ABSTRACT
Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), presence of diabetes, and baseline SUA level, were described. Even though there is a consensus that the lowering of SUA by SGLT2is might be due to the increased urinary excretion rate of uric acid (UEUA) rather than its altered metabolism, the exact mechanism remains unknown. The influence of SGLT2is on SUA may not only be used in gout treatment but may also be of huge importance in explaining the observed pleiotropic effects of SGLT2is.
ABSTRACT
BACKGROUND: Impella is a percutaneous mechanical circulatory support device for treatment of cardiogenic shock (CS) and high-risk percutaneous coronary interventions (HR-PCIs). IMPELLA-PL is a national retrospective registry of Impella-treated CS and HR-PCI patients in 20 Polish interventional cardiological centers, conducted from January 2014 until December 2021. AIMS: We aimed to determine the efficacy and safety of Impella using real-world data from IMPELLA-PL and compare these with other registries. METHODS: IMPELLA-PL data were analyzed to determine primary endpoints: in-hospital mortality and rates of mortality and major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months post-discharge. RESULTS: Of 308 patients, 18% had CS and 82% underwent HR-PCI. In-hospital mortality rates were 76.4% and 8.3% in the CS and HR-PCI groups, respectively. The 12-month mortality rates were 80.0% and 18.2%, and post-discharge MACCE rates were 9.1% and 22.5%, respectively. Any access site bleeding occurred in 30.9% of CS patients and 14.6% of HR-PCI patients, limb ischemia in 12.7% and 2.4%, and hemolysis in 10.9% and 1.6%, respectively. CONCLUSIONS: Impella is safe and effective during HR-PCIs, in accordance with previous registry analyses. The risk profile and mortality in CS patients were higher than in other registries, and the potential benefits of Impella in CS require investigation.
Subject(s)
Heart-Assist Devices , Percutaneous Coronary Intervention , Humans , Shock, Cardiogenic/therapy , Poland , Percutaneous Coronary Intervention/adverse effects , Retrospective Studies , Aftercare , Patient Discharge , Registries , Treatment OutcomeABSTRACT
Coronary artery disease (CAD) is the leading cause of death worldwide. Patients with pre-existing CAD were shown to have a more severe course of COVID-19, but this association has not been clarified. We performed a meta-analysis to determine the association between CAD and COVID-19 outcomes. We searched Scopus, Medline (PubMed), Web of Science, Embase, and Cochrane databases up to 2 November 2021. There were 62 studies with a total population of 49,286 patients included in the meta-analysis. CAD occurrence in survivor vs. non-survivor groups varied and amounted to 9.2% vs. 22.9%, respectively (OR = 0.33; 95%CI: 0.29 to 0.39; I2 = 70%; p < 0.001). CAD was also associated with increased severity of COVID-19 disease and was (10.8% vs. 5.6%, respectively, for severe vs. non-severe groups (OR = 2.28; 95%CI: 1.59 to 3.27; I2 = 72%; p < 0.001). The role of history of CAD in mortality and severe condition in COVID-19 presents itself as prominent-although a risk of bias in retrospective trials needs to be assessed, in case of our meta-analysis the statistically significant results when it comes to higher mortality among patients with CAD compared to non-CAD patients, a more severe condition observed in patients with CAD, and a visibly more frequent admission to intensive care unit in patients with CAD, it seems that an incidence of cardiovascular events plays a role in COVID-19 prognosis.
ABSTRACT
The marine environment is a valuable resource for drug discovery due to its diversity of life and associated secondary metabolites. However, there is very little published data on the potential application of marine natural products to treat neuropsychiatric disorders. Many natural products derived from chemically defended organisms in the marine environment have pharmacophores related to serotonin or clinically utilized antidepressant drugs. Therefore, in the present study, compounds selected for their structural similarity to serotonin or established antidepressants were evaluated for antidepressant-like activity using the forced swim and tail suspension tests in mice. The antidepressant positive controls, citalopram (selective serotonin reuptake inhibitor) and despiramine (tricyclic antidepressant) both dose-dependently reduced immobility time in the forced swim and tail suspension tests. Two marine natural product compounds tested, aaptamine and 5,6-dibromo-N,N-dimethyltryptamine, also produced significant antidepressant-like activity in the forced swim test. In the tail suspension test, the antidepressant-like effects of 5,6-dibromo-N,N-dimethyltryptamine were confirmed, whereas aaptamine failed to produce significant results. None of the tested compounds induced hyperlocomotion, indicating that nonspecific stimulant effects could not account for the observed antidepressant-like actions of the compounds. These studies highlight the potential to rationally select marine derived compounds for treating depression and other neuropsychiatric disorders.
