Rescue Stenting of Isolated Middle Cerebral Artery (MCA) Dissections (MCAD) with Antithrombogenic Coated Stents and Mono-Antiplatelet Therapy (MAPT).

Objective: Acute ischemic stroke (AIS) is a leading cause of death, but isolated middle cerebral artery dissection (MCAD) is rarely reported. The aim of this article is to sum up the current information on this pathology and to explore the technical aspects of its endovascular treatment with emphasis on novel coated, antithrombogenic stents and antiplatelet management. Another part of this article offers our experience with the problematics represented by a small sample group of patients with an MCAD diagnosis who were treated in our center. Methods: We conducted literature research and a retrospective review of patients treated for anterior circulation AIS at our comprehensive stroke center from January 2022 to March 2024. The cohort included 16 patients diagnosed with isolated MCAD, 9 received antithrombogenic coated stents, while 7 received bare metal stents. Pharmacological management of coated stents involved the use of Cangrelor for acute antiplatelet therapy, transitioning to oral Ticagrelor. Results: Among the 16 patients treated, those with antithrombogenic coated stents showed no major complications and had a lower incidence of intracranial hemorrhage compared to the bare metal stent group. The average National Institutes of Health Stroke Scale (NIHSS) score at discharge improved in both groups. Functional outcomes and mortality rates were slightly better in the coated stent group, but no statistical significance was proven. Conclusions: Antithrombogenic coated stents, in conjunction with MAPT, demonstrated a safe and effective option for treating isolated MCAD. These stents offer promising potential for improved outcomes and reduced complications compared to traditional treatments. Further multicentric studies with larger cohorts are recommended to validate these findings.

Clinical Epidemiology of Extracranial Injuries in Severe Pediatric Traumatic Brain Injury in South America.

BACKGROUND: Severe traumatic brain injury (TBI) is a leading cause of pediatric mortality, with a disproportionate burden on low- and middle-income countries. The impact of concomitant extracranial injury (ECI) on these patients remains unclear. This study is the first to characterize the epidemiology and clinical course of severe pediatric TBI with extracranial injuries in any South American country. METHODS: We conducted a secondary analysis of baseline data collected prior to implementation of a clinical trial on TBI care in Argentina, Paraguay, and Chile from September 2019 to July 2020. Patients ≤18 years with CT evidence of TBI, and a Glasgow coma scale (GCS) score ≤8 were recruited. Patients were initially stratified by highest non-head abbreviated injury scale (AIS): isolated TBI (AIS=0), minor extracranial injury (MEI; AIS=1-2), and serious extracranial injury (SEI; AIS≥3). Patients were subsequently stratified by mechanism of injury. Intergroup differences were compared using ANOVA, two-tailed unpaired t-tests, and chi-square tests. RESULTS: Among the 116 children included, 33 % (n = 38) had an isolated TBI, 34 % (n = 39) had MEI, and 34 % (n = 39) had SEI. Facial (n = 53), thoracic (n = 44), and abdominal (n = 31) injuries were the most common ECIs. At discharge, there were no significant differences in median GCS, GOS, or GOS-extended between groups. Patients with SEI had a longer hospital LOS than those with isolated TBI (median 28.0 (IQR 10.6-40.1) vs 11.9 (IQR 8.7-20.7) days, p = 0.013). The most common mechanisms of injury were road traffic injuries (RTIs) (n = 50, 43 %) and falls (n = 35, 30 %). Patients with RTI-associated TBIs were more likely to be older (median 11.0 (IQR 3.0-14.0) vs 2.0 (IQR 0.8-7.0) years, p<0.001) and more likely to have an ECI (86% vs 54 %, respectively; p = 0.003). ICU and Hospital LOS for RTI patients (median 10.5 (IQR 6.1-21.1) and 24.1 (IQR 11.5-40.4) days) were longer than those of fall patients (median 6.1 (IQR 2.6-8.9) and 13.7 (IQR 7.7-24.5) days). CONCLUSIONS: Extracranial injuries are common in South American patients with severe TBI. Severe ECI is more frequently associated with RTIs and can result in a higher rate of surgical procedures and LOS. Further strategies are needed to characterize the prevention and treatment of severe pediatric TBI in the South American context.

Fatigue and health-related quality of life in paroxysmal nocturnal haemoglobinuria: A post hoc analysis of the pegcetacoplan PEGASUS trial data.

