ANTIPHOSPHOLIPID ANTIBODIES AND VASCULAR THROMBOSIS IN PATIENTS WITH THE MOST SEVERE FORMS OF COVID-19

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.

SAFETY OUTCOMES IN PATIENTS (PTS) WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH FILGOTINIB (FIL) IN FILOSOPHY: INTERIM RESULTS FROM A PROSPECTIVE OBSERVATIONAL STUDY

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.

Long-lasting brain fog is related with severity clusters of symptoms in COVID-19 patients. Background: COVID-19 patients may experience lon-lasting symptoms from weeks to even months. Aim: to evaluate long-term cognitive impairment based on the severity

Background: COVID-19 patients may experience lon-lasting symptoms from weeks to even months. Aim: To evaluate long-term cognitive impairment based on the severity of symptoms of COVID-19 infection in a primary health system setting. Material and methods: From a database of 363 patients, 83 cases aged 47 +or- 15 years, (58% females) were selected from June to August 2020. In patients who survived the virus, 24 infection-related symptoms were collected to create three severity clusters (mild, moderate, and severe). The follow-up time was at least seven months. Comparing the first two clusters with the severe cluster, the existence of brain fog and risk factors (obesity, hypertension, diabetes, chronic lung disease, and hypothyroidism) were analyzed. Results: Thirty-one patients (37%) had persistent symptoms lasting up to 240 days. Fifty-one patients (61%) experienced brain fog. Concentration was affected by symptom severity (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.26-10.46, p = 0.02). Short- or long-term memory loss was not affected. Moreover, symptom severity was related to brain fog (OR 3.16, 95% CI 1.05-9.51, p = 0.04). Patients with persistent symptoms had a concentration impairment associated with severity patterns (OR 24.3, 95% CI 1.73-340.11, p = 0.03). Conclusions: Brain fog is associated with symptom severity in COVID-19 survivors and lasts for more than eight months.

Oral lesions in patients with severe COVID-19 in the National Institute of Respiratory Diseases in Mexico: Case series

Introduction SARS-CoV-2 is a neurotropic, mucotropic, and sialotropic virus that can affect the salivary glands' function, taste sensations, smell, and oral mucosa integrity.1 The oral cavity is a perfect habitat for SARS-CoV-2 invasion due to the special affinity the virus has for cells with angiotensinconverting enzyme (ACE2) receptors, such as those from the respiratory tract, oral mucosa, tongue, and salivary glands. Aphthous lesions with necrosis and hemorrhagic crusts have been described to manifest more regularly in older adults with immunosuppression and severe COVID-19 infection;one hypothesis for the development of aphthous lesions and/or ulcers is given due to the ACE2 receptor and the SARS-CoV-2 interaction, which could alter the epithelial lining of salivary glands and keratinocytes, causing lesions in the oral cavity.4 At the same time, different etiological factors such as infections, immune system alterations, and direct trauma to the oral mucosa or epithelium,5 may be related to the stress of a prolonged hospital stay.6 Including pressure in the oral cavity conditioned by the prone position, malposition of the endotracheal tube (mainly in the corners of the lips),7 medication-related nutritional deficiencies8 such as lopinavir, and ritonavir, oseltamivir, hydroxychloroquine, among others.9-12 Thrombotic vasculopathy secondary to COVID-19 has also been described, induced by system mediators in the microvascular walls, which impairs endothelial cells, and activates coagulation factors13 and a possible hypersensitivity reaction of the mucosa to the presence of SARS-CoV-2 in the epithelium14,15;there is also the hypothesis that it could be associated with an exanthem pattern induced by the inflammatory action of the SARSCoV-2 virus,16 presented as increased levels of cytokines (including interleukin-1, tumor necrosis facto-a), and arachidonic acid metabolites (prostaglandins) secondary to the stem cell factor production and the basic fibroblast growth factor of keratinocytes from the basal layer, in relation to post-inflammatory pigmentations that could appear in areas previously affected by trauma or chronic inflammation.17 Oral manifestations in COVID-19 patients appear, on many occasions, even before respiratory symptoms, although exanthematic lesions observed in COVID-19 patients can also be observed in other viral processes. Physical examination revealed a patient in a supine position with orotracheal intubation and orogastric tube, with aphthous-type ulcers, some of them had blood crusts of different sizes on the lower lip (both skin and mucosa), dorsum, and lateral edge of the tongue, gum, and vestibular fornix (Figure 3). Initial physical examination shows the patient in a supine position supported by high-flow nasal prongs, upper and lower lips edema and ulcer-like lesions with hematic crusts on both lips (Figure 4), topical management with steroids and GELCLAIRE® Oral Gel (glycyrrhetinic acid and polyvinylpyrrolidone) is observed.

