Brain Arteriovenous Malformation In Vitro Model for Transvenous Embolization Using 3D Printing and Real Patient Data.

BACKGROUND AND PURPOSE: Transvenous embolization has emerged as a novel technique for treating selected brain AVMs with high reported occlusion rates. However, it requires anatomic and technical skills to be successful and to ensure patient safety. Therefore, training and testing are essential for preparing clinicians to perform these procedures. Our aim was to develop and test a novel, patient-specific brain AVM in vitro model for transvenous embolization by using 3D printing technology. MATERIALS AND METHODS: We developed a brain AVM in vitro model based on real patient data by using stereolithography resin 3D printing. We created a closed pulsed circuit with flow passing from the arterial side to the venous side, and we tested the effect of mean arterial pressure on retrograde nidal filling with contrast injections. Transvenous embolization simulations were conducted for each of the 12 identical models divided into 2 groups (2×6). This involved the use of an ethylene-vinyl alcohol liquid embolic agent injected through microcatheters either without or with a coil in the vein (groups 1 and 2, respectively). RESULTS: Retrograde contrast advance to nidus was directly related to lower mean arterial pressure. Transvenous embolization tests with a liquid embolic agent adequately reproduced the usual embolization plug and push technique. We found no differences between the 2 group conditions, and additional venous coil neither increased nidus penetration nor reduced injection time in the model (57.6 versus 61.2% nidus occlusion rate, respectively). CONCLUSIONS: We were able to develop and test a functional in vitro brain AVM model for transvenous embolization by using 3D printing to emulate its conditions and characteristics. Better contrast penetration was achieved with less mean arterial pressure, and no embolization advantage was found by adding coil to the vein in this model.

Alteraciones genéticas asociadas a la enfermedad de Parkinson y Alzheimer: evolución y respuesta al tratamiento / Genetic Alterations Associated with Parkinson's and Alzheimer's Disease: Evolution and Response to Treatment

La enfermedad de Parkinson y Alzheimer son las enfermedades neurodegenerativas más frecuentes a nivel mundial. Tienen etiología multifactorial, entre ellas, la genética; y son motivo de interés en la investigación científica actual. Se realizó una revisión narrativa con el objetivo de determinar las alteraciones genéticas asociadas a estas patologías, además su influencia en la evolución y respuesta al tratamiento de ellas. Se consultaron artículos originales, revisiones bibliográficas, sistemáticas, metaanálisis en inglés y español, con fecha de publicación entre el 1 enero de 2018 y el 20 de mayo de 2023, en bases como PubMed y Medline. Se utilizaron los términos MeSH «Alzheimer Disease¼, «Parkinson Disease¼, «Drug Therapy¼ y «Mutations¼. El riesgo hereditario para la enfermedad de Parkinson suele ser poligenético, sin embargo, existen genes relacionados con mutaciones monogénicas. Se identifican alteraciones en genes de α-sinucleína, glucocerebrosidasa y quinasa 2 rica en leucina que se relacionan con mayor riesgo de desarrollar Parkinson, además de variaciones en el cuadro clínico y edad de inicio de síntomas. En cuanto a la enfermedad de Alzheimer, las alteraciones en los genes de la proteína precursora amiloide, presenilina 1 y 2 se relacionan con la forma familiar de la enfermedad; por otra parte, las de apolipoproteína E4 se han identificado en la forma esporádica, por lo que se consideran como el factor de riesgo genético más importante para su desarrollo

Parkinson's and Alzheimer's are the most frequent neurodegenerative diseases worldwide. They have a multifactorial etiology, including genetics, and are of interest in current scientific research. A narrative review was carried out with the aim of determining the genetic alterations associated with these pathologies, as well as their influence on their evolution and response to treatment. Original articles, literature reviews, systematic reviews, meta-analyses in English and Spanish, with publication date between January 1, 2018 and May 20, 2023, were consulted in databases such as PubMed and Medline. MeSH terms "Alzheimer Disease", "Parkinson Disease", "Drug Therapy" and "Mutation" were used. Hereditary risk for Parkinson's disease is usually polygenetic, however, there are genes related to monogenic mutations. Alterations in α-synuclein, glucocerebrosidase and leucine-rich kinase 2 genes have been identified that are related to an increased risk of developing Parkinson's disease, in addition to variations in the clinical picture and age of symptom onset. As for Alzheimer's disease, alterations in the genes of the amyloid precursor protein, presenilin 1 and 2 are related to the familial form of the disease; on the other hand, those of apolipoprotein E4 have been identified in the sporadic form, and are therefore considered to be the most important genetic risk factor for its development

