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BackgroundThe presence of antiphospholipid antibodies (aPL) has been observed in patients with COVID-19 (1,2), suggesting that they may be associated with deep vein thrombosis, pulmonary embolism, or stroke in severe cases (3). Antiphospholipid syndrome (APS) is a systemic autoimmune disorder and the most common form of acquired thrombophilia globally. At least one clinical criterion, vascular thrombosis (arterial, venous or microthrombosis) or pregnancy morbidity and at least one laboratory criterion- positive aPL two times at least 12 weeks apart: lupus anticoagulant (LA), anticardiolipin (aCL), anti-β2-glycoprotein 1 (anti-β2GPI) antibody, have to be met for international APS classification criteria(4). Several reports also associate anti-phosphatidylserine/prothrombin antibodies (aPS/PT) with APS.ObjectivesTo combine clinical data on arterial/venous thrombosis and pregnancy complications before and during hospitalisation with aPL laboratory findings at 4 time points (hospital admission, worsening of COVID-19, hospital discharge, and follow-up) in patients with the most severe forms of COVID-19 infection.MethodsPatients with COVID-19 pneumonia were consequetively enrolled, as they were admitted to the General hospital Pancevo. Exclusion criteria were previous diagnosis of inflammatory rheumatic disease and diagnosis of APS. Clinical data were obtained from the medical records. Laboratory results, including LA, aCL, anti-β2GPI, and aPS/PT antibodies were taken at hospital admission, worsening (defined as cytokine storm, connection of the patient to the respirator, use of the anti-IL-6 drug- Tocilizumab), at hospital discharge and at 3-months follow-up and sent to University Medical Centre Ljubljana, Slovenia for analysis. Statistics was performed by using SPSS 21.Results111 patients with COVID-19 pneumonia were recruited;7 patients died during hospitalisation (none were aPL-positive on admission and at the time of worsening), 3 due to pulmonary artery embolism. All patients were treated according to a predefined protocol which included antibiotics, corticosteroids, anticoagulation therapy and specific comorbidity drugs;patients with hypoxia were supported with oxygen. During hospitalisation, pulmonary artery thrombosis occurred in 5 patients, one was aPL-positive at all time points (was diagnosed with APS), others were negative. In addition, 9/101 patients had a history of thrombosis (5 arterial thrombosis (coronary and cerebral arteries), none of whom was aPL-positive on admission and at follow-up, and 4 venous thrombosis, one of which was aPL-positive at all time points and received an APS diagnosis). Among 9/101 patients with a history of thrombosis, 55.6% were transiently positive at the time of discharge, compared to patients without prior thrombosis, in whom 26.1% were transiently positive at the hospital release (p=0.074). Two patients had a history of pregnancy complications (both had miscarriage after 10th week of gestation), but did not have aPL positivity at any time point.ConclusionAlthough aPL was expected to be associated with vascular disease in the most severe forms of COVID-19, all patients that have died in our cohort were aPL negative. At hospital discharge, 56% of patients with a history of arterial or venous thrombosis had positive aPL that became negative at the 3-months follow-up (were transienlty positive), which should be considered when prescribing therapy after hospitalisation.References[1]Trahtemberg U, Rottapel R, Dos Santos CC, et al. Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients. Annals of the Rheumatic Diseases 2021;80:1236-1240.[2]Stelzer M, Henes J, Saur S. The Role of Antiphospholipid Antibodies in COVID-19. Curr Rheumatol Rep. 2021;23(9):72-4.[3]Xie Y, Wang X, Yang P, Zhang S. COVID-19 complicated by acute pulmonary embolism. Radiology: Cardiothoracic Imaging 2020: 2: e200067.[4]Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, et al. J.Thromb.Haemost. 2006;4: 295-306.Acknowledgements:NIL.Disclosure of nterestsNone Declared.
