Flying Fox Hemolytic Fever, Description of a New Zoonosis Caused by Candidatus Mycoplasma haemohominis.

BACKGROUND: Hemotropic mycoplasmas, previously classified in the genus Eperythrozoon, have been reported as causing human infections in Brazil, China, Japan, and Spain. METHODS: In 2017, we detected DNA from Candidatus Mycoplasma haemohominis in the blood of a Melanesian patient from New Caledonia presenting with febrile splenomegaly, weight loss, life-threatening autoimmune hemolytic anemia, and hemophagocytosis. The full genome of the bacterium was sequenced from a blood isolate. Subsequently, we retrospectively (2011-2017) and prospectively (2018-2019) tested patients who had been hospitalized with a similar clinico-biological picture. In addition, as these patients had been in contact with frugivorous bats (authorized under conditions for hunting and eating in New Caledonia), we investigated the role of these animals and their biting flies by testing them for hemotropic mycoplasmas. RESULTS: There were 15 patients found to be infected by this hemotropic mycoplasma. Among them, 4 (27%) died following splenectomy performed either for spontaneous spleen rupture or to cure refractory autoimmune hemolytic anemia. The bacterium was cultivated from the patient's blood. The full genome of the Neocaledonian Candidatus M. haemohominis strain differed from that of a recently identified Japanese strain. Of 40 tested Pteropus bats, 40% were positive; 100% of collected bat flies Cyclopodia horsfieldi (Nycteribiidae, Diptera) were positive. Human, bat, and dipteran strains were highly similar. CONCLUSIONS: The bacterium being widely distributed in bats, Candidatus M. haemohominis, should be regarded as a potential cause of severe infections in humans.

Real-life analysis of the causes of death in patients consecutively followed for giant cell arteritis in a French centre of expertise.

OBJECTIVES: To describe, in a real-life setting, the direct causes of death in a cohort of consecutive patients with GCA. METHODS: We retrospectively analysed the deaths that occurred in a cohort of 470 consecutive GCA patients from a centre of expertise between January 2000 and December 2019. Among the 120 patients who died, we retrieved data from the medical files of 101 patients. RESULTS: Cardiovascular events were the dominant cause of death (n = 41, 41%) followed by infections (n = 22, 22%), geriatric situations (i.e. falls or senile deterioration; n = 17, 17%) and cancers (n = 15, 15%). Patients in each of these four groups were compared with the other deceased patients pooled together. Patients who died from cardiovascular events were more frequently male (46 vs 27%; P = 0.04) with a past history of coronary artery disease (29 vs 8%; P = 0.006). Patients who died from infections mostly had ongoing glucocorticoid treatment (82 vs 53%; P = 0.02) with higher cumulative doses (13 994 vs 9150 mg; P = 0.03). Patients who died from geriatric causes more frequently had osteoporosis (56 vs 17%; P = 0.0009) and had mostly discontinued glucocorticoid treatment (76 vs 33%; P = 0.001). The predictive factors of death in multivariate analysis were a history of coronary disease [hazard ratio (HR) 2.39; 95% CI 1.27, 4.21; P = 0.008], strokes at GCA diagnosis (HR 2.54; 95% CI 1.05, 5.24; P = 0.04), any infection during follow-up (HR 1.93; 95% CI 1.24, 2.98; P = 0.004) and fever at GCA diagnosis (HR 1.99; 95% CI 1.16, 3.28; P = 0.01). CONCLUSION: Our study provides real-life insight on the cause-specific mortality in GCA patients.

Investigating Balloon-Vessel Contact Pressure Patterns in Angioplasty: In Silico Insights for Drug-Coated Balloons.