Endovascular treatment simulations using a novel in vitro brain arteriovenous malformation model based on three-dimensional printing millifluidic technology.

BACKGROUND: Brain arteriovenous malformations (bAVM) are complex vascular diseases. Several models have been used to simulate endovascular treatments; thus in vitro models have not been widely employed because it has been difficult to recreate realistic phantoms of this disease. OBJECTIVE: To describe the development and evaluate the preliminary experience of a novel bAVM in vitro model for endovascular embolization using millifluidic three-dimensional (3D) printing technology. METHODS: We designed a bAVM phantom starting from simple to more complex designs, composed of a nidus, feeding arteries and draining vein. We recreate the design by using millifluidic technology with stereolithography 3D printing. Structural and functional tests were performed using angiographic images and computer flow dynamics. Treatment simulations with ethylene vinyl alcohol were tested using two different microcatheter position techniques. A Likert-scale questionnaire was applied to perform a qualitative evaluation of the model. RESULTS: We developed a realistic model of a bAVM with hollow channels. The structural evaluation showed a high precision of the 3D printing process. Embolization tests with the liquid agent gave similar sensations and material behaviour as in vivo cases. There were no significant differences between microcatheter position techniques, thus we observed a trend for better nidus filling with a deeper in-nidus position technique. CONCLUSIONS: We were able to create and test a novel bAVM in vitro model with stereolithography 3D printing in resin. It showed a high capacity for simulating endovascular embolization characteristics, with an excellent user experience. It could be potentially used for training and testing of bAVM embolizations.

A high throughput bispecific antibody discovery pipeline.

Bispecific antibodies (BsAbs) represent an emerging class of immunotherapy, but inefficiency in the current discovery has limited their broad clinical availability. Here we report a high throughput, agnostic, single-cell-based functional screening pipeline, comprising molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification and functionality characterization. Using a CD19xCD3 bispecific T cell engager (BiTE) as a model, we demonstrate that our single-cell platform possesses a high throughput screening efficiency of up to one and a half million variant library cells per run and can isolate rare functional clones at a low abundance of 0.008%. Using a complex CD19xCD3 BiTE-expressing cell library with approximately 22,300 unique variants comprising combinatorially varied scFvs, connecting linkers and VL/VH orientations, we have identified 98 unique clones, including extremely rare ones (~ 0.001% abundance). We also discovered BiTEs that exhibit novel properties and insights to design variable preferences for functionality. We expect our single-cell platform to not only increase the discovery efficiency of new immunotherapeutics, but also enable identifying generalizable design principles based on an in-depth understanding of the inter-relationships between sequence, structure, and function.

The impact of a two-year long COVID-19 public health restriction program on mechanical thrombectomy outcomes in a stroke network.

OBJECTIVE: The purpose of this study was to evaluate the impact of COVID-19 pandemic public health restrictions on our drip and ship mechanical thrombectomy program in Santiago Chile. MATERIALS AND METHODS: This was a retrospective analysis of a prospectively collected database comparing two cohorts, one during a two-year period before COVID-19 and the second during the two years of the pandemic at our metropolitan stroke program. RESULTS: A total of 100 patients were included in the pre COVID-19 cohort (cohort 1) and 121 in the COVID-19 cohort (cohort 2). There was a significant difference between cohorts, with older patients, different occlusion sites and higher door to arterial puncture time during the COVID-19 period. A non-significant trend for worse 90-day outcomes and higher mortality was present in cohort 2. There were no statistical differences in safety treatment parameters. CONCLUSIONS: COVID-19 pandemic has had a measurable impact on our mechanical thrombectomy program. Results showed similarities to other reported Latin American series, where less robust health systems could adapt less efficiently compared to developed countries. After two years of public health restrictions, there were changes in the treatment population characteristics, delay in some internal management metrics and a non-significant trend to worse 90-day outcomes and higher mortality.

