with the Pfizer-BioNTech COVID-19 vaccine (BNT162b2, also known as tozinameran) has been approved. We report a 56-year-old female patient with underlying essential hypertension who experienced intracranial hemorrhage after receiving her first dose of tozinameran. The patient underwent immediate surgical evacuation of the hematoma, during which a left middle cerebral artery bifurcation aneurysm was macroscopically identified and clipped. The patient was pronounced deceased on the second postoperative day. This is the second case of intracranial hemorrhage following tozinameran administration caused by a ruptured middle cerebral artery bifurcation aneurysm. Upon analyzing the case, there might be a connection between the vaccine's potential immune-triggering effect on hemodynamic patterns and the rupture of the previously unknown cerebral aneurysm. However, these severe complications do not justify avoiding vaccines; further studies are needed. This study emphasizes the need for increased vigilance in patients with underlying systemic comorbidities who have recently been vaccinated and to share our insights into the potential relationship between tozinameran and intracranial hemorrhage.

An Rp-Hplc Method for the Quantitative Determination of Remdesivir in Intravenous Dosage Form

The worldwide epidemic of Coronavirus disease 2019 (COVID-19), caused by a new virus known as severe acute respiratory syndrome (SARS) coronavirus 2, has posed a growing threat to public health (SARS-CoV-2). The only antiviral drug authorized by the FDA for treating adult and pediatric patients hospitalized with a severe disease is remdesivir, which is given intravenously (IV). Although only a few methods for estimating remdesivir in pharmaceutical formulations using high-pressure liquid chromatography (HPLC) have been described, its determination still requires an accurate, precise, quick, and easy analytical methodology. The main goal of this study was to develop and validate a reliable and accurate HPLC method for quantitative estimation of remdesivir in its intravenous dosage formulation. The separation was performed on a C18 (4.6 mm x 150 mm, 5.0 microm) column with a flow rate of 0.7 mL/min and a total run duration of 6 minutes using a simple isocratic mobile phase of acetonitrile and 0.1 percent formic acid. The method was validated for the system suitability, linearity, precision, accuracy, robustness, and others as per the International Council for Harmonization (ICH) Q2 (R1) guideline. The results show that the method for measuring remdesivir using HPLC is simple, quick, sensitive, accurate, precise and robust. The described approach was successfully used to quantify remdesivir in a commercially available pharmaceutical formulation.Copyright All © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research.

A Non-traumatic Non-aneurysmal Subarachnoid Hemorrhage in a Mild COVID-19 Infection: A Case Report.

Both subarachnoid hemorrhage and intraparenchymal hemorrhage have been reported in patients with coronavirus disease 2019 (COVID-19) infection. We report a 38-year-old male patient who was initially admitted for alcoholic hepatitis and had a mild COVID-19 infection that was confirmed 10 days prior to presentation. During his hospitalization, he reported worsening of his occipital headache that started when he tested positive for COVID-19. Neurological examination was intact and no history of trauma, hypertension, illicit drug use, or family history of brain aneurysm was reported. Investigating his worsening headache revealed a tiny, right-sided, posterior subarachnoid hemorrhage. No coagulopathy was evident. No aneurysm was seen on the cerebral angiogram. The patient was managed conservatively. This case raises the point of the importance of investigating headaches even in mild COVID-19 infection, as it may herald intracranial bleeding.

Stability Indicating RP-HPLC Method for the estimation of Favipiravir in API and Pharmaceutical Dosage Forms (Tablets)

Favipiravir is an anti-viral agent used for the treatment of a large number of RNA viruses including influenza and was considered for the treatment of COVID-19. A new stability indicating RP-HPLC has been developed for the estimation of Favipiravir and the method was validated. Hypersil BDS C18 column was used for the chromatographic study with a flow rate 1ml/min (Detection wavelength 230nm). The LOD and LOQ were found to be 0.2918mug/mL and 0.9207mug/mL respectively. Linearity was observed over the concentration 1-300mug/mL with linear regression equation, y = 28444x + 21853 (R2 = 09998) and the method is precise, accurate and robust. Stress degradation studies were performed and the method was found to be selective and specific. Copyright © RJPT All right reserved u.

