ASSOCIATION OF URIC ACID LEVELS WITH COVID-19 SEVERITY DURING 2020 AND 2021 YEARS

BackgroundThe decrease in uric acid levels attracts more and more attention from clinicians every year [1]. In particular, a factor such as Covid-19 can cause a significant decrease in uric acid due to its increased excretion by the kidneys [2]. This retrospective study aimed to determine changes in the level of uric acid in different years, which allows us to assume the influence of different strains of Covid-19 on uric acid.ObjectivesTo analyze the relationship between uric acid levels through admission to the hospital and Covid-19 severity during 2020 and 2021 years.MethodsOur retrospective study includes 127 hospitalized patients with confirmed Covid-19 in 2021 and 63 patients in 2020 (only patients who didn't receive urate-lowering therapy). Most patients were over 45 years old (84,2% vs 90,5%), women and men almost equally. The severity of Covid-19 we determined by the type and presence of oxygen support ((1) without O2, (2) O2 by mask or nasal cannula, (3) continuous positive airway pressure, (4) positive bi-pressure in the airways or high-flow oxygen, (5) invasive ventilation). A chi-squared test and comparison of means were used.ResultsWe cannot establish the dependence of the uric acid level on the severity of the course of the Covid-19 disease, which is determined by the type of oxygen support in both 2020 and 2021. For example, in 2021, the difference between the least severe type (without O2) and the most severe (invasive ventilation) was almost the same (246.2 vs 277.12 µmol/L), as between O2 by mask or nasal cannula and positive bi-pressure in the airways or high-flow oxygen (257 vs 239.1 µmol/L). However, it was established that in 2020, higher indicators of the level of uric acid were observed for all types of oxygen support. For example, for patients who were without O2, it is higher by 72.95 µmol/L, which is statistically significant. In addition, we analyzed the dependence of the uric acid level on such indicators as the patient's age, the level of lymphocytes, C-reactive protein, and LDH at admission to the hospital. As a result of the analysis, it was found that the dependence is present for the LDH indicator (the lower the LDH, the higher the uric acid: chi-square at the level of 0.05), and for all other indicators, it was absent in 2021. In 2020, a positive relationship between CRP, LDH, and uric acid levels was also observed.ConclusionAlthough there is a trend towards lower uric acid levels in the background of Covid-19, it is not a marker of a severe disease course. The lower uric acid levels in 2021 are likely due to a feature of the strains circulating in 2021 that caused more significant renal excretion of uric acid.References[1]Hu F, Guo Y, Lin J, Zeng Y, Wang J, Li M, Cong L. Association of serum uric acid levels with COVID-19 severity. BMC Endocr Disord. 2021 May 8;21(1):97. DOI: 10.1186/s12902-021-00745-2. PMID: 33964922;PMCID: PMC8106517.[2]Dufour I, Werion A, Belkhir L, Wisniewska A, Perrot M, De Greef J, Schmit G, Yombi JC, Wittebole X, Laterre PF, Jadoul M, Gérard L, Morelle J;CUSL COVID-19 Research Group. Serum uric acid, disease severity, and outcomes in COVID-19. Crit Care. 2021 Jun 14;25(1):212. DOI: 10.1186/s13054-021-03616-3. PMID: 34127048;PMCID: PMC8201458.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

An Audit Showing the Successful Operation of a Nurse-Led Gout Clinic during the Covid-19 Pandemic

Background/Aims Research has shown nurse-led gout clinics provide better outcomes compared to usual care. This District General Hospital set up a pilot nurse-led gout clinic in autumn 2019. This aimed to improve patients' understanding of their condition, achieve better control of serum uric acid levels (SUA), reduce flares and prevent Emergency Department attendances. Methods A modified clinic protocol, closely modelled on BSR guidance was agreed within the department. With consultant supervision, one nurse specialist provided a mix of in-person and telephone appointments. Targets were set aiming for SUA <360mumol/L for most patients and <300mumol/L for those with erosive change or tophi. All patients were offered prophylaxis. Patients required a rheumatologist's diagnosis of gout or crystal confirmation for enrolment. Exclusion criteria were significant renal or hepatic derangement. Within 3 months of the service starting SARS-CoV-2 impacted the operation of healthcare worldwide and led to the closure of routine outpatient clinics in Northern Ireland. A decision was made to switch the gout clinic to run entirely by telephone. Blood testing was facilitated through primary care and phlebotomy hubs. Results Over a 19-month period, 78 patients were treated and audited through this clinic: 69 men and 9 women. Average age was 57, mean SUA 509 mumol/L at referral and 322 mumol/L on discharge. 69 patients received allopurinol and 9 received febuxostat. No patients required uricosuric drugs. All patients were offered and agreed to take prophylaxis with a majority (85.8%) remaining on it for 3-6 months. Patients required a mean of 3.38 appointments prior to discharge from the clinic. The mean dose of urate lowering therapy on discharge was 315.9mg allopurinol and 93.3mg febuxostat. 95% experienced >=2 flares during their enrolment in the clinic with no patients requiring Emergency Department attendance due to gout flare. Conclusion The nurse-led gout clinic was well received by patients and was effective as a telephone service during the pandemic when so many services were stood down. The clinic was able to continue to provide education, deliver effective reductions in uric acid as well as reduce incidence of flares and Emergency Department attendances. Lower doses of urate lowering therapy than expected were needed to achieve target. A small number of patients were discharged prior to enrolment for initial non-engagement which may have been exacerbated by the lack of face-to-face appointments. Our COVID-19 model did struggle with those patients needing an interpreter. In-person initial appointments have since been restarted;however, a greater proportion of reviews will continue to be offered by telephone given the unexpected success of the model. This audit showed that a nurse-led gout clinic can run successfully, even during a pandemic with a significant reliance on telephone consultations.

