Browsing by Author "Christodoulides, Alexei"
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Item Determining the Effects of Varying Blood Storage Conditions on Clot Formation and Digestion Under Shear(Wiley, 2024) Christodoulides, Alexei; Zeng, Ziqian; Hall, Abigail R.; Alves, Nathan J.; Emergency Medicine, School of MedicineStudies aiming to understand the effects of storage on whole blood clotting often rely on characterizing coagulation under static conditions. Minimal work has explored the effects of physiologic shear on clot formation and thrombolysis utilizing fractionated and reconstituted whole blood products. Whole blood (WB) was fractionated into platelet free plasma (PFP), packed red blood cells (pRBCs), and platelets storing each component under its ideal conditions - including platelet cryopreservation. Recombination at their native ratios was accomplished over 91-days of storage and clotting/thrombolysis was analyzed utilizing thromboelastography (TEG) and Chandler loop. Reconstituted whole blood (rWB) preserved clot strength through 91 days with minimal deviation from baseline, in contrast to WB stored at 4°C which experienced a significant decline by storage day-42. Clot formation under shear for both rWB and WB led to increased clot mass through storage. No significant deviation from baseline was appreciated until day-70 of storage in rWB. Increasing degrees of thrombolysis were seen in both groups, with rWB significantly deviating from baseline at day-70. No significant changes in overall clot architecture occurred throughout storage and recombination. This fractionation and recombination protocol serves as a method to further develop reproducible in vitro clot analogs for preclinical thrombolytic therapy screening.Item 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 MedicineThrombosis 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.Item Endovascular treatment of penetrating nail gun injury of the cervical spine and vertebral artery: a case report(The Korean Society of Traumatology, 2022) Christodoulides, Alexei; Mitchell, Scott; Bohnstedt, Bradley N.; Neurological Surgery, School of MedicineIn this report, we present a case of high cervical penetrating trauma with vertebral artery injury and outline preprocedural, procedural, and postprocedural considerations with recommendations for the treatment of similar injuries. Management involves multiple imaging modalities, including X-ray imaging, computed tomography, computed tomography angiography, magnetic resonance imaging, and catheter angiography. We recommend endovascular treatment of these injuries when possible, based on the improved ability to achieve proximal and distal control and manage hemorrhage risk.Item 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 MedicineThis 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.Item 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 MedicinePURPOSE: 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.Item Rapid neurological recovery with spontaneous resolution of acute subdural hematoma after severe head trauma: A case report of auto-decompression phenomena(Elsevier, 2025) Obeng-Gyasi, Barnabas; Chinthala, Anoop S.; Christodoulides, Alexei; Ordaz, Josue; Mao, Gordon; Neurological Surgery, School of MedicineIntroduction: The spontaneous resolution of acute subdural hematoma (aSDH) represents an ill-defined but clinically significant phenomenon in traumatic brain injury (TBI). While surgical evacuation remains the standard of care for significant aSDH, rare cases of spontaneous resolution, termed auto-decompression in literature, suggest alternative pathways of hematoma clearance that warrant further investigation. Case presentation: We discuss the case of a 40-year-old male with background seizure disorder who fell off a ladder. His Glasgow Coma Score (GCS) at presentation was 5. Brain Computed Tomography (CT) scan revealed bilateral aSDH and multiple skull fractures. Within 24 h, his GCS quickly improved to 9 T. Repeat brain CT done 72 h post-trauma showed resolution of the aSDH following non-operative management. Discussion: Spontaneous resolution of bilateral aSDH with rapid neurological improvement is a rare but possible occurrence, often attributed to auto-decompression phenomenon in patients with severe head trauma and specific predisposing factors. Our discussion revolves around this patients presentation with polytrauma, complex skull fractures, history of craniotomy, and acute coagulopathy contributing to the spontaneous resolution of the hematoma. Given the complex nature of TBI and the unpredictable course of recovery, clinicians must remain vigilant in continuously reassessing neurological status. Conclusion: This case discusses the unpredictable nature of TBI and highlights the rapid and unexpected resolution of aSDH in a patient with complex neurosurgical history, coagulopathy, and polytrauma. The findings showcase the problems of polytraumatized patients and exemplify the importance of individualized care even when initial signs indicate poor prognosis.Item 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 MedicineA 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.Item 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 MedicineIn 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.Item Tracking Fibrinolysis of Chandler Loop-formed Whole Blood Clots Under Shear Flow in an In-vitro Thrombolysis Model(MyJoVE, 2024-04-19) Christodoulides, Alexei; Hall, Abigail R.; Umesh, Anushri; Alves, Nathan J.; Emergency Medicine, School of MedicineThromboembolism and related complications are a leading cause of morbidity and mortality worldwide and various assays have been developed to test thrombolytic drug efficiency both in vitro and in vivo. There is increasing demand for more physiologically relevant in-vitro clot models for drug development due to the complexity and cost associated with animal models in addition to their often lack of translatability to human physiology. Flow, pressure, and shear rate are important characteristics of the circulatory system, with clots that are formed under flow displaying different morphology and digestion characteristics than statically formed clots. These factors are often unrepresented in conventional in-vitro clot digestion assays, which can have pharmacological implications that impact drug translational success rates. The Real-Time Fluorometric Flowing Fibrinolysis (RT-FluFF) assay was developed as a high-fidelity thrombolysis testing platform that uses fluorescently tagged clots formed under shear flow, which are then digested using circulating plasma in the presence or absence of fibrinolytic pharmaceutical agents. Modifying the flow rates of both clot formation and clot digestion steps allows the system to imitate arterial, pulmonary, and venous conditions across highly diverse experimental setups. Measurements can be taken continuously using an in-line fluorometer or by taking discrete time points, as well as a conventional end point clot mass measurement. The RT-FluFF assay is a flexible system that allows for the real-time tracking of clot digestion under flow conditions that more accurately represent in-vivo physiological conditions while retaining the control and reproducibility of an in-vitro testing system.Item 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 MedicineLong-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.