Down Syndrome-Basque Alzheimer Initiative (DS-BAI): Clinic-Biological Cohort.

BACKGROUND: Down syndrome (DS) is the most common genetically determined intellectual disability. In recent decades, it has experienced an exponential increase in life expectancy, leading to a rise in age-related diseases, including Alzheimer's disease (AD). Specific health plans for the comprehensive care of the DS community are an unmet need, which is crucial for the early and accurate diagnosis of main medical comorbidities. We present the protocol of a newly created clinical and research cohort and its feasibility in real life. METHODS: The Down Syndrome-Basque Alzheimer Initiative (DS-BAI) is a population-based, inclusive, multidisciplinary initiative for the clinical-assistance and clinical-biological research approach to aging in DS led by the CITA-Alzheimer Foundation (Donostia, Basque Country). It aims to achieve the following: (1) provide comprehensive care for adults with DS, (2) optimize access to rigorous and quality training for socio-family and healthcare references, and (3) create a valuable multimodal clinical-biological research platform. RESULTS: During the first year, 114 adults with DS joined the initiative, with 36% of them showing symptoms indicative of AD. Furthermore, adherence to training programs for healthcare professionals and families has been high, and the willingness to collaborate in basic and translational research has been encouraging. CONCLUSION: Specific health plans for DS and conducting clinical and translational research on the challenges of aging, including AD, are necessary and feasible.

Clinical and Radiological Outcomes of Computer-Assisted versus Conventional Total Knee Arthroplasty at 5-Year Follow-Up: Is There Any Benefit?

Computer-assisted total knee arthroplasty (CAS) remains controversial. Some authors defend that its improvement in knee alignment and positioning positively impacts arthroplasty survival rates, while others have stated that there is minimal or no difference compared to the conventional technique (cTKA). This paper features a retrospective, single-center, single-surgeon study, evaluating CAS surgery vs. regular cTKA in patients who consecutively underwent surgery between 2015 and 2017 (60 CAS patients vs. 59 cTKA). Data collection includes surgery duration, length of stay, blood loss and both preoperative and postoperative clinical outcome evaluation using WOMAC, SF-12, Forgotten Joint Score and VAS. Radiograph evaluation includes the tibiofemoral angle, posterior condylar offset and its ratio, and notching frequency and measurement. A total of 119 patients were included: 60 in the CAS group and 59 in the cTKA. Mean follow-up was 5.61 years (Max 7.83-Min 5.02 years). No clinically relevant preoperative differences were observed between the groups. Postoperatively, both groups showed similar functional results (WOMAC, SF-12, FJS, KSS, and VAS) with similar complication rates. The CAS group had an increased surgery time by a mean of 12 min (107.02 ± 15.22 vs. 95.32 + 13.87; p = 0.00) as well as a higher notching frequency and size (40% vs. 13.60%; p = 0.013; 1.239 mm ± 1.7604 vs. 0.501 mm ± 1.4179; p = 0.031). CAS obtained similar functional, radiological, and complication rates to cTKA at the expense of increasing surgery time and notching frequency and size.

Endovascular thrombectomy first-pass reperfusion and ancillary device placement.