Basilar artery occlusion management: Specialist perspectives from an international survey.

BACKGROUND AND PURPOSE: Two early basilar artery occlusion (BAO) randomized controlled trials did not establish the superiority of endovascular thrombectomy (EVT) over medical management. While many providers continue to recommend EVT for acute BAO, perceptions of equipoise in randomizing patients with BAO to EVT versus medical management may differ between clinician specialties. METHODS: We conducted an international survey (January 18, 2022 to March 31, 2022) regarding management strategies in acute BAO prior to the announcement of two trials indicating the superiority of EVT, and compared responses between interventionalists (INTs) and non-interventionalists (nINTs). Selection practices for routine EVT and perceptions of equipoise regarding randomizing to medical management based on neuroimaging and clinical features were compared between the two groups using descriptive statistics. RESULTS: Among the 1245 respondents (nINTs = 702), INTs more commonly believed that EVT was superior to medical management in acute BAO (98.5% vs. 95.1%, p < .01). A similar proportion of INTs and nINTs responded that they would not randomize a patient with BAO to EVT (29.4% vs. 26.7%), or that they would only under specific clinical circumstances (p = .45). Among respondents who would recommend EVT for BAO, there was no difference in the maximum prestroke disability, minimum stroke severity, or infarct burden on computed tomography between the two groups (p > .05), although nINTs more commonly preferred perfusion imaging (24.2% vs. 19.7%, p = .04). Among respondents who indicated they would randomize to medical management, INTs were more likely to randomize when the National Institutes of Health Stroke Scale was ≥10 (15.9% vs. 6.9%, p < .01). CONCLUSIONS: Following the publication of two neutral clinical trials in BAO EVT, most stroke providers believed EVT to be superior to medical management in carefully selected patients, with most indicating they would not randomize a BAO patient to medical treatment. There were small differences in preference for advanced neuroimaging for patient selection, although these preferences were unsupported by clinical trial data at the time of the survey.

A novel self-expanding shape memory polymer coil for intracranial aneurysm embolization: 1 year follow-up in Chile.

BACKGROUND: Aneurysm recurrence remains a challenge when coiling cerebral aneurysms. Development of next generation coils has focused on accelerating thrombus maturation and increasing coil packing density. Ultra low density shape memory polymer is a novel embolic material designed for this purpose. The polymer is crimped over a platinum-tungsten coil for catheter delivery and self-expands to a predefined volume on contact with blood. METHODS: This prospective study in humans evaluated aneurysms 5-16 mm (inclusive) in diameter that were indicated for endovascular coil embolization. At least 70% coil volume was required to be shape memory polymer coils. Patients were followed-up according to standard of care for 12 months. RESULTS: Nine patients (89% women, mean age 55.8±11.7 years) were treated with shape memory polymer coils and completed 12 months of follow-up. Aneurysms were all unruptured and were in the ophthalmic segment of the internal carotid artery (n=7), posterior communicating artery, and anterior cerebral artery A1-A2 segment. Aneurysms were a mean of 7.8±2.9 mm in diameter (range 5.2-14.9 mm). The mean packing density based on unexpanded polymer was 17±6%. Packing density based on expanded polymer was 43±13%. At 12 months, no recurrence had occurred, and a Raymond-Roy occlusion classification of 1 (n=5) or 2 (n=4) was observed. No serious adverse events related to the study device occurred over the 12 months after the procedure. CONCLUSIONS: Shape memory polymer coils were safe and effective in treating intracranial aneurysms over 12 months in this first study in human subjects.

A clinical mutation in glucokinase causing maturity-onset diabetes in the young type 2 increases enzyme activity.

