An Intramyocardial Mass Mimicking ST-Segment Elevation Myocardial Infarct at Presentation.

ST-segment elevation on the electrocardiogram typically indicates acute myocardial infarction but can mimic ST-segment elevation myocardial infarction in various conditions. We present a case of a patient with an intramyocardial mass and anterior ST-segment elevation without significant myocardial biomarker elevation. Multimodality imaging was crucial in revealing cardiac metastasis as the attributable cause.

Understanding the flow behavior around marine biofilms.

In vitro platforms capable of mimicking the hydrodynamic conditions prevailing in natural aquatic environments have been previously validated and used to predict the fouling behavior on different surfaces. Computational Fluid Dynamics (CFD) has been used to predict the shear forces occurring in these platforms. In general, these predictions are made for the initial stages of biofilm formation, where the amount of biofilm does not affect the flow behavior, enabling the estimation of the shear forces that initial adhering organisms have to withstand. In this work, we go a step further in understanding the flow behavior when a mature biofilm is present in such platforms to better understand the shear rate distribution affecting marine biofilms. Using 3D images obtained by Optical Coherence Tomography, a mesh was produced and used in CFD simulations. Biofilms of two different marine cyanobacteria were developed in agitated microtiter plates incubated at two different shaking frequencies for 7 weeks. The biofilm-flow interactions were characterized in terms of the velocity field and shear rate distribution. Results show that global hydrodynamics imposed by the different shaking frequencies affect biofilm architecture and also that this architecture affects local hydrodynamics, causing a large heterogeneity in the shear rate field. Biofilm cells located in the streamers of the biofilm are subjected to much higher shear values than those located on the bottom of the streamers and this dispersion in shear rate values increases at lower bulk fluid velocities. This heterogeneity in the shear force field may be a contributing factor for the heterogeneous behavior in metabolic activity, growth status, gene expression pattern, and antibiotic resistance often associated with nutrient availability within the biofilm.

"A Double Twist" Presentation - A Case Report of Purulent Cardiac Tamponade following a Rare Complication of Small-Cell Lung Cancer Radiotherapy.

Background: Small cell lung cancer is an aggressive tumor with a poor prognosis that requires prompt treatment. While radiotherapy may enhance survival when superior vena cava syndrome is present, radiation therapy-induced pericardial disease can be a potential complication. Case Report: A 55-year-old man, who recently underwent radiotherapy for stage IV small-cell lung cancer complicated by superior vena cava syndrome, presented with chest pain and dyspnea. In the emergency room, he was dyspneic, hypotensive, and tachycardic. Pulmonary auscultation revealed the absence of lung sounds on the right. The initial electrocardiogram showed ST-segment elevation in lateral leads and in lead DII, with reciprocal changes in lead DIII. A bedside transthoracic echocardiogram revealed cardiac tamponade and emergent pericardiocentesis was performed, removing 500 ml of purulent fluid, resulting in an immediate clinical improvement. Thoracentesis was also performed, showing no empyema. Large spectrum empirical antibiotic therapy was started. Cultures from the pericardial fluid and peripheral blood grew multi-sensitive Streptococcus pneumoniae. Cytological analysis of the pericardial fluid was consistent with infection. The patient improved after 2 weeks of targeted antibiotic therapy and underwent the first cycle of chemotherapy. He was discharged with an early scheduled pulmonology appointment. Conclusions: Although the most common causes of pericardial effusion in lung cancer are malignant, non-malignant etiologies should also be considered. This patient had an infectious pericardial effusion most probably due to a pericardial-mediastinal mass fistula caused by radiotherapy. This was a diagnostic challenge, both in the emergency room as well in the inpatient setting. LEARNING POINTS: Small cell lung cancer is a fast-growing cancer that exhibits aggressive behavior.In patients with lung cancer, malignant pericardial effusions are more common than non-malignant ones.Purulent pericardial effusions, especially those due to lung cancer, are rare in developed countries with very few reports in the literature.