Drug-Coated Balloons have shown promising results as a minimally invasive approach to treat stenotic arteries, but recent animal studies have revealed limited, non-uniform coating transfer onto the arterial lumen. In vitro data suggested that local coating transfer tracks the local Contact Pressure (CP) between the balloon and the endothelium. Therefore, this work aimed to investigate in silico how different interventional and device parameters may affect the spatial distribution of CP during the inflation of an angioplasty balloon within idealized vessels that resemble healthy femoral arteries in size and compliance. An angioplasty balloon computational model was developed, considering longitudinal non-uniform wall thickness, due to its forming process, and the folding procedure of the balloon. To identify the conditions leading to non-uniform CP, sensitivity finite element analyses were performed comparing different values for balloon working length, longitudinally varying wall thickness, friction coefficient on the balloon-vessel interface, vessel wall stiffness and thickness, and balloon-to-vessel diameter ratio. Findings indicate a significant irregularity of contact between the balloon and the vessel, mainly affected by the balloon's unfolding and longitudinal thickness variation. Mirroring published data on coating transfer distribution in animal studies, the interfacial CP distribution was maximal at the middle of the balloon treatment site, while exhibiting a circumferential pattern of linear peaks as a consequence of the particular balloon-vessel interaction during unfolding. A high ratio of balloon-to-vessel diameter, higher vessel stiffness, and thickness was found to increase significantly the amplitude and spatial distribution of the CP, while a higher friction coefficient at the balloon-to-vessel interface further exacerbated the non-uniformity of CP. Evaluation of balloon design effects revealed that the thicker tapered part caused CP reduction in the areas that interacted with the extremities of the balloon, whereas total length only weakly impacted the CP. Taken together, this study offers a deeper understanding of the factors influencing the irregularity of balloon-tissue contact, a key step toward uniformity in drug-coating transfer and potential clinical effectiveness.

An experimental investigation into the physical, thermal and mechanical degradation of a polymeric bioresorbable scaffold.

This study presents a comprehensive evaluation of the mechanical, micro-mechanical and physical properties of Reva Medical Fantom Encore Bioresorbable Scaffolds (BRS) subjected to a thermally-accelerated degradation protocol. The Fantom Encore BRS were immersed in phosphate buffered saline solution at 50 °C for 112 days with radial compression testing, nanoindentation, differential scanning calorimetry, gel permeation chromatography and mass loss characterisation performed at consecutive time points. In the initial stages of degradation (Days 0-21), the Fantom Encore BRS showed increases in radial strength and stiffness, despite a substantial reduction in in molecular weight, with a slight increase in the melt temperature also observed. In the second phase (Days 35-54), the radial strength of the BRS samples were maintained despite a continued loss in molecular weight. However, during this phase, the ductility of the stent showed a reduction, with stent fracture occurring earlier in the crimp process and with lower amounts of plastic deformation evident under visual examination post-fracture. In the final phase (Days 63-112), the load-bearing capacity of the Fantom Encore BRS showed continued reduction, with decreases in radial stiffness and strength, and drastic reduction in the work-to-fracture of the devices. Throughout each phase, there was a steady increase in the relative crystallinity, with limited mass loss until day 112 and only minor changes in glass transition and melt temperatures. Limited changes were observed in nano-mechanical properties, with measured local elastic moduli and hardness values remaining largely similar throughout degradation. Given that the thermally-accelerated in vitro conditions represented a four-fold acceleration of physiological conditions, these results suggest that the BRS scaffolds could exhibit substantially brittle behaviour after âˆ¼ one year of implantation.

A proof-of-concept study for the simulation of blood flow in a post arterial segment for different blood rheology models.

Cardiovascular disease (CVD) and especially atherosclerosis are chronic inflammatory diseases which cause the atherosclerotic plaque growth in the arterial vessels and the blood flow reduction. Stents have revolutionized the treatment of this disease to a great extent by restoring the blood flow in the vessel. The present study investigates the performance of the blood flow after stent implantation in patient-specific coronary artery and demonstrates the effect of using Newtonian vs. non-Newtonian blood fluid models in the distribution of endothelial shear stress. In particular, the Navier-Stokes and continuity equations were employed, and three non-Newtonian fluid models were investigated (Carreau, Carreau-Yasuda and the Casson model). Computational finite elements models were used for the simulation of blood flow. The comparison of the results demonstrates that the Newtonian fluid model underestimates the calculation of Endothelial Shear Stress, while the three non-Newtonian fluids present similar distribution of shear stress. Keywords: Blood flow dynamics, stented artery, non-Newtonian fluid. Clinical Relevance- This work demonstrates that when blood flow modeling is performed at stented arteries and predictive models are developed, the non-Newtonian nature of blood must be considered.