OBJECTIVES: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, non-malignant haematological disorder associated with disabling fatigue and reduced health-related quality of life. Post hoc analysis of PEGASUS phase 3 trial (NCT03500549) characterised improvements in patient-reported fatigue measured by functional assessment of chronic illness therapy-fatigue (FACIT-fatigue) instrument item-level ratings for pegcetacoplan and eculizumab for the treatment of PNH. METHODS: Item-level responder analysis was conducted on a ≥2-level change from baseline (CFB) clinically important response (CIR) for the FACIT-fatigue 13 individual items rated on a 5-level Likert scale. We evaluated ≥2-level change against the minimal clinically important difference (MCID) of the FACIT-fatigue total score (≥5 points) and clinical parameters, haemoglobin (Hb; ≥1 g/dL) and normalised absolute reticulocyte count (ARC; 30-100 pg/cells). Logistic regressions estimated baseline-to-Week-16 FACIT-fatigue item-level transitional probabilities; Kaplan-Meier analysis estimated time to FACIT-fatigue item CIR. RESULTS: Pegcetacoplan versus eculizumab was associated with significantly greater odds of Week 16 CIR across 8/13 items and on total score MCID (OR [CI] = 11.19 [3.73, 33.57]) and faster times to responses. The item-level CIR threshold also showed clinical relevance on Hb level and ARC normalization. CONCLUSIONS: Compared with eculizumab, pegcetacoplan was associated with clinically meaningful greater improvements on a majority of FACIT-fatigue items.

Clinical benefit of long-term use of dual antiplatelet therapy for acute myocardial infarction patients with the PEGASUS-TIMI 54 criteria.

Background: We evaluated the effectiveness of extended dual antiplatelet therapy (DAPT) usage after 2nd-generation drug elution stent implantation in acute myocardial infarction (AMI) survivors with high ischemic risk characteristics who had no major bleeding for 24 months under at least 1 year of DAPT maintenance. Materials and methods: The primary ischemic and bleeding endpoints were the risk of mortality and the risk of BARC 3 or 5 (major) bleeding. We investigated the event rates for 2-5 years after the index procedure. Results: Of 3382 post-AMI survivors who met the PEGASUS-TIMI 54 (PEGASUS) criteria and without major bleeding until 2 years, 2281 (67.4%) maintained DAPT over 24 months, and 1101 (32.5%) switched DAPT to a single antiplatelet agent. The >24 M DAPT group showed a lower risk of mortality than the 12-24 M DAPT group (7.2 vs. 9.2%; adjusted hazard ratio: 0.648; 95% confidence interval: 0.595-0.976; p < 0.001). The mortality risk was significantly greater as the number of PEGASUS criteria increased (p < 0.001). DAPT > 24 months was not significantly associated with a decreased risk for major bleeding in the population meeting the PEGASUS criteria (2.0 vs. 1.1%; p = 0.093). The results were consistent after propensity-score matching and inverse probability weighting to adjust for baseline differences. Conclusion: Extended DAPT over 24 months was associated with a lower risk of mortality without increasing the risk of major bleeding among 2 years survivors after AMI who met the PEGASUS criteria and had no major bleeding events before 24 months.

PEGASUS: the Design of an Intervention to Facilitate Shared Decision-making in Breast Reconstruction.

Studies have found varying levels of satisfaction after breast reconstruction surgery with a substantial group of patients reporting some level of regret about their decision. The variable outcomes reported by women undergoing breast reconstruction surgery suggest a role for improved pre-operative communication and shared decision-making (SDM) between patient and health professional. Pragmatic approaches such as decision aids have been evaluated, but the aim of the Patient Expectations and Goals Assisting Shared Understanding of Surgery (PEGASUS) intervention is to facilitate closer interaction between the patient and clinical team. PEGASUS is a standardised two-stage process, in which patients' goals are first elicited, ranked in importance and recorded before being used to frame discussion and decision-making with the surgeon managing care. Following the Medical Research Council (MRC) model, feasibility and acceptability studies have already been reported and a 4-year multicentre randomised controlled trial of 180 participants is underway, (completion 2020). This paper therefore focuses on the design of the intervention itself, in line with recent advice that interventions, in comparison with evaluations, commonly lack a theoretical base and are often under reported. We report a retrospective application of the Capability, Opportunity, Motivation-Behaviour (COM-B) model to provide explicit detail of each step in the intervention design. This is intended to facilitate replication by other clinicians and to provide systematic guidance for others wishing to develop PEGASUS as a strategy for implementing SDM in other clinical populations. Trial Registration: ISRCTN 18000391 (DOI 10.1186/ISRCTN18000391) 27/01/2016.

A new species of Pegasus (Syngnathiformes: Pegasidae) from the South China Sea.

