Analysis of the coating integrityduring a coronary stent deployment

Las afecciones cardiovasculares constituyen en la actualidad una causa frecuente de muerte. Una de estas afecciones es la ateroesclerosis, la cual provoca la reducción de la luz arterial. En aras de solucionar tal afección se han desarrollado varios tratamientos, ganando terreno la Angioplastia Coronaria Transluminar Percutánea (PTCA) con colocación de estent. En la actualidad muchos de estos dispositivos son recubiertos para aumentar la biocompatibilidad y disminuir los riesgos de reestenosis. Dado la posibilidad de fallas o roturas de los recubrimientos y los riesgos asociados a estas, es de gran importancia el estudio del comportamiento de la unión estentrecubrimiento durante la fase de expansión del estent. En esta investigación se estudia la posible ocurrencia de delaminación del recubrimiento durante la expansión de un estent y la influencia de parámetros como el espesor y el material del mismo. El estudio parte de la obtención de un modelo geométrico de una celda del estent Sirius Carbostent para su posterior procesamiento por el Método de Elementos Finitos. La simulación por tal método, se desarrolló, aplicando restricciones al movimiento de forma tal que la celda modelada simule su comportamiento durante la expansión de un estent. Considerando estos aspectos fue posible evaluar la integridad del recubrimiento. Con los modelos desarrollados se logró predecir la ocurrencia de delaminación durante la expansión del estent y se determinó que al aumentar el espesor del recubrimiento aumenta el riesgo de ocurrencia de la misma. Se obtuvo además una ecuación general que permite determinar el esfuerzo máximo de contacto para celdas en forma de U.The cardiovascular diseases constitute one of the main causes of death worldwide. One of the main diseases is atherosclerosis, which causes narrowing of the arterial lumen. In order to solve this condition, several treatments have been developed, and Percutaneous Transluminal Coronary Angioplasty (PTCA) with the placement of stent have gained relevancy. Many of these devices are currently coated to increase the biocompatibility and to decrease the restenosis risks. The biomechanical studies of the stent-coating interface behavior are necessary given the associated risks to possibility of failures or breakages of the coating during stent deployment. In this study the possible occurrence of coating delamination during stent deployment and the influence of parameters as the thickness and material were studied. The study starts by obtaining a geometric model of a stent unit of the Sirius Carbostent stent for the further processing by the Finite Element Method. The simulation was developed by applying restrictions so that the modeled stent hinge simulates his behavior during stent deployment. Considering these aspects it was possible to evaluation the coating integrity. With this model it was possible to predict the occurrence of delamination during stent deployment and to determine that the delamination risks increases with increasing the coating thickness. Finally, it was obtained a general function that allows to determine the maximal contact stress for a stent hinge with an U shape.Peer Reviewe

What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Analysis of the coating integrity during a coronary stent deployment

The cardiovascular diseases constitute one of the main causes of death worldwide. One of the main diseases is atherosclerosis, which causes narrowing of the arterial lumen. In order to solve this condition, several treatments have been developed, and Percutaneous Transluminal Coronary Angioplasty (PTCA) with the placement of stent have gained relevancy. Many of these devices are currently coated to increase the biocompatibility and to decrease the restenosis risks. The biomechanical studies of the stent-coating interface behavior are necessary given the associated risks to possibility of failures or breakages of the coating during stent deployment. In this study the possible occurrence of coating delamination during stent deployment and the influence of parameters as the thickness and material were studied. The study starts by obtaining a geometric model of a stent unit of the Sirius Carbostent stent for the further processing by the Finite Element Method. The simulation was developed by applying restrictions so that the modeled stent hinge simulates his behavior during stent deployment. Considering these aspects it was possible to evaluation the coating integrity. With this model it was possible to predict the occurrence of delamination during stent deployment and to determine that the delamination risks increases with increasing the coating thickness. Finally, it was obtained a general function that allows to determine the maximal contact stress for a stent hinge with an U shape

In vivo analysis of the effect of panobinostat on cell-associated HIV RNA and DNA levels and latent HIV infection

Abstract Background The latent reservoir in resting CD4+ T cells presents a major barrier to HIV cure. Latency-reversing agents are therefore being developed with the ultimate goal of disrupting the latent state, resulting in induction of HIV expression and clearance of infected cells. Histone deacetylase inhibitors (HDACi) have received a significant amount of attention for their potential as latency-reversing agents. Results Here, we have investigated the in vitro and systemic in vivo effect of panobinostat, a clinically relevant HDACi, on HIV latency. We showed that panobinostat induces histone acetylation in human PBMCs. Further, we showed that panobinostat induced HIV RNA expression and allowed the outgrowth of replication-competent virus ex vivo from resting CD4+ T cells of HIV-infected patients on suppressive antiretroviral therapy (ART). Next, we demonstrated that panobinostat induced systemic histone acetylation in vivo in the tissues of BLT humanized mice. Finally, in HIV-infected, ART-suppressed BLT mice, we evaluated the effect of panobinostat on systemic cell-associated HIV RNA and DNA levels and the total frequency of latently infected resting CD4+ T cells. Our data indicate that panobinostat treatment resulted in systemic increases in cellular levels of histone acetylation, a key biomarker for in vivo activity. However, panobinostat did not affect the levels of cell-associated HIV RNA, HIV DNA, or latently infected resting CD4+ T cells. Conclusion We have demonstrated robust levels of systemic histone acetylation after panobinostat treatment of BLT humanized mice; and we did not observe a detectable change in the levels of cell-associated HIV RNA, HIV DNA, or latently infected resting CD4+ T cells in HIV-infected, ART-suppressed BLT mice. These results are consistent with the modest effects noted in vitro and suggest that combination therapies may be necessary to reverse latency and enable clearance. Animal models will contribute to the progress towards an HIV cure