Cardiovascular complications in patients after coronavirus disease-2019

The data of the modern literature describing the long-term consequences of infection of the body with SARS-CoV-2 on the cardiovascular system in the framework of postcovid syndrome are analyzed. To date, postcovid syndrome refers to a condition in which symptoms continue to persist for more than 12 weeks from the moment of diagnosis of COVID-19. Various complaints of patients after undergoing a new coronavirus infection are described, the distinguishing feature of which is their versatility, where cardiovascular manifestations are assigned one of the leading roles. Postural orthostatic tachycardia syndrome, cardiac arrhythmia and conduction disorders are considered. The role of SARS-CoV-2 in the formation of de novo and decompensation of pre-existing cardiovascular diseases has been demonstrated. The possibility of developing heart failure in patients with COVID-19 as an outcome of inflammation of the heart muscle is shown. Particular attention is paid to the analysis of the incidence of myocarditis after 3 months or more from the diagnosis of COVID-19, as well as thrombotic complications, in the genesis of which the main role belongs to the formation of endothelial dysfunction resulting from the interaction of SARS-CoV-2 with vascular endothelial cells. The autoimmune component of the pathogenesis of damage to the cardiovascular system as a result of the formation of endothelial dysfunction in COVID-19 is also considered. The authors present a laboratory-instrumental algorithm for determining cardiovascular complications in people who have undergone COVID-19, including the determination of the N-terminal fragment of the brain natriuretic peptide B-type prohormone, the level of anticardial antibodies, electrocardiography, echocardiography, as well as magnetic resonance imaging of the heart with contrast.

Assessment of role of HRCT, RT-PCR in the evaluation of COVID-19 symptomatic patients

Background: To assess role of HRCT, RT-PCR in the evaluation of COVID-19 symptomatic patients. Material and Methods: This retrospective study was conducted in the department of Radiology and Microbiology at Aarupadaiveedu Meddical College and Hospital . Eighty- five clinically suspects of COVID-19 patients of either gender was enrolled in the study and underwent RT-PCR test and HRCT Thorax . HRCT images were studied by Three radiologists independently. CURB- 65 and SOFA was recorded. Results: There were 50 males and 35 females in our study. Disease severity CURB was 1 and SOFA was 3. Chest CT had suspicious for COVID-19 in 45 and RT-PCR SARS-CoV2 positive in 40.42 had no comorbidity, 8 had peripheral vascular disease, 12 had cerebrovascular disease 13 had hypertension and 10 had diabetes mellitus. The difference was significant (P< 0.05). In all 40 patients of PCR SARS-CoV-2 positive, 35 HRCT were judged as suspicious for COVID-19. In 45 cases of PCR SARS-CoV-2 negative, 10 HRCT scans were judged as not suspicious for COVID-19. HRCT Thorax had a sensitivity of 87.5%, specificity of 77.8%, PPV of 77% and NPV of 87.5%. Conclusion: The diagnostic accuracy of HRCT Thorax in symptomatic patients is good, but not good enough to safely diagnose or exclude COVID-19 patients. RT- PCR is useful in addition with HRCT in diagnosis of COVID-19 patients.