A new fish species from the South China Sea, Pegasus nanhaiensis sp. nov., is described herein. The new species is readily distinguished from all other species of the genus Pegasus with the following characteristics: A rounded hump-like tubercle on each of dorsal plates I, II, and III. Noticeable hexagonal patterns on the dorsal carapace with a clear boundary, and two paired caudolateral plates overlapping the junctions between tail rings II and III, and between tail rings IV and V. The integrated evidence from both morphological and genetic studies indicates that P. nanhaiensis represents an independent lineage within the genus Pegasus.

Functional decomposition-A contribution to overcome the parameter space explosion during validation of highly automated driving.

Objective: Particular testing by functional decomposition of the automated driving function can potentially contribute to reducing the effort of validating highly automated driving functions. In this study, the required size of test suites for scenario-based testing and the potential to reduce it by functional decomposition are quantified for the first time. Methods: The required size of test suites for scenario-based approval of a so-called Autobahn-Chauffeur (SAE Level 3) is analyzed for an exemplary set of scenarios. Based on studies of data from failure analyses in other domains, the possible range for the required test coverage is narrowed down and suitable discretization steps, as well as ranges for the influence parameters, are assumed. Based on those assumptions, the size of the test suites for testing the complete system is quantified. The effects that lead to a reduction in the parameter space for particular testing of the decomposed driving function are analyzed and the potential to reduce the validation effort is estimated by comparing the resulting test suite sizes for both methods. Results: The combination of all effects leads to a reduction in the test suites' size by a factor between 20 and 130, depending on the required test coverage. This means that the size of the required test suite can be reduced by 95-99% by particular testing compared to scenario-based testing of the complete system. Conclusions: The reduction potential is a valuable contribution to overcome the parameter space explosion during the validation of highly automated driving. However, this study is based on assumptions and only a small set of exemplary scenarios. Thus, the findings have to be validated in further studies.

A new score based on the PEGASUS-TIMI 54 criteria for risk stratification of patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) patients are at increased risk of death and recurrent ischemic events. We aimed to elaborate a risk score, based on the PEGASUS-TIMI 54 criteria, to predict mortality and non-fatal AMI in AMI patients. METHODS: We retrospectively analyzed two prospectively collected AMI cohorts. We calculated a cut-off for the developed score and investigated its 1-year prognostic power in the derivation cohort (n = 1257). We externally validated our score in 913 AMI patients with a longer follow-up. RESULTS: In the derivation cohort, the area under the curve of the score for the primary endpoint (1-year death and non-fatal AMI) was 0.70 (95% CI 0.65-0.76; P < 0.0001) and a cut-off of 6 was identified. The primary endpoint incidence in patients with a score above and below the cut-off was 12% and 3% (P < 0.001) in the derivation cohort and 16% and 6% in the validation cohort (P < 0.001). At multivariate analysis, the HR for the primary endpoint associated with a score ≥ 6 was 4.45 (P < 0.0001) in the derivation cohort and 2.86 (P < 0.0001) in the validation cohort. One-year major bleeding rate was low (<0.2% overall) and similar between risk groups. The prognostic performance of the score cut-off persisted beyond the first year after AMI in the validation cohort, maintaining a similar risk for death and non-fatal AMI (HR 3) at every following year. CONCLUSIONS: Our score, based on the PEGASUS-TIMI 54 criteria, may identify AMI patients at high risk of recurrent ischemic events, who might benefit from thorough preventive strategies.

A study protocol of the effectiveness of PEGASUS: a multi-centred study comparing an intervention to promote shared decision making about breast reconstruction with treatment as usual.

BACKGROUND: Increasingly, women elect breast reconstruction after mastectomy. However, their expectations of surgery are often not met, and dissatisfaction with outcome and ongoing psychosocial concerns and distress are common. We developed a patient-centered intervention, PEGASUS:(Patients' Expectations and Goals: Assisting Shared Understanding of Surgery) which supports shared decision making by helping women clarify their own, individual goals about reconstruction so that they can discuss these with their surgeon. Our acceptability/feasibility work has shown it is well received by patients and health professionals alike. We now need to establish whether PEGASUS improves patients' experiences of breast reconstruction decision making and outcomes. The purpose of this study is, therefore, to examine the effectiveness of PEGASUS, an intervention designed to support shared decision making about breast reconstruction. METHODS: A multi-centered sequential study will compare the impact of PEGASUS with usual care, in terms of patient reported outcomes (self-reported satisfaction with the outcome of surgery, involvement in decision making and in the consultation) and health economics. Initially we will collect data from our comparison (usual care) group (90 women) who will complete standardized measures (Breast-Q, EQ5D -5 L and ICECAP- A) at the time of decision making, 3, 6 and 12 months after surgery. Health professionals will then be trained to use PEGASUS, which will be delivered to the intervention group (another 90 women completing the same measures at the time of decision making, and 3, 6 and 12 months after surgery). Health professionals and a purposefully selected sample of participants will be interviewed about whether their expectations of reconstruction were met, and their experiences of PEGASUS (if appropriate). DISCUSSION: PEGASUS may have the potential to provide health professionals with an easily accessible tool aiming to support shared decision making and improve patients' satisfaction with breast reconstruction. Results of this study will be available at the end of 2019. TRIAL REGISTRATION: ISRCTN 18000391 (DOI 10.1186/ISRCTN18000391) 27/01/2016.

