Circumferential Fiber Research Articles

Fabrication and mechanical characterization of near field electrospun bioresorbable vascular grafts with fibrous architecture mimicking the arterial extracellular matrix

Cardiovascular disease, arteriosclerosis, is characterized by the thickening of blood vessel (arteries) walls restricting blood flow and is a global health problem. One treatment option is a surgical procedure utilizing an autologous or synthetic vascular graft to bypass or replace the diseased arterial segment. The goal of this study was to fabricate and mechanically characterize near field electrospun bioresorbable vascular grafts with a fibrous architecture that mimics the arterial extracellular matrix. Polydioxanone vascular constructs with circumferential fiber alignment angles of 15°/75° and 30°/60° (0° representing circumferential fiber alignment) were fabricated using a custom built near-field electrospinning (NFES) system. The vascular construct mechanical properties were compared to the saphenous vein (SV) and internal mammary artery (IMA) through longitudinal and circumferential uniaxial mechanical testing, suture retention, and burst pressure evaluations. The results demonstrated that the 15°/75° templates were closest to mimicking the native vessel target properties as compared to the 30°/60°; however, neither of the vascular template designs achieved or exceeded all the target values. For the ultimate tensile strength, both the constructs met the SV value on the circumferential axis (2.61 MPa) and the IMA value on the longitudinal axis (4.3 MPa). In terms of suture retention, the 15°/75° template was the only construct that was in the IMA and SV targeted range of 138–200 gf. Finally, the burst pressure testing results indicated that neither of the vascular constructs achieved the level of the SV or IMA (1600–3196 mmHg), however, the 15° constructs were within the lower error of the SV. In conclusion, with further design modifications, NFES constructs have demonstrated promise as small-diameter vascular grafts by mimicking native arterial architecture and mechanical properties.

Effects of conditioning on the left ventricular function of young purebred Arabian horses.

The effects of conditioning on cardiac function in young horses is still unknown. For this reason, this study evaluated the left ventricular (LV) function of young horses by echocardiography after six weeks of conditioning. Fourteen untrained young purebred Arabian horses were evaluated at rest and after a stress test (ST) before and after a six-week conditioning program. There was an increase in V4 (p < 0.001) after conditioning, as well as a reduction in both heart rate (HR) at rest and peak HR during the ST (p < 0.001). There was also a reduction in internal diameter, along with an increase in interventricular septal, free wall and mean thicknesses and LV mass (p < 0.05). After the ST, the conditioned animals showed higher values of velocity time integral, stroke volume, systolic and cardiac indices, ejection (ET) and deceleration times (DT), end-diastolic volume, time to onset of radial myocardial velocity during early diastole and time to peak of transmitral flow velocity, in addition to reduced pre-ejection period (PEP), PEP/ET ratio and mean velocity of circumferential fiber shortening (p < 0.05). The conditioning protocol promoted physiological adaptations that indicate an improvement in the animals' aerobic capacity associated with an enhanced left ventricular function.

Stress Analysis on Mesiolingual Cavity of Endodontically Treated Molar Restored Using Bidirectional Fiber-Reinforced Composite (Wallpapering Technique).

Endodontically treated teeth (ETT) undergo extensive structure change and experience high stress during biomechanical function. Stress distribution is influenced by the restoration material and the type of bond between material and tooth structure. The selection of materials that can distribute stress will affect the resistance and retention of ETT to mastication forces, thus biomechanical functions were achieved. Composite has mechanical properties similar to dentin, it can transmit and distribute stresses throughout the tooth surface. The disadvantage of composites in large cavities is their lack of toughness. The addition of fiber to composites can increase their toughness. This research is to determine the stress distribution of a fiber-reinforced composite made of polyethylene and e-glass on the mesiolingual cavity of ETT. A three-dimensional model of the mandibular molar was prepared for cavity preparation and the formation of restorations using SolidWorks 2021. The models were analyzed with Abaqus 2020 to determine stress concentrations after given vertical and oblique loading. The maximum and minimum principal stress data were obtained to assess material resistance and interfacial damage criterion. Polyethylene fiber shows a more homogeneous stress distribution because the modulus of elasticity is close to the dentin and has a thickness that can reduce the volume of the composite. The E-glass shows the stress concentration on the circumferential fiber and cavity floor. The stress distribution of fiber-reinforced composite on the buccolingual cavity of ETT using the finite element method did not show structural failure in the polyethylene group because the maximum and minimum principal stresses were lower than the strength of the material. Interfacial bond failure occurs at the enamel portion. The maximum and minimum principal values of e-glass indicate structural failure in the circumferential fiber and the base fiber because the stress exceeds the strength of the material. Interfacial bond failure occurred on the circumferential and the cavity floor.