Follow-up 24-Urine Studies during and Post-Covid-19 Pandemic

INTRODUCTION AND OBJECTIVE: In New York State, March 16, 2020 marked the end of any in-restaurant dining due to the COVID- 19 pandemic. The general population was forced to do more cooking at home and less dining out. Dietary modifications like this are considered first line therapy for calcium stone formers due to an effort to reduce dietary sodium intake which is known to affect lithogenic risk factors including hypernatriuria and hypercalciuria. This study aims to see if dietary changes made during the pandemic changed the risk of stone disease as evidenced in 24-hour urine studies and if these changes ceased after the end of widespread shutdowns. METHOD(S): All patients with nephrolithiasis seen for an outpatient visit from April 1, 2020-December 31, 2020 were queried and included if they had a 24-hour urine study pre-COVID (before March 16, 2020) and during-COVID (March 16, 2020-December 31, 2020);a post- COVID study was included if available (January 1, 2021- October 31, 2022). Values were compared using paired, 2-tailed t-tests. RESULT(S): 93 patients (54 males, 39 females, mean age 60.1) were studied pre-COVID, during-COVID, and post-COVID time periods with 24-hour urine studies. Stone analysis revealed calcium oxalate (61%), calcium phosphate (15%), uric acid (15%), other (9%). The 24-hour urine revealed a significant reduction in urinary sodium (uNa) and urinary calcium (uCa) in these patients. uNa levels decreased from 166.15+/-7.5 mEq/L pre-COVID to 149.09+/-7.6 mEq/L during- COVID (p=0.015) and maintained improved at 138.55+/-6.83 mEq/L post-COVID era (p=0.0035). uCa levels decreased from 214.18+/-13.05 mEq/L pre-COVID to 191.48+/-13.03 mEq/L during- COVID levels (p=0.010) and remained improved at 185.33+/-12.61 mEq/L post-COVID (p=0.012). There were no significant differences in 24-hour urine total volume, magnesium, or citrate levels. CONCLUSION(S): During the COVID-19 lockdown, dietary choices limited to home cooked meals allowed patients to better identify their food choices. This study demonstrates that known urinary risk factors for lithogenesis, such as urinary sodium and calcium, improved during the lockdown and these improvements were maintained even after restrictions in restaurants were lifted. Moving forward, it will be imperative to monitor patient's 24-hour urine to ensure these dietary modifications are continued in the postpandemic era and to see if these improved urinary parameters will impact stone formation in these patients.

Effect of the COVID-19 pandemic on young stroke

Background & Objective: Covid-19 infection has diverse effect on human health. We aimed to evaluate the effect of COVID-19 pandemic on the young stroke cases in an emergency services in a tertiary hospital in Istanbul, Turkey. Method: A total of 86 patients younger than 50 years confirmed to have stroke seen between January 1, 2019 and December 31, 2020 were included in the study. The year 2019 was defined as the pre-pandemic period and the year 2020 as the pandemic period. The patients' stroke type, localization, mortality, laboratory and imaging data were evaluated. Results: Eighty-six patients were included in the study. The mean age was 38.69±5.39 years, 49 (57%) were female. Of the patients, 78 (90.7%) were ischemic and 8 (9.3%) were hemorrhagic stroke. In the pandemic group, ischemic stroke was observed in 55 (96.5%) and hemorrhagic stroke in 2 (3.5%) (p=0.010). While the mean age of the patients in the survival group was 39.24±5.70 years, it was 36.61±3.38 years in the mortality group (p=0.008). While the mortality was 18 (20.9%) overall, it was 16 (18.6%) patients during the pandemic period, and 2 (2.3%) patients in the pre-pandemic period, the difference was statistically significant. (p=0.014). Conclusion: COVID-19 infection appear to increase the risk of ischemic stroke and worsens the mortality among the young. More comprehensive and prospective studies are needed to confirm this observation. © 2023, ASEAN Neurological Association. All rights reserved.