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Objectives: The aim of this study was to assess Jordanian physicians' awareness about venous thromboembolism (VTE) risk among COVID-19 patients and its treatment protocol. Method(s): This was a cross-sectional-based survey that was conducted in Jordan in 2020. During the study period, a convenience sample of physicians working in various Jordanian hospitals were invited to participate in this study. Physicians' knowledge was evaluated and physicians gained one point for each correct answer. Then, a knowledge score out of 23 was calculated for each. Key Findings: In this study, 102 physicians were recruited. Results from this study showed that most of the physicians realize that all COVID-19 patients need VTE risk assessment (n = 69, 67.6%). Regarding VTE prophylaxis, the majority of physicians (n = 91, 89.2%) agreed that low molecular weight heparin (LMWH) is the best prophylactic option for mild-moderate COVID-19 patients with high VTE risk. Regarding severe/critically ill COVID-19 patients, 75.5% of physicians (n = 77) recognized that LMWH is the correct prophylactic option in this case, while 80.4% of them (n = 82) knew that mechanical prevention is the preferred prophylactic option for severe/critically ill COVID-19 patients with high bleeding risk. Moreover, 77.5% of physicians (n = 79) knew that LMWH is the treatment of choice for COVID-19 patients diagnosed with VTE. Finally, linear regression analysis showed that consultants had an overall higher knowledge score about VTE prevention and treatment in COVID-19 patients compared with residents (P = 0.009). Conclusion(s): All physicians knew about VTE risk factors for COVID-19 patients. However, consultants showed better awareness of VTE prophylaxis and treatment compared with residents. We recommend educational workshops be conducted to enhance physicians' knowledge and awareness about VTE thromboprophylaxis and management in COVID-19 patients.Copyright © 2022 The Author(s). Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved.
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Introduction: The COVID-19 pandemic has required clinical teams to function with an unprecedented amount of uncertainty, balancing complex risks and benefits in a highly fluid environment. This is especially the case when considering the delivery of a pregnant woman critically unwell with COVID-19. This is one maternal critical care team's reflections on establishing best practice and a shared mental model when undertaking a Caesarean section in critically unwell patients with COVID-19. Objective(s): We describe our experience of balancing the risks and streamlining the process of this high-risk intervention. Method(s): We used our standard clinical governance forums across four specialties (Obstetrics, Intensive care, Anaesthetics and Neonatology) to identify key challenges and learning points. We developed a working group to combine our learning and develop a shared mental model across the involved teams. Result(s): 1. The decision to deliver must be multidisciplinary involving Obstetrics, Intensive care, Anaesthetics, Neonatology and the patient according to their capacity to participate. The existing structure of twice daily ITU ward rounds could be leveraged as a 'pause' moment to consider the need for imminent delivery and review the risk-benefit balance of continued enhanced pharmacological thromboprophylaxis. 2. We identified a range of scenarios that our teams might be exposed to: 3. Perimortem Caesarean section 4. Critically unwell - unsafe to move to theatre 5. Critically unwell - safe to move to theatre 6. Recreating an obstetric theatre in the ICU Advantages Avoids moving a critically unstable patient, although our experience is increasing moving patients for ECMO. Some forms of maximal non-invasive therapy such as High Flow Nasal Oxygen may require interruption to move to theatre with resultant risk of harm or be difficult to continue in transport mode through a bulky ICU ventilator e.g. CPAP Disadvantages Significant logistics and coordination burden: multiple items of specialist equipment needing to be brought to the ICU. Human factors burden: performing a caesarean section in an unfamiliar environment is a significant increase in cognitive load for participating teams. Environmental factors: ICU side rooms may offer limited space vs the need to control the space if performed on an open unit. Delivering a Neonate into a COVID bubble. Conclusion(s): Developing a shared mental model across the key teams involved in delivering an emergency caesarean section in this cohort of critically unwell patients has enabled our group to own a common understanding of the key decisions and risks involved. We recommend a patient centred MDT decision making model, with a structure for regular reassessment by senior members of the teams involved. In most circumstances the human factors and logistical burden of recreating an operating theatre in the ICU outweighs the risk of transport to theatre. Pre-defined checklists and action cards mitigate the cognitive and logistical burden when multiple teams do perform an operative delivery in ICU. Action cards highlight key aspects of routine obstetric care to be replicated in the ICU environment.