Glucokinase (GCK) is the pancreatic ß-cell glucose sensor, and its kinetics are key to that purpose. A slow transition step, displayed as non-hyperbolic kinetics, and a low affinity for glucose characterize GCK. Mutations in GCK associated with maturity-onset diabetes of the young type 2 (MODY2) previously described reduce the functionality of the human pancreatic ß-cell, leading to diabetic clinical phenotypes. We present a kinetic characterization of the G448D mutation identified in a MODY2 patient, which is one of the first mutations to exhibit increased functionality. This mutant displays increased activity, high affinity for both Mg2+ -ATP and glucose, hyperbolic kinetics and increased phosphorylation potential. Hyperbolic kinetics and assays in the presence of glycerol indicate that G448D lacks the slow transition step crucial for the pancreatic ß-cell glucose sensor function.

Fiscal Reform in Costa Rica: Price Elasticities of Major Food Categories to Inform Decision-Making.

In the context of fiscal reform in Costa Rica (value added tax revision), the definition of a new basic tax basket, "canasta básica tributaria" (CBT) in Spanish, incorporating nutritional criteria is underway in the country. In this study, price elasticities of major food categories were analyzed using a Quadratic Almost Ideal Demand System (QUAIDS) model. Data from the 2018 National Survey of Household Income and Expenditures was used. Measuring price elasticities is essential because it allows: knowing the extent to which food demand reacts to price changes, anticipating changes in the quantities demanded as a result of fiscal policy changes, measuring potential substitution and complementary effects between food groups, and potential nutritional effects of fiscal policies. As a result, it helps providing recommendations on the content of a CBT with nutritional criteria. Results show that the food categories with the most elastic demand are "Bread and cereals," soft drinks and "Milk, cheese and eggs." Substitution effects exist between the following groups: "Fruits" and "Oils and fats," "Fruits" and "Bread and cereals," and between "Milk, cheese and eggs" and "Oils and fats." For this last food category and for the one which includes sweets and chocolates, the consumption decreases when the price of "Bread and cereals" increases. They are complementary goods. These relations between food groups need to be taken into account when defining a national CBT with nutritional criteria and with the objective of promoting the consumption of healthier food groups while disincentivizing the consumption of the unhealthy ones. Lastly, it is important that the consumption of the healthiest foods within each food group be fiscally promoted. Clinical Trial Registration: JEL codes: D12, H3, I18.

The curvature of gold nanoparticles influences the exposure of amyloid-ß and modulates its aggregation process.

Gold nanoparticles (GNP) are tunable nanomaterials that can be used to develop rational therapeutic inhibitors against the formation of pathological aggregates of proteins. In the case of the pathological aggregation of the amyloid-ß protein (Aß), the shape of the GNP can slow down or accelerate its aggregation kinetics. However, there is a lack of elementary knowledge about how the curvature of GNP alters the interaction with the Aß peptide and how this interaction modifies key molecular steps of fibril formation. In this study, we analysed the effect of flat gold nanoprisms (GNPr) and curved gold nanospheres (GNS) on in vitro Aß42 fibril formation kinetics by using the thioflavin-based kinetic assay and global fitting analysis, with several models of aggregation. Whereas GNPr accelerate the aggregation process and maintain the molecular mechanism of aggregation, GNS slow down this process and modify the molecular mechanism to one of fragmentation/secondary nucleation, with respect to controls. These results can be explained by a differential interaction between the Aß peptide and GNP observed by Raman spectroscopy. While flat GNPr expose key hydrophobic residues involved in the Aß peptide aggregation, curved GNS hide these residues from the solvent. Thus, this study provides mechanistic insights to improve the rational design of GNP nanomaterials for biomedical applications in the field of amyloid-related aggregation.

Single-molecule optical tweezers reveals folding steps of the domain swapping mechanism of a protein.

Domain swapping is a mechanism of protein oligomerization by which two or more subunits exchange structural elements to generate an intertwined complex. Numerous studies support a diversity of swapping mechanisms in which structural elements can be exchanged at different stages of the folding pathway of a subunit. Here, we used single-molecule optical tweezers technique to analyze the swapping mechanism of the forkhead DNA-binding domain of human transcription factor FoxP1. FoxP1 populates folded monomers in equilibrium with a swapped dimer. We generated a fusion protein linking two FoxP1 domains in tandem to obtain repetitive mechanical folding and unfolding trajectories. Thus, by stretching the same molecule several times, we detected either the independent folding of each domain or the elusive swapping step between domains. We found that a swapped dimer can be formed directly from fully or mostly folded monomer. In this situation, the interaction between the monomers in route to the domain-swapped dimer is the rate-limiting step. This approach is a useful strategy to test the different proposed domain swapping mechanisms for proteins with relevant physiological functions.