The role of the adrenalectomy in the management of pheochromocytoma: the experience of a Portuguese referral center.

PURPOSE: Pheochromocytoma is a rare neuroendocrine tumor. Despite the low incidence, these tumors are of indisputable importance. This study aimed to analyze the management of pheochromocytoma in a referral center, with an emphasis on the minimally invasive adrenalectomy, which is the preferred therapeutic approach. METHODS: A retrospective analysis was performed on a cohort of patients diagnosed with pheochromocytoma who underwent adrenalectomy between January 2013 and December 2022. Clinical data including demographics, timelines, symptomatology, comorbidities, biochemical markers, genetic testing, surgical details, and follow-up outcomes, were collected and analyzed. RESULTS: The cohort included 44 patients, predominantly women (52.27%), with a median age of 53.39 years (range 13-83). Most of patients exhibited paroxysmal symptoms suggesting catecholamine excess. Documented hypertension was the most frequent (86.36%), along with glucose anomalies (40.01%) and anxiety disorder (31.82%). Genetic testing was performed in 36 (81.81%) patients and 14 (38.88%) revealed a positive result, predominantly RET pathogenic variant. Laparoscopic surgery was performed in 34 (79.07%) patients, showing significantly shorter operative time (2.5 h vs. 4.25 h, t-test p < 0,001) and fewer complications (23.53% vs 77.78%, p = 0.008). Postoperative complications occurred in 36.36% of the patients, mostly mild (grade I, 56.25%), with no mortality. SDHB pathogenic variant correlated with both recurrent and metastatic disease (p = 0.006). One-year follow-up reported 9.09% recurrence and 6.82% metastasis. CONCLUSIONS: Adrenalectomy demonstrated a high safety and effectiveness. This study exhibited a higher rate of genetic testing referral than other studies. Despite past advances, there is still a need for further studies to establish protocols and evaluate new techniques.

Isolation and Identification of Lichen Photobionts Collected from Different Environments in North of Portugal and Evaluation of Bioactivities of Their Extracts.

Lichens are organisms constituted by a symbiotic relationship between a fungus (mycobiont) and a photoautotrophic partner (photobiont). Lichens produce several bioactive compounds; however, the biotechnological exploitation of this organism is hampered by its slow growth. To start studying the possibility of exploiting lichens as alternative sources of bioactive compounds, eighteen lichens were collected in the north of Portugal in order to isolate and study the bioactivity of their photobionts. It was possible to isolate and cultivate only eight photobionts. Three of them, LFR1, LFA2 and LCF3, belong to the Coelastrella genus, the other two (LFA1 and LCF1) belong to the Chlorella genus and for the remaining three photobionts, LFS1, LCA1 and LCR1, it was impossible to isolate their microalgae. These only grow in consortium with bacteria and/or cyanobacteria. All extracts showed antioxidant activity, mainly at a concentration of 10 mg.mL-1. LFS1, a consortium extract, showed the highest antioxidant power, as well as the highest concentration of phenolic compounds (5.16 ± 0.53 mg of gallic acid equivalents (GAE).g-1). The extracts under study did not show significant antibacterial activity against Escherichia coli, Listeria or Salmonella. The Coelastrella sp. and LFA1 extracts showed the highest hyaluronidase inhibition. The LFR1 extract at a concentration of 5 mg.mL-1 showed the highest anti-inflammatory activity (79.77 ± 7.66%). The extracts of Coelastrella sp. and LFA1 also showed greater antidiabetic activity, demonstrating the high inhibitory power of α-amylase and α-glucosidase. LFR1 at a concentration of 5 mg.mL-1, due to its selective cytotoxicity inhibiting the growth of cancer cells (Caco-2 cells), is a promising anticancer agent.

Leptochelins A-C, Cytotoxic Metallophores Produced by Geographically Dispersed Leptothoe Strains of Marine Cyanobacteria.