Exposure-Response Analyses Supporting Ticagrelor Dosing Recommendation in Patients With Prior Myocardial Infarction.

The relationships between drug exposure and the composite risk of cardiovascular (CV) death, myocardial infarction (MI), and stroke as well as the risk of TIMI major bleeding were estimated following long-term treatment with ticagrelor 60 or 90 mg twice daily in 20,942 patients with prior MI. These analyses support the primary reported efficacy and safety evaluations by showing that there were clear separations from placebo early in treatment with both doses, regardless of ticagrelor exposure, for both endpoints. In addition, the exposure-response analyses provided new insight into the contribution of individual exposure levels, rather than dose, as a predictor of events and accounted for differences in the baseline risk between patients. The predicted risks of CV death/MI/stroke were similar despite an increase in the median predicted ticagrelor average steady-state concentration from 606 nmol/L with ticagrelor 60 mg to 998 nmol/L with ticagrelor 90 mg (hazard ratios vs placebo of 0.83 and 0.81, respectively). The corresponding predicted risk of TIMI major bleeding slightly increased (hazard ratios vs placebo of 2.4 and 2.6, respectively). Apart from Japanese patients, showing a lower risk of CV death/MI/stroke, the response to ticagrelor was consistent across the study population, as supported by the combination of relatively flat exposure-response relationships in the studied exposure range, similar sensitivity to ticagrelor exposure, and small exposure differences. Consequently, the present analyses support the selection of the 60-mg dose for all demographic subgroups of patients studied.

Facilitating shared decision-making with breast augmentation patients: Acceptability of the PEGASUS intervention.

BACKGROUND: PEGASUS is an intervention to facilitate shared decision-making by helping prospective patients consider their expectations of surgery, so that surgeons have a clear understanding of their individual goals. To date, shared decision-making interventions within aesthetic surgery are lacking. The present mixed methods study therefore explored the acceptability of implementing PEGASUS into routine private practice with breast augmentation patients and aesthetic providers. METHOD: Seventeen women presenting for breast augmentation surgery from three practices received the PEGASUS intervention pre-operatively and completed a process evaluation post-operatively. Semi-structured interviews exploring 3 aesthetic providers' experiences of using PEGASUS were subjected to a thematic analysis, whilst a content analysis was conducted on the 77 goals identified by patients. RESULTS: The majority of patients reported that the PEGASUS intervention was relevant, helpful and useful, and they felt comfortable during it. Qualitatively, patients and aesthetic providers found that PEGASUS enabled them to reflect on and discuss about their expectations from surgery. Aesthetic providers discussed some of the issues and barriers associated with implementing PEGASUS in routine private practice, factors that must be considered prior to further evaluation. CONCLUSION: This study provides preliminary support for the acceptability of PEGASUS to breast augmentation patients and to aesthetic providers working in the private sector.

Effects of active fraction from Pegasus laternarius Cuvier on proliferation and apoptosis of human cervical cancer HeLa cells / 中国药理学通报

Aim To isolate HeLa cell proliferation-inhibitory active fraction from Pegasus laternarius Cuvier and explore its potential apoptosis-inducing mechanism.Methods To obtain the active fraction,the ethanol extract of Pegasus laternarius Cuvier was chromatographed by silica gel and sephadex LH-20 columns;MTT assay was used to evaluate the proliferation-inhibitory ability of active fraction on HeLa cells;AO/EB,PI and Annexin V-FITC/PI fluorescent staining flow cytometry were used to evaluate its apoptosis-inducing ability;the possible mechanism was investigated by analyzing the enzyme activity of caspase-3 and the protein expression of apoptosis-related genes in tumor cells.Results A fraction of C22 with high HeLa proliferation-inhibitory activity was isolated,with a yield of 0.73 ‰ and an IC50 of 36.3 mg · L-1;fraction C22 could increase the proportion of cells in sub-G0/G1 phase,phosphatidylserine eversion and other typical cell apoptosis in a dose-dependent manner;fraction C22 could down-regulate the expression of Bcl-2 and increase the enzyme of caspase-3 in HeLa cells.Conclusions The active fraction C22 from Pegasus laternarius Cuvier can inhibit the proliferation of HeLa cells by inducing apoptosis.The effect of inducing apoptosis may be conducted through mediating the mitochondrial Bcl2/caspase pathway.

