Browsing by Author "Christodoulides, Alexei"

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    Effect of Chandler loop shear and tubing size on thrombus architecture
    (Springer, 2023-05-12) Zeng, Ziqian; Chakravarthula, Tanmaye Nallan; Christodoulides, Alexei; Hall, Abigail; Alves, Nathan J.; Emergency Medicine, School of Medicine
    Thrombosis can lead to a wide variety of life-threatening circumstances. As current thrombolytic drug screening models often poorly predict drug profiles, leading to failure of thrombolytic therapy or clinical translation, more representative clot substrates are necessary for drug evaluation. Utilizing a Chandler loop device to form clot analogs at high shear has gained popularity in stroke societies. However, shear-dependent clot microstructure has not been fully addressed and low shear conditions are often overlooked. We herein characterized the impact of wall shear rate (126 to 951 s-1) on clot properties in the Chandler loop. Different revolutions (20-60) per minute and tubing sizes (3.2 to 7.9 mm) were employed to create different sized clots to mimic various thrombosis applications. Increased shear resulted in decreased RBC counts (76.9 ± 4.3% to 17.6 ± 0.9%) and increased fibrin (10 to 60%) based on clot histology. Increased fibrin sheet morphology and platelet aggregates were observed at higher shear under scanning electron microscope. These results show the significant impact of shear and tubing size on resulting clot properties and demonstrate the capability of forming a variety of reproducible in-vivo-like clot analogs in the Chandler loop device controlling for simple parameters to tune clot characteristics.
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    Exploring microplastic impact on whole blood clotting dynamics utilizing thromboelastography
    (Frontiers Media, 2023-07-13) Christodoulides, Alexei; Hall, Abigail; Alves, Nathan J.; Emergency Medicine, School of Medicine
    This study investigates the influence of microplastics on blood clotting. It addresses the lack of comprehensive research on the effects of microplastic size and surface modification on clotting dynamics in human whole blood. Thromboelastography was used to examine aminated (aPS), carboxylated (cPS), and non-functionalized (nPS) polystyrene particles with sizes of 50, 100, and 500  nm. Results show that cPS consistently activated the clotting cascade, demonstrating increased fibrin polymerization rates, and enhanced clot strength in a size and concentration-dependent manner. nPS had minimal effects on clotting dynamics except for 50  nm particles at the lowest concentration. The clotting effects of aPS (100  nm particles) resembled those of cPS but were diminished in the 500  nm aPS group. These findings emphasize the importance of microplastic surface modification, size, concentration, and surface area on in-vitro whole blood clotting dynamics.
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    High Rates of Nicotine Use Relapse and Ulcer Development Following Roux-en-Y Gastric Bypass
    (Springer, 2021-02) Athanasiadis, Dimitrios I.; Christodoulides, Alexei; Monfared, Sara; Hilgendorf, William; Embry, Marisa; Stefanidis, Dimitrios; Surgery, School of Medicine
    PURPOSE: Given that smoking is known to contribute to gastrojejunal anastomotic (GJA) ulcers, cessation is recommended prior to laparoscopic Roux-en-Y gastric bypass (LRYGB). However, smoking relapse rates and the exact ulcer risk remain unknown. This study aimed to define smoking relapse, risk of GJA ulceration, and complications after LRYGB. MATERIALS AND METHODS: We performed a retrospective cohort study of patients who underwent primary LRYGB during 2011-2015. Initially, three patient categories were identified: lifetime non-smokers, patients who were smoking during the initial visit at the bariatric clinic or within the prior year (recent smokers), and patients who had ceased smoking more than a year prior to their initial clinic visit (former smokers). Smoking relapse, GJA ulcer occurrences, reinterventions, and reoperations were recorded and compared. RESULTS: A total of 766 patients were included in the analysis. After surgery, 53 (64.6%) recent smokers had resumed smoking. Out of these relapsed smokers, 51% developed GJA ulcers compared with 14.8% in non-relapsed recent smokers, 16.1% in former smokers, and 6% in lifetime nonsmokers (p < 0.001). Furthermore, relapsed smokers required more frequently endoscopic reinterventions (60.4%) compared with non-relapsed smokers (20.8%, p < 0.001), former smokers (20.7%, p < 0.001), and lifetime non-smokers (15.4%, p < 0.001). Additionally, relapsed smokers required a reoperation (18.9%) more often than non-relapsed recent smokers (5.7%, p < 0.001) and lifetime non-smokers (1.3%, p < 0.001). CONCLUSION: Smokers relapse frequently after LRYGB, and the majority experience GJA complications. They should be counseled about this risk preoperatively and directed towards less ulcerogenic procedures when possible. Alternatively, longer periods of preoperative smoking abstinence might be needed.