Metals are important cofactors in the metabolic processes of cyanobacteria, including photosynthesis, cellular respiration, DNA replication, and the biosynthesis of primary and secondary metabolites. In adaptation to the marine environment, cyanobacteria use metallophores to acquire trace metals when necessary as well as to reduce potential toxicity from excessive metal concentrations. Leptochelins A-C were identified as structurally novel metallophores from three geographically dispersed cyanobacteria of the genus Leptothoe. Determination of the complex structures of these metabolites presented numerous challenges, but they were ultimately solved using integrated data from NMR, mass spectrometry and deductions from the biosynthetic gene cluster. The leptochelins are comprised of halogenated linear NRPS-PKS hybrid products with multiple heterocycles that have potential for hexadentate and tetradentate coordination with metal ions. The genomes of the three leptochelin producers were sequenced, and retrobiosynthetic analysis revealed one candidate biosynthetic gene cluster (BGC) consistent with the structure of leptochelin. The putative BGC is highly homologous in all three Leptothoe strains, and all possess genetic signatures associated with metallophores. Postcolumn infusion of metals using an LC-MS metabolomics workflow performed with leptochelins A and B revealed promiscuous binding of iron, copper, cobalt, and zinc, with greatest preference for copper. Iron depletion and copper toxicity experiments support the hypothesis that leptochelin metallophores may play key ecological roles in iron acquisition and in copper detoxification. In addition, the leptochelins possess significant cytotoxicity against several cancer cell lines.

Non-traditional sources for health surveillance: using emergency data for early-detection / O uso de fontes não-tradicionais para a vigilância em saúde: atendimentos de urgência para detecção precoce de eventos

Preparation and response to Public Health emergencies involve efforts in developing systems for early detection, alert and response. Models for dealing with notification delay and diversification of data sources are some of the commonly used strategies for faster information and action. In this paper, we present the strategy implemented in Rio de Janeiro municipality, where data from urgency and emergency visits were acquired and modeled, in order to detect trend shifts and generate alerts. From the ICD-10 field in electronic records, time series representing events of interest were created. A GAM model was fitted for smoothing, slope determination in each point, and alert generation. The results obtained are displayed in a dashboard, monitored daily. From 2023, multiple events of interest were identified through the dashboard, some of which lead to coordinated communication and actions in the territory. We draw attention to the potentials in the use of these type of data on identifying events of interest in a timely manner, approaching the concepts of a modern surveillance.

A preparação e resposta às emergências em Saúde Pública envolve o investimento em sistemas de detecção precoce, alerta e resposta. Modelos de correção de atraso de notificação e a diversificação de fontes de dados utilizadas são algumas abordagens comumente utilizadas para geração de informação e ação mais oportunos. Neste artigo é apresentada a estratégia implementada no município do Rio de Janeiro de utilização de dados de atendimentos de urgência e emergência unida à aplicação de modelos de detecção de tendências para geração automatizada de alertas. A partir de CIDs marcados nos prontuários eletrônicos de atendimentos, monitoram-se séries temporais de eventos de interesse no município. Um modelo GAM é ajustado às séries para suavização, determinação da inclinação e geração dos alertas. Os resultados são exibidos em painel e monitorados diariamente. Desde 2023, múltiplos eventos de interesse foram identificados através do painel e resultaram em comunicação coordenada e ações no território. Os resultados exaltam a potencialidade no uso desses dados na identificação de eventos de interesse em tempo oportuno, alinhando-se a conceitos de uma vigilância moderna.

Exploring the Potential of Machine Learning Algorithms Associated with the Use of Inertial Sensors for Goat Kidding Detection.