Hypertension as a risk factor for COVID-19 severity and mortality: an integrative review

The new coronavirus illness (COVID-19) produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swiftly grown into a global epidemic. Hypertension has been identified as the most common cardiovascular comorbidity in COVID-19 patients, and it has been shown to increase the risk of hospitalization and mortality. Initial research suggested that renin-angiotensin-aldosterone system inhibitors might raise the likelihood of viral infection and worsen illness severity, generating concern considering the global prevalence of hypertension. Nonetheless, further research supported the use of antihypertensive medicines, noting that they do not worsen the severity of COVID-19 infection in hypertensive individuals, but may have a favorable impact. To yet, the specific mechanism through which hypertension predisposes to adverse outcomes in COVID-19 individuals is unclear. In this study, we discuss the incidence of SARS-CoV-2 infection and hypertension, as well as probable causes, with an emphasis on the dual roles of angiotensin-converting enzyme 2 in COVID-19 and hypertension. The effects of pro-inflammatory factors released by the immune system and gastrointestinal dysfunction in COVID-19 are also discussed, as well as how to manage hypertension with covid-19.

Predictors of mortality in COVID-19 disease

Background: COVID-19, an acute viral respiratory illness, was first noted in 2019, soon turned into pandemic with considerable mortality. With the objective of studying effect of comorbidities on COVID-19 disease severity and to identify laboratory markers associated with severe COVID-19 disease, we did a retrospective observational study in a tertiary care centre. Aims and Objectives: The objectives of this study were as follows: 1. To study effect of comorbidity on COVID-19 disease severity and 2. to identify laboratory markers associated with severe COVID-19 infection and mortality. Materials and Methods: This is an retrospective observational study conducted at SDMCMS&H, Dharwad from July 2020 to September 2020. A total of 402 cases who fall in the age group of 18 years and above were collected from medical record department. Statistical analysis used: The data were recorded in the Microsoft Excel sheet and analysis is done using Chi-square analysis and Cox linear regression method. Results: There were 402 patients whose data were collected. Out of 402 patients, 64 patients (15.92%) were in the age group of 18-39 years, 183 patients (45.52%) seen were in the age group of 40-60 years, 155 patients (38.56%) above 60 years, and consisting 291 male patients (72.39%) and 111 female patients (27.9%). Most common comorbidities seen were diabetes mellitus in 194 patients (48.26%) and hypertension in 182 patients (45.27%), followed by chronic kidney disease in 32 patients (7.96%) and ischemic heart disease in 24 patients (5.97%). Out 402 patients, 141 patients (35.07%) were on supplemental oxygen, which included 68 patients (48.23%) on low flow oxygen by face mask, seven patients (4.96%) were on non-rebreathing mask, 3 (2.13%) patients required NIV, and 63 patients (44.68%) required intubation and mechanical ventilation. It was found that uncontrolled diabetes rather than just presence of diabetes had significant impact on mortality with P=-0.0001 (95% CI OR 1.5-4.38). Patients with increased laboratory markers of inflammation such as Ferritin (95% CI OR 1.84-6.81) and LDH (95% CI OR 1.86-31.26) had strong association with mortality. The presence of thrombocytopenia showed significant association with mortality (95% CI OR 1.03-3.63). Conclusion: The presence of preceding uncontrolled hyperglycemia has significant effect on mortality. A state of hyperinflammation is directly associated with poor outcome.

COVID-19-associated lung microvascular endotheliopathy: a "from the bench" perspective

Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2;inactivated viral particles;or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.

Minimalist Nanocomplex with Dual Regulation of Endothelial Function and Inflammation for Targeted Therapy of Inflammatory Vascular Diseases.