Incidence and influencing factors of favipiravir-associated serum uric acid elevation in patients with coronavirus disease 2019.

Objective To explore the occurrence and influencing factors of serum uric acid elevation in patients with coronavirus disease 2019 (COVID-19) treated with favipiravir. Methods Medical records of patients with COVID-19 who were hospitalized in Beijing Ditan Hospital between June 1, 2020 and June 30, 2021 and treated with the 5- or 10-day regimen of favipiravir were collected and retrospectively analyzed. After favipiravir withdrawal, if the elevation in serum uric acid was >=30% of baseline level, it was defined as serum uric acid elevation. Then patients were divided into serum uric acid elevation group and non-serum uric acid elevation group. The clinical characteristics such as gender, age, body mass index, comorbidities, smoking and drinking behavior, COVID-19 grade, favipiravir regimen, and serum uric acid level and renal function before treatment in patients between the 2 groups were compared. Influencing factors of favipiravir-associated serum uric acid elevation was analyzed using multivariate logistic regression method. Results A total of 179 patients were included in the analysis, including 104 (58.1%) males and 75 (41.9%) females, aged from 19 to 70 years with a median age of 43 years. The level of serum uric acid in 179 patients after favipiravir treatment was significantly higher than before [(451+/-119) mumol/L vs. (332+/-94) mumol/L, P<0.001]. The change rate of serum uric acid from baseline level ranged from -57.1% to 157.8% with the median of 38.6%. The elevation in serum uric acid of >= 30% of baseline level occurred in 108 (60.3%) patients. The incidences of serum uric acid elevation in patients treated with 5-day and 10-day regi- mens of favipiravir were 46.8% (36/77) and 70.6% (72/102), respectively, and the difference between them was significant (P=0.001). Multivariate logistic regression analysis showed that body mass index 24.0 to <28.0 kg/m2 (OR=3.109, 95%CI: 1.209-7.994, P=0.019) and 10-day regimen of favipiravir (OR=3.017, 95%CI: 1.526-5.964, P=0.001) were independent risk factors for favipiravir-associated serum uric acid elevation. Conclusions More than half of COVID-19 patients treated with favipiravir can develop serum uric acid elevation. Overweight and 10-day regimen of favipiravir are independent risk factors for serum uric acid elevation in patients.Copyright © 2022 Adverse Drug Reactions Journal.

Uric acid as a prognostic predictor in COVID-19.

Objective: The purpose of our study was to investigate the incidence and prognostic significance of baseline and control uric acid values in COVID-19. Methods: The study population included patients admitted with the diagnosis of SARS-CoV-2 between March 2020 and March 2021. The demographic data, clinical, laboratory, and radiological findings were recorded. Uric acid levels were measured at the time of admission for 498 patients and at the most severe period of the disease in 143 patients. Length of hospital stay, need for admission to intensive care unit, the course, and outcomes during hospitalization were recorded. Results: The mean age of 261 male and 207 female patients was 62.7(21-95) years. At the time of admission, 21 patients had hypouricemia and 170 had hyperuricemia. The need for ICU was 47.6% in the hypouricemic, 19.2% in the normouricemic, and 21.2% in the hyperuricemic groups. The mean uric acid level was 5.24±2.54 mg/dl in patients who required ICU admission and 5.18±1.98 mg/dl in patients who were discharged from the ward. The difference was not statistically significant. The mean uric acid level was not significantly different in the deceased and survivors. In 143 subjects, uric acid levels were measured after the progression of COVID-19; 73 of them were admitted to the ICU. The mean uric acid levels were found to be significantly decreased in patients with a negative prognosis. Conclusion: In our study, hypouricemia was not found to be a major feature of SARS-CoV-2 infection. Low baseline uric acid levels were associated with increased ICU admission. The decline in uric acid levels during hospital stay predicted poor prognosis, as well.

