IMPACT OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH AS USING BIOLOGIC AGENTS

BackgroundAlthough renal involvement is an rare extra-articular involvement in patients with ankylosing spondylitis (AS), medications and accopamyning comorbidities may adversly affect renal functions [1].ObjectivesTo determine the frequency and impact of CKD in patients with AS using biologic disease modyfying anti-rheumatic drugs (bDMARDs).MethodsBetween 2005 and November 2021, 3207 patients diagnosed with AS according to the modified New York criteria were enrolled in the Hacettepe University biological database (HUR-BIO). The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guideline was used for the definition of CKD to evaluate the renal function of patients. Glomerular filtration rate (GFR) was calculated with the MDRD (modified Modification of Diet in Renal Disease) formula, taking into account the creatinine value, age and gender parameters of the patients [2]. CKD was detected in 39 (1,2%) patients. Age-sex matched 41 non-CKD AS patients were selected as the control group. Demographic and clinical characteristics and mortality rates of AS patients with and without CKD were compared.ResultsOf 39 AS-CKD patients, 25 (64.1%) had CKD before the initation of bDMARD and and 14 (35.8%) developed CKD during follow-up after treatment was started. Patients with AS-CKD had longer duration of symptoms and disease (Table 1). Comorbidities such as hypertension, coronary artery disease and amyloidosis were more prevalent in patients with AS-CKD. At a median follow-up of 2.48(0.1-20.1) years, mortality was observed in 11(28.2%) patients in the AS-CKD group, while no mortality was observed in the age-sex matched AS-nonCKD group (p<0.001, Figure 1). The mortality rate in patients with AS-CKD was 12.6 per 1000 patient-years, and 4 (10.2%) of deaths were during the COVID-19 pandemia.Figure 1.Table 1.AS-CKD group (n=39)AS-nonCKD group (n=41)PTotal AS patients, (n=3207)Age, mean(SD), years68.2 (12.0)58.8(12.6)-47.9±(11.2)Male, n(%)27 (69.2)27(65.9)-1716(53.5)53.1)Symptom duration, years median (min-max)20 (5-42)11(2-30)0.0110(1-44)Disease duration, years median (min-max)14,5(5-42)7(1-29)0.046(1-37)HLA-B27 positivity, n(%)13(33.3)12(29.2)0.5826/2014(41.0)Uveitis, n(%)6/354/360.2339/2946(11.5)Inflammatory bowel disease, n(%)4/353/360.4135/2946(4.58)Smoking, ever, n(%)22/34 (64.7)20/36(55.5)0.31781/2942(60.5)BMI (kg/m2), mean(SD)28 (6.08)28.2(5.01)0.828.1(5.5)Amiloidosis, n(%)14/36(38.9)1(2.4)<0.00133/2949(1.11)Comotbidities n(%)• Diabetes Mellitus,7/34(20.6)4/36(11.1)0.2199/2949(6.7)• Hypertension27/34(79.4)9/36(25)<0.001442/2949(14.9)• CAD8/21(38.1)1/25(4)0.005110/1882(5.8)• COPD5/21(23.8)0/240.004117/1774(6.59)CRP, med(min-max)1.6(0.4-12.4)1.77(0.1-23.6)0.81.07(0.1-45)• at the initiation of bDMARDs, at the last visit,0.7(0.16-14)0.55(0.1-7.5)0.30.5(0.1-14)ESR, med(min-max)• at the initiation of bDMARDs,48(12-140)30(2-96)0.119(1-140)• at the last visit, med(min-max)25(3-93)15(2-70)0.113(1-110)BASDAI, mean (SD)• At the initiation of bDMARDs4.5(±2.1) 5.46(±2.07) 0.5 5.7(±2.04) • At the last vizit3.94(±2.35)2.95(±2.33)0.093.69(±2.5)CAD: Coronary artery disease, COPD: Chronic Obstructive pulmonary disease, BMI: Body mass index, BASDAI: Bath AS Disease Activity IndexConclusionBoth comorbid disease burden and mortality seem to be increased in patients with AS-CKD. Increased mortality was more pronounced during the COVID-19 pandemia.References[1]Coşkun, B.N., et al., Anti-TNF treatment in ankylosing spondylitis patients with chronic kidney disease: Is it effective and safe? Eur J Rheumatol, 2022. 9(2): p. 68-74.[2]Stevens, P.E. and A. Levin, Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med, 2013. 158(11): p. 825-30.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