Analytical Method Development And Validation Parameters Of Drug Ivermectin

An accurate, easy, detailed, selective and fast RP-HPLC stability representative technique was developed and validated for assessment of ivermectin in tablet dosage form. The Reverse Phase High Performance Liquid Chromatographic technique was developed for routine quantification of ivermectin in laboratory prepared mixtures as well as in combined dosage forms. The chromatographic separation was accomplished with INERTSIL C-18 ODS 250x4.6mm, 5 mu m particle size column along with acetonitrile and methanol as the mobile phase at a flow rate of 1 ml/min. Quantification was completed by using a UV detector at 245 nm and the run time was 10 minutes. The retention time was found to be 4.198 min for ivermectin. The linearity was observed in the range of 1-32 mu g/ml with correlation coefficient r= 0.9798. The % RSD for intraday and interday precision was 1.352 and 1.589 respectively. The LOD and LOQ values were found to be 2.93 and 8.79, respectively. The system suitability parameters for ivermectin such as theoretical plates and tailing factor were found to be 129.949 and 2.0, respectively. Robustness was also studied and there was no significant variation in the system suitability of the analytical method by incorporating small changes in experimental parameters. The technique has been validated for linearity, precision, accuracy and other parameters as approved by ICH guidelines. The results obtained by RP- HPLC methods are found to be fast, detailed, selective and accurate. Therefore, proposed analytical method can be used for regular analysis of ivermectin in injection, tablet and other formulations.

Development and Validation of RP-HPLC Method for the Quantitative Estimation of Favipiravir in Bulk and Pharmaceutical Dosage Form

Favipiravir is an antiviral drug, used in the treatment of SARS-COV-2, novel corona virus. It is a pyrazine carboxamide derivative with activity against RNA viruses A sensitive new RP-HPLC method was developed for the quantitative estimation of Favipiravir in bulk and pharmaceutical dosage form using Rivaroxaban as internal standard (IS). The separation of drug was achieved by Enable C18 column using acetonitrile and water as mobile phase at a ratio of 70:30 %v/v with a flow rate of 1mL/min and wavelength at 296nm respectively. The retention time of Favipiravir and Rivaroxaban were found to be 3.110 and 4.287 mins. The developed method was validated according to ICH Q2 (R1) guidelines over the concentration range of 5-25 μg /mL. The LOD and LOQ were found to be 2.17 μg /mL and 6.58 μg /mL. The method was found to be linear, specific, accurate, precise and robust. The developed method was used for determination of Favipiravir in pharmaceutical dosage forms. © 2022 University of Stockholm. All rights reserved.

Perspectives for licensing vaccines in Mexico.

Vaccine products represent one of the most successful public health measure to this day. This has been reflected during the current COVID-19 pandemic where more than 4.87 billion people have received at least one vaccine dose. In Latin America, Mexico occupies the second position in terms of the number of vaccinated people with 83.97 million people receiving at least a single dose. As in other countries, regulatory approval in Mexico is one of the key aspects that influences the public access to vaccines. This creates an active interplay between regulatory authorities establishing a regulatory framework to assure the quality, safety and efficacy of the vaccines, and applicants fulfilling this information. Mexico is a member of the International Council for Harmonisation (ICH) and it has adopted the Common Technical Document (CTD) for providing this information. This is particularly useful for vaccines developed abroad where it is expected to speed the evaluation of the new product. The Secretariat of Health of Mexico (SALUD) has published guidelines and laws or regulations related to GMP, labeling, stability, clinical trials, biocomparability and pharmacovigilance for drug products including vaccines which are classified as biological products. SALUD has also established guidelines and international homologating agreements to facilitate the application process for vaccine approval. Nevertheless, technical and scientific information and administrative processes for vaccine approval might be relatively concealed. Therefore, we aim to enable researchers and manufacturers in Mexico and overseas to better understand these requirements. To our knowledge, this is the most up-to-date and comprehensive attempt to present this information, also including information for COVID-19 vaccines. Here we describe the current requirements and processes by COFEPRIS, the national regulatory agency, for vaccine licensing and for emergency use authorization for COVID-19 vaccines in Mexico.