Lympho-no: a happy ending to a mediastinal mass

Case Report: Mediastinal masses are rare with an incidence of 1 in 100 000 [1]. While the differential is broad, the risk of malignancy is higher in the pediatric population. Lymphomas account for about 50% of mediastinal masses [2].We present a patient with superior vena cava (SVC) syndrome from a mediastinal mass, concerning for lymphoma. After extensive work up, the mass was determined to be reactive. Case Presentation: A 5-year-old male, presented with one day of left sided face and neck swelling. Review of systemswas positive for a fewweeks of cough but notably negative for night sweats, fatigue, fever, or weight loss. Computed tomography (CT) scan (Figure 1, left) showed a heterogeneous mass, most concerning for lymphoma. Blood work was notable for lymphopenia (640 x 103/uL), elevated lactate dehydrogenase and uric acid (549 U/L and 7.1 mg/dL respectively). He tested positive for SARs- CoV2 RNA on nasopharyngeal PCR. Upon admission, he was started on methylprednisolone and allopurinol. A bone marrow biopsy and a lumbar puncture were unrevealing for immunophenotypic evidence of lymphoid neoplasm. A mediastinal biopsy showed fibrosis with patchy inflammation and inadequate number of viable cells to allow for flow cytometric analysis. A post-biopsy echocardiogram revealed a moderate sized pericardial effusion which eventually resolved. He was discharged with infectious disease and oncology follow up. Later, histoplasma and bartonella antibodies, and T spot were negative. A CT (Figure 1, right), ten days after initial presentation showed significant decrease in size of the mediastinal mass. At one month follow up, he remained clinically well with a normal chest x-ray. [Figure presented] Fig 1: A CT ten days after initial presentation showed significant decrease in size of the mediastinal mass Conclusion(s): This patient presented with SVC syndrome from a mediastinal mass that resolved with 3 days of intravenous steroids. The initial presumed diagnosis of lymphoma was ultimately inconsistent with the extensive workup, and the mass was ultimately deemed reactive. COVID-19 related mediastinal mass is not described in the literature, and although possible, remains unlikely. This case represents the importance of avoiding premature closure and keeping a broad differential diagnosis. 1. Park DR, Vallieres E. The mediastinal mass. Murray and Nadel's Textbook of Respiratory Medicine. 5th edn. Philadelphia, PA: Saunders;2010. pp. 1814-35. 2. Glick R. D., & La Quaglia M. P. (1999). Lymphomas of the anterior mediastinum. Seminars in Pediatric Surgery, 8(2),69-77.Copyright © 2023 Southern Society for Clinical Investigation.

Atypical presentation of covid-19 as acute leukemia: A case report

In the absence of respiratory system involvement, COVID-19 patients developing ARDS can clinically mimic other diseases including acute leukemia due to presence of atypical lymphocytes in peripheral blood smear and increased serum lactate dehydrogenase and serum uric acid levels. Herein, we report a case who was initially suspected to have acute leukemia based on his atypical symptoms without any respiratory system involvement and deranged laboratory parameters and finally, diagnosed with COVID-19. Our patient presented with fever, myalgia, gum bleed, and petechiae. On clinical and laboratory evaluation, he was suspected to have acute leukemia based on markedly deranged serum lactate dehydrogenase and serum uric acid and the presence of atypical cells in peripheral blood smear and bone marrow. On day 3 of hospitalization, he developed respiratory symptoms, breathing difficulty which progressed to ARDS, and subsequently, he succumbed to his illness. His real-time reverse transcriptase-polymerase chain reaction test for severe acute respiratory syndrome coronavirus-2 yielded positive results. Also, Flow cytometry and fluorescence in situ hybridization studies for leukemia workup did not show any abnormalities. Although we are reporting the findings of only a single case, we aim to enhance and contribute further to the understanding of this novel infection.Copyright © 2021 Necati Ozpinar. All right reserved.

Comment on: "Risk of Erectile Dysfunction in Male Patients with Gout Treated with Febuxostat or Allopurinol: A Propensity Score-Matched Cohort Study"/Authors' Reply to Huang and Zhang: Comment on "Risk of Erectile Dysfunction in Male Patients with Gout Treated with Febuxostat or Allopurinol: A Propensity Score-Matched Cohort Study"

[...]a time frame could be set before the Covid-19 epidemic attack in January 2020, owing to the association between Covid-19 infection (ICD-10-CM B34.2, U07.1, U07.2, J12.81, J12.82, B97.29) and new-onset ED, which was recently detected in the same database [6]. According to the National Institute for Health and Care Excellence (NICE) guideline [15], treat-to-target (T2T) approach should be adhered to with serum urate level of at least < 360

Inflammation Related to Association of Low Uric Acid and Progression to Severe Disease in Patients Hospitalized for Non-Severe Coronavirus Disease 2019.

Uric acid has antioxidant properties. To examine whether a low uric acid level is associated with severe coronavirus disease 2019 (COVID-19) progression via inflammation, alveolar damage, and/or coagulation abnormality, a retrospective observational study of 488 patients with non-severe COVID-19 and serum uric acid level ≤7 mg/dL at admission was conducted. Serum C-reactive protein (CRP), serum Krebs von den Lungen 6 (KL-6), and plasma D-dimer levels were also measured as markers of inflammation, alveolar damage, and coagulation abnormality, respectively. Median values for uric acid, CRP, KL-6, and D-dimer at admission were 4.4 mg/dL, 3.33 mg/dL, 252.0 U/mL, and 0.8 µg/mL, respectively. Among the total cohort, 95 (19.5%) progressed to severe COVID-19 with a median (interquartile range) time of 7 (4-14) days. Multivariable Cox proportional hazards regression analysis showed that low uric acid level was associated with a higher rate of severe COVID-19 progression. However, uric acid level was inversely associated with CRP level, and the association between the level of uric acid and severe COVID-19 progression was significantly different with and without CRP level inclusion. In contrast, no such association was found for KL-6 or D-dimer level. Low uric acid may contribute to severe COVID-19 progression via increased inflammation in subjects without hyperuricemia.