The autonomous identification of animal births has a significant added value, since it enables for a prompt timely human intervention in the process, protecting the young and the mothers' health, without requiring continuous human surveillance. Wearable inertial sensors have been employed for a variety of animal monitoring applications, thanks to their low cost and the fact that they allow less invasive monitoring process. Alarms triggered by the occurrence of events must be generated close to the events to avoid delays caused by communication latency, which is why this type of mechanism is typically implemented at the network's edge and integrated with existing auxiliary mechanisms on the Internet. Although the detection of births in cattle has been carried out commercially for some years, there is no solution for small ruminants, especially goats, where the literature does not even report any attempts. The current work consisted of a first attempt at developing an automatic birth monitor using inertial sensing, as well as detection techniques based on Machine Learning, implemented in a network edge device to assure real-time alarm triggering. Thus, two concept drift detection techniques and seven kidding detection mechanisms were developed using data classification models. The work also includes the testing and comparison of learning results, both in terms of accuracy and of computational costs of the detection module, for algorithms implemented. The results revealed that, despite their simplicity, concept drift algorithms do not allow kidding detection, whereas classification-algorithm-based static learning models do, despite the unbalanced character of the dataset and its reduced size. The learning findings are quite promising in terms of computational cost and its suitability for deployment on edge devices. The algorithm demonstrates behavior changes four hours before kidding and allows for the identification of the kidding hour with an accuracy of 61%, as well as the capacity to improve the overall learning process with a larger dataset.

Antitumor Activity of the Xanthonoside XGAc in Triple-Negative Breast, Ovarian and Pancreatic Cancer by Inhibiting DNA Repair.

Dysregulation of the DNA damage response may contribute to the sensitization of cancer cells to DNA-targeting agents by impelling cell death. In fact, the inhibition of the DNA repair pathway is considered a promising anticancer therapeutic strategy, particularly in combination with standard-of-care agents. The xanthonoside XGAc was previously described as a potent inhibitor of cancer cell growth. Herein, we explored its antitumor activity against triple-negative breast cancer (TNBC), ovarian cancer and pancreatic ductal adenocarcinoma (PDAC) cells as a single agent and in combination with the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib. We demonstrated that XGAc inhibited the growth of TNBC, ovarian and PDAC cells by inducing cell cycle arrest and apoptosis. XGAc also induced genotoxicity, inhibiting the expression of DNA repair proteins particularly involved in homologous recombination, including BRCA1, BRCA2 and RAD51. Moreover, it displayed potent synergistic effects with olaparib in TNBC, ovarian cancer and PDAC cells. Importantly, this growth inhibitory activity of XGAc was further reinforced in a TNBC spheroid model and in patient-derived ovarian cancer cells. Also, drug-resistant cancer cells showed no cross-resistance to XGAc. Additionally, the ability of XGAc to prevent cancer cell migration was evidenced in TNBC, ovarian cancer and PDAC cells. Altogether, these results highlight the great potential of acetylated xanthonosides such as XGAc as promising anticancer agents against hard-to-treat cancers.

First Polyphasic Study of Cheffia Reservoir (Algeria) Cyanobacteria Isolates Reveals Toxic Picocyanobacteria Genotype.

Monitoring water supply requires, among other quality indicators, the identification of the cyanobacteria community and taking into account their potential impact in terms of water quality. In this work, cyanobacteria strains were isolated from the Cheffia Reservoir and identified based on morphological features, the 16S rRNA gene, phylogenetic analysis, and toxin production by polymerase chain reaction PCR screening of the genes involved in the biosynthesis of cyanotoxins (mcyA, mcyE, sxtA, sxtG, sxtI, cyrJ, and anaC). Thirteen strains representing six different genera: Aphanothece, Microcystis, Geitlerinema, Lyngbya, Microcoleus, and Pseudanabaena were obtained. The results demonstrated the importance of morphological features in determining the genus or the species when incongruence between the morphological and phylogenetic analysis occurs and only the utility of the 16S rRNA gene in determining higher taxonomic levels. The phylogenetic analysis confirmed the polyphyly of cyanobacteria for the Microcystis and Oscillatoriales genera. Unexpectedly, Aphanothece sp. CR 11 had the genetic potential to produce microcystins. Our study gives new insight into species with picoplanktonic (or small) cell size and potentially toxic genotypes in this ecosystem. Thus, conventional water treatment methods in this ecosystem have to be adapted, indicating the requirement for pre-treatment methods that can effectively eliminate picocyanobacteria while preserving cell integrity to prevent toxin release.