BACKGROUND: Recent randomized trials have demonstrated the efficacy of mechanical thrombectomy in treating acute ischemic stroke, however, further research is required to optimize this technique. We aimed to evaluate the impact of guide catheter position and clot crossing on revascularization rates using A Direct Aspiration First Pass Technique (ADAPT). METHODS: Data were collected between January 2018 and August 2019 as part of the Spanish ADAPT Registry on ACE catheters (SARA), a multicenter observational study assessing real-world thrombectomy outcomes. Demographic, clinical, and angiographic data were collected. Subgroup analyses assessed the relationship between guide catheter/microguidewire position and modified Trombolysis in Cerebral Infarction (mTICI) scores. First pass effect (FPE) was defined as mTICI 3 after single pass of the device. RESULTS: From a total of 589 patients, 80.8% underwent frontline aspiration thrombectomy. The median score on the National Institutes of Health Stroke Scale (NIHSS) was 16.0. After adjusting for confounders, the likelihood of achieving FPE (adjusted Odds Ratio (aOR), 0.587; 95% confidence interval (CI), 0.38 to 0.92; p=0.0194) were higher among patients with more distal petrocavernous placement of guide catheter. The likelihood of achieving FPE (aOR, 0.592; 95% CI, 0.39 to 0.90; p=0.0138) and final angiogram complete reperfusion (aOR, 0.465; 95% CI, 0.30 to 0.73; p=0.0008) were higher among patients without microguidewire crossing the clot. No difference was noted for time from arterial puncture to reperfusion in any study group. At the 90-day follow-up, the mortality rate was 9.2% and 65.8% of patients across the entire study cohort were functionally independent (modified Rankin Scale (mRS) 0-2). CONCLUSIONS: Petrocavernous guide catheter placement improved first-pass revascularization. Crossing the occlusion with a microguidewire lowered the likelihood of achieving FPE and complete reperfusion after final angiogram.

Thrombectomy aspiration post-market study in acute stroke with the Q aspiration catheter: the TAPAS study.

BACKGROUND: The Q Aspiration Catheter (MIVI Neuro) has demonstrated greater aspiration flow rates and ingestion forces compared with conventional catheters in vitro. The safety and performance of the Q Catheter was assessed using a direct aspiration first pass technique in patients with acute ischemic stroke at four neurointerventional centers in Spain. METHODS: We included adult patients who underwent mechanical thrombectomy between March 2019 and March 2020 using the Q Catheter as first-line therapy. Performance endpoints included final successful revascularization of the target vessel (defined as modified thrombolysis in cerebral infarction (mTICI) grade 2B/3), first pass revascularization, and overall Q Catheter revascularization. Safety endpoints were symptomatic intracranial hemorrhage (sICH), embolization to new territory (ENT), and procedural complications. Modified Rankin Scale (mRS) score and all-cause mortality were also assessed. RESULTS: Forty-five subjects were enrolled. The Q Catheter successfully navigated to the lesion in 95.5% (43/45) of patients. Final successful mTICI 2B/3 revascularization was achieved in 93.3% (42/45), first pass mTICI 2B/3 revascularization with the Q Catheter was 55.3% (21/38), and overall with Q Catheter mTICI 2B/3 revascularization was 65.8% (25/38). Favorable clinical outcome of mRS 0-2 was achieved in 55.6% (25/45). There were no cases of ENT. sICH and mortality rates were 2.2% (1/45) and 13.3% (6/45), respectively. CONCLUSION: In this multicenter, observational study, the Q Aspiration Catheter used as first-line therapy demonstrated a good and safe profile in terms of navigation, revascularization, and safety in patients with acute ischemic stroke.

Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial.

BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

Endothelial NO synthase 786T/T polymorphism increases hemorrhagic transformation after endovascular thrombectomy.

BACKGROUND AND PURPOSE: This study examined whether the 786 NOS3 polymorphism is associated with the risk of hemorrhagic transformation (HT) in stroke patients with anterior large vessel occlusion (ALVO) treated using endovascular thrombectomy (EVT). METHODS: We performed an observational cohort study that included 118 patients with ALVO who underwent EVT. HT was assessed in follow-up CT and MRI. HT and non-HT patients were compared in terms of the 786 NOS3 polymorphism, flow mediated dilation (FMD) values within 3 days after the stroke, and collateral status based on three grading scales. Demographics, vascular risk factors, additional radiological data including ASPECT score, thrombus length and infarct size, and EVT procedure and outcome variables were also included. RESULTS: Radiological HT occurred in 55 (46.6%) patients and the 786T/T NOS3 polymorphism was associated with HT (unadjusted OR of 2.33, 95%CI: 1.05-5.20, adjusted OR of 3.14, 95%CI: 1.16-8.54). Collateral status and systemic endothelial function assessed by FMD were not mediators of this relationship as no differences were seen in the median FMD percentage values or collateral status between NOS3 genotypes. CONCLUSIONS: Our results suggest that genetic variations affecting the NO pathway, such as the 786 NOS3 polymorphism, may contribute to individual variability in the occurrence of HT and these results support involvement of this pathway in the pathogenesis of ischemia-reperfusion injury after EVT.