Surface control approach for growth of cerium oxide on flower-like molybdenum disulfide nanosheets enables superior removal of uremic toxins

Due to the high incidence of kidney disease, there is an urgent need to develop wearable artificial kidneys. This need is further exacerbated by the coronavirus disease 2019 pandemic. However, the dialysate regeneration system of the wearable artificial kidney has a low adsorption capacity for urea, which severely limits its application. Therefore, nanomaterials that can effectively remove uremic toxins, especially urea, to regenerate dialysate are required and should be further investigated and developed. Herein, flower-like molybdenum disulphide (MoS2) nanosheets decorated with highly dispersed cerium oxide (CeO2) were prepared (MoS2/CeO2), and their adsorption performances for urea, creatinine, and uric acid were studied in detail. Due to the open interlayer structures and the combination of MoS2 and CeO2, which can provide abundant adsorption active sites, the MoS2/CeO2 nanomaterials present excellent uremic toxin adsorption activities. Further, uremic toxin adsorption capacities were also assessed using a self-made fixed bed device under dynamic conditions, with the aim of developing MoS2/CeO2 for the practical adsorption of uremic toxins. In addition, the biocompatibility of MoS2/CeO2 was systematically analyzed using hemocompatibility and cytotoxicity assays. Our data suggest that MoS2/CeO2 can be safely used for applications requiring close contact with blood. Our findings confirm that novel 2-dimensional nanomaterial adsorbents have significant potential for dialysis fluid regeneration. © 2022

Study of renal function during acute phase and recovery in patients with COVID - 19 in Baghdad/Iraq

This study aims to investigate traces of COVID - 19 on renal system during infection & after recovery in city of Baghdad from October 2021 till April 2022. Method(s): Patients were consisted of 120 individuals with acute then to convalescent phase of COVID-19 and 60 healthy controls, all aged between 19 & 61 years. They were consisted of equal halves of males & females, for both patients & controls. Tests that were depended in this study are: Blood urea, serum creatinine & serum uric acid;all samples are of serum;that had been done using Roche - Integra 400 plus auto analyser at Al-Karkh Medical Laboratory in Baghdad. Result(s): Renal impairment & problems were of several dilemmas that raised highly with proceeding of COVID - 19, made dysfunction of kidneys & other correlated parts of renal system parts a very significant criterion among patients suffering this problem;especially if there was a familiar history in these organs;like renal stone formation, uricemia & recurrent urinary tract infection;making consequences of this disease the worst among other problems that can take effect on renal system;rather than chemical toxification & cancers. Blood urea had scored in males in acute & recovery phases of (38.08+/-15.36) & (43.27+/-18.13) respectively, while in females was (28.57+/-7.56) & (32.25+/-8.49) in same attribute, with high significance of (p<0.01 HS) in acute phase & (p>0.05 NS) for recovery phase. Serum creatinine levels were lower in females than of males in both phases;where scores at (0.6517+/-0.19) in acute phase & (0.81+/-0.19) after recovery;which means that they stayed in normal ranges;while in males level of creatinine scored (0.94+/-0.370) & (1.19+/-0.45) in cue;hitting the highest normal ranges & made males in higher risk for any renal proper functioning, with high significance of (p<0.01 HS) for both. Results of S. uric acid were slightly near the upper limits for females at (5.23+/-1.13) & (5.48+/-0.79) for acute & recovery phases in correspondence, while males crossed the borders of normal ranges in both phases;(6.31+/-1.17) & (7.07+/-1.09) respectively, (p<0.01 HS) for both. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

A review on 2D-ZnO nanostructure based biosensors: from materials to devices

During the COVID'19 outbreak, biosensing devices won increasing relevance, demonstrating their potential in the medical diagnostic field. Hence, the present review reports on the main advances in 2D-ZnO nanostructure-based biosensors. So far, bulk ZnO has shown potential for biosensing, optical, and power electronic applications, mainly based on its wide band gap. In the post graphene era, its 2-D allotropes like ZnO sheets and ZnO nanoribbons have outperformed the bulk ZnO structures for specific applications. ZnO demonstrates various stable and feasible morphologies: nanotubes, nanowires, nanorods, nanosheets, nanoparticles, and nanobelts. As a matrix layer in biosensing applications, ZnO strongly binds to biomolecules due to its high isoelectric point (IEP) and shows a strong sensitivity due to the high surface-to-volume ratio. Further, ZnO nanostructures used as a matrix layer play an important role in inhibiting specific biological interactions and hence improve the sensitivity of sensing devices. Further, bioselective layers are typically immobilized onto ZnO either by direct adsorption or by covalent binding. ZnO based biosensors are categorized into optical, piezoelectric, and electrochemical biosensors, among others, based on their biosensing mechanism. In particular, electrochemical sensors produce signals via an electrical pathway for detecting and monitoring the target molecules. Optical sensors produce signals based on luminescence or reflectance, among others. Piezoelectric biosensors produce signals by mass loading of the piezoelectric material. ZnO-based FET biosensors are also reported, showing sensing application by the change in the channel's conductance. Further, recent literature on the detection of COVID-19 using ZnO nanostructures is presented.

