Recent Advances in Computational Modeling of Biomechanics and Biorheology of Red Blood Cells in Diabetes

Diabetes mellitus, a metabolic disease characterized by chronically elevated blood glucose levels, affects about 29 million Americans and more than 422 million adults all over the world. Particularly, type 2 diabetes mellitus (T2DM) accounts for 90–95% of the cases of vascular disease and its prevalence is increasing due to the rising obesity rates in modern societies. Although multiple factors associated with diabetes, such as reduced red blood cell (RBC) deformability, enhanced RBC aggregation and adhesion to the endothelium, as well as elevated blood viscosity are thought to contribute to the hemodynamic impairment and vascular occlusion, clinical or experimental studies cannot directly quantify the contributions of these factors to the abnormal hematology in T2DM. Recently, computational modeling has been employed to dissect the impacts of the aberrant biomechanics of diabetic RBCs and their adverse effects on microcirculation. In this review, we summarize the recent advances in the developments and applications of computational models in investigating the abnormal properties of diabetic blood from the cellular level to the vascular level. We expect that this review will motivate and steer the development of new models in this area and shift the attention of the community from conventional laboratory studies to combined experimental and computational investigations, aiming to provide new inspirations for the development of advanced tools to improve our understanding of the pathogenesis and pathology of T2DM.

THE PROS AND CONS OF CO2 CT ANGIOGRAPHY VERSUS CONVENTIONAL CONTRAST ENHANCED CT ANGIOGRAPHY IN THE TREATMENT OF PERIPHERAL VASCULAR OCCLUSIONS

Over the past two decades, the field of vascular surgery has experienced tremendous advances in technique and technology. After the description of vascular anastomosis by Dr. Alexis Carrel almost one hundred years ago, the subsequent years were slowly crowned by the differentiation of general and vascular surgeons (Friedman 2016). Notably, surgeons were able to distinguish themselves by developing and acquiring techniques that are specific to operations in vascular surgery. This type of surgery involves diseases associated with the vascular system, which specifically includes the arteries, veins, and the lymphatic structure. Thus, vascular surgery provides treatment for diseases associated with the veins and arteries and is used in cases where less invasive methods cannot be incorporated (Reis and Roever 2017). Importantly, vascular diseases arise from damaged vessels or the presence of inflammations or blood clots leading to the occurrence of illnesses like peripheral vascular disease or peripheral arterial disease (PAD) that is occlusive in nature. Notably, vascular occlusion can be defined as the blockage of blood vessels due to the growth of an abnormality or the accumulation of fat or calcium in the inner lining of the venous structure. Occlusion is a common characteristic of PAD where the diameter of the blood vessels narrows considerably (Rotzinger, Lu, Kawkabani, Marques-Vidal, Fetz and Qanadli 2020). Another good example of peripheral vascular occlusion arises from atherosclerosis. This is an occlusive disease where the arteries harden due to fat or calcium, leading to the narrowing of the internal diameter of the vessels (Rotzinger et al. 2020). Over time, this diameter narrows greatly resulting in the formation of clots that restrict the supply of blood to the entire area past the blockage, leading to the development of PVD/PAD.

Retinal Occlusive Vasculitis in a Patient with Hyperimmunoglobulin E Syndrome

Background. Hyperimmunoglobulin E syndrome (HIES), or Job’s syndrome, is a primary immunodeficiency disorder that is characterized by an elevated level of IgE with values reaching over 2000 IU ( normal < 200 IU ), eczema, and recurrent staphylococcus infection. Affected individuals are predisposed to infection, autoimmunity, and inflammation. Herein, we report a case of HIES with clinical findings of retinal occlusive vasculitis. Case Presentation. A 10-year-old boy with a known case of hyperimmunoglobulin E syndrome had exhibited loss of vision and bilateral dilated fixed pupil. Fundoscopic examination revealed peripheral retinal hemorrhaging, vascular sheathing around the retinal arteries and veins, and vascular occlusion in both eyes. A fluorescein angiography of the right eye showed hyper- and hypofluorescence in the macula and hypofluorescence in the periphery of the retina, peripheral arterial narrowing, and arterial occlusion. A fluorescein angiography of the left eye showed hyper- and hypofluorescence in the supranasal area of the optic disc. Macular optical coherence tomography of the right eye showed inner and outer retinal layer distortion. A genetic study was performed that confirmed mutations of the dedicator of cytokinesis 8 (DOCK 8). HSV polymerase chain reaction testing on aqueous humor and vitreous was negative, and finally, the patient was diagnosed with retinal occlusive vasculitis. Conclusion. Occlusive retinal vasculitis should be considered as a differential diagnosis in patients with hyperimmunoglobulin E syndrome presenting with visual loss.

Long-term Microglial Phase-specific Dynamics During Single Vessel Occlusion and Recanalization

Vascular occlusion leading to brain dysfunctions is usually considered evoking microglia-induced inflammation response. However, it remains unclear how microglia interact with blood vessels in the development of vascular occlusion-related brain disorders. Here, we illuminate long-term spatiotemporal dynamics of microglia and their activation pattern during single vessel occlusion and recanalization. The results show that microglia display remarkable response characteristics in different phases, including acute reaction, rapid diffusion, transition and chronic effect. Microglial cell body represents a unique filament-shape migration and has slower motility compared to the immediate reaction of processes to occlusion. We capture single microglia with few processes moves out of the cluster and redistributes territory with increasing ramified processes. Microglial cluster resolves gradually until microglial number and morphology become stabilized. Therefore, our study offers a comprehensive analysis of spatiotemporal dynamics of microglia to both vessel occlusion and recanalization. Microglial phase-specific response suggests the morphological feature-oriented phased intervention would be an attractive option for vascular occlusion-related diseases treatments.