Severe Intractable Headache as a Presentation of COVID-19 in a 23-Year-Old.

Severe acute respiratory syndrome coronavirus type 2 is a novel betacoronavirus with a new genome sequence that causes coronavirus disease 2019 (COVID-19), which primarily affects the lungs, thus causing pneumonia which can progress to severe acute respiratory distress syndrome. New emerging cases of extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiac, renal, and/or central nervous system involvement. Although an ischemic stroke converting to a hemorrhagic stroke is more commonly seen, spontaneous intracranial hemorrhage (ICH) in hospitalized COVID-19 patients is on the rise. This case report describes a 23-year-old female who tested positive (via a polymerase chain reaction test) for COVID-19 and presented with new onset of severe intractable headache. The investigation suggested COVID-19 as the most probable cause of this patients' spontaneous ICH. This case emphasizes the importance of adding COVID-19 to the differential diagnosis of hemorrhagic cerebrovascular accidents in patients with a spontaneous ICH of unclear etiology and, in the process, performing COVID testing.

Development of HPTLC method for the simultaneous estimation of quercetin, curcumin, and ascorbic acid in herbal formulations

Antioxidants can scavenge free radicals in the human body and have been associated with a protective effect on the human body against a variety of diseases. As a part of normal cellular function, free radical production occurs continuously within the body at a cellular level. Excess-free radical production from endogenous or exogenous sources may result in a variety of diseases. Vitamins (A, C, and E), carotenoids, polyphenols, and flavonoids are some examples of common natural antioxidants. Among the different antioxidants quercetin, curcumin, and ascorbic acids have been extensively studied, and numerous reports on their antioxidant activity are available in the literature. Antioxidants are regarded as a key player in the current pandemic situation, and they play a key role as a preventive and controlling tool. There are a variety of herbal formulations and immune booster therapies available, many of which claim to contain various antioxidants and are effective against covid-19. Numerous herbal formulations and immune booster therapies are available and claimed to have different antioxidants and other constituents. In the present study simple, rapid, accurate, precise, and sensitive high-performance thin-layer chromatographic analytical method was developed for simultaneous estimation of quercetin, curcumin, and ascorbic acid. The developed method can effectively employ for different polyherbal formulations. The developed method was validated according to ICH guidelines. In the present study, an aluminum plate precoated with 60F 254 silica gel was used as a stationary phase whereas chloroform: ethyl acetate: formic acid (6:6:2.5 v/v/v) was used as a mobile phase. Chromatographic detection was performed with a Camag TLC scanner at 265 nm. The linearity range for the proposed method was found to be 500–1000 ng/band for all three analytes. The antioxidant potentiality of selected antioxidants was evaluated by an optimized UV visible spectroscopic-reducing power method. The reducing power method was optimized for the concentration and volume of reagent, incubation temperature, and time. The results of the study revealed that quercetin is having the best antioxidant potential compared to curcumin and ascorbic acid. [ FROM AUTHOR] Copyright of Journal of the Iranian Chemical Society is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Marking 2-Years of New Thinking in Clinical Trials: The Estimand Journey.

The ICH E9(R1) addendum on Estimands and Sensitivity Analyses in Clinical Trials has introduced a new estimand framework for the design, conduct, analysis, and interpretation of clinical trials. We share Pharmaceutical Industry experiences of implementing the estimand framework in the first two years since the final guidance became available with key lessons learned and highlight what else needs to be done to continue the journey in embedding the estimand framework in clinical trials. Emerging best practices and points to consider on strategies for implementing a new estimand thinking process are provided. Whilst much of the focus of implementing ICH E9(R1) to date has been on defining estimands, we highlight some of the important aspects relating to the choice of statistical analysis methods and sensitivity analyses to ensure estimands can be estimated robustly with minimal bias. In particular, we discuss the implications if complete follow-up is not possible when the treatment policy strategy is being used to handle intercurrent events. ICH E9(R1) was introduced just before the start of the COVID-19 pandemic, but a positive outcome from the pandemic has been an acceleration in the adoption of the estimand framework, including differentiating intercurrent events related or not related to the pandemic. In summary, much has been learned on the estimand journey and continued sharing of case studies will help to further advance the understanding and increase awareness across all clinical researchers of the estimand framework.