Subject(s)
Antidepressive Agents/pharmacology , Biological Products/pharmacology , Animals , Antidepressive Agents/chemistry , Antidepressive Agents, Tricyclic/pharmacology , Biological Products/chemistry , Citalopram/pharmacology , Desipramine/pharmacology , Drug Evaluation, Preclinical , Hindlimb Suspension/psychology , Male , Mice , Mice, Inbred DBA , Motor Activity/drug effects , Swimming/psychologyABSTRACT
PURPOSE: Navigation systems commonly used in neurosurgery suffer from two main drawbacks: (1) their accuracy degrades over the course of the operation and (2) they require the surgeon to mentally map images from the monitor to the patient. In this paper, we introduce the Intraoperative Brain Imaging System (IBIS), an open-source image-guided neurosurgery research platform that implements a novel workflow where navigation accuracy is improved using tracked intraoperative ultrasound (iUS) and the visualization of navigation information is facilitated through the use of augmented reality (AR). METHODS: The IBIS platform allows a surgeon to capture tracked iUS images and use them to automatically update preoperative patient models and plans through fast GPU-based reconstruction and registration methods. Navigation, resection and iUS-based brain shift correction can all be performed using an AR view. IBIS has an intuitive graphical user interface for the calibration of a US probe, a surgical pointer as well as video devices used for AR (e.g., a surgical microscope). RESULTS: The components of IBIS have been validated in the laboratory and evaluated in the operating room. Image-to-patient registration accuracy is on the order of [Formula: see text] and can be improved with iUS to a median target registration error of 2.54 mm. The accuracy of the US probe calibration is between 0.49 and 0.82 mm. The average reprojection error of the AR system is [Formula: see text]. The system has been used in the operating room for various types of surgery, including brain tumor resection, vascular neurosurgery, spine surgery and DBS electrode implantation. CONCLUSIONS: The IBIS platform is a validated system that allows researchers to quickly bring the results of their work into the operating room for evaluation. It is the first open-source navigation system to provide a complete solution for AR visualization.
Subject(s)
Brain/surgery , Neuronavigation/methods , Neurosurgical Procedures/methods , Surgery, Computer-Assisted/methods , Brain/diagnostic imaging , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Deep Brain Stimulation , Humans , Microsurgery , Operating Rooms , Prosthesis Implantation , Ultrasonography , User-Computer Interface , Vascular Surgical Procedures/methods , WorkflowABSTRACT
PURPOSE: As an inexpensive, noninvasive, and portable clinical imaging modality, ultrasound (US) has been widely employed in many interventional procedures for monitoring potential tissue deformation, surgical tool placement, and locating surgical targets. The application requires the spatial mapping between 2D US images and 3D coordinates of the patient. Although positions of the devices (i.e., ultrasound transducer) and the patient can be easily recorded by a motion tracking system, the spatial relationship between the US image and the tracker attached to the US transducer needs to be estimated through an US calibration procedure. Previously, various calibration techniques have been proposed, where a spatial transformation is computed to match the coordinates of corresponding features in a physical phantom and those seen in the US scans. However, most of these methods are difficult to use for novel users. METHODS: We proposed an ultrasound calibration method by constructing a phantom from simple Lego bricks and applying an automated multi-slice 2D-3D registration scheme without volumetric reconstruction. The method was validated for its calibration accuracy and reproducibility. RESULTS: Our method yields a calibration accuracy of [Formula: see text] mm and a calibration reproducibility of 1.29 mm. CONCLUSION: We have proposed a robust, inexpensive, and easy-to-use ultrasound calibration method.