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Objectives: Cases of fulminant myocarditis after mRNA COVID-19 vaccination have been reported. The most severe may need venoarterial extracorporeal membrane oxygenation (V-A ECMO) support. Here we report two cases successfully rescued with V-A ECMO. Method(s): We included all the cases supported with V-A ECMO for refractory cardiogenic shock due to myocarditis secondary to a mRNA SARS-COV2 vaccine in the high-volume adult ECMO Program in Vall Hebron University Hospital since January 2020. Result(s): We identified two cases (table). One of them was admitted for out-of-hospital cardiac arrest. In both, a peripheral V-A ECMO was implanted in the cath lab. An intra-aortic balloon pump was needed in one case for left ventricle unloading. Support could be successfully withdrawn in a mean of five days. No major bleeding or thrombosis complications occurred. Definite microscopic diagnosis could be reached in one case (Image, 3). Treatment was the same, using 1000mg of methylprednisolone/day for 3 days. A cardiac magnetic resonance 10 days after admission showed a significant improvement in systolic function and diffuse oedema and subepicardial contrast intake in different segments (Image, 1-2). Both patients were discharged fully recovered. Conclusion(s): V-A ECMO should be established in cases of COVID-19 vaccine-associated myocarditis with refractory cardiogenic shock during the acute phase. (Table Presented).
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BackgroundConsideration is needed when using Janus kinase (JAK) inhibitors to treat RA in pts aged ≥65 years or those with cardiovascular (CV) risk factors. The JAK1 preferential inhibitor FIL was generally well tolerated in clinical trials[1];safety has not been determined in a real-world setting.ObjectivesTo report baseline characteristics and up to 6-month safety data from the first 480 pts treated with FIL in the FILOSOPHY study (NCT04871919), and in two mutually exclusive subgroups based on age and CV risk.MethodsFILOSOPHY is an ongoing, phase 4, non-interventional, European study of pts with RA who have been prescribed FIL for the first time and in accordance with the product label in daily practice. Baseline characteristics and the incidence of select adverse events (AEs) are assessed in pts aged ≥65 years and/or with ≥1 CV risk factor (Table 1), and in those aged <65 years with no CV risk factors.ResultsAs of the end of June 2022, 480 pts had been treated: 441 received FIL 200 mg and 39 received FIL 100 mg. Of the 480 pts, 148 (30.8%) were aged ≥65 years;332 (69.2%) were aged <65 years. In total, 86 (17.9%) were former smokers, 81 (16.9%) were current smokers and 203 (42.3%) were non-smokers (data were missing for 110 pts [22.9%]). In addition to smoking, the most frequent CV risk factors included a history of hypertension (32.3%), a history of dyslipidemia (10.2%) and a family history of myocardial infarction (8.5%;Table 1).23 pts (4.8%) discontinued treatment due to AEs. Of the 354 pts aged ≥65 years or with ≥1 CV risk factor, infections affected 64 pts (18.1%), 34 (9.6%) had COVID-19, 2 (0.6%) had herpes zoster, and cardiac disorders (angina pectoris, atrial fibrillation, palpitations and tachycardia) affected 5 pts (1.4%);no cases of malignancies were observed. In the subgroup aged <65 years and with no CV risk factors (n=126), infections occurred in 18 pts (14.3%) (9 [7.1%] had COVID-19;3 [2.4%] had herpes zoster) and malignancies (myeloproliferative neoplasm) affected 1 pt (0.8%);no pts had cardiac disorders. There were no cases of deep vein thrombosis or pulmonary embolism in either subgroup.ConclusionIn this interim analysis of FILOSOPHY, no unexpected safety signals emerged at up to 6 months. Although infections and cardiac disorders affected a numerically greater proportion of pts aged ≥65 years or with ≥1 CV risk vs those aged <65 years with no CV risk, longer follow-up on a broader cohort is necessary to further characterize the safety of FIL in different groups of pts with RA.Reference[1]Winthrop K, et al. Ann Rheum Dis 2022;81:184–92Table 1.Baseline characteristics and CV risk factorsBaseline demographics/CV risk factorsAll FIL-treated pts (N=480)≥65 years or with ≥1 CV risk factor (n=354)<65 years and no CV risk factor (n=126)*Female sex, n (%)351 (73.1)252 (71.2)99 (78.6)Age, years, mean (SD)57.6 (11.5)60.4 (10.8)49.6 (9.6)Rheumatoid factor positive, n (%)†228 (47.5)167 (47.2)61 (48.4)Anti-citrullinated protein antibody positive, n (%)‡243 (50.6)176 (49.7)67 (53. 