Covid-19 Pandemic’s Influence on Popular/Folk Culture and Tourism in Greece: Shaping the Future and Beyond

Popular/folk culture, mainly expressed through music and dance performances, was always very important for human societies. In addition to offering entertainment and being a tourist attraction, it can convey different messages according to the context, such as aesthetic/artistic, cultural, religious/spiritual and/or social aspects. Therefore, it is strongly linked to local identity and tourism, thus being an invaluable resource for local communities that needs to be preserved. Pandemics and their consequences pose a huge risk for this community asset, affecting not only the artists practicing it, but the entire associated culture and tourism industry. In this paper, we study how the recent covid-19 pandemic has affected the Greek popular/folk music scene and give insights on new ways and solutions, mainly based on modern information technologies, to mitigate these negative impacts. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.

DEVELOPMENT AND VALIDATION OF A NEW HPLC BIOANALYTICAL INTERNAL STANDARD METHOD FOR THE ANALYSIS OF REMDESIVIRIN HUMAN PLASMA

Remdesivir (RMDSVR) is a pro-drug of an ATP analog, with antiviral activity against RNA viruses. In 2016 RMDSVR is used in the treatment of Ebola and 2017 RMDSVR was tested against SARS-CoV-2. The HPLC analysis was performed on the Agilent 1100 series HPLC with Quaternary G1311 A pump, ChromosilC18 column (250 X 4.6 mm, 5μ) column, with a mixture of Acetonitrile, Methanol and 0.1% OPA in the ratio of 65:30:5 (v/v) as the mobile phase, at 0.8 mL/min flow rate and UV detection at 272 nm. Abacavir (ABVR) is considered an internal standard and the retention time was observed at 6.0 min and 9.1 min for RMDSVR and ABVR respectively. The calibration curve was obtained linearly in the concentration range of 10-70 ng/mL. the method was validated and all the validated parameters were within the acceptable limit confirms that the method is suitable for the analysis of RMDSVR in spiked human plasma. © 2021, Rasayan Journal of Chemistry, c/o Dr. Pratima Sharma. All rights reserved.

Neurosurgical Considerations Regarding Decompressive Craniectomy for Intracerebral Hemorrhage after SARS-CoV-2-Vaccination in Vaccine Induced Thrombotic Thrombocytopenia-VITT.

Given the ongoing global SARS-CoV-2-vaccination efforts, clinical awareness needs to be raised regarding the possibility of an increased incidence of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia in patients with intracerebral hemorrhage (ICH) secondary to cerebral sinus and vein thrombosis (CVT) requiring (emergency) neurosurgical treatment in the context of vaccine-induced immune thrombotic thrombocytopenia (VITT). Only recently, an association of vaccinations and cerebral sinus and vein thrombosis has been described. In a number of cases, neurosurgical treatment is warranted for these patients and special considerations are warranted when addressing the perioperative coagulation. We, herein, describe the past management of patients with VITT and established a literature-guided algorithm for the treatment of patients when addressing the impaired coagulation in these patients. Increasing insights addressing the pathophysiology of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia guide physicians in developing an interdisciplinary algorithm taking into account the special considerations of this disease.

Intracerebral Hemorrhage and SARS-CoV-2: Association or Causation.

BACKGROUND: Recent respiratory infection including SARS-CoV-2 is an independent risk factor for acute cerebrovascular disease. PURPOSE: There have been reports linking haemorrhagic strokes to SARS-CoV-2 infection during this pandemic, which lead us to evaluate if SARS-CoV-2 infection could be associated with increased risk of intracerebral haemorrhage (ICH). METHODS: A retrospective observational study evaluating all stroke cases admitted in our centre in the past one month. RESULTS: More than half (56%) had ICH, compared to 22% last year. Two patients with ICH were SARS-CoV-2 positive and they had no or mild respiratory symptoms and had higher occurrence of renal dysfunction. CONCLUSION: There could be possible association between ICH and SARS-CoV-2 infections. However, a prospective study with larger sample size is needed to elucidate the pathogenesis.