Age-dependent changes in collagen crosslinks reduce the mechanical toughness of human meniscus.

The mechanical resilience of the knee meniscus is provided by a group of structural proteins in the extracellular matrix. Aging can alter the quantity and molecular structure of these proteins making the meniscus more susceptible to debilitating tears. In this study, we determined the effect of aging on the quantity of structural proteins and collagen crosslinks in human lateral meniscus, and examined whether the quantity of these molecules was predictive of tensile toughness (area under the stress-strain curve). Two age groups were tested: a young group under 40 and an older group over 65 years old. Using mass spectrometry, we quantified the abundance of proteins and collagen crosslinks in meniscal tissue that was adjacent tothe dumbbell-shaped specimens used to measure uniaxial tensile toughness parallel or perpendicular to the circumferential fiber orientation. We found that the enzymatic collagen crosslink deoxypyridinoline had a significant positive correlation with toughness, and reductions in the quantity of this crosslink with aging were associated with a loss of toughness in the ground substance and fibers. The non-enzymatic collagen crosslink carboxymethyl-lysine increased in quantity with aging, and these increases corresponded to reductions in ground substance toughness. For the collagenous (Types I, II, IV, VI, VIII) and non-collagenous structural proteins (elastin, decorin, biglycan, prolargin) analyzed in this study, only the quantity of collagen VIII was predictive of toughness. This study provides valuable insights on the structure-function relationships of the human meniscus, and how aging causes structural adaptations that weaken the tissue's mechanical integrity.

Artificial intelligence technology applied to an unoccluded catheter for recognition of hemodynamic changes

This study seeks to provide a reliable means for physicians to diagnose hemorrhagic complications associated with patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. We employ the YOLOv4 algorithm to analyze cardiac parameters from the echocardiography device's ultrasonic wave, such as left ventricular ejection time (LVET), left ventricular internal dimension-diastole (LVIDd), left ventricular internal dimension-systole (LVIDs), posterior wall thickness at end-systole (HES), and RR interval. The proposed model has achieved an impressive average detection accuracy of 89.4% for these five parameters. Additionally, the further evaluation of cardiac function can be done by deriving the end-systolic wall stress (ESWS) and left ventricle rate-corrected mean velocity of circumferential fiber shortening (mVcFc) values from these parameters. As a result, it indicates that the accuracy of ESWS and mVcFc values is 88.7% and 90.3%, respectively. With this deep learning-based approach, physicians can confidently evaluate the cardiac function of ELBW infants and diagnose PDA-related hemorrhagic complications.

Meniscal Circumferential Fiber Augmentation: A Biomechanical Arthroscopic Meniscal Repair Technique

Radial tears of the human knee meniscus result in the loss of circumferential hoop stress and are highly correlated with knee degeneration. Although a variety of surgical techniques are available to repair radial meniscal tears, including inside-out, outside-in, and all-inside techniques, conventional repair techniques focus only on stabilizing the damaged portion. This Technical Note describes a biomechanical meniscus repair technique of meniscal circumferential fiber augmentation, concomitant with conventional repair, to promote meniscal healing from a biomechanical perspective.

The Effect of Glycemic Control on Left Ventricular Function in Clinical and Experimental Diabetes

BackgroundGlycemic control in diabetes mellitus (DM) has not improved cardiovascular outcomes with normal left ventricular (LV) function. We assessed the effect on LV dysfunction using a canine model of LV dysfunction and DM, and in patients with DM and LV dysfunction. MethodsChronic LV dysfunction was produced by coronary microsphere embolization in 34 canines (15-25 kg). Following 8 weeks of stabilization, DM was induced in 24 canines and randomized to good or poor glycemic control for 3 months. Ten canines without DM were controls. Hemodynamic and Doppler echocardiographic data were obtained prior to and following pressure loading. We reviewed the Doppler-echocardiography at baseline and follow-up in 207 patients with DM with reduced ejection fraction (EF; median follow-up = 612 days) and 60 age- and sex-matched non-DM patients with normal EF. Laboratory results, medications, and incident adverse events from medical records were obtained. ResultsEF = 43.8% ± 11.2% for all canines at 8 weeks. Canines with poor glycemic control (hemoglobin [Hb]A1c = 8.05% ± 3.02%) demonstrated reduced LV mass and rate-corrected velocity of circumferential fiber shortening, compared to those with LV dysfunction (1.36 ± 0.73 vs 0.88 ± 0.13 circumference per second, P < 0.01). Good glycemic control (HbA1c = 3.88% ± 0.89%) demonstrated similar LV parameters, compared to controls (HbA1c = 2.99% ± 0.44%). EF was similar among groups. Patients with vs without DM were followed for up to 3 years. Patients with DM and poor glycemic control had reduced EF, lower rate-corrected velocity of circumferential fiber shortening = 0.93 ± 0.26 vs 1.11 ± 0.26, P < 0.001), and greater incidence of heart failure. ConclusionsPoor glycemic control had an adverse effect on preexisting LV dysfunction experimentally and in patients with type 2 diabetes.