Numerical Analysis of the ACL, with Sprains of Different Degrees after Trauma.

Nowadays, cruciate ligament injuries have increased in incidence, since practicing a sport or physical activity has become a trend in current societies. Although this lifestyle generates multiple benefits, as a consequence, injury has also increased. Due to its nature and complexity, the ligaments of the knee are those that are most frequently affected, mainly the ACL (anterior cruciate ligament). This tissue reacts to overexertion or movements out of range, either caused by the exercise itself or caused by trauma caused by the practice of physical activity, causing various degrees of sprain. Whatever the etiology of these injuries, they will require a therapy indicated for each degree of injury. This therapy initially entails immobilization of the affected area and later; physical therapy will be required to a lesser or greater degree. Commonly, in the physiotherapy of these injuries, rehabilitation exercises are prescribed, where the physiotherapist asks a patient to use equipment with an estimated weight. However, the effectiveness of a generalized therapy in this way does not always give the expected results. This is related to the fact that these therapies are standardized and do not consider some factors such as the remaining muscle fibres that are not directly affected by the sprain, which does not mean that they should not be considered. Therefore, in the present work, a biomodel of a human knee has been developed and used to evaluate numerically how the ACL acts under an external load, when there are different degrees of injuries, caused by trauma. Four case studies were considered: Case 1 (control case) where the ACL is healthy, Case 2 where the ACL presents a 1st-degree sprain, Case 3 where the ACL presents a 2nd-degree sprain, and finally Case 4 where the ACL presents a 3rd-sprain grade. After performing the analyses, in the control case, it was found that it presents a balance between tensile and compressive stresses. While in the 4th case, the most critical tensile stress decreases while compression stresses increase. This shows that the ligament, having considerable damage, no longer works as it should and can eventually damage the collateral structures. It was found that, when there was a sprain, where the continuity of the ligament is compromised, a second torsional moment occurs in the ACL which causes the tissue fibres not to act according to their normal physiology or in a healthy state. The results obtained from the present study provide the possibility of predicting where the following injuries will occur by considering the von Mises failure criterion. Likewise, they will allow to improve the therapeutic procedures considering not only the injured structure but also the system as a whole.

Predicting and Characterizing Neurodegenerative Subtypes with Multimodal Neurocognitive Signatures of Social and Cognitive Processes.

BACKGROUND: Social cognition is critically compromised across neurodegenerative diseases, including the behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, no previous study has used social cognition and other cognitive tasks to predict diagnoses of these conditions, let alone reporting the brain correlates of prediction outcomes. OBJECTIVE: We performed a diagnostic classification analysis using social cognition, cognitive screening (CS), and executive function (EF) measures, and explored which anatomical and functional networks were associated with main predictors. METHODS: Multiple group discriminant function analyses (MDAs) and ROC analyses of social cognition (facial emotional recognition, theory of mind), CS, and EF were implemented in 223 participants (bvFTD, AD, PD, controls). Gray matter volume and functional connectivity correlates of top discriminant scores were investigated. RESULTS: Although all patient groups revealed deficits in social cognition, CS, and EF, our classification approach provided robust discriminatory characterizations. Regarding controls, probabilistic social cognition outcomes provided the best characterization for bvFTD (together with CS) and PD, but not AD (for which CS alone was the best predictor). Within patient groups, the best MDA probabilities scores yielded high classification rates for bvFTD versus PD (98.3%, social cognition), AD versus PD (98.6%, social cognition + CS), and bvFTD versus AD (71.7%, social cognition + CS). Top MDA scores were associated with specific patterns of atrophy and functional networks across neurodegenerative conditions. CONCLUSION: Standardized validated measures of social cognition, in combination with CS, can provide a dimensional classification with specific pathophysiological markers of neurodegeneration diagnoses.