An in silico trials platform for the evaluation of stent design effect in post-implantation outcomes.

Bioresorbable Vascular Scaffolds (BVS), developed to allow drug deliver and mechanical support, followed by complete resorption, have revolutionized atherosclerosis treatment. InSilc is a Cloud platform for in silico clinical trials (ISCT) used in the design, development and evaluation pipeline of stents. The platform integrates beyond the state-of-the-art multi-disciplinary and multiscale models, which predict the scaffold's performance in the short/acute and medium/long term. In this study, a use case scenario of two Bioabsorbable Vascular Stents (BVSs) implanted in the same arterial anatomy is presented, allowing the whole InSilc in silico pipeline to be applied and predict how the different aspects of this intervention affect the success of stenting process.

Validation of the computational model of a coronary stent: a fundamental step towards in silico trials.

The proof of the reliability of a numerical model is becoming of paramount importance in the era of in silico clinical trials. When dealing with a coronary stenting procedure, the virtual scenario should be able to replicate the real device, passing through the different stages of the procedure, which has to maintain the atherosclerotic vessel opened. Nevertheless, most of the published studies adopted commercially resembling geometries and generic material parameters, without a specific validation of the employed numerical models. In this work, a workflow for the generation and validation of the computational model of a coronary stent was proposed. Possible sources of variability in the results, such as the inter-batches variability in the material properties and the choice of proper simulation strategies, were accounted for and discussed. Then, a group of in vitro tests, representative of the device intended use was used as a comparator to validate the model. The free expansion simulation, which is the most used simulation in the literature, was shown to be only partially useful for stent model validation purposes. On the other hand, the choice of proper additional experiments, as the suggested uniaxial tensile tests on the stent and deployment tests into a deformable tube, could provide further suitable information to prove the efficacy of the numerical approach.

From the real device to the digital twin: A coupled experimental-numerical strategy to investigate a novel bioresorbable vascular scaffold.

The purpose of this work is to propose a workflow that couples experimental and computational activities aimed at developing a credible digital twin of a commercial coronary bioresorbable vascular scaffold when direct access to data about material mechanical properties is not possible. Such a situation is be faced when the manufacturer is not involved in the study, thus directly investigating the actual device is the only source of information available. The object of the work is the Fantom® Encore polymeric stent (REVA Medical) made of Tyrocore™. Four devices were purchased and used in mechanical tests that are easily reproducible in any mechanical laboratory, i.e. free expansion and uniaxial tension testing, the latter performed with protocols that emphasized the rate-dependent properties of the polymer. Given the complexity of the mechanical behaviour observed experimentally, it was chosen to use the Parallel Rehological Framework material model, already used in the literature to describe the behaviour of other polymers, such as PLLA. Calibration of the material model was based on simulations that replicate the tensile test performed on the device. Given the high number of material parameters, a plan of simulations was done to find the most suitable set, varying each parameter value in a feasible range and considering a single repetitive unit of the stent, neglecting residual stresses generated by crimping and expansion. This strategy resulted in a significant reduction of computational cost. The performance of the set of parameters thus identified was finally evaluated considering the whole delivery system, by comparing the experimental results with the data collected simulating free expansion and uniaxial tension testing. Moreover, radial force testing was numerically performed and compared with literature data. The obtained results demonstrated the effectiveness of the digital twin development pipeline, a path applicable to any commercial device whose geometric structure is based on repetitive units.

Comprehensive computational analysis of the crimping procedure of PLLA BVS: effects of material viscous-plastic and temperature dependent behavior.