Impact on functional outcome of an adaptive Stroke Unit based system of care for patients undergoing endovascular treatment during pandemic times.

Introduction: The COVID19 pandemic collapsed intensive care units (ICUs) all around the world, conditioning systems of care (SOC) for other critical conditions such as severe ischemic stroke requiring endovascular treatment (EVT). Our aim was to evaluate the impact of an adaptive Stroke Unit (SU) based SOC on functional outcomes, with the goal of avoiding both general anesthesia (GA) and ICU admission in stroke patients treated with EVT. Material and methods: We performed an observational study comparing data from our traditional ICU-GA based SOC and the adaptive SU-Conscious Sedation (CS) based SOC (consecutive patients undergoing EVT 1 year prior and after onset of the pandemic). Primary outcome was 90-days modified Rankin Scale (mRS), and secondary outcomes included, among others, in-hospital complications, and hospital length of stay (LOS). Results: A total of 210 EVT were performed during the study period (107 under the traditional-SOC and 103 under the adaptive-SOC). A significantly greater proportion of patient was treated under CS (15.9% vs 57.3%; p < 0.001) and admitted for post-procedural care at SU (15% vs 66%; p < 0.001) in the adaptive SOC. Rates of in-hospital complications were similar in both periods, with reduced hospital LOS in the adaptive SOC (10 (7-15) vs 8 (6-12); p = 0.005). The adaptive SOC was associated with higher odds for 90 days favorable outcome (mRS 0-2) (aOR 3.15 (1.34-7.39); p = 0.008). Conclusion: In our case, an adaptive SOC that combined both preference for CS and postprocedural care in SU was associated with better functional outcomes and reduced healthcare resource use for patients undergoing EVT.

Nivel de conocimiento sobre higiene bucal, Unidad Educativa "Pablo Palacio", Guayas durante la pandemia COVID-19 / Level of knowledge on oral hygiene, Educational Unit "Pablo Palacio", Guayas during the COVID-19 pandemic / Nível de conhecimento sobre higiene bucal, Unidade Educacional "Pablo Palacio", Guayas durante a pandemia COVID-19

Una enfermedad es anunciada a inicios del 2020, denominada SARSCOV-2 (COVID-19), la cual llega a convertirse en una pandemia mundial. Presenta una alta tasa de infección y mortalidad lo que produjo restricciones, lo cual provocó un descuido en la salud bucal. Los niños, con mayor frecuencia presentan un alto índice de caries dental y alteraciones periodontales. Describir el nivel de conocimiento sobre higiene bucal pediátrica que presentan los padres durante la pandemia de SARSCOV-2 (COVID-19). Se presentó un estudio descriptivo experimental con un enfoque cuantitativo y de investigación prospectivo y transversal. Para la obtención de los datos se realizó una encuesta a padres de los estudiantes de la Unidad Educativa "Pablo Palacio" del cantón Durán, provincia del Guayas. Se determinó que conocimiento sobre higiene bucal por los padres es menor de 50% en todas las áreas de interés. El uso de cepillo dental y pasta dental presento un 98% y 100%, siendo los elementos de higiene bucal más utilizados. La caries un 98% de conocimiento por los padres. El cepillado dental en niños de 4 a 6 años presentó un 29%. Niños de 6 hasta 11 años presentó un 44%. Las visitas al odontólogo con un 40% una vez al año. El conocimiento sobre higiene bucal pediátrica en la pandemia fue decadente. El control sobre el cepillado dental presentó menos del 50% de interés por los padres. Las visitas al odontólogo anuales obtuvieron un 48% en visitas 2 veces al año.