Comparative Numerical Analysis between Two Types of Orthodontic Wire for the Lingual Technique, Using the Finite Element Method.

In the lingual orthodontic technique, there are two paradigms regarding the type of wire used. Regardless of the material or gauge, some orthodontists choose to use the straight wire and resin and bond it to the surface of the tooth; they call it compensations. Other orthodontists prefer to bend the wire, giving it a mushroom shape. There is no specific indication for the use of each type of wire, so orthodontists use them according to their criteria. The present study establishes the bases so that it is possible to find the indications for each type of wire. A clinical trial of a lingual orthodontic patient was used. To carry out the comparative study, a straight arch was placed in his right arch and a mushroom arch in the left arch. Using 3D imaging, a high-biofidelity biomodel of the patient's mandible was generated, with which the FEM analysis was performed, which allowed comparing the reactions of the mandibular bone and appliances with the different arches. It was found that, on the side with the straight arch, there were greater deformations, and in the mushroom arch, there were greater stresses. With this, it is possible to find which clinical cases in each type of wire are indicated.

First multicenter experience using the Silk Vista flow diverter in 60 consecutive intracranial aneurysms: technical aspects.

BACKGROUND: The aim of this study was to assess the technical success and procedural safety of the new Silk Vista device (SV) by evaluating the intraprocedural and periprocedural complication rate after its use in several institutions worldwide. METHODS: The study involved a retrospective review of multicenter data regarding a consecutive series of patients with intracranial aneurysms, treated with the SV between September 2020 and January 2021. Clinical, intra/periprocedural and angiographic data, including approach, materials used, aneurysm size and location, device/s, technical details and initial angiographic aneurysm occlusion, were analyzed. RESULTS: 60 aneurysms were treated with SV in 57 procedures. 66 devices were used, 3 removed and 63 implanted. The devices opened instantaneously in 60 out of 66 (91%) cases and complete wall apposition was achieved in 58 out of 63 (92%) devices implanted. In 4 out of 66 (6%) devices a partial opening of the distal end occurred, and in 5 (8%) devices incomplete apposition was reported. There were 3 (5%) intraprocedural thromboembolic events managed successfully with no permanent neurological morbidity, and 4 (7%) postprocedural events. There was no mortality in this study. The initial occlusion rates in the 60 aneurysms were as follows: O'Kelly-Marotta (OKM) A in 34 (57%) cases, OKM B in 15 (25%) cases, OKM C in 6 (10%) cases, and OKM D in 5 (8%) cases. CONCLUSIONS: Our study demonstrated that the use of the new flow diverter Silk Vista for the treatment of intracranial aneurysms is feasible and technically safe.

High Biofidelity 3D Biomodel Reconstruction from Soft and Hard Tissues (Knee), FEM, and 3D Printing: A Three-Dimensional Methodological Proposal.

The modelling of biological structures has allowed great advances in Engineering, Biology, and Medicine. In turn, these advances are seen from the design of footwear and sports accessories, to the design of prostheses, accessories and rehabilitation treatments. The reproduction of the various tissues has gone through an important evolution thanks to the development of computer systems and programs. However, knowledge of the medical-biological and engineering areas continues to be required, and it involves a considerable investment of time and resources. The resulting biomodels still require great precision. The present work shows a methodology that allows to optimize computational resources and reduce elaboration time of biomodels. Through this methodology, it is possible to generate a biomodel of high biofidelity of a human knee. This biomodel is constituted by hard tissues (cortical and trabecular bones) and soft tissues (ligaments and meniscus) resulting in the modelling of the lower third of the femur, the tibial plateaus, the anterior cruciate ligament, posterior cruciate ligament, external lateral ligament, interior lateral ligaments, and the meniscus. With this model and methodology, it is possible to perform numerical analyses that will provide results very similar to those of real life. As, the methodology allows to assign the mechanical properties to each tissue and the anatomical structure.

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.

Breaking the breach in Latin America: A pilot study of mechanical thrombectomy in the public healthcare system in Chile.