Recognizing a "Hot Phase" of An Arrhythmogenic Left Ventricular Cardiomyopathy: A Case Report.

A 35-year-old male, with a medical history of acute myocarditis, presented with palpitations. Further investigation revealed non-sustained ventricular tachycardia and a slightly reduced left ventricular systolic function. Cardiac magnetic resonance showed extended late gadolinium enhancement of the left ventricle and fat infiltration. Genetic testing was positive for a pathogenic desmoplakin mutation, fulfilling the criteria of arrhythmogenic left ventricular cardiomyopathy. In conclusion, the authors described a case of a mimicked acute myocarditis at a young age in a patient with an arrhythmogenic left ventricular cardiomyopathy. Therefore, the genetic study is essential for both diagnosis and management.

Petersen Hernia After Abdominoplasty: A Provocative Factor or a Coincidence?

Abdominal contouring procedures are frequently performed following massive weight loss after a Roux-en-Y gastric bypass. This last procedure can be associated with late complications like the development of internal hernias (e.g., Petersen hernia). The purpose of this article is to present a case of Petersen hernia after complete abdominoplasty. A 42-year-old female presented to the emergency department with acute abdominal pain three days after undergoing a complete abdominoplasty following massive weight loss post laparoscopic gastric bypass (Roux-en-Y). The patient was diagnosed with a mechanical small bowel obstruction, likely due to an internal hernia (Petersen hernia) and underwent surgical correction. Gastric bypass surgery may be associated with small bowel obstruction from internal herniation. A sudden rise in abdominal pressure, as occurs with abdominoplasty with rectus plication and subsequent use of compression garments, may result in strangulation and intestinal ischemia. A high degree of suspicion of intra-abdominal complications after abdominoplasty is essential, particularly in the setting of post-bariatric surgery.

Sustainable Pickering Emulsions with Nanocellulose: Innovations and Challenges.

The proper mix of nanocellulose to a dispersion of polar and nonpolar liquids creates emulsions stabilized by finely divided solids (instead of tensoactive chemicals) named Pickering emulsions. These mixtures can be engineered to develop new food products with innovative functions, potentially more eco-friendly characteristics, and reduced risks to consumers. Although cellulose-based Pickering emulsion preparation is an exciting approach to creating new food products, there are many legal, technical, environmental, and economic gaps to be filled through research. The diversity of different types of nanocellulose makes it difficult to perform long-term studies on workers' occupational health, cytotoxicity for consumers, and environmental impacts. This review aims to identify some of these gaps and outline potential topics for future research and cooperation. Pickering emulsion research is still concentrated in a few countries, especially developed and emerging countries, with low levels of participation from Asian and African nations. There is a need for the development of scaling-up technologies to allow for the production of kilograms or liters per hour of products. More research is needed on the sustainability and eco-design of products. Finally, countries must approve a regulatory framework that allows for food products with Pickering emulsions to be put on the market.

Effect of Hydrogen Peroxide on Cyanobacterial Biofilms.

Although a range of disinfecting formulations is commercially available, hydrogen peroxide is one of the safest chemical agents used for disinfection in aquatic environments. However, its effect on cyanobacterial biofilms is poorly investigated. In this work, biofilm formation by two filamentous cyanobacterial strains was evaluated over seven weeks on two surfaces commonly used in marine environments: glass and silicone-based paint (Sil-Ref) under controlled hydrodynamic conditions. After seven weeks, the biofilms were treated with a solution of hydrogen peroxide (H2O2) to assess if disinfection could affect long-term biofilm development. The cyanobacterial biofilms appeared to be tolerant to H2O2 treatment, and two weeks after treatment, the biofilms that developed on glass by one of the strains presented higher biomass amounts than the untreated biofilms. This result emphasizes the need to correctly evaluate the efficiency of disinfection in cyanobacterial biofilms, including assessing the possible consequences of inefficient disinfection on the regrowth of these biofilms.