OSG-GEM: Gene Expression Matrix Construction Using the Open Science Grid.

High-throughput DNA sequencing technology has revolutionized the study of gene expression while introducing significant computational challenges for biologists. These computational challenges include access to sufficient computer hardware and functional data processing workflows. Both these challenges are addressed with our scalable, open-source Pegasus workflow for processing high-throughput DNA sequence datasets into a gene expression matrix (GEM) using computational resources available to U.S.-based researchers on the Open Science Grid (OSG). We describe the usage of the workflow (OSG-GEM), discuss workflow design, inspect performance data, and assess accuracy in mapping paired-end sequencing reads to a reference genome. A target OSG-GEM user is proficient with the Linux command line and possesses basic bioinformatics experience. The user may run this workflow directly on the OSG or adapt it to novel computing environments.

Variation in seizure prophylaxis in severe pediatric traumatic brain injury.

OBJECTIVE Posttraumatic seizure is a major complication following traumatic brain injury (TBI). The aim of this study was to determine the variation in seizure prophylaxis in select pediatric trauma centers. The authors hypothesized that there would be wide variation in seizure prophylaxis selection and use, within and between pediatric trauma centers. METHODS In this retrospective multicenter cohort study including 5 regional pediatric trauma centers affiliated with academic medical centers, the authors examined data from 236 children (age < 18 years) with severe TBI (admission Glasgow Coma Scale score ≤ 8, ICD-9 diagnosis codes of 800.0-801.9, 803.0-804.9, 850.0-854.1, 959.01, 950.1-950.3, 995.55, maximum head Abbreviated Injury Scale score ≥ 3) who received tracheal intubation for ≥ 48 hours in the ICU between 2007 and 2011. RESULTS Of 236 patients, 187 (79%) received seizure prophylaxis. In 2 of the 5 centers, 100% of the patients received seizure prophylaxis medication. Use of seizure prophylaxis was associated with younger patient age (p < 0.001), inflicted TBI (p < 0.001), subdural hematoma (p = 0.02), cerebral infarction (p < 0.001), and use of electroencephalography (p = 0.023), but not higher Injury Severity Score. In 63% cases in which seizure prophylaxis was used, the patients were given the first medication within 24 hours of injury, and 50% of the patients received the first dose in the prehospital or emergency department setting. Initial seizure prophylaxis was most commonly with fosphenytoin (47%), followed by phenytoin (40%). CONCLUSIONS While fosphenytoin was the most commonly used medication for seizure prophylaxis, there was large variation within and between trauma centers with respect to timing and choice of seizure prophylaxis in severe pediatric TBI. The heterogeneity in seizure prophylaxis use may explain the previously observed lack of relationship between seizure prophylaxis and outcomes.

The acceptability of PEGASUS: an intervention to facilitate shared decision-making with women contemplating breast reconstruction.

Good practice guidelines recommend that women who undergo mastectomy are offered reconstructive surgery. However, many who choose this option report a degree of decisional regret and dissatisfaction because their pre-surgical expectations were not met. This paper reports an acceptability study of a new intervention (PEGASUS) that aims to support shared decision-making by eliciting women's pre-surgical expectations and setting patient-centred goals. Eighteen women contemplating breast reconstruction completed the PEGASUS intervention. Semi-structured interviews were conducted with 12 women and 3 health professionals to explore their experiences of using PEGASUS. Interview transcripts were subjected to a thematic analysis, and a content analysis was conducted on 79 goals that the 18 women identified. Feedback was extremely positive--women found that completing PEGASUS alongside a discussion with a specially trained health professional helped them prepare for the surgical consultation and increased their trust in their surgeon. Staff reported that PEGASUS facilitated patient-centred discussions and informed the decisions made about potential surgery. This preliminary study suggests that this novel intervention is acceptable to patients and health professionals alike. Further work is needed to evaluate its efficacy and then its effectiveness with a larger sample of women, and its potential use with other patient groups.