A disease is announced in early 2020, called SARSCOV-2 (COVID-19), which becomes a global pandemic. It has a high rate of infection and mortality, which produced restrictions, which caused a neglect in oral health. Children more often have a high rate of dental caries and periodontal alterations. To describe the level of knowledge about pediatric oral hygiene that parents presented during the SARSCOV-2 (COVID-19) pandemic. An experimental descriptive study with a quantitative focus and prospective and cross-sectional research was presented. To obtain the data, a survey was carried out with the parents of the students of the "Pablo Palacio" Educational Unit of Duran, Guayas province. It was determined that knowledge about oral hygiene by parents is less than 50% in all areas of interest. The use of toothbrush and toothpaste presented 98% and 100%, being the most used oral hygiene elements. Caries 98% of knowledge by parents. Tooth brushing in children 4 to 6 years old presented 29%. Children from 6 to 11 years old presented 44%. Visits to the dentist with 40% once a year. Knowledge about pediatric oral hygiene in the pandemic was declining. Control over tooth brushing presented less than 50% interest by parents. Annual dental visits obtained 48% in visits 2 times a year.

Uma doença é anunciada no início de 2020, chamada SARSCOV-2 (COVID-19), que se torna uma pandemia global. Possui uma alta taxa de infecção e mortalidade que produziu restrições, o que causou um descuido na saúde bucal. As crianças geralmente têm uma alta taxa de cárie dentária e alterações periodontais. Determinar o nível de conhecimento sobre higiene bucal pediátrica apresentado pelos pais durante a pandemia SARSCOV-2 (COVID-19). Foi apresentado um estudo experimental descritivo com abordagem de pesquisa quantitativa e prospectiva e transversal. Para obter os dados, foi realizada uma pesquisa com os pais dos alunos da Unidade Educacional "Pablo Palacio" do cantão de Durán, província de Guayas. Foi determinado que o conhecimento sobre higiene bucal pelos pais é inferior a 50% em todas as áreas de interesse. O uso de escova de dentes e pasta de dente apresentou 98% e 100%, sendo os elementos de higiene bucal mais utilizados. Cárcie um conhecimento de 98% pelos pais. A escovação dentária em crianças de 4 a 6 anos apresentou 29%. As crianças de 6 a 11 anos apresentaram 44%. Visitas ao dentista com 40% uma vez por ano. O conhecimento sobre higiene bucal pediátrica na pandemia foi decadente. O controle sobre a escovação dentária apresentou menos de 50% de juros pelos pais. As consultas odontológicas anuais obtiveram 48% em consultas 2 vezes ao ano.

Long-Term Results of Joint Arthroplasty with Total Prosthesis for Trapeziometacarpal Osteoarthritis in Patients over 65 Years of Age.

Trapeziometacarpal osteoarthritis (TMCOA) is a highly prevalent disease in the older population. Many different types of surgical treatments are possible, depending on the degree of joint involvement, the personal and professional circumstances of the patient and the preferences of the orthopedic surgeon. This paper evaluated the clinical and radiological results of consecutive cohorts of patients over 65 years old treated with total joint arthroplasties (TJA) of the ball and socket type (B&S) for TMCOA, with a minimum of 10 years follow-up. The survival rate (Kaplan-Meier) of the functional prostheses at 10 years was 92.2% (95% CI (89.1%, 96.1%). These functional arthroplasty patients, after 10 years of follow-up, showed little or no pain, good function and good key pinch, without radiological alterations. TJAs of the B&S type are a long lasting, effective and reliable alternative to surgical treatment of TMCOA in patients over 65 years of age, when they are performed with the patient selection criteria and surgical technique described throughout this study.

Total Knee Arthroplasty in Octogenarians: Should We Still Be so Restrictive?