The use of the CNIC-Polypill in real-life clinical practice: opportunities and challenges in patients at very high risk of atherosclerotic cardiovascular disease - expert panel meeting report.

Although the cardiovascular (CV) polypill concept is not new and several guidelines state that a CV polypill should be considered an integral part of a comprehensive CV disease (CVD) prevention strategy, there are still some barriers to its implementation in the real-world setting, mainly in secondary CV prevention. As the CNIC-polypill is the only one approved for secondary CV prevention in patients with atherosclerotic CVD in 27 countries worldwide, a panel of four discussants and 30 participants from 18 countries conveyed in a virtual meeting on April 21, 2022, to discuss key clinical questions regarding the practical use of the CNIC-Polypill and barriers to its implementation.Data presented showed that, although the use of the CV polypill is not explicitly mentioned in the current 2021 European Society of Cardiology guidelines on CVD prevention, it may be used in any patient for secondary CVD prevention tolerating all their components to improve outcomes through different aspects. The favourable results of the Secondary Prevention of Cardiovascular Disease in the Elderly (SECURE) trial now reinforce this recommendation. The panellists presented algorithms on how to switch from any baseline regimen when starting treatment with the CNIC-polypill in different situations, including patients with hypertension, dyslipidaemia, and a previous CV event; at discharge after a cardiovascular event; in chronic ischemic conditions; and in cases of polypharmacy. The panellists and expert discussants did agree that available studies conducted so far with the CNIC-polypill demonstrate that it is as efficacious as the monocomponents, equipotent drugs, or other therapies; reduces the risk of experiencing recurrent major CV events; improves medication adherence; reduces health care costs and resources compared to patients treated with loose drugs; and the patients prefer it over the multipill strategy.In conclusion, the data presented by the participants provided the evidence behind the use of the CNIC-polypill to help fulfil the goal of encouraging its adoption by physicians.

Bioprospecting for industrially relevant exopolysaccharide-producing cyanobacteria under Portuguese simulated climate.

Cyanobacterial exopolysaccharides (EPS) are potential candidates for the production of sustainable biopolymers. Although the bioactive and physicochemical properties of cyanobacterial-based EPS are attractive, their commercial exploitation is limited by the high production costs. Bioprospecting and characterizing novel EPS-producing strains for industrially relevant conditions is key to facilitate their implementation in various biotechnological applications and fields. In the present work, we selected twenty-five Portuguese cyanobacterial strains from a diverse taxonomic range (including some genera studied for the first time) to be grown in diel light and temperature, simulating the Portuguese climate conditions, and evaluated their growth performance and proximal composition of macronutrients. Synechocystis and Cyanobium genera, from marine and freshwater origin, were highlighted as fast-growing (0.1-0.2 g L-1 day-1) with distinct biomass composition. Synechocystis sp. LEGE 07367 and Chroococcales cyanobacterium LEGE 19970, showed a production of 0.3 and 0.4 g L-1 of released polysaccharides (RPS). These were found to be glucan-based polymers with high molecular weight and a low number of monosaccharides than usually reported for cyanobacterial EPS. In addition, the absence of known cyanotoxins in these two RPS producers was also confirmed. This work provides the initial steps for the development of cyanobacterial EPS bioprocesses under the Portuguese climate.

[Data processing of the Brazilian National System of Controlled Product Management for drug utilization research with antimicrobials]. / Tratamento de dados do Sistema Nacional de Gerenciamento de Produtos Controlados para estudos de utilização de medicamentos com antimicrobianos.