Laser ablation under intraductal cholangioscopic guidance for cholangiocarcinoma.

An 82-year-old man was admitted for progressively worsening jaundice. Magnetic resonance cholangiopancreatography (MRCP) showed a stenosis of 2 cm in length in the common bile duct, with dilatation of the biliary system above ([Fig. 1]). Endoscopic retrograde cholangiopancreatography (ERCP)-guided cytologic brushing confirmed adenocarcinoma. The patient refused surgery owing to his age and significant co-morbidities. Another ERCP with intraductal cholangioscopic (SpyGlass) observation was arranged. Some mucosal erosions and nodular hyperplasia were found endoscopically ([Fig. 2]). A circumferential irradiation fiber was introduced through the channel of the endoscope ([Fig. 3]) and connected to a laser system (Leonardo, 1470 nm and 980 nm dual wavelength; CeramOpteec GmbH of Biolitec AG, Bonn, Germany). Continuous ablation was carried out until all visualized tumors had been burned to a whitish and necrotic appearance, producing a wider lumen ([Fig. 4]), before a metal stent was placed ([Fig. 5]). The patient recovered unremarkably and was discharged 5 days later ([Video 1]).

A comparative study on various cell sources for constructing tissue-engineered meniscus.

Injury to the meniscus is a common occurrence in the knee joint and its management remains a significant challenge in the clinic. Appropriate cell source is essential to cell-based tissue regeneration and cell therapy. Herein, three commonly used cell sources, namely, bone marrow mesenchymal stem cell (BMSC), adipose-derived stem cell (ADSC), and articular chondrocyte, were comparatively evaluated to determine their potential for engineered meniscus tissue in the absence of growth factor stimulus. Cells were seeded on electrospun nanofiber yarn scaffolds that share similar aligned fibrous configurations with native meniscus tissue for constructing meniscus tissue in vitro. Our results show that cells proliferated robustly along nanofiber yarns to form organized cell-scaffold constructs, which recapitulate the typical circumferential fiber bundles of native meniscus. Chondrocytes exhibited different proliferative characteristics and formed engineered tissues with distinct biochemical and biomechanical properties compared to BMSC and ADSC. Chondrocytes maintained good chondrogenesis gene expression profiles and produced significantly increased chondrogenic matrix and form mature cartilage-like tissue as revealed by typical cartilage lacunae. In contrast, stem cells underwent predominately fibroblastic differentiation and generated greater collagen, which contributes to improved tensile strengths of cell-scaffold constructs in comparison to the chondrocyte. ADSC showed greater proliferative activity and increased collagen production than BMSC. These findings indicate that chondrocytes are superior to stem cells for constructing chondrogenic tissues while the latter is feasible to form fibroblastic tissue. Combination of chondrocytes and stem cells might be a possible solution to construct fibrocartilage tissue and meniscus repair and regeneration.

Construction of Mussel-Inspired “Inorganic–Organic” Hybrids onto a Cylindrical Carbon Fiber via Green and Rapid Manufacturing toward Enhanced Interfacial Adhesion of Composites

A mussel-inspired “inorganic–organic” hybrid coating with laminated architecture was used to wrap a circumferential carbon fiber through integrated utilization of polydopamine (PDA) nanosphere-decorated graphene oxide (GOPDA NPs) and PDA–polyether amine (PEA) under vacuum filtration, which has not been applied in fiber surface engineering. This modification process did not involve harsh conditions, toxic chemicals, and tedious operation, providing a facile, efficient, and sustainable procedure. By adjusting the deposition amount, an optimal structure and the corresponding strongest interfacial adhesion were achieved under addition of 30 mL. A growth of 88.6% up to 114.5 MPa in interfacial shear strength compared to that of the desized fiber (60.7 MPa) is visible. The reasons are associated with the improved wetting behavior and subsequent strong multi-interactions between the fiber and epoxy resin. The closely packed GOPDA NPs layers could effectively hinder crack extension, thus leading to great energy dissipation. Our strategy offers an attractive platform in surface engineering of one-dimensional fibers for producing high-performance composites to be applied in fields where energy saving, lightweight, and high performance characteristics are needed.