Vascular disorders, characterized by vascular endothelial dysfunction combined with inflammation, are correlated with numerous fatal diseases, such as coronavirus disease-19 and atherosclerosis. Achieving vascular normalization is an urgent problem that must be solved when treating inflammatory vascular diseases. Inspired by the vascular regulatory versatility of nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) catalyzing l-arginine (l-Arg), the eNOS-activating effects of l-Arg, and the powerful anti-inflammatory and eNOS-replenishing effects of budesonide (BUD), we constructed a bi-prodrug minimalist nanoplatform co-loaded with BUD and l-Arg via polysialic acid (PSA) to form BUD-l-Arg@PSA. This promoted vascular normalization by simultaneously regulating vascular endothelial dysfunction and inflammation. Mediated by the special affinity between PSA and E-selectin, which is highly expressed on the surface of activated endothelial cells (ECs), BUD-l-Arg@PSA selectively accumulated in activated ECs, targeted eNOS expression and activation, and promoted NO production. Consequently, the binary synergistic regulation of the NO/eNOS signaling pathway occurred and improved vascular endothelial function. NO-induced nuclear factor-kappa B alpha inhibitor (IκBα) stabilization and BUD-induced nuclear factor-kappa B (NF-κB) response gene site occupancy achieved dual-site blockade of the NF-κB signaling pathway, thereby reducing the inflammatory response and inhibiting the infiltration of inflammation-related immune cells. In a renal ischemia-reperfusion injury mouse model, BUD-l-Arg@PSA reduced acute injury. In an atherosclerosis mouse model, BUD-l-Arg@PSA decreased atherosclerotic plaque burden and improved vasodilation. This represents a revolutionary therapeutic strategy for inflammatory vascular diseases.

Analysis of the first 106 telemedicine consultations in a vascular surgery service

Background: Telemedicine became a relevant means to provide healthcare without face-to-face medical evaluation during the COVID-19 pandemic. Aim(s): To describe the effectiveness of telemedicine in vascular surgery. Material(s) and Method(s): Review of medical records of all vascular surgery consultations carried out in a clinical hospital between April and October 2020. The main outcome measured was the resolution of the reason for consultation. Secondary outcomes were the need to request laboratory tests or imaging, the need to evaluate the patient in person, and the need for referral to hospitalization or emergency service. Result(s): One hundred-six new consultations and their follow-up (remotely or in person) were analyzed. A definitive diagnosis could be reached in 74% of consultations, treatment could be instituted or modified in 69% of them, and the reason for consultation could be resolved in 74% of cases. Laboratory and imaging tests were requested in 36 and 63% of consultations, respectively. Four percent of patients were referred to the emergency department or hospitalization. Conclusion(s): In the vast majority of consultations, it was possible to achieve a definitive diagnosis, prescribe a treatment and resolve the reason for consultation without the need for a face-to-face medical evaluation. Copyright © 2022 Sociedad Medica de Santiago. All rights reserved.

Influence of arterial hypertension risk factors on the course of COVID-19

The study showed that the higher the degree and risk of hypertension, the more severe COVID-19 is. In the groups with severe and extremely severe COVID-19, higher rates of hyperlipidemia were found;DM in 23.7% of patients with severe and 34.8% of patients with extremely severe disease;LVH was detected in 16.1% of patients with severe and 22.9% of patients with extremely severe COVID-19;nephropathy was detected in 18.6% of patients with severe and 28.8% of patients with extremely severe disease.

Influencing factors of proteinuria in patients with hypertension in Qinghai-Tibet Plateau

Objective: To investigate the risk factors of proteinuria in patients with hypertension in Qinghai-Tibet Plateau.

Effect of miR-221-3p targeting TIMP-2 on proliferation and apoptosis of vascular smooth muscle cells in abdominal aortic aneurysm

Objective: To investigate the effects of miR-221-3p on the proliferation and apoptosis of vascular smooth muscle cells (VSMC) in abdominal aortic aneurysm (AAA) by targeting tissue inhibitor of metalloproteinase- 2 (TIMP-2).

DEVELOPMENT OF CONDITIONS FOR ANALYTICAL DIAGNOSIS OF POISONING WITH CLOPIDOGREL.