RISK OF APS AND aPLs POSITIVE PATIENTS FOR THROMBOSIS WITH COVID-19

BackgroundCoagulopathy, thromboembolic events and DIC during COVID-19 infection has been reported. Antiphospholipid antibodies (aPLs), present in 1–5 % of healthy individuals. aPLs are associated with the risk of antiphospholipid syndrome (APS) which is associated with higher risk of thrombosis.ObjectivesWe wanted to see if patients with known APS or aPLs only are at higher risk of a thrombotic event compared to control when developed COVID-19. We retrospectively review EMR for over a year for thrombotic events in patients with COVID and prior history of APS or aPLs only and matched them to control.MethodsPatient characteristics and laboratory testing were summarized according to the following groups: APS, aPLs detected or control. The control were matched according to age and gender for each group. Continuous variable were summarized as median (range) and mean (standard deviation), while categorical variables were reported as frequency (percentage). The binary patient outcome of thrombotic event, hospitalization for COVID, death, and composite event (the combined occurrence of thrombotic events, hospitalization, death) were calculated and interpreted as the multiplicative increase in odds of the given outcome for aPL group compared to control group. Multivariable logistic regression models were adjusted for potential risk factors (immobilization, hypertension, coronary artery disease, diabetes mellitus, and smoking) one at a time due to the rare occurrences of events studied.ResultsIn single variable analysis (unadjusted) the odds of the patient having a thrombotic event was approximately 27 times higher in patients with aPL only compared to Controls (P<0.001). We see similar results in multivariable analyses (adjusted) adjusting for the following variables one at a time: immobilization, hypertension, coronary artery disease, diabetes mellitus, and smoking. In each of the multivariable analyses, the adjusted odds of a thrombotic event was between approximately 24 and 29 times higher in patients with aPL Antibody Only compared to Controls (all P<0.001) indicating that association of aPL Antibody Only with thrombotic event was independent of immobilization, hypertension, coronary artery disease, diabetes, and smoking. There was no statistically significant risk of thrombosis in APS group vs control. Majority of patients with APS were on chronic anticoagulation.ConclusionWe found a statistical significantly difference in patient with aPLs only versus control regarding risk of thrombosis when developed COVID-19. No statistically significant risk was noted in patients with APS. While chronic anticoagulation in APS patients is protective it seemed that patient with aPLs only do carry a high risk of thrombosis if any inciting factors like COVID-19.References[1]C. Huang, Y. Wang, X. Li et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet 395 (2020)[2]A. Jayarangaiah, P.T. Kariyanna, X. Chen, A. Jayarangaiah, A. Kumar, COVID-19- Associated coagulopathy: an exacerbated immunothrombosis response, Clin. Appl. Thromb. 26 (2020)[3]Y. Zhang, M. Xiao, S. Zhang et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19, N. Engl. J. Med. 382 (2020)[4]K.J. Lackner, N. Müller-Calleja, Pathogenesis of antiphospholipid syndrome: recent insights and emerging concepts, Expert Rev. Clin. Immunol. 15 (2019)Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Coronary artery calcification: Effects on severity and survival in patients with COVID-19.

Background: The aim of this study was to evaluate the effect of coronary artery calcification on disease severity and prognosis in patients with coronavirus disease-2019 (COVID-19). Materials and Methods: One hundred and forty-one patients with COVID-19 were included in this study. The severity of pulmonary involvement and calcification of coronary arteries were assessed by computed tomography scan and calcification was classified by two methods: Weston and segmental. In both the methods, patients were divided into three groups with scores of 0, 1-6, and 7-12, which are called groups 1, 2, and 3, respectively. Results: The mean age of patients was 54.26 ± 14.55. Difference in score of pulmonary involvement was reported to be significant between deceased and discharged patients (11.73 ± 5.26 and 7.28 ± 4.47, P = 0.002, respectively). In Weston score system, the chance of recovery of Group 1 patients was significantly higher than Group 3 (odds ratio [OR] =6.72, P = 0.05, 95% confidence interval [CI] =1.901-50.257). Similar results were observed in the segmental scoring system (OR =6.34, P = 0.049, 95% CI =1.814-49.416). Despite the higher chance of severe disease in patients with coronary artery calcification, this increase was not statistically significant in either Weston or segmental methods (OR =0.47, P = 0.23 and OR =0.85, P = 0.79, respectively). Conclusion: Coronary artery calcification in patients with COVID-19 has a significant association with poor prognosis. However, no significant relationship was observed between this issue and the severity.