Demand for total knee arthroplasty (TKA) in octogenarians will increase in subsequent years as society ages. We conducted a retrospective observational study in octogenarians operated on with TKA between 2015 and 2019, comparing preoperative and postoperative Knee Society Score (KSS), Knee Society Function Score (KSFS), extension and flexion balance, and radiologic alignment using a paired Student t-test. A chi-squared test was used to correlate mortality with Charlson comorbidities index score and with ASA scale. Kaplan-Meier analysis was performed to calculate patient survival. In this period 36 patients ≥80 years underwent TKA, with a mean age of 81.6 years. Of these, 24 patients (66.7%) were classified as ASA II and 12 (33.3%) as ASA III. Sixteen patients (44.4%) were Charlson 0, 14 (38.9%) Charlson 1, two (5.6%) Charlson 2, and four (11.1%) Charlson 3. KSS, KSFS, flexion and extension range, and radiologic alignment were statistically significant (p < 0.001) when comparing preoperatory and post-operatory data. No correlation (p > 0.05) was found between mortality and ASA or Charlson score. Seven patients (19.4%) suffered a medical complication and two patients experienced surgical complications. Four patient died (11.1%) during follow-up. The mean patient survival was 67.4 months. Patients ≥80 years achieve clinical improvement after TKA. Comorbidities, not age, are the burden for surgery in older patients.

Cryptococcal meningoencephalitis presenting as cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is characterized by its variety of neurological manifestations and difficulty in diagnosis. In subacute cases, the main symptoms are secondary to increased intracranial pressure. This condition is associated with an extensive range of medical disorders, but only 2% are caused by a CNS infection in recent series. We report a 45-year-old patient, with no previous medical history, who developed a syndrome of increased intracranial pressure as the presentation of a cryptococcal meningoencephalitis (CM) complicated with a CVT. The patient was first diagnosed of a CVT, and later on, the VIH infection and the CM diagnosis were made. Despite being treated with anticoagulation, liposomal amphotericin B, and a therapeutic lumbar puncture, the patient continued to deteriorate and suffered a respiratory arrest secondary to the increased intracranial pressure, with subsequent brain death. Cryptococcus is an infrequent cause of CNS infection in developed countries, despite being the most frequent cause of meningits in adults in several countries with high rates of HIV infection. CVT is a very rare complication of CM which can contribute to worsen the increased intracranial pressure and in consequence, its prognosis and outcome. A high level of suspicion is needed for diagnosing CM as the underlying cause of CVT and the subsequent increased intracranial pressure should be managed exhaustively.

Main histological parameters to be evaluated in an experimental model of myocardial infarct treated by stem cells on pigs.

Myocardial infarction has been carefully studied in numerous experimental models. Most of these models are based on electrophysiological and functional data, and pay less attention to histological discoveries. During the last decade, treatment using advanced therapies, mainly cell therapy, has prevailed from among all the options to be studied for treating myocardial infarction. In our study we wanted to show the fundamental histological parameters to be evaluated during the development of an infarction on an experimental model as well as treatment with mesenchymal stem cells derived from adipose tissue applied intra-lesionally. The fundamental parameters to study in infarcted tissue at the histological level are the cells involved in the inflammatory process (lymphocytes, macrophages and M2, neutrophils, mast cells and plasma cells), neovascularization processes (capillaries and arterioles) and cardiac cells (cardiomyocytes and Purkinje fibers). In our study, we used intramyocardial injection of mesenchymal stem cells into the myocardial infarction area 1 hour after arterial occlusion and allowed 1 month of evolution before analyzing the modifications on the normal tissue inflammatory infiltrate. Acute inflammation was shortened, leading to chronic inflammation with abundant plasma cells and mast cells and complete disappearance of neutrophils. Another benefit was an increase in the number of vessels formed. Cardiomyocytes and Purkinje fibers were better conserved, both from a structural and metabolic point of view, possibly leading to reduced morbidity in the long term. With this study we present the main histological aspects to be evaluated in future assays, complementing or explaining the electrophysiological and functional findings.

