Incidence of Thromboembolism in COVID-19 Patients in Intensive Care Units: A Retrospective Cohort Analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) infection was declared a pandemic, causing high mortality and morbidity worldwide. It predisposes patients to both arterial and venous thromboembolism, which causes high mortality, and is one of the most serious complications of the disease. OBJECTIVE: The aim of this retrospective study was to determine the frequency of thromboembolic events in patients diagnosed with COVID-19 in the intensive care unit (ICU) and to identify the factors causing thromboembolism. MATERIAL AND METHODS: The digital records of patients admitted to the adult ICU of Derince Training and Research Hospital, Kocaeli, Turkey, with a diagnosis of COVID-19 between March 13, 2020, and December 31, 2021, were retrospectively reviewed. RESULTS: Data of 484 patients, 248 (51.2%) female and 236 (48.8%) male, aged between 18-98 years were analyzed. The overall, arterial and venous incidence of thromboembolism was 14.8%, 11.3%, and 3.5%, respectively. There was no significant association between COVID-19 variants and the development of thromboembolism. The effect of various patient variables on the development of thromboembolism was evaluated, including cardiovascular disease (p<0.001), age (p=0.003), use of acetylsalicylic acid (ASA) (p<0.001), antiplatelet therapy (p<0. 001), acute physiology and chronic health evaluation (APACHE) II score (p=0.003), D-dimer (p=0.015), fibrinogen (p=0.032), ferritin (p=0.015), prothrombin time (PT) (p=0.015), international normalized ratio (INR) (p=0.012), troponin (p=0.012) values at the ICU admission were found statistically significant. The cut-off values were 2.565 (µg/mL) for D-dimer, 435.51 (mg) for fibrinogen, 633.55 (ml/ng) for ferritin, 1.155 for INR, and 0.085 (ng/mL) for troponin. CONCLUSION:  Although low-molecular-weight heparin (LMWH) is the first choice, it may be appropriate to add ASA and other antiplatelet agents to reduce the risk of thromboembolism in patients with high thromboembolic risk including advanced age, cardiovascular disease, and elevated levels of D-dimer, troponin, ferritin, and fibrinogen.

A Comparison of the Effects of Dexamethasone and Methylprednisolone, Used on Level-3 Intensive Care COVID-19 Patients, on Mortality: A Multi-Center Retrospective Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often a mild disease, usually manifesting with respiratory complaints, and is sometimes mortal due to multiple organ failure. Hyperinflammation is a known COVID-19 component and is associated with organ dysfunction, disease severity and mortality. Controlling hyperinflammatory response is crucial in determining treatment direction. An important agent in providing this control is corticosteroids. This study aimed to determine whether dexamethasone and methylprednisolone, doses, administration time and duration in COVID-19 treatment are associated with improved treatment outcomes. METHODS: This retrospective multicenter study was conducted with participation of 6 healthcare centers which collected data by retrospectively examining files of 1,340 patients admitted to intensive care unit due to COVID-19 between March 2020 and September 2021, diagnosed with polymerase chain reaction (+) and/or clinically and radiologically. RESULTS: Mortality in the pulse methylprednisolone group was statistically significantly higher than that in the other 3 groups. Mortality was higher in older patients with comorbidities such as hypertension, diabetes mellitus, chronic kidney failure, coronary artery disease, and dementia. Pulse and mini-pulse steroid doses were less effective than standard methylprednisolone and dexamethasone doses, pulse steroid doses being associated with high mortality. Standard-dose methylprednisolone and dexamethasone led to similar effects, but standard dose methylprednisolone was more effective in severe patients who required mechanical ventilation (MV). Infection development was related to steroid treatment duration, not cumulative steroid dose. CONCLUSION: Corticosteroids are shown to be beneficial in critical COVID-19, but the role of early corticosteroids in mild COVID-19 patients remains unclear. The anti-inflammatory effects of corticosteroids may have a positive effect by reducing mortality in severe COVID-19 patients. Although dexamethasone was first used for this purpose, methylprednisolone was found to be as effective at standard doses. Methylprednisolone administered at standard doses was associated with greater PaO2/FiO2 ratios than dexamethasone, especially in the severe group requiring MV. High dose pulse steroid doses are closely associated with mortality and standard methylprednisolone dose is recommended.