The Brazilian National System of Controlled Product Management (SNGPC) stores data on the dispensing of manufactured and compounded drugs and pharmaceutical inputs, whether controlled and antimicrobial, based on the records of private pharmacies and drugstores. This study assessed the quality of SNGPC data from the dispensing records of manufactured antibiotics, aiming to propose their use in drug utilization researchs (DURs), with a descriptive and retrospective design, analyzing the raw dataset of the SNGPC from January 2014 to December 2020. A total of 475,805,207 drug-dispensing records were collected. On average, antibiotics corresponded to 54.5% of the total records. The quality dimension "unreported" was systematically identified in the variables "active ingredient", "sex", "age" and "ICD-10". The amount of vials/bottles and packages ranged from one to 536 units and the amount of pharmaceutical inputs dispensed, from one to 7,500 units. Results show that 25% of the records exceed an individual therapy and the SNGPC has no critical mechanism to avoid dispensations outside the therapeutic standard for the class. Despite vulnerabilities due to data quality, which can be overcome, the SNGPC allows for the construction of different analytical plans, involving time and other aggregations, in the analysis of community use of antimicrobials and controlled drugs, which makes it a powerful source of data for DUR.

O Sistema Nacional de Gerenciamento de Produtos Controlados (SNGPC) armazena dados de dispensação de medicamentos industrializados, manipulados e insumos farmacêuticos sob controle especial e antimicrobianos, a partir dos registros de farmácias e drogarias privadas. Este trabalho explorou a qualidade dos dados inseridos no SNGPC, a partir dos registros de dispensação de antibióticos industrializados, com o objetivo de propor seu emprego em estudos de utilização de medicamentos (DUR). A pesquisa foi desenvolvida por meio de desenho descritivo e retrospectivo, examinando o conjunto dados brutos do sistema, para o período de janeiro de 2014 a dezembro de 2020. Um total de 475.805.207 registros de dispensação de medicamentos foi coletado. Os antibióticos corresponderam em média a 54,5% do total de registros. A dimensão de qualidade "não informado" foi identificada, sistematicamente, nas variáveis "princípio ativo", "sexo", "idade" e "CID-10". As quantidades de frascos e caixas variaram de 1 a 536 unidades, e as quantidades de formas farmacêuticas dispensadas de 1 a 7.500 unidades. Os resultados mostram que 25% dos registros extrapolam uma terapia individual e que o sistema não apresenta um mecanismo de crítica para evitar dispensações não conformes ao padrão terapêutico para a classe. Apesar das vulnerabilidades decorrentes da qualidade dos dados, que podem ser superadas, o SNGPC possibilita construir diferentes planos analíticos, envolvendo tempo e outras agregações, na investigação de uso comunitário de antimicrobianos e medicamentos sob controle especial, o que faz dele uma potente fonte de dados para DUR.

El Sistema Nacional de Gestión de Productos Controlados (SNGPC) almacena datos sobre la dispensación de medicamentos industrializados, manipulados, insumos farmacéuticos bajo control especial y de antimicrobianos con base en los registros de farmacias y de boticas privadas. Este trabajo analizó la calidad de los datos ingresados en el SNGPC relacionados a los registros de la dispensación de antibióticos industrializados, para proponer su posible aplicación en estudios sobre el uso de medicamentos (DUR); para ello, realizó un análisis descriptivo y retrospectivo del conjunto de datos brutos para el periodo de enero de 2014 a diciembre de 2020. Se recogieron un total de 475.805.207 registros de dispensación de medicamentos. Los antibióticos correspondieron en promedio al 54,5% del total de los registros. La dimensión de calidad "no informado" se identificó sistemáticamente en las variables "principio activo", "sexo", "edad" y "CIE-10". Las cantidades de viales y cajas oscilaron entre 1 y 536 unidades, y las cantidades de formas farmacéuticas dispensadas entre 1 y 7.500 unidades. Los resultados muestran que el 25% de los registros exceden una terapia individual y que el sistema no tiene un mecanismo crítico para evitar la dispensación que no se ajusta al patrón terapéutico de la clase. A pesar de las vulnerabilidades derivadas de la calidad de los datos, que pueden ser superadas, el SNGPC permite la construcción de diferentes planes analíticos, involucrando tiempo y otras agregaciones, en la investigación del uso comunitario de antimicrobianos y medicamentos bajo control especial, lo que hace que el Sistema sea una potente fuente de datos para DUR.