2)Body mass index, kg/m2, mean (SD)27.6 (5.7) n=43728.0 (5.4) n=33126.3 (6.4) n=106RA disease duration, years, mean (SD)10.4 (9.4) n=47810.5 (9.5) n=35310.0 (8.8) n=125Tender joint count 28, mean (SD)8.6 (6.9) n=4578.7 (7.1) n=3408.3 (6.3) n=117Swollen joint count 28, mean (SD)5.6 (5.2) n=4525.7 (5.4) n=3365.4 (4.4) n=116Former smoker, n (%)§86 (17.9)86 (24.3)0Current smoker, n (%)§81 (16.9)81 (22.9)0Non-smoker, n (%)§203 (42.3)130 (36.7)73 (57.9)Family history of myocardial infarction, n (%)41 (8.5)41 (11.6)0Medical history of: n (%) CV disease33 (6.9)33 (9.3)0 Diabetes35 (7.3)35 (9.9)0 Dyslipidemia49 (10.2)49 (13.8)0 Hypertension155 (32.3)155 (43.8)0 Ischemic CNS vascular disorders11 (2.3)11 (3.1)0 Peripheral vascular disease17 (3.5)17 (4.8)0*Includes 53 pts with missing smoking status data who were aged <65 years with no other CV risk factors.†Missing/unknown in 154 pts;‡Missing in 153 pts;§Smoking status data missing in 110 pts (22.9%).AcknowledgementsWe thank the physicia s and patients who participated in this study. The study was funded by Galapagos NV, Mechelen, Belgium. Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsPatrick Verschueren Speakers bureau: AbbVie, Eli Lilly, Galapagos, Roularta, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Sidekick Health, Grant/research support from: Galapagos, Pfizer, Jérôme Avouac Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sandoz, Sanofi, Consultant of: AbbVie, Fresenius Kabi, Galapagos, Sanofi, Grant/research support from: BMS, Fresenius Kabi, Novartis, Pfizer, Karen Bevers Grant/research support from: Galapagos, Susana Romero-Yuste Speakers bureau: AbbVie, Biogen, BMS, Lilly, Pfizer, Consultant of: Sanofi, Lilly, Grant/research support from: Lilly, MSD, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Thomas Debray Consultant of: Biogen, Galapagos, Gilead, Francesco De Leonardis Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Grant/research support from: AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax, Pfizer, Monia Zignani Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer, Sanofi, Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer, Sanofi.
ABSTRACT
COVID-19 infection is characterized by different clinical presentations. The thrombotic complications play the leading role in COVID-19 infection. SARS-CoV-2 virus can activate hemostasis at different levels: pulmonary tissue damage with subsequent plasma coagulation activation;local endothelial dysfunction and platelet activation during the course of the disease. Routine use of the anticoagulation treatment seems reasonable in hospitalized patients with COVID-19.Copyright © Creative Cardiology 2021.
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BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.
ABSTRACT
The cavernous sinus is one of the dural venous sinuses which plays an important role in venous outflow from the brain and eye sockets and in the regulation of intracranial circulation. We report a case of septic cavernous sinus thrombosis in a female patient with COVID-19. The disease often results in alterations of blood rheology, thrombosis in different organs, and septic complications. This article aims to raise awareness of healthcare professionals about the characteristics of COVID-19 that might cause septic cavernous sinus thrombosis in patients with severe comorbidities. Laboratory testing revealed severe comorbidities, including diabetes mellitus and liver cirrhosis caused by hepatitis C. They manifested with an impaired protein production in the liver and coagulation disorders. Systemic effects of SARS-CoV-2 on the vascular endothelium aggravated preexisting coagulation disorders and led to hemorrhage into retrobulbar tissue and clinical signs of septic cavernous sinus thrombosis, including swelling of the eyelids, bilateral exophthalmos, and ophthalmoplegia, followed by necrosis of the facial skin.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Problem: Several large studies have demonstrated that COVID-19 pregnant individuals are at a significant risk for severe disease and adverse pregnancy outcomes. The mechanisms underlying these phenomena remain to be elucidated and are the focus of our project. Although fetal and placental infection is rare, placental abnormalities and adverse pregnancy outcomes associated with placental dysfunction in COVID-19 cases have been widely reported. In particular, placental thrombosis and lesions consistent with maternal vascular malperfusion (MVM) of the placenta are common in individuals with COVID-19. Since thrombotic complications have been associated with COVID-19, it is not surprising that pregnant individuals with COVID- 19 are at risk for placental thrombosis. Method of Study: Placentas were evaluated histologically. Extracellular vesicles were isolated by serial centrifugation. Result(s): Adverse pregnancy outcomes associated with these placental lesions, including hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), small for gestational age (SGA, birthweight < 10th percentile for gestational age), and preterm birth (PTB, < 37 weeks) are significantly increased among pregnant individuals with COVID-19. Placental infection with SARSCoV- 2 is uncommon, but multiple inflammatory and metabolic factors are likely to affect the placenta, including circulating extracellular vesicles (EVs) derived from various