Myocardial perfusion and function dichotomy in growth restricted preterm infants.

Compared to preterm appropriate for gestational age (AGA) fetuses, fetuses with fetal growth restriction (FGR) have earlier visualisation of coronary artery blood flow (CABF) but impaired cardiac function. This dichotomy remains uncharacterised during postnatal life. This study compared CABF and cardiac function in preterm FGR infants, against AGA infants during the postnatal period. FGR was defined as birthweight < 10th centile for gestation and sex with absent/reversed antenatal umbilical artery Doppler. Diastolic CABF was measured in the left anterior descending coronary artery. Twenty-eight FGR infants were compared with 26 AGA infants (gestation and birthweight, 29.7 ± 1.3 vs 29.9 ± 1 weeks, P = 0.6 and 918 ± 174 vs 1398 ± 263g, P < 0.001, respectively). Echocardiography was performed in the second week of life. FGR infants had higher CABF (velocity time integral, 2.4 ± 0.9 vs 1.6 ± 0.8 cm, P = 0.002). Diastolic function was impaired (↑ trans-mitral E/A ratio in FGR infants; 0.84 ± 0.05 vs 0.79 ± 0.03, P = 0.0002) while the systolic function was also affected (mean velocity of circumferential fibre shortening [mVCFc], 1.9 ± 0.3 vs 2.7 ± 0.5 circ/s, P < 0.001). Indexing CABF to cardiac function noted significant differences between the groups (CABF: E/A [FGR vs AGA], 2.9 ± 1.1 vs 2.1 ± 1, P = 0.01 and CABF: mVCFc [FGR vs AGA], 1.3 ± 0.5 vs 0.6 ± 0.3, P < 0.001). Diastolic blood pressure (BP) was significantly higher, and CABF to diastolic BP ratio trended higher in FGR infants (30 ± 2 vs 25 ± 3 mmHg, P < 0.001 and 0.08 ± 0.03 vs 0.06 ± 0.03, P = 0.059, respectively). Greater CABF in FGR infants did not translate into better cardiac function. This dichotomy may be a persistent response to fetal hypoxaemia (fetal programming) and/or reflection of altered cardiac architecture.

Transtibial single-tunnel all-inside technique for repair of a complete radial meniscal tear

IntroductionRadial meniscus tears significantly compromise knee biomechanics due to loss of the circumferential fiber connections and have been shown to be biomechanically equivalent to a total meniscectomy. There is a paucity of data regarding the biomechanical performance of radial meniscal repairs and numerous technical challenges associated with surgical repair. Further, current repair methods have been shown to lead to high rates of incomplete, nonanatomical healing of the meniscus and can potentially cause progressive joint degeneration and osteoarthritis. This is particularly true for the avascular portions of the meniscus. As a result, such injuries have been historically treated with a partial meniscectomy. There has been a growing interest in transtibial repair mechanisms as a potential solution to this challenging pathology. ObjectivesThe purpose of this technical note is to detail a method for repairing a complete radial tear of the medial meniscus using a single-tunnel transtibial technique. MethodsAfter a thorough history and clinical examination, and imaging, the patient was diagnosed with a complex medial meniscal tear with a primary radial tear component. A single tunnel transtibial meniscal repair was indicated and performed. ResultsAn anatomic repair was achieved with tension across the defect. The patient successfully returned to activities. ConclusionsSingle-tunnel transtibial repairs of radial tears in the meniscus may provide increased stability by anchoring the meniscal leaflets to the tibia as well as a potential biological benefit by releasing growth factors and progenitor cells from the bone marrow.