Introduction. Clopidogrel bisulfate (Clopidogrel) is one of the main drugs for the treatment of various cardiovascular diseases (acute coronary syndrome, ischemic stroke, transient ischemic attack, peripheral artery disease, etc.). Especially, this drug is very relevant in the treatment of COVID-19. Clopidogrel has repeatedly been the cause of lethal poisoning, and cases of clopidogrel being used for suicide are very common in China. According to the studied literature data, the analysis of this drug in the biological material is not presented. Objective: The aim of the research was to establish the distinctive ability of conventional methods of isolating medicinal substances from biological material in relation to clopidogrel in chemical and toxicological analysis (CTA). Material and methods. The study was carried out with model samples of pig liver that had not undergone putrefactive changes, which contained the studied drug. Detection and quantification of clopidogrel in extracts were carried out using thin-layer chromatography (TLC) and UV spectrophotometry. Results. The isolation efficiency of clopidogrel according to the method of A.A. Vasilyeva was 57.75±5.08%, according to the method of V.P. Kramarenko – 64.23±5.44%. When using the isolation method of A.A. Vasilyeva, the detection limit of clopidogrel was 1.04%, according to the method of V.P. Kramarenko – 1.09%. The limit of quantitative determination of clopidogrel according to the method of A.A. Vasilyeva is 3.31%, according to the method of V.P. Kramarenko – 3.34%, respectively. Conclusion. For analytical diagnostics in case of clopidogrel poisoning, TLC screening and UV spectrophotometric determination must be carried out with preliminary TLC purification. Isolation of clopidogrel with water acidified with ethyl alcohol (the Stas-Otto method) does not work. The effectiveness of isolating the drug by the method of V.P. Kramarenko is 64.23±5.44%. The greatest selectivity of the UV spectrophotometric method for determining clopidogrel in biological material in relation to matrix components was provided by the method of isolation with water acidified with sulfuric acid (V.P. Kramarenko's method). (English) [ FROM AUTHOR] Введение. Клопидогрела бисульфат (клопидогрел) является одним из основных лекарственных препаратов для лечения различных сердечно-сосудистых заболеваний (острый коронарный синдром, ишемический инсульт, транзиторная ишемическая атака, заболевания переферических артерий и др.). Данный препарат особенно актуален при лечении СОVID-19. Неоднократно клопидогрел был причиной летальных отравлений, например, в Китае очень часто встречаются случаи использования клопидо- грела в целях самоубийства. Анализа данного препарата в биологическом материале по литературным данным не представлено. Целью исследований явилось установление отличительной способности клопидогрела, общепринятой в химико-токсико- логическом анализе методов изолирования лекарственных веществ из биологического материала. Материал и методы. Исследование проводили с модельными пробами свиной печени, не претерпевшей гнилостных изме- нений, которые содержали исследуемый препарат. Обнаружение и количественное определение клопидогрела в экстрактах проводили с помощью тонкослойной хроматографии (ТСХ) и УФ-спектрофотометрии. Результаты. Эффективность изолирования клопидогрела по методу А.А. Васильевой составила 57,75±5,08%, по методу В.П. Крамаренко – 64,23±5,44%. При использовании метода изолирования А.А. Васильевой предел обнаружения клопидогрела составлял 1,04%, по методу В.П. Крамаренко – 1,09%. Предел количественного определения клопидогрела по методу А.А. Васильевой – 3,31%, по методу В.П. Крамаренко – 3,34%. Заключение. Для проведения аналитической диагностики при отравлении клопидогрелом ТСХ-скрининг и УФ-спектрофотометрическое определение необходимо проводить с предварительной ТСХ-очисткой. Изолирование клопидо- грела водой, подкисленной этиловым спиртом (метод Стаса–Отто), не происходит. Наибольшую селективность УФ-спектрофотометрического метода определения клопидогрела в биологическом материале по отношению к матричным компонентам обеспечивал метод изолирования водой, подкисленной серной кислотой (метод В.П. Крамаренко). Эффективность изолирования препарата по методу В.П. Крамаренко составляет 64,23±5,44%. (Russian) [ FROM AUTHOR] Copyright of Farmatsiya (Pharmacy) is the property of Russian Physician Public House Ltd. 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.)