organs that have been associated with COVID-19 pathology and disease severity.We have analyzed over 500 placentas from COVID-19 pregnancies and found marked changes in placental morphology, characterized by abnormal maternal and fetal vessels, intervillous thrombi, and fibrin deposition, even in the face of mild or asymptomatic disease. We detected increased levels of small EVs in maternal serum from COVID-19 cases compared to controls and increased levels of mitochondrial DNA in EVs from COVID-19 cases. In in vitro experiments, we found increased oxidative stress in uterine endothelial cells and primary trophoblasts. Syncytialization of trophoblast cells following exposure to EVs from pregnant COVID-19 patients was markedly reduced. RNAseq of trophoblast cells exposed to EVs from pregnant COVID-19 patients revealed disruption of multiple pathways related to mitochondria function, oxidative stress, coagulation defects, and inflammation. Timing of infection during pregnancy (first, second, and third trimester) altered EV size distribution, cargo content, and functional consequences of trophoblast EV exposure. Conclusion(s): Our studies show that COVID-19 infection during pregnancy has profound effects on placenta morphology and function. It remains to be determined what the long-term consequences are on the offspring.
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AIM Analysis of the outcomes of endovascular stent thrombectomy in patients with acute arterial thrombosis of the lower extremities on the background of COVID-19. MATERIAL AND METHODS This retrospective study for the period from January 1, 2020 to March 1, 2022 included 34 patients with acute lower limb ischemia who were diagnosed with the novel coronavirus infection SARS-COV-2. Endovascular stent thrombectomy was performed according to the standard technique using a Destination 8F guiding sheath (Terumo), an Advantage 0.014" guidewire fTerumo), and a Casper stent (Microvention, Terumo) as a stent retriever. In case of fragmentation of thrombotic masses in the guide sheath, manual aspiration of thrombi was performed using a standard 50, 0 ml syringe. Self-expanding nitinol stents were implanted in 11 clinical cases. RESULTS Intraoperative bleeding from the puncture site of the artery developed in 14.7% of cases, which required additional manipulation to achieve hemostasis. Every tenth (11.8%) patient developed myocardial infarction, in 2.9% of cases - ischemic stroke. In the hospital postoperative period during the first hours after surgery, 26.5% of patients developed rethrombosis which required re-intervention. In 8.8% of cases, retrombectomy was unsuccessful, and limb amputation was performed. A fatal outcome occurred in 67.6% of cases, which was due to an increase in multiple organ failure and the development of sepsis. CONCLUSION Endovascular stent thrombectomy is characterized by a low risk of rethrombosis and amputation in the context of COVID-19. © 2023 Sklifosovsky Research Institute for Emergency Medicine. All rights reserved.
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The coronavirus SARS-CoV-2 was detected in isolates of pneumonia patients in January 2020. The virus cannot multiply extracellularly but requires access to the cells of a host organism. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor, to which it docks with its spikes. ACE2 belongs to the renin angiotensin system (RAS), whose inhibitors have been used for years against high blood pressure. Renin is an endopeptidase that is predominantly formed in the juxtaglomerular apparatus of the kidney and cleaves the decapeptide angiotensin I (Ang I) from angiotensinogen. Through the angiotensin-converting enzyme (ACE), another 2 C-terminal amino acids are removed from Ang I, so that finally the active octapeptide angiotensin II (Ang II) is formed. The biological effect of Ang II via the angiotensin II receptor subtype 1 (AT1-R) consists of vasoconstriction, fibrosis, proliferation, inflammation, and thrombosis formation. ACE2 is a peptidase that is a homolog of ACE. ACE2 is predominantly expressed by pulmonary alveolar epithelial cells in humans and has been detected in arterial and venous endothelial cells. In contrast to the dicarboxy-peptidase ACE, ACE2 is a monocarboxypeptidase that cleaves only one amino acid from the C-terminal end of the peptides. ACE2 can hydrolyze the nonapeptide Ang-(1-9) from the decapeptide Ang I and the heptapeptide Ang-(1-7) from the octapeptide Ang II. Ang-(1-7) acts predominantly antagonistically (vasodilatory, anti-fibrotic, anti-proliferative, anti-inflammatory, anti-thrombogenetically) via the G protein-coupled Mas receptor to the AT1-R-mediated effects of Ang II. In the pathogenesis of COVID-19 infection, it is therefore assumed that there is an imbalance due to overstimulation of the AT1 receptor in conjunction with a weakening of the biological effects of the Mas receptor.Copyright © 2022 Dustri-Verlag Dr. K. Feistle.