Two-dimensional polydopamine nano-protrusion-modified graphene oxide encapsulation of cylindrical carbon fiber by vacuum filtration to strengthen the interphase of epoxy composites

Interfacial delamination is an everlasting problem that exists in carbon fiber reinforced polymer composites and restricts their ability to undertake greater shear load. Herein, vacuum filtration technique is first successfully utilized to realize the functionalization of cylindrical carbon fiber by two-dimensional graphene oxide (GO) and polydopamine nano-protrusions modified GO (GOPDA) as a rapid, simple and versatile means to realize the improvement of interfacial adhesion of epoxy composites. Compared to the GO modifier (37.6% augmentation), the GOPDA addition results in higher gain in interfacial shear strength (68.4%) over that of de-sized fiber. This belongs to that the adherence of smaller-sized GOPDA and its nano-protrusion structure facilitate the high surface energy, excellent wetting, mechanical interlocking and covalent linking with epoxy resin. Our research highlights the great possibility to implement vacuum filtration to modify the traditional circumferential fiber and realize the interphase optimization of composites.

Glaucoma Cascade Screening in a High Risk Afro-Caribbean Haitian Population: A Pilot Study.

Précis:Glaucoma cascade screening in first-degree relatives (FDRs) of young Haitian glaucoma patients had high yield for diagnosing manifest and suspected glaucoma in 30.8% of those screened despite modest participation.Purpose:To evaluate the outcomes of glaucoma cascade screening in FDRs (parents, siblings, and offspring) of Haitian juvenile open-angle glaucoma (JOAG) patients.Patients and Methods:Consecutive index patients (Haitians with JOAG) were identified, and the number/type of FDRs residing in South Florida were recorded. These FDRs were invited for free glaucoma screening, which included a comprehensive ophthalmic exam, gonioscopy, automated visual field testing and optical coherence tomographic analysis of the retinal nerve fiber layers. FDR characteristics and clinical findings from screening are reported.Results:A total of 77 FDRs were invited, 26 (33.8%) agreed to undergo screening (18 females, 9 males), which revealed 2 (7.7%) with manifest glaucoma (mean age 77.5 y; one of whom was previously unaware of his glaucoma diagnosis), 6 (23.1%) with suspected glaucoma (mean age 29.8±18.3 y), and 18 (69.2%) without manifest or suspected glaucoma (mean age 37.2±21.8 y). Siblings of index patients were least likely to participate in cascade glaucoma screening when compared with index patients’ parents or offspring. FDR eyes with manifest glaucoma had significantly worse best-corrected visual acuities, higher intraocular pressures, thinner central corneal thicknesses, and thinner circumferential papillary retinal nerve fiber layer thicknesses than those without glaucoma.Conclusion:Glaucoma cascade screening of Haitian JOAG patients’ FDRs revealed that 30.8% had suspected or manifest glaucoma. Future efforts centered on provider-initiated recruitment and improving public glaucoma awareness and education may increase screening participation.