Subject(s)
Algorithms , Imaging, Three-Dimensional/methods , Phantoms, Imaging , Ultrasonography/methods , Calibration , Humans , Motion , Reproducibility of ResultsABSTRACT
PURPOSE: The aim of this report is to present IBIS (Interactive Brain Imaging System) NeuroNav, a new prototype neuronavigation system that has been developed in our research laboratory over the past decade that uses tracked intraoperative ultrasound to address surgical navigation issues related to brain shift. The unique feature of the system is its ability, when needed, to improve the initial patient-to-preoperative image alignment based on the intraoperative ultrasound data. Parts of IBIS Neuronav source code are now publicly available on-line. METHODS: Four aspects of the system are characterized in this paper: the ultrasound probe calibration, the temporal calibration, the patient-to-image registration and the MRI-ultrasound registration. In order to characterize its real clinical precision and accuracy, the system was tested in a series of adult brain tumor cases. RESULTS: Three metrics were computed to evaluate the precision and accuracy of the ultrasound calibration. 1) Reproducibility: 1.77 mm and 1.65 mm for the bottom corners of the ultrasound image, 2) point reconstruction precision 0.62-0.90 mm: and 3) point reconstruction accuracy: 0.49-0.74 mm. The temporal calibration error was estimated to be 0.82 ms. The mean fiducial registration error (FRE) of the homologous-point-based patient-to-MRI registration for our clinical data is 4.9 ± 1.1 mm. After the skin landmark-based registration, the mean misalignment between the ultrasound and MR images in the tumor region is 6.1 ± 3.4 mm. CONCLUSIONS: The components and functionality of a new prototype system are described and its precision and accuracy evaluated. It was found to have an accuracy similar to other comparable systems in the literature.
Subject(s)
Brain Neoplasms/surgery , Brain/surgery , Monitoring, Intraoperative/instrumentation , Neuronavigation/instrumentation , Neurosurgical Procedures , Preoperative Care/methods , Ultrasonography, Doppler, Transcranial/instrumentation , Adult , Brain Neoplasms/diagnosis , Equipment Design , Humans , Magnetic Resonance Imaging/methods , User-Computer InterfaceABSTRACT
Brominated indole alkaloids are a common class of metabolites reported from sponges of the order Verongida. Herein we report the isolation, structure determination, and activity of metabolites from three Florida sponges, namely, Verongula rigida (order Verongida, family Aplysinidae), Smenospongia aurea, and S. cerebriformis (order Dictyoceratida, family Thorectidae). All three species were investigated chemically, revealing similarities in secondary metabolites. Brominated compounds, as well as sesquiterpene quinones and hydroquinones, were identified from both V. rigida and S. aurea despite their apparent taxonomic differences at the ordinal level. Similar metabolites found in these distinct sponge species of two different genera provide evidence for a microbial origin of the metabolites. Isolated compounds were evaluated in the Porsolt forced swim test (FST) and the chick anxiety-depression continuum model. Among the isolated compounds, 5,6-dibromo- N,N-dimethyltryptamine ( 1) exhibited significant antidepressant-like action in the rodent FST model, while 5-bromo- N,N-dimethyltryptamine ( 2) caused significant reduction of locomotor activity indicative of a potential sedative action. The current study provides ample evidence that marine natural products with the diversity of brominated marine alkaloids will provide potential leads for antidepressant and anxiolytic drugs.
Subject(s)
Antidepressive Agents/isolation & purification , Antidepressive Agents/pharmacology , Hydrocarbons, Brominated/isolation & purification , Hydrocarbons, Brominated/pharmacology , Indole Alkaloids/isolation & purification , Indole Alkaloids/pharmacology , N,N-Dimethyltryptamine/analogs & derivatives , N,N-Dimethyltryptamine/isolation & purification , N,N-Dimethyltryptamine/pharmacology , Porifera/chemistry , Animals , Anti-Anxiety Agents/chemistry , Anti-Anxiety Agents/isolation & purification , Anti-Anxiety Agents/pharmacology , Antidepressive Agents/chemistry , Chickens , Disease Models, Animal , Dose-Response Relationship, Drug , Florida , Hydrocarbons, Brominated/chemistry , Indole Alkaloids/chemistry , Marine Biology , Mice , Molecular Structure , N,N-Dimethyltryptamine/chemistryABSTRACT
With â¼ 40 years of research completed after the development of self-contained underwater breathing apparatus, drug discovery opportunities in the sea are still too numerous to count. Since the FDA approval of the direct-from-the-sea calcium channel blocker ziconotide, marine natural products have been validated as a source for new medicines. However, the demand for natural products is extremely high due to the development of high-throughput assays and this bottleneck has created the need for an intense focus on increasing the rate of isolating and elucidating the structures of new bioactive secondary metabolites. In addition to highlighting the drug discovery potential of the marine environment, this review discusses several of the pressing needs to increase the rate of drug discovery in marine natural products, and describes some of the work and new technologies that are contributing in this regard.