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Introduction: Lactate is a common biomarker used in multiple surgical subspecialties. No one has previously measured coronary sinus lactate reduction as a result of drug administration. We therefore tested the hypothesis that IV geranylgeranylacetone (GGA), a novel agent used to treat human peptic ulcer disease, would result in reduced coronary sinus lactate production. Method(s): New Zealand adult rabbits (N=5 each) received IV 50 mg/kg GGA 24 hours before intervention, which consisted of Langendorff perfusion, 30 min of global normothermic cardioplegic arrest, followed by reperfusion. Myocardial release of lactate was measured. HSP70 was quantified by western blot. Differences between GGA+ and GGA- groups pre- and post-ischemia were analyzed by unpaired t-tests. Result(s): In the GGA- group, lactate increased immediately at one minute and throughout the duration of reperfusion. However, in GGA+ hearts, lactate also increased at one min of reperfusion but then continued to decrease throughout the remainder of reperfusion. Lactate was significantly less at every time point of reperfusion in GGA+. Integrated lactate area was significantly less throughout reperfusion in GGA+. Conclusion(s): GGA induced caused a marked decrease in coronary sinus lactate release during reperfusion. Simultaneously intravenously GGA induced myocardial HSP70i and reduced myocardial damage. Further study of the effects and mechanisms involved is indicated. Application to other organs is useful as well. Heat shock proteins (HSPS) are also antithrombotic. Given the thrombotic nature of Covid, induction of HSPS may be beneficial in decreasing the cardiac thoracic and vascular complications of Covid and allowing faster resolution of this disease during to vascular complications.
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Background: People with chronic diseases of the immune system, such as multiple sclerosis (MS), are at risk for Covid-19 disease. However, more research is needed with long-term follow-up. The aim of the study was to follow up people with MS (PwMS) for up to three months after AstraZeneca vaccination for the recurrence of MS and Covid-19 infection. Method(s): This study was a case study (descriptive-analytical) of follow-up type. The study population was PwMS over 18 years of age in Kermanshah province who received both doses of the AstraZeneca vaccine. This study was conducted from August to November 2021. Sampling was done with existing methods based on the National MS Registry of Iran (NMSRI). Demographic information of patients was extracted from NMSRI. A researcher-made form was used to collect information by telephone three months after vaccination about clinical characteristics, Covid-19 infection, and recurrence of MS. Data were analyzed using SPSS-25 software. Result(s): Study participants were 40 MS patients with a mean (SD) age of 39.27 (8.8) years, including 32 (80.0%) women. A mean of 9.39 (4.6) years had passed since The patients were diagnosed with MS, and 29 (76.4%) had RR type MS. Four patients (10%) relapsed between the second dose and three months later, of whom two (50%) had sensory symptoms, one (25%) had optic nerve involvement, and one (25%) had motor symptoms and pyramidal pathway involvement. The symptoms of Covid-19 were mild in three patients (10%), while severe symptoms developed in one patient (10%) who received rituximab. Among the patients, no cases of thrombosis were observed. Infusion therapy, a leg fracture, and kidney stones were the only hospitalized cases. Conclusion(s): Covid-19 and MS relapse prevalence did not differ significantly in the three months before and after vaccination. There is a need for further studies with a longer follow-up period.Copyright © 2022 Razazian et al. Published by Tehran University of Medical Sciences.