Аналіз застосування Мексикору у хворих із гострим коронарним синдромом

Матеріали та методи. Під спостереженням знаходилися дві групи хворих із гострим коронарним синдромом. Перша група включала 48 хворих із нестабільною стенокардією (НС) віком 58,5 ± 3,8 року. Діагноз НС верифікований на підставі скарг хворих і змін на електрокардіограмі — підйому або депресії інтервалу на 1 мм тривалістю не більше 3 діб, відсутності зон гіпокінезії при УЗД серця, негативного тропонінового тесту. Другу групу становили 45 хворих із гострим інфарктом міокарда. Діагноз верифіковано за допомогою тропонінового тесту і змін на ЕКГ. У цю групу включалися хворі з Q-позитивним гострим інфарктом міокарда (ГІМ). Чоловіки — 83,2 %, жінки — 16,8 %. Середній вік хворих становив 60,3 ± 1,2 року. Задньобазальна локалізація виявлена у 40,2 %, передня — у 59,8 %. В анамнезі у 70 % хворих гіпертонічна хвороба ІІ ст. «Стаж» ішемічної хвороби серця становив у середньому 10,8 ± 4,5 року. 80 % хворих цієї групи неодноразово лікувалися в кардіологічних стаціонарах із приводу загострень ішемічної хвороби серця. У 38,5 % хворих на момент надходження відзначені надшлуночкові і шлуночкові (екстрасистолія) порушення ритму. Результати. Застосування Мексикору у хворих із ГІМ значно покращувало систолічну функцію серця, що проявлялося у вірогідній різниці основних показників, що її відображають (фракція викиду, швидкість циркуляторного скорочення волокон, серцевого викиду), і відповідних показників у хворих контрольної групи. Подібні сприятливі зміни були виявлені і при вивченні в динаміці показників діастолічної функції серця, що визначаються за швидкістю трансмітрального потоку. Обговорення. Зазначені зміни ми пов’язуємо з відновленням або поліпшенням скоротливості ішемізованого міокарда та функціонального стану так званих інтактних відділів серця, що компенсують своєю діяльністю втрату скоротливості некротизованих ділянок. Це підтверджується динамікою стану зон акінезії і дискінезії у хворих на ІМ, де відстежується відновлення скоротливості окремих ділянок серця на фоні застосування Мексикору (перехід граничних із зонами інфаркту сегментів зі стану акінезії в гіпокінез, гіпокинезу — в нормокінез), і практично зворотною динамікою у хворих контрольної групи. Мексикор сприяв поліпшенню клінічного перебігу ІМ, що проявлялося в обмеженні величини вогнища некрозу і стимуляції репаративних процесів, поліпшенні скорочувальної функції серця і газообміну, зменшенні частоти пролонгованого і рецидивного перебігу, ймовірності розвитку аневризми серця і випадків серцевої недостатності, порушень ритму і провідності, недостатності кровообігу і в кінцевому підсумку летальності. За результатами холтерівського моніторування у хворих на НС Мексикор прискорював стабілізацію стенокардії і зменшував, порівняно з контрольною групою, добову частоту і тривалість періодів ішемії міокарда, епізодів порушень ритму, сприятливо впливав на зміну інтеграла зміщення ST і співвідношення больових/безбольових періодів ішемії. Висновки. Включення Мексикору в традиційну терапію гострого коронарного синдрому вже на догоспітальному етапі дозволяє істотно зменшити прояви окислювального стресу, сприяє нормалізації діяльності серцево-судинної системи і покращує клінічний перебіг захворювань.

СОВРЕМЕННЫЕ ПОДХОДЫ К МЕДИЦИНСКОЙ ПРОФИЛАКТИКЕ КАРДИОТОКСИЧЕСКИХ ЭФФЕКТОВ КОМПЛЕКСНОГО ЛЕЧЕНИЯ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ

Objectives. To study the effect of complex treatment of breast cancer (BC) on the parameters of the structural and functional state of the cardiovascular system. To develop a model for predicting the ejection fraction (EF) of the left ventricle (LV) measured by the Simpson method after the end of antitumor therapy on the basis of initial laboratory and instrumental data. Methods. The cardiovascular system was examined in 100 women who received complex treatment of BC. The groups were formed depending on the presence of arterial hypertension (AH) and on the cardiotropic therapy (CT) received: the BC group, the BC+ CT group, the BC+ AH+CT group. Results. The research showed a decrease in LVEF measured by the Simpson method from 66,0 (62,0; 71,0)% to 60,0 (57,0-66,0)%, an increase in LV end systolic diameter from 27,0 (24,0–29,0) mm to 27,0 (25,0–31,0) mm, LV end systolic volume from 27,0 (22,0; 32,0) ml to 28,0 (24,0; 37,0) ml; a decrease in the mitral ratio of peaks early to late diastolic filling velocity from 1,4 (1,1; 1,8) to 1,2 (1,1; 1,5), in the ratio of early to late diastolic mitral annular velocity from 1,4 (1,2; 1,7) to 1,2 (1,0; 1,6); in the of early to late diastolic tricuspid annular velocity from 1,4 (1,2; 1,7) to 1,0 (0,8; 1,1), reduction of the increase in the diameter (d) of the brachial artery (BA) after performing a post-occlusion test from 12,5 (11,0; 16,0)% to 9,0 (6,0; 12,0)%, the reduction of heart rate variability: standard deviation of NN intervals from 57,7 (44,9; 72,9) ms to 54,1 (44,0; 63,3) ms, root mean square of successive RR interval differences from 29,6 (17,5; 43,3) ms to 20,0 (15,2; 28,0) ms, total power of the spectrum from 1326,3 (996,4; 2061,7) to 1132,4 (824,3; 1649,8) ms2/ Hz; power of the high-frequency (HF) from 647,3 (416,8; 921,4) to 443,7 (315,9; 669,0) ms2/ Hz; an increase in ratio of low-frequency to HF from 0,8 (0,7; 1,0) to 1,05 (0,8; 1,2). A Simpson-based EF prognostic model after the end of BC treatment has been developed. It includes the total dose of doxorubicin calculated for the body surface area, the peak early diastolic filling velocity of transtricuspid flow, the diameter of the pulmonary artery, the velocity of circumferential fiber shortening, the intima-medial thickness of the left common carotid artery, HF, % increase of the d of the BA. The developed model has a high prognostic ability. Conclusions. Breast cancer treatment negatively affects the structural and functional state of the cardiovascular system. The administration of a combination of valsartan and carvedilol prevents the development of adverse changes. The developed EF prognostic model allows to identify patients for the preventive administration of cardiotropic therapy.