Accelerated kynurenine pathway downregulates immune activation in patients with axial spondyloarthritis.

Various studies reported that the kynurenine (Kyn) pathway plays a pivotal role in regulating the balance between activation and inhibition of the immune system. Proinflammatory cytokines can accelerate the Kyn pathway by altering indoleamine (2, 3)- dioxygenase (IDO) allosteric enzyme activity. Excessive cytokine release and immune system activation have essential roles in the pathogenesis of axial spondyloarthritis (axSpA). We aimed to investigate the relationship of the Kyn pathway with proinflammatory cytokines and with the severity of the disease in patients with axSpA. The study included 104 patients with axSpA and 54 healthy volunteers. The severity of the disease was determined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The Kyn pathway was evaluated by IDO activity calculated with Kyn/Tryptophan (Trp) ratio. Plasma Trp and Kyn concentrations were measured with tandem mass spectrometry. Serum IL 17/23 and IFN-γ concentrations were measured with ELISA. These groups were compared in terms of IDO, IL-17, IL-23, IFN-γ, and BASDAI. Plasma IDO activity was significantly increased, however, serum IL-17, IL-23, and IFN-γ levels were significantly decreased in patients compared to healthy volunteers. While IFN-γ was positively correlated with the severity of the disease (p = 0.02), it also had a significant inverse correlation with IDO activity (p < 0.001). However, these correlations are weak. As a result of this study, the Kyn pathway is accelerated and proinflammatory cytokine levels are decreased in patients with axSpA. All of these results with an indirect weak negative association between high IDO and low disease activity suggest that an accelerated Kyn pathway may limit the immune system activation in axSpA disease.

Elevated Kynurenine Levels in Patients with Primary Sjögren's Syndrome.

OBJECTIVE: We aimed to investigate the plasma levels of tryptophan (Trp) and its metabolites in patients with primary Sjögren's syndrome (pSS). METHODS: The study included 34 pSS patients and 42 healthy individuals, and serum Trp and kynurenine (Kyn) concentrations were measured by liquid chromatography with tandem mass spectrometry. Trp degradation was predicted using the ratio of Kyn and Trp concentrations (Kyn/Trp). RESULTS: In our study, the mean serum Trp concentration was found to be considerably lower in the pSS group than in the control group (P = .001). The levels of Kyn (P = .019) and the Kyn/Trp ratio (P < .001) were significantly higher in the pSS group than in the control group. The Kyn/Trp ratio was negatively correlated with C-reactive protein (r = -0.369, P = .032). CONCLUSION: We found that Kyn pathway metabolism was altered in patients with pSS. This suggests that Trp metabolism may be closely linked to the disease pathogenesis of pSS.

Investigation of the effects of pneumatic tube transport system on routine biochemistry, hematology, and coagulation tests in Ankara City Hospital.

OBJECTIVES: Academics are far from a consensus regarding the effects of pneumatic tube system (PTS) delivery on sample integrity and laboratory test results. As for the reasons for conflicting opinions, each PTS is uniquely designed, sample tubes and patient characteristics differ among studies. This study aims to validate the PTS utilized in Ankara City Hospital for routine chemistry, coagulation, and hematology tests by comparing samples delivered via PTS and porter. METHODS: The study comprises 50 healthy volunteers. Blood samples were drawn into three biochemistry, two coagulation, and two hemogram tubes from each participant. Each of the duplicate samples was transferred to the emergency laboratory via Swiss log PTS (aka PTS-immediately) or by a porter. The last of the biochemistry tubes were delivered via the PTS, upon completion of coagulation of the blood (aka PTS-after). The results of the analysis in these groups were compared with multiple statistical analyses. RESULTS: The study did not reveal any correlation between the PTS and serum hemolysis index. There were statistically significant differences in several biochemistry tests. However, none of them reached the clinical significance threshold. Basophil and large unidentified cell (LUC) tests had poor correlations (r=0.47 and r=0.60; respectively) and reached clinical significance threshold (the average percentages of bias, 10.2%, and 15.4%, respectively). The remainder of the hematology and coagulation parameters did not reach clinical significance level either. CONCLUSIONS: The modern PTS validated in this study is safe for sample transportation for routine chemistry, coagulation, and hematology tests frequently requested in healthy individuals except for basophil and LUC.