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Coronavirus disease 2019 (COVID-19) is an emerging infectious disease. Bilateral pneumonia, acute respiratory failure, systemic inflammation, endothelial dysfunction, and coagulation activation have been described as key features of severe COVID-19. Fibrinogen and D-dimer are typically increased. Moreover, the risk for venous thromboembolism is markedly increased, especially in patients in the intensive care unit, often despite prophylactic-dose anticoagulation. Pulmonary microvascular thrombosis has also been described and the risk for arterial thrombotic diseases also appears to be increased. Bleeding is less common than thrombosis but can occur. Evaluation for venous thromboembolism may be challenging because symptoms of pulmonary embolism overlap with COVID-19, and imaging studies may not be feasible in all cases. All inpatients should receive thromboprophylaxis unless contraindicated. In hospitalized patients with COVID-19, prophylactic dosing rather than more intensive (intermediate or therapeutic) dosing are suggested. On the other hand, therapeutic dose of anticoagulation is always appropriate to treat deep venous thrombosis or pulmonary embolism, unless contraindicated. This article reviews evaluation and management of coagulation abnormalities in individuals with COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.
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Early identification of PNH, a rare life-threatening disease is essential to ensure appropriate management via the UK PNH service. Since testing for PNH is expensive (75.97 per test), we set out to assess the suitability of PNH requests against guidelines with the aim to feedback to colleagues and reduce unnecessary testing. To determine whether PNH requests at UHNM were in line with criteria in British Society for Haematology (BSH) guidelines. All patients over 18 years of age who had PNH testing for the first time and those who had repeat testing for monitoring between 01/04/2019 and 31/03/2020 were included. Patients were selected from electronic records of PNH sample receipt to laboratories. Hospital records were reviewed for clinical details and investigation Results. 82 requests including 79 individual patients were audited. 57% were male and 43% were female. Median age was 56 years. 97.6% of PNH tests were requested by a haematologist whilst only 2.5% requests were done by non-haematology clinicians. 52.4% requests were in keeping with BSH recommendations, whilst 47.6% tests did not meet criteria for testing. All patients tested outside of guideline recommendations were negative. Of the reasonable requests, only 23.3% (10) were positive. Of the PNH positive patients, 8 patients were known to have a PNH clone with aplastic anaemia;one patient had a hypoplastic bone marrow and a known PNH clone whilst only one patient with cytopenia had a new positivity for PNH. The frequency monitoring for aplastic anaemia and a PNH clone was 100% concordant with BSH recommendations. With appropriate testing, only one new patient was identified. Our audit has limitations. We have not been able to assess whether any patients outside of those monitored for PNH in aplastic anaemia have been overlooked for testing. Also, the time period includes the COVID-19 pandemic so our findings may not reflect usual practice. New BSH guidelines for thrombophilia testing were published in 2022 and recommend testing for PNH in patients with thrombosis at unusual sites and abnormal haematological parameters and for patients with arterial thrombosis and abnormal blood parameters. This will likely limit excess tests although the sensitivity and specificity of such an approach has not been formally evaluated. In a finite health system, it is our responsibility to rationalise investigations. The cost of a year's testing was 6229.54 and that of inappropriate testing was 2962.83. As a department, we could, therefore, save 2962.83.
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Objective. To assess the impact of obesity and overweight on the course of COVID-19. Patients and methods. This prospective study included 218 patients with SARS-CoV-2 infection aged 18 to 94 years hospitalized between June 2020 and March 2021. We evaluated their clinical and laboratory parameters and their association with body weight. All patients were divided into 3 groups depending on their body mass index (BMI). Group 1 included 81 patients with grade 1-3 obesity (BMI >=30);group 2 comprised 71 overweight patients (BMI >=25 and <30);group 3 included 66 patients with normal body weight (BMI >=18.5 and <25). We analyzed clinical symptoms (including shortness of breath, fever, myalgia, headache, fatigue, changes in the oropharynx, cough, rhinorrhea, sore throat, anosmia, and diarrhea), prevalence of concomitant disorders and complications, findings of computed tomography and pulse oximetry, and findings of instrumental and laboratory examinations (complete blood count, urine test, electrocardiography, echo cardiography, biochemical assays, including C-reactive protein, procalcitonin, alanine aminotransferase, aspartate aminotransferase, lactate, lactate dehydrogenase, activated partial thromboplastin time, prothrombin index, D-dimer, ferritin). Data analysis was performed using the Statistica 6.0 software. Results. We found that overweight and obese patients were more likely to have the main COVID-19 symptoms and comorbidities than those with normal weight. Overweight and obese patients also required respiratory support more frequently than patients with normal weight. Obese and overweight patients had more severe systemic inflammation (CRP, procalcitonin), cytolysis (ALT, AST), and thrombosis (D-dimer). Conclusion. Our findings suggest that obesity and overweight are the factors associated with a more severe SARS-CoV-2 infection, which should be considered when planning their treatment and developing resource strategies.