Uricase Crowding via Polyelectrolyte Layers Coacervation for Carbon Fiber-Based Electrochemical Detection of Uric Acid.

Urate oxidase (UOx) surrounded by synthetic macromolecules, such as polyethyleneimine (PEI), poly(allylamine hydrochloride) (PAH), and poly(sodium 4-styrenesulfonate) (PSS) is a convenient model of redox-active biomacromolecules in a crowded environment and could display high enzymatic activity towards uric acid, an important marker of COVID-19 patients. In this work, the carbon fiber electrode was modified with Prussian blue (PB) redox mediator, UOx layer, and a layer-by-layer assembled polyelectrolyte film, which forms a complex coacervate consisting of a weakly charged polyelectrolyte (PEI or PAH) and a highly charged one (PSS). The film deposition process was controlled by cyclic voltammetry and scanning electron microscopy coupled with energy-dispersive X-ray analysis (at the stage of PB deposition) and through quartz crystal microbalance technique (at latter stages) revealed uniform distribution of the polyelectrolyte layers. Variation of the polyelectrolyte film composition derived the following statements. (1) There is a linear correlation between electrochemical signal and concentration of uric acid in the range of 10-4-10-6 M. (2) An increase in the number of polyelectrolyte layers provides more reproducible values for uric acid concentration in real urine samples of SARS-CoV-2 patients measured by electrochemical enzyme assay, which are comparable to those of spectrophotometric assay. (3) The PAH/UOx/PSS/(PAH/PSS)2-coated carbon fiber electrode displays the highest sensitivity towards uric acid. (4) There is a high enzyme activity of UOx immobilized into the hydrogel nanolayer (values of the Michaelis-Menten constant are up to 2 µM) and, consequently, high affinity to uric acid.

Redox imbalance in COVID-19 pathophysiology.

BACKGROUND: The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. METHODS: COVID-19 subjects (n = 64) and control subjects (n = 19) were enrolled, and blood was drawn within 72 h of diagnosis. Serum multiplex assays and peripheral blood mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. RESULTS: Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects. CONCLUSION: Herein we demonstrate a significant redox imbalance during COVID-19 infection affirming the potential for manipulation of oxidative stress pathways as a new therapeutic strategy COVID-19. However, further work is requisite for detailed identification of oxidants (O2•-, H2O2 and/or circulating transition metals such as Fe or Cu) contributing to this imbalance to avoid the repetition of failures using non-specific antioxidant supplementation.

Pegloticase for Uncontrolled Gout in Kidney Transplant Recipients: Provisional Data Report of a Multicenter, Open-Label, Efficacy and Safety Study

Purpose: Gout in kidney transplant (KT) recipients can be severe and particularly challenging to manage. Pegloticase co-therapy with immunomodulators improved urate lowering therapy (ULT) response rates over phase 3 monotherapy trials by reducing anti-drug antibodies.1,2 This open-label trial (PROTECT NCT04087720) examined pegloticase safety and efficacy in KT patients with uncontrolled gout. Method(s): KT recipients with uncontrolled gout (serum urate [SU]>=7 mg/dL, intolerance/ inefficacy to ULT and >=1 of the following: tophi, chronic gouty arthritis, >=2 flares in past year) and functioning KT graft (eGFR>=15 ml/min/l.73m2) on stable immunosuppressive (IS) therapy (KT>l year earlier) received pegloticase (8 mg every 2 weeks for 24 weeks). SU response during Month 6 (SU <6 mg/dL for >=80% of time) and Health Assessment Questionnaire (HAQ) pain (most severe: 100) and Disability Index (HAQ-DI, max: 3) scores were evaluated. Patients discontinuing treatment before Month 6 were considered nonresponders. Patients discontinuing due to COVID-19 concerns were excluded from analysis if no data points were available in Month 6. Result(s): 20 patients enrolled (mean+/-SD;age: 53.9+/-10.9 years, 85% male, time since KT: 14.7+/-6.9 years, SU: 9.4+/-1.5 mg/dL, gout duration: 7.9+/-11.6 years;all on >=2 IS) and 14/20 completed treatment. 16/18 (88.9% [95% CI: 65.3, 98.6]) were SU responders vs 43.5% previously reported3 without immunomodulation. Substantial SU reductions during treatments were reported in 18/20 patients completing or discontinuing for non-SU monitoring rule reasons (pre-dose SU>6 mg/dL at 2 consecutive visits). No notable eGFR changes were observed up to 3 months follow-up. In patients completing treatment, HAQ-pain and HAQ-DI mean scores improved by 35.5+/-31.5 and 0.3+/-0.6, respectively, at Week 24 (n=13 and n=14). 7 serious adverse events, deemed unrelated to pegloticase, were reported in 5 patients. No anaphylaxis or infusion reaction events occurred. Conclusion(s): Pegloticase was safe and effective in treated KT patients with uncontrolled gout, achieving a higher durable response rate than in previously-reported patients not on IS therapy along with improved HAQ scores indicative of quality of life impact. These findings are consistent with other reports of immunomodulation with pegloticase.