Recently, researchers focused their attention on the use of polymeric bioresorbable vascular scaffolds (BVSs) as alternative to permanent metallic drug-eluting stents (DESs) for the treatment of atherosclerotic coronary arteries. Due to the different mechanical properties, polymeric stents, if compared to DESs, are characterized by larger strut size and specific design. It implies that during the crimping phase, BVSs undergo higher deformation and the packing of the struts, making this process potentially critical for the onset of damage. In this work, a computational study on the crimping procedure of a PLLA stent, inspired by the Absorb GT1 (Abbott Vascular) design, is performed, with the aim of evaluating how different strategies (loading steps, velocities and temperatures) can influence the results in terms of damage risk and final crimped diameter. For these simulations, an elastic-viscous-plastic model was adopted, based on experimental results, obtained from tensile testing of PLLA specimens loaded according to ad hoc experimental protocols. Furthermore, the results of these simulations were compared with those obtained by neglecting strain rate and temperature dependence in the material model (as often done in the literature), showing how this lead to significant differences in the prediction of the crimped diameter and internal stress state.

How to Validate in silico Deployment of Coronary Stents: Strategies and Limitations in the Choice of Comparator.

This study aims at proposing and discussing useful indications to all those who need to validate a numerical model of coronary stent deployment. The proof of the reliability of a numerical model is becoming of paramount importance in the era of in silico trials. Recently, the ASME V&V Standard Committee for medical devices prepared the V&V 40 standard document that provides a framework that guides users in establishing and assessing the relevance and adequacy of verification and validation activities performed for proving the credibility of models. To the knowledge of the authors, only a few examples of the application of the V&V 40 framework to medical devices are available in the literature, but none about stents. Specifically, in this study, the authors wish to emphasize the choice of a relevant set of experimental activities to provide data for the validation of computational models aiming to predict coronary stent deployment. Attention is focused on the use of ad hoc 3D-printed mock vessels in the validation plan, which could allow evaluating aspects of clinical relevance in a representative but controlled environment.

Multimodal Loading Environment Predicts Bioresorbable Vascular Scaffolds' Durability.

Bioresorbable vascular scaffolds were considered the fourth generation of endovascular implants deemed to revolutionize cardiovascular interventions. Yet, unexpected high risk of scaffold thrombosis and post-procedural myocardial infractions quenched the early enthusiasm and highlighted the gap between benchtop predictions and clinical observations. To better understand scaffold behavior in the mechanical environment of vessels, animal, and benchtop tests with multimodal loading environment were conducted using industrial standard scaffolds. Finite element analysis was also performed to study the relationship among structural failure, scaffold design, and load types. We identified that applying the combination of bending, axial compression, and torsion better reflects incidence observed in-vivo, far more than tranditional single mode loads. Predication of fracture locations is also more accurate when at least bending and axial compression are applied during benchtop tests (>60% fractures at connected peak). These structural failures may be initiated by implantation-induced microstructural damages and worsened by cyclic loads from the beating heart. Ignoring the multi-modal loading environment in benchtop fatigue tests and computational platforms can lead to undetected potential design defects, calling for redefining consensus evaluation strategies for scaffold performance. With the robust evaluation strategy presented herein, which exploits the results of in-vivo, in-vitro and in-silico investigations, we may be able to compare alternative designs of prototypes at the early stages of device development and optimize the performance of endovascular implants according to patients-specific vessel dynamics and lesion configurations in the future.

An in silico trials platform for the evaluation of effect of the arterial anatomy configuration on stent implantation.

The introduction of Bioresorbable Vascular Scaffolds (BVS) has revolutionized the treatment of atherosclerosis. InSilc is an in silico clinical trial (ISCT) platform in a Cloud-based environment used for the design, development and evaluation of BVS. Advanced multi-disciplinary and multiscale models are integrated in the platform towards predicting the short/acute and medium/long term scaffold performance. In this study, InSilc platform is employed in a use case scenario and demonstrates how the whole in silico pipeline allows the interpretation of the effect of the arterial anatomy configuration on stent implantation.

Biomechanical interpretation of observed fatigue fractures of peripheral Nitinol stents in the superficial femoral arteries through in silico modelling.