Farmacovigilancia: un paso importante en la seguridad del paciente / Pharmacovigilance: an important step in patient safety

Resumen Aunque la conciencia por el correcto uso de las sustancias empleadas para el tratamiento de las diferentes enfermedades tiene el mismo principio hipocrático de «primero no hacer daño¼, ésta no fue concretada como una actividad exprofeso para la vigilancia de sus efectos, lo que en épocas recientes se denomina farmacovigilancia. Las actividades de farmacovigilancia se impulsaron a partir de importantes reacciones adversas graves a medicamentos que fueron señales para advertir que, si bien éstos tienen como propósito mejorar el estado de salud, también tienen potencialidad de ser perjudiciales de manera importante, incluso fatal. Las actividades de farmacovigilancia como esfuerzo mundial procuran la mejora de la seguridad de los medicamentos mediante la monitorización de las reacciones adversas que se presentan postcomercialización en población abierta. Con el devenir histórico de la ciencia médica, también se ha hecho evidente la necesidad de implementar mecanismos para disminuir el potencial error humano, así como identificar y gestionar los riesgos y problemas relacionados con los medicamentos; ha sido importante, también, impulsar la cultura del reporte a fin de percibir la problemática y analizar su causalidad, y con el esfuerzo de todos, establecer mecanismos que influyan en la mejora del perfil de seguridad del sistema de medicación de las naciones. México, como un actor importante en la toma de decisiones globales, no se ha mantenido aislado ante este escenario y se suma a los esfuerzos dando importantes pasos desde las mismas autoridades sanitarias, implementando acciones que van desde el ámbito normativo y que han permeado en todo el sector salud de nuestro país. Ante este esperanzador panorama, sería irresponsable bajar la guardia; al contrario, hay que redoblar esfuerzos para concretar el programa de farmacovigilancia. Dichos esfuerzos no escapan a nuestro medio; con la creación de la Unidad de Farmacovigilancia Hospitalaria del Hospital Central Militar en 2014, nuestra institución es consistente con la visión de la calidad y seguridad en salud.

Abstract Although awareness of the correct use of substances used for the treatment of different diseases has the same Hippocratic principle of: «first do no harm¼, this was not made concrete as an ex-professed activity for the monitoring of its effects, which in recent times is called pharmacovigilance. Pharmacovigilance activities were prompted by major serious adverse reactions to drugs that were warning signs that, while they are intended to improve health status, they also have the potential to be harmful in significant, even fatal, ways. Pharmacovigilance activities, as a global effort, aim to improve the safety of medicines by monitoring post-marketing adverse reactions in the open population. With the historical development of medical science, it has also become evident the need to implement mechanisms to reduce the potential for human error, as well as to identify and manage the risks and problems related to medicines; it has also been important to promote a reporting culture in order to warn of the problem, analyze its causality, and with everybody's effort, establish mechanisms that improve the safety profile of the nations' medication system. Mexico, as an important actor in global decision-making, has not remained isolated in the face of this scenario, and joins the efforts of the health authorities themselves in taking important steps, implementing actions that go from the regulatory sphere, and have permeated the entire health sector of our country. Faced with this hopeful scenario, it would be irresponsible to lower our guard; on the contrary, we must redouble our efforts to implement a pharmacovigilance programme. These efforts do not escape us, and that with the creation of the Hospital Pharmacovigilance Unit of the Central Military Hospital in 2014, our institution is consistent with the vision of quality and health safety.

Congenital Spinal Malformation and Stroke: Aneurysmal Dilatations and Bilateral Rotational Vertebral Artery Occlusion.

A 30-year-old woman suffered from acute vertebrobasilar stroke. Cranial tomography (CT) scans showed multiple vertebral abnormalities suggestive of congenital spine malformation, and angiographic CT revealed aneurysmal dilatations (ADs) at segment V2 of both vertebral arteries (VAs). Dynamic neuroimaging tests including angiography and angio-CT were performed and showed occlusion of both VAs at the point of the ADs with contralateral rotation of the neck. The presence of a bony structure causing the artery compression was excluded and embolic phenomena originating at the AD was proposed as the likely source of stroke. Even if infrequent, the presence of craniocervical anomalies should be considered in vertebrobasilar stroke of indeterminate etiology.

Initial experience using the 3MAX cerebral reperfusion catheter in the endovascular treatment of acute ischemic stroke of distal arteries.