Case Series Evaluating Lymphocyte Subgroups at Diagnosis and After Treatment in Multisystem Inflammatory Syndrome Associated with COVID-19 in Children: Journal of Pediatric Infection

Lymphopenia, Increased B cell count, reversal of the CD4/CD8 ratio, and Increased active T cell count may be beneficial In the early diagnosis of MIS-C. Since It Is thought that the cytokine storm causes complications In MIS-C, Immediate administration of IVIG treatment Is considered essential. The disease was considered a new multisystem inflammatory syndrome, and with the increase in awareness, it has been reported more frequently in children (MIS-C) in Europe and the United States (2,3). Since the disease is thought to cause complications by leading to cytokine storms, immediate administration of intravenous immunoglobulin (IVIG) treatment is deemed important, and it is also essential to emphasize that IVIG treatment leads to marked cellular changes. Case 2 A nine-year-old male patient presented with fever, abdominal pain, headache, and diarrhea that had been present for five days, followed by a rash, conjunctivitis, and cervical lymphadenopathy. [...]the patient was considered to have atypical Kawasaki disease. According to a review, the most common signs and symptoms reported during MIS-C consisted of abdominal pain (61.9%), vomiting (61.8%), skin rash (55.3%), diarrhea (53.2%), hypotension (49.5%), and conjunctivitis (48.4%), and particularly gastrointestinal (90.9%), cardiovascular (86.5%), or dermatological or mucocutaneous (70.9%) involvement (2).

Aortic calcification . . . and other stories

Among 900 older women, median age 80, those who ate a diet rich in foods containing flavonoids, such as tea, fruit, red wine, and dark chocolate, were less likely to have abdominal aortic calcification detected in x rays of the lateral lumbar spine (Arterioscler Thromb Vasc Biol doi:10.1161/ATVBAHA.122.318408). In the Rush Memory and Aging Project, a prospective study of community dwelling people in Chicago, those with the highest intake of flavonoids experienced a slower decline in cognitive performance, even after adjustment for age, sex, and smoking. Missing persons Despite the best efforts of investigators, people drop out of studies. Because those who leave differ from those who stay, this can introduce bias.

Development and diseases of the coronary microvasculature and its communication with the myocardium.

We review the current understanding of formation and development of the coronary microvasculature which supplies oxygen and nutrients to the heart myocardium and removes waste. We emphasize the close relationship, mutual development, and communication between microvasculature endothelial cells and surrounding cardiomyocytes. The first part of the review is focused on formation of microvasculature during embryonic development. We summarize knowledge about establishing the heart microvasculature density based on diffusion distance. Then signaling mechanisms which are involved in forming the microvasculature are discussed. This includes details of cardiomyocyte-endothelial cell interactions involving hypoxia, VEGF, NOTCH, angiopoietin, PDGF, and other signaling factors. The microvasculature is understudied due to difficulties in its visualization. Therefore, currently available imaging methods to delineate the coronary microvasculature in development and in adults are discussed. The second part of the review is dedicated to the importance of the coronary vasculature in disease. Coronary microvasculature pathologies are present in many congenital heart diseases (CHD), especially in pulmonary atresia, and worsen outcomes. In CHDs, where the development of the myocardium is impaired, microvasculature is also affected. In adult patients coronary microvascular disease is one of the main causes of sudden cardiac death, especially in women. Coronary microvasculature pathologies affect myocardial ischemia and vice versa; myocardial pathologies such as cardiomyopathies are closely connected with coronary microvasculature dysfunction. Microvasculature inflammation also worsens the outcomes of COVID-19 disease. Our review stresses the importance of coronary microvasculature and provides an overview of its formation and signaling mechanisms and the importance of coronary vasculature pathologies in CHDs and adult diseases. This article is categorized under: Cardiovascular Diseases > Stem Cells and Development Congenital Diseases > Molecular and Cellular Physiology Cardiovascular Diseases > Molecular and Cellular Physiology.