EVALUATION OF SERIAL BIOMARKERS IN INTERMEDIATE-RISK PATIENTS WITH ACUTE PULMONARY EMBOLISM

SESSION TITLE: All About the CLOT: VTE SESSION TYPE: Original Investigations PRESENTED ON: 10/16/2022 10:30 am - 11:30 am PURPOSE: Patients diagnosed with intermediate high-risk pulmonary embolism (IHRPE) may develop early clinical decompensation requiring advanced reperfusion therapy. The clinical parameters and biomarkers which may prognosticate this progression to high risk acute PE are not clearly defined in the current clinical practice guidelines. There remains a critical knowledge gap regarding identifying the 5-17% of patients who will demonstrate decompensation within the first 72 hours after initial presentation. We measured serial acute PE biomarkers to better understand their patterns of evolution. METHODS: Single arm prospective observational pilot study measuring serial biomarkers in newly diagnosed and hospitalized IHRPE patients (age >18 years) meeting ESC 2019 criteria. Vital signs (HR, SBP, SI, SPO2/FiO2 index) were recorded at seven pre-specified times to assess clinical course during the first 72 hours. Blood biomarkers were evaluated during the same pre-specified time blocks. Cardiac biomarkers (NT Pro BNP, troponin) were measured every 8 hours for first 24 hours and then every 12 hours. Non-cardiac biomarkers (uric acid, lactate) were measured once every 24 hours. RESULTS: Total of 20 subjects (16M) were diagnosed via CT angiogram and enrolled after informed consent. Median age was 61.5 years (IQR 53, 72.5). Comorbidities included underlying malignancy (5), prior history of VTE (3) and Covid-19 (1). Radiographic embolus patterns included saddle (9), distal main PA/lobar (9) and segmental/sub-segmental (2). Lower extremity DVT were found in 14 subjects. Median admission vital signs (IQR) at time of presentation were: Heart rate 110 BPM (101,118), SBP 116 mmHg (100, 132);RR 21 per min (16, 23);Shock index 0.9 (0.8, 1.1);SPO2 85% (85, 96);and SPO2/FiO2 ratio 289 (246, 454). Subjects were admitted to the medical ward (13) and ICU (7). 16 remained clinically stable and 4 had clinical decompensation (2 respiratory failure, 2 shock) of whom 2 expired. At enrollment, troponin (TNT) was elevated in 20/20 subjects, NT proBNP in 18/20subjects, lactate in 8/20 subjects, and uric acid in 9/20 subjects;biomarkers normalized at different rates, with marked inter-individual variation. The median (IQR) peak values were: TNT, 0.05 (0.025, 0.078) ng/ml;NTproBNP, 2458 (1147, 5599) pg/ml;lactate, 1.8 (1.4, 3.4) mmol/L;and, uric acid, 6.2 (5.0, 7.4) mg/dl. 1/16 (6.3%) stable patients showed an 8-16 hr increase in TNT, compared with 2/4 (50%) of the decompensated patients, who required subsequent advanced PE interventions (p=0.088). CONCLUSIONS: Biomarkers in IHRPE patients evolve with variable time-courses. The potential of rising troponin at 16 hours to identify risk for circulatory or respiratory decompensation deserves further investigation. CLINICAL IMPLICATIONS: Abnormal biomarkers may aid clinical decision-making regarding advanced therapies in IHRPE patients. DISCLOSURES: No relevant relationships by Wendy Craig No relevant relationships by Ariel McKenna No relevant relationships by Victoria Molina No relevant relationships by Alexander Smith No relevant relationships by Hilamber Subba Advisory Committee Member relationship with ACI Clinical Please note: 2020-2022 Added 04/04/2022 by Joel Wirth, value=Salary