Thiol/Disulfide Homeostasis in Bipolar and Unipolar Depression.

OBJECTIVE: Bipolar disorder and unipolar depressive disorder are complex phenotypes. There appear to be phenotypical, mechanistic, and therapeutic differences between bipolar depression (BD) and unipolar depression (UD). There is a need for understanding the underlying biological variation between these clinical entities. The role of oxidative processes underlying bipolar disorder and depression has been demonstrated. Thiol-disulfide homeostasis (TDH) is a recent oxidative stress marker. In this study, we aimed to inspect patients with bipolar depression and unipolar depression in terms of thiol-disulfide balance and to compare them with healthy controls. METHODS: Patients admitted to the outpatient clinic of Ankara Numune Training and Research Hospital and diagnosed either as a depressive episode with bipolar disorder (n = 37) or unipolar depression (n = 24) according to DSM-5 criteria, along with healthy controls (HC) (n = 50), were included in the study. Native thiol, total thiol, and disulfide levels were compared across the groups. RESULTS: In comparison to HC, both BD and UD groups had higher disulfide levels, disulfide/native thiol ratio, and disulfide/total thiol ratio. No significant differences between BD and UD were detected in terms of disulfide level, disulfide/ native thiol ratio, and disulfide/total thiol ratio. CONCLUSION: Increased levels of disulfide, native thiol, and disulfide/total thiol ratios compared to healthy controls in both UD and BD groups may be indicative of the presence of oxidative damage in these two clinical conditions. To clarify the role of oxidative stress in the pathophysiology of depressive disorders and investigate TDH, longitudinal studies in patients with medication-free UD and BD are required.

The Variation of Disulfides in the Progression of Type 2 Diabetes Mellitus.

AIM: The purpose of this study was to examine thiol-disulfide balance in patients with type 2 diabetes mellitus. METHODS: This study included 32 subjects with known type 2 diabetes mellitus without complications, 30 patients with type 2 diabetes mellitus with complications, 28 newly diagnosed patients with type 2 diabetes mellitus, and 45 healthy individuals. Thiol-disulfide profile tests were quantified in all groups. RESULTS: Compared to the control group, patients in each of the diabetic groups had significantly lower native and total thiol levels, higher disulfide levels, and higher disulfide/native thiol and disulfide/total thiol ratios (p<0.05 for all). Disulfide levels were significantly lower in the newly diagnosed group than in other diabetic groups (p<0.05). There were significant associations between glycemic parameters and thiol-disulfide tests (p<0.05). CONCLUSIONS: A disequilibrium between thiol-disulfide pairs occurs in patients with type 2 diabetes mellitus, and a gradual increase to disulfide levels may contribute to the disease's severity. Deteriorated thiol-disulfide homeostasis may be relevant to the pathophysiology of type 2 diabetes mellitus.

Does extracorporeal shockwave lithotripsy therapy affect thiol-disulfide homeostasis?

OBJECTIVE: Extracorporeal Shockwave Lithotripsy (ESWL) is a non-invasive method that is effective at crushing stones in the upper urinary tract. Disturbance of the thiol/disulfide homeostasis, in favor of the disulfide, has been shown to be involved in the disease pathogenesis. METHODS: A total of 36 individuals that underwent ESWL had blood samples collected before ESWL (0hrs), 6hrs, and one week after the ESWL. Sera native and total as wells as disulfide amount was measured using an automated method sodium borohydrate (NaBH4) reduction. In addition, Ischemia Modified Albumin (IMA) levels were measured using colorimetric assay method. RESULTS: Native thiol level was reduced at the 6th hour following ESWL compared to baseline. While the ratios of disulfide level, Disulfide/Total Thiol (DTT), Disulfide/Native Thiol (DNT) and IMA level were increased at the 6th hour following ESWL compared to baseline, they were found to be similar with their baseline values at the end of 1st week. Total thiol and native /total thiol did not show any significant change. CONCLUSIONS: ESWL treatment disrupts thiol/disulfide homeostasis and the structure of albumin at the acute term. Therefore, it increases protein oxidation and leads to increased oxidative stress. However, this state is transient and returns to normal within the proceeding days.