Abstract 11777: Global Radial Strain Predicts Cardiovascular Events in Patients With Myocarditis Related to the Use of Immune Checkpoint Inhibitors

Introduction: Myocarditis is as a major immune-related adverse event following the use of immune checkpoint inhibitors (ICI). Global radial strain (GRS) reflects both longitudinal and circumferential fiber shortening but no data exist regarding its utility for diagnosis and risk stratification of ICI-myocarditis. Hypothesis: We hypothesized that GRS from echocardiography data would be reduced in patients with ICI-myocarditis and its reduction would have prognostic implications. Methods: Leveraging a multicenter international registry, we measured GRS from 76 patients with myocarditis and 49 ICI treated patients with no myocarditis. Pre-ICI GRS values were available for 10 cases and 38 controls. Measures were performed in a central laboratory blinded to group and time (TomTec, Germany). Major adverse cardiac event was a composite of cardiogenic shock, cardiac arrest, complete heart block and cardiac death. Results: Groups had similar age (66±15 vs. 63±12 years; p=0.20), sex distribution (male: 72% vs. 61%; p= 0.27) and cancer type (p=0.07). Pre-ICI GRS values were similar between cases and controls (47.4±2.9 vs. 45.4±6.0; p=0.12). A total of 57% of myocarditis patients had LVEF of &gt;50% at presentation. The GRS was lower in patients with myocarditis compared with controls (28.6±6.7 vs. 47±7.4; p&lt;0.01). This lower GRS value was noted in patients with both preserved EF (31.7±5.5 vs. 47.0±7.6, p&lt;0.001) and reduced EF (24.7±6.1 vs. 49.2±4.7, p&lt;0.005). In total, 28 events occurred during a median follow-up of 30 days. In survival analysis, a GRS &lt; the median (29.4%) was associated with an increased rate of events (HR: 3.92, 95% CI: 1.42-10.78, p=0.008) adjusted for age and LVEF. The association between GRS and events was also noted when the variable is treated as continuous adjusted for age and LVEF (HR: 1.07, 95% CI: 1.001-1.15 p=0.04). Conclusions: Global radial strain is lower in ICI- myocarditis and the magnitude of the reduction is associated with a higher rate of events.

Abstract 11855: Disruption of β-arrestin-2 Signaling Resulted in Impaired Systolic and Diastolic Function During Aging

Introduction: Angiotensin II (ang II) signaling at ang II receptor type 1 (AT1R), which is a G-protein coupled receptor (GPCR), promotes both G-protein signaling as well as β-arrestin-2 signaling. β-arrestin-2 participates in GPCR desensitization, internalization, but also acts a scaffold for adaptive signal transduction that may occur independently or in parallel to G-protein signaling. Hypothesis: We tested the hypothesis that β-arrestin-2 is an important element in the preservation of cardiac function during aging. Methods: We tested this hypothesis by aging β-arrestin-2 knock-out (KO) mice, and wild-type equivalent (WT) to 12-16 months. We performed echocardiography studies, and Western blot analysis. Results: By echocardiography we found that compared to controls aged KO mice exhibited enlarged left atria (2.2±0.1 vs 2.5±0.1 mm) and left ventricular diameters (4.2±0.2 vs 4.5 ±0.1mm) as well as depressed contractility parameters such as s’ (23.2±1.4 vs 21.4±0.8 mm/s) and decreased circumferential fiber shortening velocity (5.5±0.4 vs 4.5±0.2) with preserved ejection fraction (EF&gt;50%). Aged KO also exhibited depressed relaxation parameters such as e’ (29.2±1.4 vs 21.4±0,6 mm/s) and E/e’ (27.4±1.6 vs 35.6±2.0) when compared to WT controls at the same age. Cardiac dysfunction in aged KO mice was correlated with decreased phosphorylation of RLC and increased phosphorylation of cMyBP-C at Ser302. Among other kinases, cMyBP-C phosphorylation at Ser302 is a PKCε target which activation is negatively regulated by β-arrestin-2 signaling. To determine the direct effects of PKCε over-activation on cMyBP-C phosphorylation, we used mice that over-expresses constitutively active PKC ε in the heart. We found that similarly to our aged KO mice, PKCε overexpression model exhibited significantly higher levels of cMyBP-C phosphorylation at Ser302, when aged to 12 - 15 months. Conclusions: Deletion of β-arrestin-2 signaling in KO mice affected aged mice, resulting in changes in the phosphorylation of myofilament proteins consisting of decreased phosphorylation of RLC and increased phosphorylation of cMyBP-C at Ser302 through the unrestricted activity of PKCε. These changes negatively affected systolic and diastolic function in aged KO mice.