Emerging trends in the nanomedicine applications of functionalized magnetic nanoparticles as novel therapies for acute and chronic diseases.

High-quality point-of-care is critical for timely decision of disease diagnosis and healthcare management. In this regard, biosensors have revolutionized the field of rapid testing and screening, however, are confounded by several technical challenges including material cost, half-life, stability, site-specific targeting, analytes specificity, and detection sensitivity that affect the overall diagnostic potential and therapeutic profile. Despite their advances in point-of-care testing, very few classical biosensors have proven effective and commercially viable in situations of healthcare emergency including the recent COVID-19 pandemic. To overcome these challenges functionalized magnetic nanoparticles (MNPs) have emerged as key players in advancing the biomedical and healthcare sector with promising applications during the ongoing healthcare crises. This critical review focus on understanding recent developments in theranostic applications of functionalized magnetic nanoparticles (MNPs). Given the profound global economic and health burden, we discuss the therapeutic impact of functionalized MNPs in acute and chronic diseases like small RNA therapeutics, vascular diseases, neurological disorders, and cancer, as well as for COVID-19 testing. Lastly, we culminate with a futuristic perspective on the scope of this field and provide an insight into the emerging opportunities whose impact is anticipated to disrupt the healthcare industry.

Non-COVID excess deaths, 2020-21: collateral damage of policy choices?

From April 2020 through at least the end of 2021, Americans died from non-Covid causes at an average annual rate 97,000 in excess of previous trends. Hypertension and heart disease deaths combined were elevated 32,000. Diabetes or obesity, drug-induced causes, and alcohol-induced causes were each elevated 12,000 to 15,000 above previous (upward) trends. Drug deaths especially followed an alarming trend, only to significantly exceed it during the pandemic to reach 108,000 for calendar year 2021. Homicide and motor-vehicle fatalities combined were elevated almost 10,000. Various other causes combined to add 18,000. While Covid deaths overwhelmingly afflict senior citizens, absolute numbers of non-Covid excess deaths are similar for each of the 18-44, 45-64, and over-65 age groups, with essentially no aggregate excess deaths of children. Mortality from all causes during the pandemic was elevated 26 percent for working-age adults (18-64), as compared to 18 percent for the elderly. Other data on drug addictions, non-fatal shootings, weight gain, and cancer screenings point to a historic, yet largely unacknowledged, health emergency.

Hospitalizations for Cardiovascular Diseases During the Early Stage of the COVID-19 Pandemic in Japan.

Background: Although reductions in hospitalizations for myocardial infarction and heart failure have been reported during the period of COVID-19 pandemic restrictions, it is unclear how the overall number of hospitalizations for cardiovascular disease (CVD) treatment changed in the early stages of the pandemic. Methods and Results: We analyzed the records of 574 certified hospitals affiliated with the Japanese Circulation Society and retrieved data from April 2015 to March 2020. Records were obtained from the nationwide Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination database. A quasi-Poisson regression model was used to estimate the number of hospitalizations for CVD treatment. Between January and March 2020, when the number of COVID-19 cases was relatively low in Japan, the actual/estimated number of hospitalizations for acute CVD was 18,233/21,634 (84.3%), whereas the actual/estimated number of scheduled hospitalizations was 16,921/19,066 (88.7%). The number of hospitalizations for acute heart failure and scheduled hospitalizations for valvular disease and aortic aneurysm were 81.1%, 84.6%, and 83.8% of the estimated values, respectively. A subanalysis that considered only facilities without hospitalization restrictions did not alter the results for these diseases. Conclusions: The spread of COVID-19 was associated with a decreased number of hospitalizations for CVD in Japan, even in the early stages of the pandemic.