INTRODUCTION: The advancement of technology has allowed the development of new catheters that may provide safe intracranial navigation. OBJECTIVE: To report our first experience with the direct aspiration first pass technique in small arteries as the primary method for recanalization with the Penumbra 3MAX cerebral reperfusion catheter. METHODS: A retrospective case series analysis study of patients with acute ischemic stroke endovascularly treated with the direct aspiration technique using the 3MAX reperfusion catheter in our hospital in the past year. RESULTS: We treated six patients in our hospital for acute ischemic stroke using the 3MAX aspiration catheter as first choice. The patients had a median National Institutes of Health Strokes Scale (NIHSS) score of 12 (range 10-17) at admission, with occlusions of an M2 segment of a middle cerebral artery (MCA) treated through an anterior communicating artery, pericallosal artery, P2 artery, and M2-MCA and M3-MCA arteries. Recanalization (TICI 2b-3) was achieved in all cases and no complications occurred. It was not necessary to combine treatment with a stent retriever in any of the patients. All the patients showed early neurological improvement. The median NIHSS score at discharge was 1 (0-3) and 5/6 (83%) patients had a modified Rankin Scale score 0-2 at discharge. CONCLUSIONS: Our initial experience suggests that treatment of distal cerebrovascular occlusions with the 3MAX catheter is feasible. We achieved complete recanalization in all cases without unexpected complications while obtaining good clinical results. However, larger studies are necessary to establish its benefits and its safety.

Characterization of the NF-?B signaling triggered by doxorubicin.

Doxorubicin (DOX) is an antibiotic used in the treatment of various cancers. However, its clinical use is limited due to the toxic effects it causes. In several biological systems reactive oxygen species (ROS) derived from DOX metabolism have been associated with its toxicity because they can alter several signal transduction pathways. One of the major signal transduction pathways activated in response to oxidant stress is that of the nuclear transcription factor ?B (NF-?B), which is crucial for cell survival, cell proliferation, and immune responses. Previous studies from our laboratory have described that DOX triggersthe activation of the MAPK (ERK, p38, and JNK) pathways, NF-?B mobilization and caspase activation in rat hepatocytes. These events were indirectly ascribed to ROS generation by pharmacological approaches. Although NF-?B mobilization is usually accompanied by up-regulation of the genes with regulatory ?B elements, our gene expression analysis rendered a quite different scenario. The aim of this work was to verify the implication of ROS in the DOX-mediated signaling and to explore the transcriptional regulatory behaviour of NF-?B mobilized by DOX. Results showed that DOX treatment induces ROS generation, particularly H2O2. DOX-induced caspase-3 activation was ROS dependent, whereas the NF-?B mobilization was a process independent of H2O2. Furthermore, DOX-mobilized NF-?B complexes were dimmers formed by p65 with all the members of the Rel family, excepting Rel B. The analysis of the NF-?B transcriptional activity performed by reporter gene assays suggests that these DOX-mobilized NF-?B complexes are not transcriptionally competent.

C/EBPα induces highly efficient macrophage transdifferentiation of B lymphoma and leukemia cell lines and impairs their tumorigenicity.

Earlier work demonstrated that the transcription factor C/EBPα can convert immature and mature murine B lineage cells into functional macrophages. Testing >20 human lymphoma and leukemia B cell lines, we found that most can be transdifferentiated at least partially into macrophage-like cells, provided that C/EBPα is expressed at sufficiently high levels. A tamoxifen-inducible subclone of the Seraphina Burkitt lymphoma line, expressing C/EBPαER, could be efficiently converted into phagocytic and quiescent cells with a transcriptome resembling normal macrophages. The converted cells retained their phenotype even when C/EBPα was inactivated, a hallmark of cell reprogramming. Interestingly, C/EBPα induction also impaired the cells' tumorigenicity. Likewise, C/EBPα efficiently converted a lymphoblastic leukemia B cell line into macrophage-like cells, again dramatically impairing their tumorigenicity. Our experiments show that human cancer cells can be induced by C/EBPα to transdifferentiate into seemingly normal cells at high frequencies and provide a proof of principle for a potential new therapeutic strategy for treating B cell malignancies.