BACKGROUND: Mechanical Thrombectomy (MT) is the standard of care for treatment of large vessel occlusion stroke. Until the beginning of 2020 MT was not funded nor widely implemented at the public healthcare level in Chile. OBJECTIVE: To describe the results of a pilot program created to provide access to public MT in Santiago - Chile. METHODS: Analysis from a prospectively collected database of MT cases performed between September 2017 and September 2019 in one center. A stroke network was developed with a single MT capable stroke center and five primary stroke centers. The primary efficacy endpoint was the rate of functional independence (mRS 0-2) at 90 days. Successful reperfusion was defined as 2 b-3 according to the thrombolysis in cerebral infarction scale. Safety outcomes include the rates of symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 100 patients were treated over the study period. Their mean age was 62.8 ± 11.8 years and median baseline National Institute of Health Stroke Scale (NIHSS) measurement was 17. Seventy-seven percent of the patients received intra venous thrombolysis. Successful reperfusion was achieved in 95% of the cases. NIHSS at 24 hours showed a median drop of 7 points from baseline (p < 0.00001) and 50% of the follow-up patients were functionally independent at 90 days. Symptomatic Intracerebral hemorrhage occurred in 5% of the patients and 90-day all case mortality was 11%. CONCLUSIONS: We demonstrated the feasibility of a publicly funded MT program in Chile, with similar results as other international randomized control trials.

GERO Cohort Protocol, Chile, 2017-2022: Community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly.

BACKGROUND: With the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years. Cognitive complaint is considered a predictor for cognitive and functional decline, incident mild cognitive impairment, and incident dementia. The GERO cohort is the Chilean core clinical project of the Geroscience Center for Brain Health and Metabolism (GERO). The objective of the GERO cohort is to analyze the rate of functional decline and progression to clinical dementia and their associated risk factors in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. We also aim to undertake clinical research on brain ageing and dementia disorders, to create data and biobanks with the appropriate infrastructure to conduct other studies and facilitate to the national and international scientific community access to the data and samples for research. METHODS: The GERO cohort aims the recruitment of 300 elderly subjects (> 70 years) from Santiago (Chile), following them up for at least 3 years. Eligible people are adults not diagnosed with dementia with subjective cognitive complaint, which are reported either by the participant, a proxy or both. Participants are identified through a household census. The protocol for evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool samples are also obtained. This multidimensional evaluation is carried out in a baseline and 2 follow-ups assessments, at 18 and 36 months. In addition, in months 6, 12, 24, and 30, a telephone interview is performed in order to keep contact with the participants and to assess general well-being. DISCUSSION: Our work will allow us to determine multidimensional risks factors associated with functional decline and conversion to dementia in elderly with subjective cognitive complain. The aim of our GERO group is to establish the capacity to foster cutting edge and multidisciplinary research on aging in Chile including basic and clinical research. TRIAL REGISTRATION: NCT04265482 in ClinicalTrials.gov. Registration Date: February 11, 2020. Retrospectively Registered.

High-Biofidelity Biomodel Generated from Three-Dimensional Imaging (Cone-Beam Computed Tomography): A Methodological Proposal.

Experimental research on living beings faces several obstacles, which are more than ethical and moral issues. One of the proposed solutions to these situations is the computational modelling of anatomical structures. The present study shows a methodology for obtaining high-biofidelity biomodels, where a novel imagenological technique is used, which applies several CAM/CAD computer programs that allow a better precision for obtaining a biomodel, with highly accurate morphological specifications of the molar and tissues that shape the biomodel. The biomodel developed is the first lower molar subjected to a basic chewing simulation through the application of the finite element method, resulting in a viable model, able to be subjected to various simulations to analyse molar biomechanical characteristics, as well as pathological conditions to evaluate restorative materials and develop treatment plans. When research is focused in medical and dental investigation aspects, numerical analyses could allow the implementation of several tools commonly used by mechanical engineers to provide new answers to old problems in these areas. With this methodology, it is possible to perform high-fidelity models no matter the size of the anatomical structure, nor the complexity of its structure and internal tissues. So, it can be used in any area of medicine.