PURPOSE: To suggest an in silico modelling approach to estimate the fatigue failure on peripheral Nitinol stents implanted in the superficial femoral artery (SFA) and interpret the clinically observed stent fractures of a retrospective series of patients. MATERIALS AND METHODS: Preoperative data of 27 patients who underwent SFA Nitinol stenting were retrospectively analyzed. Data about preoperative features of the SFA and the lesion were collected. Follow-up data were also collected about the occurrence of restenosis/occlusion and stent fracture. RESULTS: After a lengthening of the entire vessel, the occluded region was slightly stretched due to its high stiffness, whereas the healthy regions accommodated the artery length variation. The stent fatigue was predicted to be higher in the regions of low stiffness and higher shortening. In 7 out of 27 patients a stent fracture was clinically recorded. The model resulted to be accurate in 90% of the cases. CONCLUSIONS: The clinical outcomes in terms of biomechanical fatigue behavior of peripheral Nitinol stents of the SFA could be interpreted by our new approach.

Rhupus: a systematic literature review.

"Rhupus" or "rhupus syndrome" is a poorly described and underdiagnosed disease in which features of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) appear in the same patient, most often sequentially. The SLE-related involvement is usually mild, dominated by hematological abnormalities and skin, serosal and renal involvement. The natural history of rhupus arthritis follows an RA-like pattern and can progress towards typical inflammatory erosions, deformations and disability. Despite the lack of consensus on the definition of rhupus and on its place in the spectrum of autoimmunity, a growing number of studies are pointing towards a true overlap between RA and SLE. However, the inclusion criteria employed in the literature during the last 4 decades are heterogeneous, making the already rare cohorts and case reports difficult to analyze. Because of this heterogeneity and due to the rarity of the disease, the prevalence, pathophysiology and natural history as well as the radiological and immunological profiles of rhupus are poorly described. Moreover, since there is no validated therapeutic strategy, treatment is based on clinicians' experience and on the results of a few studies. We herein present a systematic literature review to analyze the clinical and laboratory data of all reported rhupus patients and to provide up-to-date information about recent advances in the understanding of the pathophysiological mechanisms, diagnostic tools and treatment options.

Design and implementation of in silico clinical trial for Bioresorbable Vascular Scaffolds.

In the recent years, Bioresorbable Vascular Scaffolds (BVS) for the treatment of atherosclerosis have been introduced. InSilc is a cloud based in silico clinical trial (ISCT) platform for drug-eluting BVS. The platform integrates multidisciplinary and multiscale models predicting the BVS performance. In this study, we present a use case scenario and demonstrate the functioning of the individual modules and of the whole pipeline and the ability to predict BVS short, medium, long-term outcomes.

[Myocardial and cerebral infarction as initial presentation of antiphospholipid syndrome]. / Infarto miocardico e cerebrale come presentazione iniziale di una sindrome da anticorpi antifosfolipidi.

The antiphospholipid antibody syndrome is the most common acquired thrombophilia; it is a systemic autoimmune disease characterized by recurrent arterial and venous thrombosis and/or pregnancy loss, in association with circulating antiphospholipid antibodies. The pathogenic mechanisms in antiphospholipid antibody syndrome that lead to in vivo injury are incompletely understood. Like other autoimmune diseases, a combination of genetic and environmental factors is involved. We report the case of a 50-year-old woman suffering from an antero-lateral non-ST-elevation myocardial infarction. After few days, coronary angiography showed a severe occlusive arterial disease, involving anterior descending, circumflex e right coronary arteries. Percutaneous coronary intervention was performed with the implantation of a drug-eluting stent in the proximal segment of the anterior descending coronary artery. One day after discharge (10 days after the first hospitalization) the patient experienced dizziness, nausea, vomiting, swelling in absence of any electrocardiographic abnormalities or myocardial enzyme elevation; then she was hospitalized in the neurology department. Because of a similar episode, urgent cerebral computed tomography scan was performed 5 days later; it revealed two different acute ischemic areas, parietal in the right hemisphere and cerebellar in the left hemisphere. The diagnosis of antiphospholipid antibody syndrome was confirmed by high anticardiolipin antibody titers, also present in medium titer at 5 and 17 weeks apart. She was discharged without any sequelae, on warfarin and double antiplatelet therapy (aspirin and clopidogrel for 6 months), then warfarin and aspirin.