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    Real-time tracking of fibrinolysis under constant wall shear and various pulsatile flows in an in-vitro thrombolysis model
    (Wiley, 2023-04-11) Zeng, Ziqian; Christodoulides, Alexei; Alves, Nathan J.; Emergency Medicine, School of Medicine
    A great need exists for the development of a more representative in‐vitro model to efficiently screen novel thrombolytic therapies. We herein report the design, validation, and characterization of a highly reproducible, physiological scale, flowing clot lysis platform with real‐time fibrinolysis monitoring to screen thrombolytic drugs utilizing a fluorescein isothiocyanate (FITC)‐labeled clot analog. Using this Real‐Time Fluorometric Flowing Fibrinolysis assay (RT‐FluFF assay), a tPa‐dependent degree of thrombolysis was observed both via clot mass loss as well as fluorometrically monitored release of FITC‐labeled fibrin degradation products. Percent clot mass loss ranged from 33.6% to 85.9% with fluorescence release rates of 0.53 to 1.17 RFU/min in 40 and 1000 ng/mL tPa conditions, respectively. The platform is easily adapted to produce pulsatile flows. Hemodynamics of human main pulmonary artery were mimicked through matching dimensionless flow parameters calculated using clinical data. Increasing pressure amplitude range (4–40 mmHg) results in a 20% increase of fibrinolysis at 1000 ng/mL tPA. Increasing shear flow rate (205–913 s−1) significantly increases fibrinolysis and mechanical digestion. These findings suggest pulsatile level affects thrombolytic drug activities and the proposed in‐vitro clot model offers a versatile testing platform for thrombolytic drug screening.
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    Subarachnoid haemorrhage associated with pituitary apoplexy and radiographically occult supraclinoid internal carotid artery aneurysms
    (BMJ, 2023-09-18) Christodoulides, Alexei; Burket, Noah J.; Virtanen, Piiamaria; Lane, Brandon C.; Neurological Surgery, School of Medicine
    In patients with pituitary adenomas, incidental intracranial aneurysms have been documented. Previous studies have highlighted the importance of preoperative imaging in these patients. However, imaging may be limited and fail to show the presence of vascular abnormalities. In this report, we discuss a case of a man in his 30s presenting with a newly diagnosed pituitary adenoma. CT and MRI, on admission, showed a pituitary mass with extension into the right cavernous sinus. After a sudden neurological deterioration, emergent CT/CT angiography revealed pituitary apoplexy with subarachnoid extension without vascular abnormalities. Successful emergency transsphenoidal hypophysectomy was followed by digital subtraction angiography which revealed the presence of two right supraclinoid internal carotid artery aneurysms. With this case, we aim to highlight the need for further vascular imaging in patients with pituitary apoplexy and subarachnoid haemorrhage, as preoperative imaging may be negative for vascular abnormalities especially in the setting of cavernous sinus invasion.
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    Warfarin versus factor Xa inhibitors in the long-term treatment of cerebral venous sinus thrombosis a single-center retrospective analysis
    (Elsevier, 2022-06-17) Christodoulides, Alexei; Bohnstedt, Bradley N.; Neurological Surgery, School of Medicine
    Long-term anticoagulation in the treatment of Cerebral Venous Sinus Thrombosis (CVST) has revolved around the use of warfarin. The relatively recent introduction of Direct Oral Anticoagulants (DOACs), such as Factor Xa inhibitors, in treating CVSTs promises to offer numerous patient benefits. We aimed to examine the efficacy of Factor Xa inhibitors in comparison to warfarin in the long-term treatment of CVSTs. A single-center retrospective analysis was conducted in which 49 eligible patients having presented with a first-time CVST were identified. Long-term anticoagulation was achieved with Warfarin (n = 23) or Factor Xa Inhibitors (n = 26; Apixaban or Rivaroxaban). Outcomes of interest were improvements in patient functional status, modified Ranking Scores (mRS), and radiographic improvement/resolution in sinus thromboses. Secondary comparisons included complication rates, particularly recurring venous thrombotic events. Patient mRS scores by 7-to-18-month follow-up all fell within the extremely favorable range of 0-1 regardless of the long-term anticoagulant (P-value = 0.3591). Proportion of patients with radiographic improvement/resolution of thrombosed sinuses trended towards being higher in the Factor Xa Inhibitor group at the <12-month period, 69.2%, compared to 33.3% with Warfarin (P-value = 0.0548). By the >12-month follow-up period, Warfarin and Factor Xa inhibitor groups had similar rates of radiographic sinus improvement - 76.9% versus 71.4%, respectively (P-value = 0.6298). No statistically significant differences were documented between groups regarding complications. Factor Xa inhibitors are equally as effective as Warfarin in the long-term treatment of CVSTs, whether it be restoring patient functional status, sinus thrombus burden reduction, or minimizing bleeding complications whilst preventing recurrent venous thrombosis.