Placement of sutures for inside-out meniscal repair: both sutures through meniscal tissue reduces displacement on cyclical loading

PurposeThe inside-out meniscal repair is widely performed to preserve the function of meniscus. In this technique, the outer suture is passed through the capsule as well as the outer meniscus, while the inner suture is inserted into the meniscus. The aim of this study was to biomechanically compare the suture stability between meniscus-meniscus and meniscus-capsule suture methods for the longitudinal meniscal tear with inside-out technique.MethodsTwenty-seven porcine knees were dissected to maintain the femur-medial capsule/meniscus-tibia complex, and the inner meniscus was cut off along the meniscus circumferential fiber with 3 mm width of the peripheral meniscus preserved. After one needle with a 2-0 polyester suture was inserted into the inner portion of the meniscus, the other needle was inserted through 1) the peripheral meniscus (Group A), 2) capsule just above the meniscus (Group B), and 3) capsule at 10 mm apart from the meniscus-capsule junction (Group C) in the inside-out manner. Then, the suture was manually tied on the capsule. The suture gap at the repair site during 300 times of cyclic loading and the ultimate failure load in the load-to-failure test were measured. The statistical significance of the data between two groups in each combination was considered by Bonferroni correction, following a one-way analysis of variance.ResultsIn the cyclic loading test, the suture gap was 0.68 ± 0.26 mm in Group A, 1.08 ± 0.36 mm in Group B, and 1.94 ± 0.57 mm in Group C with a significant difference. In the load-to-failure test, the ultimate failure load was 59.1 ± 13.6 N in Group A, 60.0 ± 7.9 N in Group B, and 57.4 ± 4.7 N in Group C, and there was no significant difference.ConclusionThe stitching region in the inside-out technique for longitudinal meniscal tear affected the stability of the tear site, and stitching the mid-substance region of the meniscus provides good stability in response to cyclic tensile loading. In addition, the stitching region did not affect the ultimate failure load.Clinical relevanceIn the inside-out meniscal repair, the outer suture should be inserted into the remaining peripheral meniscus or the capsule near the meniscus.

Long-Term Functional Results of Patients Operated for Isolated Discrete Subaortic Stenosis.

This study aimed to examine the long-term functional results of patients with isolated discrete subaortic stenosis who underwent subaortic membrane resection and myectomy, using transthoracic M-mode echocardiography and 2D speckle-tracking echocardiography. Twenty patients operated for isolated discrete subaortic stenosis and 31 controls were included in the study. Patients underwent subaortic membrane resection and myectomy. During the long-term follow up, patients were evaluated with transthoracic M-mode echocardiography and 2D speckle-tracking echocardiography for functional assessment. The mean age at operation and mean duration of follow up was 8.1±5.6 years and 7.2±3.3 years, respectively. Interventricular septal thickness at diastole (0.9±0.1 vs. 0.8±0.1 cm, P = 0.001), ejection time (285.7±26.2 vs. 261.2±24.3 msec, P = 0.001), and aortic strain (15.6±3.7 vs. 10.5±4.0, P < 0.001) were significantly higher in patients. On the other hand, ejection fraction (64.9±6.1 vs. 75.1±5.4 %, P < 0.001), fractional shortening (35.0±5.1 vs. 43.7±5.1, P < 0.001), and corrected velocity circumferential fiber shortening (0.12±0.02 vs. 0.17±0.03, P < 0.001) were significantly lower, when compared with the controls. Longitudinal strain value significantly differed among the groups, with patients having significantly lower strain (18.8±1.8 vs. 20.1±2.1, P = 0.021). In patients operated for isolated discrete subaortic stenosis, aortic gradient seems to continue in the long-term, with the persistence of low longitudinal strain.