Lipoprotein(a) and the Effect of Alirocumab on Revascularization After Acute Coronary Syndrome.

BACKGROUND: Many patients require revascularization after index acute coronary syndrome (ACS). Lipoprotein(a) is thought to play a pathogenic role in atherothrombosis. In ODYSSEY OUTCOMES, alirocumab reduced major adverse cardiovascular events after ACS, with greater reduction among those with higher lipoprotein(a) levels. We explored whether risk of revascularization after ACS was modified by the level of lipoprotein(a) and treatment with alirocumab or placebo. METHODS: In ODYSSEY OUTCOMES alirocumab was compared with placebo in 18,924 patients with ACS and elevated atherogenic lipoprotein levels despite optimized statin treatment. In this post hoc analysis, treatment effects are summarized using competing risks proportional hazard models. RESULTS: A total of 1559 (8.2%) patients had coronary, 204 (1.1%) had limb, and 40 (0.2%) had carotid revascularization. Alirocumab reduced coronary revascularization (2.8 vs 3.2 events per 100 patient-years; hazard ratio [HR], 0.88 [95% confidence interval (CI), 0.80-0.97]; P = 0.01) and any revascularization (3.2 vs 3.7 events per 100 patient-years; HR, 0.85 [95% CI, 0.78-0.94]; P = 0.001). Baseline lipoprotein(a) quartile was directly associated with risk of coronary or any revascularization in the placebo arm and inversely related to treatment HRs (all P for trend < 0.01). Alirocumab produced the greatest reduction of coronary revascularization in patients with baseline lipoprotein(a) in the top quartile (≥ 59.6 mg/dL; HR, 0.69 [95% CI, 0.57-0.84]), but no apparent reduction in the bottom quartile (HR, 1.00 [95% CI, 0.82-1.22]). Findings were similar for the effect of alirocumab on any revascularization. CONCLUSIONS: Alirocumab reduced revascularization rates after ACS. The risk of revascularization and reduction in that risk with alirocumab were greatest in patients with elevated lipoprotein(a) at baseline.

ST3GalIV drives SLeX biosynthesis in gastrointestinal cancer cells and associates with cancer cell motility.

Expression of sialyl Lewis X (SLeX) is a well-documented event during malignant transformation of cancer cells, and largely associates with their invasive and metastatic properties. Glycoproteins and glycolipids are the main carriers of SLeX, whose biosynthesis is known to be performed by different glycosyltransferases, namely by the family of ß-galactoside-α2,3-sialyltransferases (ST3Gals). In this study, we sought to elucidate the role of ST3GalIV in the biosynthesis of SLeX and in malignant properties of gastrointestinal (GI) cancer cells. By immunofluorescent screening, we selected SLeX-positive GI cancer cell lines and silenced ST3GalIV expression via CRISPR/Cas9. Flow cytometry, immunofluorescence and western blot analysis showed that ST3GalIV KO efficiently impaired SLeX expression in most cancer cell lines, with the exception of the colon cancer cell line LS174T. The impact of ST3GalIV KO in the biosynthesis of SLeX isomer SLeA and non sialylated Lewis X and A were also evaluated and overall, ST3GalIV KO led to a decreased expression of SLeA and an increased expression in both LeX and LeA. In addition, the abrogation of SLeX on GI cancer cells led to a reduction in cell motility. Furthermore, ST3GalVI KO was performed in LS174T ST3GalIV KO cells, resulting in the complete abolishment of SLeX expression and consequent reduced motility capacity of those cells. Overall, these findings portray ST3GalIV as the main, but not the only, enzyme driving the biosynthesis of SLeX in GI cancer cells, with a functional impact on cancer cell motility.