REAL-WORLD DATA ON THE USE OF LUSPATERCEPT IN GREEK PATIENTS WITH TRANSFUSION DEPENDENT THALASSEMIA

Background: The EMA-approved, erythroid maturation agent, luspatercept, has been shown to decrease transfusion burden in patients with transfusion-dependent thalassemia (TDT). Aims: In this multicenter, retrospective cross-sectional study, real-world data from the use of luspatercept in TDT patients, managed in 5 major Thalassemia Centers in Greece are presented. Methods: Inclusion criteria included TDT patients, having received luspatercept as per approved indications for at least 3 months. Data cut-off date was 31/1/2022. We estimated the quantity of blood (in cc of Packed Red Blood Cells -PRBC) received over 12 weeks for the intervals: 12 weeks before starting treatment (baseline);1-12 weeks;5-16 weeks and 13-24 weeks post starting therapy. Changes in mean pre-transfusion hemoglobin (Hb), uric acid, creatinine, lactic acid dehydrogenase (LDH), white blood cells (WBC) and platelets counts were analyzed for these same respective periods. Adverse events (AE) were recorded. Statistical analysis performed with RStudio v.3.6.2. Results: Main results of the study are shown in Table 1. Forty-nine patients (median age: 46 years range:15-64, sex: M:F/33:16) received Luspatercept every 21 days. Data for weeks 5-16 and 13-24 were available for 30 and 16 patients, respectively. The initial dose of luspatercept was 1 mg/kg and increased selectively up to 1.25mg/kg based on tolerability and efficacy and according to guidelines. A statistically significant (p<0.005) decrease in PRBC transfused in all 12-weeks' intervals analyzed compared to baseline was observed. No statistically significant decrease of PRBC transfused was found between the intervals 5-16weeks and 13-24 weeks compared to the initial interval of 1-12 weeks. There was not a significant change for the mean pre-transfusion Hb compared to baseline. A statistically significant (p<0.005) increase in uric acid, creatinine, LDH , WBC and platelets was observed for the interval 1-12 weeks in comparison with baseline (mean: 6.42±1.64mg/dl vs 5.48±1.6mg/dl, 0.87±0.16mg/dl vs 0.83±0.18mg/dl, 352±205mg/dl vs 204±62mg/dl, 11.78x109 ±5.29x109/L vs 10.36x109±4.35x109/L, and 450x109±221x109/L vs 415x109±202x109/L, respectively. Similar difference was observed between the 13-24 weeks interval and baseline only for uric acid, LDH and platelets (mean: 6.28±1.41mg/dl vs 5.48±1.6mg/dl p=0.003, 406±301mg/dl vs 204±62mg/dl p=0.014, 467x109±226x109/L vs 415x109±202x109/L p<0.008 respectively). Twenty five out of 49 patients reported AE. The most common AE included bone pain 16/49 (32.6%) and fatigue 7/49 (14.2%). Frequent urination, headache, swelling at injection site, blurry vision, tearing, libido decrease, tachycardia, periorbital oedema, dizziness, and exacerbation of manic-depressive episodes were also reported. Twelve patients discontinued treatment. Reasons for discontinuation included: non-response to treatment (7 patients), adverse events (3 patients), non-compliance (1 patient), death due to COVID19 infection (1 patient). Summary/Conclusion: Real world data on the use of luspatercept in TDT parallel results from the trial, showing heterogeneous and lasting efficacy and acceptable toxicity. Longer follow up and increased number of patients are required to validate these initial observations. (Table Presented).

SARS-CoV-2 omicron variant clearance delayed in breakthrough cases with elevated fasting blood glucose.

BACKGROUND: Omicron variant (B.1.1.529) is a dominant variant worldwide. However, the risk factors for Omicron variant clearance are yet unknown. The present study aimed to investigate the risk factors for early viral clearance of Omicron variant in patients with a history of inactivated vaccine injection. METHODS: Demographic, clinical, and epidemiological data from 187 patients were collected retrospectively during the Omicron variant wave. RESULTS: 73/187 and 114/187 patients were administered two and three doses of vaccine, respectively. The median duration of SARS-CoV-2 RNA positivity was 9 days, and the difference between patients with two and three vaccine injections was insignificant (P = 0.722). Fever was the most common symptom (125/187), and most patients (98.4%) had a fever for < 7 days. The RNA was undetectable in 65/187 patients on day 7. Univariable logistic analysis showed that baseline glucose, uric acid, lymphocytes count, platelet count, and CD4+ T lymphocyte count were associated with SARS-CoV-2 RNA-positivity on day 7. Multivariable analysis showed that glucose ≥ 6.1 mmol/L and CD4+T lymphocytes count were independent risk factors for RNA positivity on day 7. 163/187 patients had an undetectable RNA test on day 14, and uric acid was the only independent risk factor for RNA positivity. Moreover, baseline glucose was negatively correlated with uric acid and CD4+ and CD8+ T cell count, while uric acid was positively correlated with CD4+ and CD8+ T cell count. CONCLUSIONS: Omicron variant clearance was delayed in breakthrough cases with elevated fasting blood glucose, irrespective of the doses of inactivated vaccine.