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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The pandemic caused by COVID-19 has led to radical lifestyle changes worldwide, particularly in the Republic of Bulgaria, and was a factor for global changes in economics, politics, healthcare and daily life. Aim(s): The aim of the study was to analyze the public attitudes, awareness and fears related to the COVID-19 disease in the Republic of Bulgaria. Material(s) and Method(s): The survey was conducted between August 1st, 2022 and September 1st, 2022 via an anonymous questionnaire consisting of 24 closed questions. A total of 1861 people, aged 18-69 years and older, took part in the survey after being selected randomly. The data were statistically processed via MS Excel. Result(s): The main source of information to the respondents on issues related to COVID-19 was the Internet (29,8%), followed by TV (26%) and the specialized website (Single information portal) - 15,9%. More than one-third (35,1%) of the respondents was afraid of getting infected and an equal share of participants reported that they have been infected with COVID-19. More than half of the respondents (52,5%) adhered to all the provisions of the governmental bodies related to limiting the COVID-19 pandemic. The most frequent symptom of post- COVID-19 syndrome was being easily fatigued (26,7%), followed by shortness of breath (13,4%) and persistent cough (11,6%). Conclusion(s): The survey could be useful in understanding what were the public attitudes, awareness and fears related to the COVID-19 disease in the Republic of Bulgaria during the pandemic.Copyright © 2023 D. Penchev et al., published by Sciendo.
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Objective This S2k guideline of the German Society for Gynecology and Obstetrics (DGGG) and the German Society of Perinatal Medicine (DGPM) contains consensus-based recommendations for the care and treatment of pregnant women, parturient women, women who have recently given birth, and breastfeeding women with SARS-CoV-2 infection and their newborn infants. The aim of the guideline is to provide recommendations for action in the time of the COVID-19 pandemic for professionals caring for the above-listed groups of people. Methods The PICO format was used to develop specific questions. A systematic targeted search of the literature was carried out using PubMed, and previously formulated statements and recommendations issued by the DGGG and the DGPM were used to summarize the evidence. This guideline also drew on research data from the CRONOS registry. As the data basis was insufficient for a purely evidence-based guideline, the guideline was compiled using an S2k-level consensus-based process. After summarizing and presenting the available data, the guideline authors drafted recommendations in response to the formulated PICO questions, which were then discussed and voted on. Recommendations Recommendations on hygiene measures, prevention measures and care during pregnancy, delivery, the puerperium and while breastfeeding were prepared. They also included aspects relating to the monitoring of mother and child during and after infection with COVID-19, indications for thrombosis prophylaxis, caring for women with COVID-19 while they are giving birth, the presence of birth companions, postnatal care, and testing and monitoring the neonate during rooming-in or on the pediatric ward.Copyright © 2023. Thieme. All rights reserved.
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Objective: Covid-19 is a highly infectious viral disease, and our understanding of the impact of this virus on the nervous system is limited. Therefore, we aimed to do a systematic analysis of the neurological manifestations. Methods: We retrospectively studied the clinical, laboratory, and radiological findings of patients with major neurological syndromes (MNS) in Covid-19 over 6 months. Results: We had 39 patients with major neurological syndromes (MNS). The most common MNS was cerebrovascular disease (CVD) (61.53%), in which ischemic stroke (83.33%), cortical sinus thrombosis (12.50%), and haemorrhagic stroke (4.16%) were seen. Among ischemic stroke patients, 50% had a large vessel occlusion, and 66.66% of patients with CVD had a significant residual disability. Cranial neuropathy (15.38%), GBS (10.26%), encephalitis (7.26%), and myelitis (5.12%) were the other MNS. Among the three encephalitis cases, two had CSF-Covid-19 PCR positivity and had severe manifestations and a poor outcome. Associated comorbidities included hypertension (30.76%), diabetes mellitus (12.82%), chronic kidney diseases (7.69%), and polycythaemia vera (2.56%). Lung involvement was seen in 64.1% of patients. Mortality was 17.94% in MNS with Covid-19. Conclusions: The most common major neurological syndrome associated with Covid-19 is CVD with increased frequency of large vessel occlusion causing significant morbidity and mortality. Simultaneous lung and other systemic involvement in MNS results in a deleterious outcome.