Cardiac driving bans . . . and other stories

Time at target blood pressure A secondary analysis of data in a randomised trial of a combination pill in patients with mild to moderate hypertension suggests that an outcome of time spent at target blood pressure is a better indicator of effectiveness than whether the target was achieved at the end of the trial. Physical activity in people with coronary artery disease A systematic review combined data from nine prospective studies that included 34 000 patients to show that physical activity is highly beneficial in people with established coronary artery disease. A systematic review and meta-analysis of data containing more than 2 million person years of observation concludes that, even at levels below usual public health recommendations, physical activity protects against depression.

Association of cardiometabolic risk factors with hospitalisation or death due to COVID-19: population-based cohort study in Sweden (SCAPIS)

ObjectiveTo assess the association of cardiometabolic risk factors with hospitalisation or death due to COVID-19 in the general population.Design, setting and participantsSwedish population-based cohort including 29 955 participants.ExposuresCardiometabolic risk factors assessed between 2014 and 2018.Main outcome measuresHospitalisation or death due to COVID-19, as registered in nationwide registers from 31 January 2020 through 12 September 2020. Associations of cardiometabolic risk factors with the outcome were assessed using logistic regression adjusted for age, sex, birthplace and education.ResultsMean (SD) age was 61.2 (4.5) and 51.5% were women. 69 participants experienced hospitalisation or death due to COVID-19. Examples of statistically significant associations between baseline factors and subsequent hospitalisation or death due to COVID-19 included overweight (adjusted OR (aOR) vs normal weight 2.73 (95% CI 1.25 to 5.94)), obesity (aOR vs normal weight 4.09 (95% CI 1.82 to 9.18)), pre-diabetes (aOR vs normoglycaemia 2.56 (95% CI 1.44 to 4.55)), diabetes (aOR vs normoglycaemia 3.96 (95% CI 2.13 to 7.36)), sedentary time (aOR per hour/day increase 1.10 (95% CI 1.02 to 1.17)), grade 2 hypertension (aOR vs normotension 2.44 (95% CI 1.10 to 5.44)) and high density lipoprotein cholesterol (aOR per mmol/L increase 0.33 (95% CI 0.17 to 0.65)). Statistically significant associations were not observed for grade 1 hypertension (aOR vs normotension 1.03 (95% CI 0.55 to 1.96)), current smoking (aOR 0.56 (95% CI 0.24 to 1.30)), total cholesterol (aOR per mmol/L increase 0.90 (95% CI 0.71 to 1.13)), low density lipoprotein cholesterol (aOR per mmol/L increase 0.90 (95% CI 0.69 to 1.15)) and coronary artery calcium score (aOR per 10 units increase 1.00 (95% CI 0.99 to 1.01)).ConclusionsIn a large population-based sample from the general population, several cardiometabolic risk factors were associated with hospitalisation or death due to COVID-19.

ANALYSIS OF NUTRITIONAL STATUS AND BODY COMPOSITION OF ADOLESCENTS IN THE LARGEST MUNICIPALITY IN THE FORMER YUGOSLAVIA

Dear Editor-in-Chief, Obesity is characterized as one of the leading health problems facing modern society, and scientific technological advancements has led to constant progression in body mass of many of young people (Thun, Apicella, & Henley, 2000;Bukara - Radujkovic, & Zdravkovic, 2009). First sub-sample of the examinees consisted of 63 boys, while the second sub-sample consisted of 69 girls. According to research so far, the normal value of V.F.A. for ages 10 to 15 is set at 68.57 cm2 for both genders (Lee, Park, & Yum, 2012), and the normal level range is set from 1 to 9.

Diagnosis of coronary artery rethrombosis after effective systemic thrombolytic therapy in patients with ST-segment elevation myocardial infarction.