SARS coronavirus 2 and central nervous system manifestations: causation, relation, or coexistence? a case series study and literature review.

INTRODUCTION: Recently, weeks after the COVID-19 prevalence, there were reports of brain involvement and neurologic presentations in the COVID-19. CASE PRESENTATION: We present five cases of COVID-19 and cerebrovascular events. A 34-year-old woman with IVH and ischemic stroke. A 60-year-old man with multiple small hemorrhagic foci and mild IVH in the occipital horn. A 63-year-old woman with large left parietooccipital intracerebral hemorrhage (ICH) and IVH. A 56-year-old man with left hemispheric and midbrain ICH, lateral ventricular IVH, and hydrocephalus. A 85-year-old woman with right parietal hemorrhagic infarct. The coagulation profile was normal in all of them. The chest CT scan showed the typical ground-glass appearance of COVID-19. CONCLUSIONS: Recently, there were reports of brain involvement and neurologic presentations in the COVID-19. These reports and the present study necessitate the aimed and designed studies with emphasis on neurologic presentations in COVID-19 patients to illustrate the exact effects of coronavirus-2 on the central nervous system.

Intracranial Hemorrhage in a Patient With COVID-19: Possible Explanations and Considerations.

Some of the reported neurological manifestations of COVID-19 are encephalopathy, headache, ischemic, hemorrhagic stroke, Miller Fisher syndrome, cranial neuropathies, and Guillain-Barre syndrome. We report a case of a 75-year-old COVID-19 patient with life-threatening intracranial hemorrhage. The initial labs on admission showed D-dimer of 1.04 µg/mL, which increased to 3.74 µg/mL the next day, PT/INR of 13.7 seconds/1.2, aPTT of 22 seconds, fibrinogen of 386 mg/dL, WBC of 9.71 K/µL, Hgb of 14.1 g/dL, platelet of 315 x 103/µL, LDH of 965 U/L, and CRP of 35.2 mg/dL. In addition to aspirin and Plavix (clopidogrel), the patient was started on a therapeutic dose of enoxaparin due to elevated D-dimer. A few days later, the patient had a change in the neurological examination. The CT of the head without contrast revealed a left-sided acute subdural hematoma, causing left to right midline shift, a large left temporal intraparenchymal, and subarachnoid hemorrhage with transtentorial herniation, leading to death. This case illustrates a combination of factors including hypertension, triple therapy (aspirin, clopidogrel, and enoxaparin), and underlying coagulopathy due to COVID-19, which contributed to the life-threatening intracranial hemorrhage in this patient. Therefore, this raises a concern about the safety of starting these patients preemptively on a therapeutic dose of anticoagulation.

Not a String, not a Tangle, not an Aneurysm : Emerging Pattern of Large Parenchymal Bleeding in Younger Patients Associated with Abnormal Vessels on Imaging.

PURPOSE: Intracerebral hemorrhage (ICH) accounts for up to 20% of all strokes, and there is a high rate of associated morbidity and mortality. Computed tomography (CT) findings, such as a spot sign have been shown to be an independent predictor of poor outcome. We have recently encountered a succession of ICH patients who presented with a peculiar imaging finding, which we term the spot on a string sign. This is a rare imaging finding, and interestingly, all these patients presented to our institution over the last few weeks. METHODS: This was a single high-volume center series of patients who presented to our institution between 1 April and 21 May 2020. All patients underwent initial non-contrast CT brain and subsequent CT angiography (CTA). We also present laboratory and clinical data. Our primary measure was the presence of the spot on a string sign on the CTA. We also report the clinical course of these patients. RESULTS: In this study seven large-volume ICH patients with this imaging sign were identified, with a median age of 48 years (range 30-68 years). All had tested negative for coronavirus disease 19 (COVID-19). CONCLUSION: We have described an unusual imaging finding in a cohort of younger patients with large-volume ICH, all of whom presented in a 2-month period to a high-volume neurovascular unit. The cause of these ICH presentations and associated imaging findings are unclear, but we encourage other clinicians to be aware of and vigilant for this rare phenomenon, especially in younger patients with such a bleeding pattern.