Risk factors for emerging intraocular inflammation after intravitreal brolucizumab injection for age-related macular degeneration

Purpose To analyze the risk factors associated with emerging intraocular inflammation (IOI) after intravitreal brolucizumab injection (IVBr) to treat age-related macular degeneration (AMD). Methods This study included 93 eyes of 90 patients. The incidence of emerging IOI was analyzed. The patients were classified into IOI or non-IOI groups, and background clinical characteristics in each group were compared. Results IOI occurred in 14 eyes of 14 cases (16%; five women, nine men [5:9]; IOI group) after IVBr; contrastingly, no IOI occurred in 76 patients (10 women, 66 men [10:66]; non-IOI group). The mean ages in IOI and non-IOI groups were 79.4 ± 8.1 and 73.8 ± 8.9 years old, respectively, and the average age in the IOI group was significantly higher than that in the non-IOI group (P = 0.0425). In addition, the percentages of females in the IOI and non-IOI groups were 43% and 13%, respectively, and IOI occurred predominantly in females (odds ratio: 4.95, P = 0.0076). Moreover, the prevalence of diabetes in the IOI and non-IOI groups was 64% and 32%, respectively, with a significant difference (odds ratio: 3.90, P = 0.0196). In contrast, the prevalence of hypertension in the IOI and non-IOI groups was 36% and 57%, respectively, with no significant difference (P = 0.15). Conclusion The comparison of clinical profiles of IOI or non-IOI cases in IVBr treatment for AMD suggests that the risk factors for IOI are old age, female sex, and history of diabetes; however, IOI with vasculitis or vascular occlusion in this cohort does not seem to cause severe visual impairment. Further studies are required to investigate potential risk factors for IOI.

Systematic CT perfusion acquisition in acute stroke increases vascular occlusion detection and thrombectomy rates

BackgroundIn patients with stroke, current guidelines recommend non-invasive vascular imaging to identify intracranial vessel occlusions (VO) that may benefit from endovascular treatment (EVT). However, VO can be missed in CT angiography (CTA) readings. We aim to evaluate the impact of consistently including CT perfusion (CTP) in admission stroke imaging protocols.MethodsFrom April to October 2020 all patients admitted with a suspected acute ischemic stroke underwent urgent non-contrast CT, CTA and CTP and were treated accordingly. Hypoperfusion areas defined by time-to-maximum of the tissue residue function (Tmax) >6 s, congruent with the clinical symptoms and a vascular territory, were considered VO (CTP-VO). In addition, two experienced neuroradiologists blinded to CTP but not to clinical symptoms retrospectively evaluated non-contrast CT and CTA to identify intracranial VO (CTA-VO).ResultsOf the 338 patients included in the analysis, 157 (46.5%) presented with CTP-VO (median Tmax >6s: 73 (29–127) mL). CTA-VO was identified in 83 (24.5%) of the cases. Overall CTA-VO sensitivity for the detection of CTP-VO was 50.3% and specificity was 97.8%. Higher hypoperfusion volume was associated with increased CTA-VO detection (OR 1.03; 95% CI 1.02 to 1.04). EVT was performed in 103 patients (30.5%; Tmax >6s: 102 (63–160) mL), representing 65.6% of all CTP-VO. Overall CTA-VO sensitivity for the detection of EVT-VO was 69.9% and specificity was 95.3%. Among patients who received EVT, the rate of false negative CTA-VO was 30.1% (Tmax >6s: 69 (46–99.5) mL).ConclusionSystematically including CTP in acute stroke admission imaging protocols may increase the diagnosis of VO and rate of EVT.

34 The diagnostic and therapeutic pathway of the patient with SCA: Nursing&Tech assistance

Cardiomyopathies to be the first cause of death. The patient who suffers from acute heart disease, after clinical evaluation, is subjected to a diagnostic–therapeutic process that involves several professional figures which include the doctor and the ambulance nurse, the doctor and all the emergency room staff who accept the patient and, if the clinical indication is oriented towards a vascular occlusion disease, the doctor and the technical-nursing team of the haemodynamics service activated in urgency. To diagnose with certainty the presence of vascular disease we make use of diagnostic systems that use ionizing radiation; the haemodynamics team thus finds itself operating not only in urgent conditions but also in dangerous conditions due to the presence of ionizing radiation. Nursing and technical staff need additional skills to be able to take on roles from basic care to emergency electric shock resuscitation. The purpose of this work is to illustrate the phases of the activity that stabilize the treatment in the hemodynamics room from the acute phase to the patient.

Laser treatment of macular retinal folds in late postoperative period after retinal detachment repair

Macular retinal folds are a rare yet grave complication of surgical rhegmatogenous retinal detachment repair. Clinical symptoms vary depending on the location and severity of folding. Fold located in the periphery of the ocular fundus can be asymptomatic, but macular retinal folds cause diminished visual acuity and metamorphopsia. Currently, the most effective treatment for retinal folds is repeat surgery. Its serious disadvantage is the risk of complications in the early postoperative period, including hemophthalmia, inflammation, secondary glaucoma, cataracts, RRD recurrence, macular tears, retinal vascular occlusion, etc. The clinical case described below demonstrates the potential of combination laser therapy for the treatment of macular retinal folds based on the use of modern diagnostic and therapeutic methods.