The aim of the study was to evaluate the diagnostic significance of ST-segment re-elevation episodes registered with telemetric ECG monitoring in patients with ST-segment elevation myocardial infarction (STEMI) treated with thrombolytic therapy (TLT). The study included 117 patients with STEMI following effective TLT. The elective coronary angiography followed by percutaneous coronary interventions was performed in the interval from 3 to 24 hours after a successful systemic TLT. Before and after cardiac catheterization, the telemetric ECG monitoring was performed using AstroCard Telemetry system (Meditec, Russia). During the study, two groups of patients were formed. Group 1 included 85 patients (72.6%) without new ST-segment deviations on telemetry. 77 patients (90.6%) had no recurrent coronary artery thrombosis at angiography. Eight patients (9.4%) from group 1 were diagnosed with thrombosis of the infarct-related coronary artery. Group 2 included 32 patients (27.4%) who underwent TLT and then had ST-segment re-elevation episodes of 1 mV or more in the infarct-related leads, lasting for at least 1 minute. In group 2, in 27 of 32 patients (84.4%), thrombosis of the infarct-related coronary artery was confirmed (p<0.01 compared with group 1). In 71.9% cases, the recurrent ischemic episodes were asymptomatic ('painless myocardial ischemia') (p<0.01). Thus, in patients with STEMI and successful TLT, re-elevation of ST-segment during remote ECG monitoring is strongly related to angiographically documented coronary artery thrombotic reocclusion. The absence of chest pain during recurrent myocardial ischemia requires continuous ECG telemetry to select patients for the rescue percutaneous coronary interventions at an earlier stage.

Which COVID-19 Patients Die in Intensive Care Unit (ICU) in Turkey

A comparison of deceased and surviving patients showed that being female, older than 62, and a smoker and having diabetes mellitus, hypertension, and/or coronary artery disease significantly increased mortality. Information about the patients' age, gender, comorbidities, duration of hospitalization, COVID-19-related lung tomography findings, hemogram parameters (white blood cell (WBC), neutrophil, lymphocyte, and platelet counts, haemoglobin level, neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR), biochemical parameters, and ventilatory support [mechanical ventilation, non-invasive mechanical ventilation (NIMV), high-flow oxygen (HFNO)] were retrospectively accessed in the hospital records. Since the first COVID-19 case was admitted on 15 March, 2020, a total of 618 patients have been diagnosed with COVID-19 in our hospital. The comparison of the deceased and surviving patients also displayed that smoking (p=0.004), diabetes mellitus (p=0.007), hypertension (p=0.042), and coronary artery disease (p=0.049) statistically increased mortality. In our study, the comparison of the laboratory parameters of the deceased and surviving patients showed that the platelet (p=0.006), white blood cell (p=0.048), and neutrophil counts (p=0.033), and NLR (p=0.010) and PLR (p=0.033) were significantly higher in the deceased group compared to the surviving group.

Anti-ischemic therapy in patients with COVID-19 and acute coronary syndrome

Introduction. Since the end of 2019, the pandemic caused by SARS-CoV2 has affected hundreds of millions of people, and the number of indirectly affected is many times higher. In addition to directly affecting lung tissue, the coronavirus infection predisposes patients to thrombotic events responsible for the occurrence of cardiovascular complications. The aim of our study was to observe patients with COVID-19 and acute coronary syndrome (ACS) and to evaluate the efficacy of anti-ischemic therapy with beta-blockers, molsidomine and trimetazidine.

Melatonin may decrease risk for and aid treatment of COVID-19 and other RNA viral infections.

A recent retrospective study has provided evidence that COVID-19 infection may be notably less common in those using supplemental melatonin. It is suggested that this phenomenon may reflect the fact that, via induction of silent information regulator 1 (Sirt1), melatonin can upregulate K63 polyubiquitination of the mitochondrial antiviral-signalling protein, thereby boosting virally mediated induction of type 1 interferons. Moreover, Sirt1 may enhance the antiviral efficacy of type 1 interferons by preventing hyperacetylation of high mobility group box 1 (HMGB1), enabling its retention in the nucleus, where it promotes transcription of interferon-inducible genes. This nuclear retention of HMGB1 may also be a mediator of the anti-inflammatory effect of melatonin therapy in COVID-19-complementing melatonin's suppression of nuclear factor kappa B activity and upregulation of nuclear factor erythroid 2-related factor 2. If these speculations are correct, a nutraceutical regimen including vitamin D, zinc and melatonin supplementation may have general utility for the prevention and treatment of RNA virus infections, such as COVID-19 and influenza.