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Key factors in the preoperative management of patients undergoing awake craniotomy for language mapping.
No full textGlucose-6-Phosphatase-Dehydrogenase activity as modulative association between Parkinson's disease and periodontitis.
Get PDFUNLABELLED
The association between periodontitis (PD) and Parkinson's disease (PK) is discussed due to the inflammatory component of neurodegenerative processes. PK severity and affected areas were determined using the following neuropsychological tests: Unified Parkinson's Disease Rating Score (UPDRS) and Hoehn and Yahr; non-motoric symptoms by Non-Motor Symptoms Scale (NMSS), and cognitive involvement by Mini-Mental State Examination (MMSE). Neuroinflammation and the resulting Glucose-6-Phosphatase-Dehydrogenase (G6PD) dysfunction are part of the pathophysiology of PK. This study aimed to evaluate these associations in periodontal inflammation. Clinical data and saliva-, serum-, and RNA-biobank samples of 50 well-characterized diametric patients with PK and five age- and sex-matched neurologically healthy participants were analyzed for G6PD function, periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, Campylobacter rectus, Fusobacterium nucleatum, and Filifactor alocis), monocyte chemoattractant protein (MCP) 1, and interleukin (IL) 1-beta. Regression analysis was used to identify associations between clinical and behavioral data, and t-tests were used to compare health and disease. Compared with PK, no pathogens and lower inflammatory markers (p < 0.001) were detectible in healthy saliva and serum, PK-severity/UPDRS interrelated with the occurrence of Prevotella intermedia in serum as well as IL1-beta levels in serum and saliva (p = 0.006, 0.019, 0.034), Hoehn and Yahr correlated with Porphyromonas gingivalis, Prevotella intermedia, RNA IL1-beta regulation, serum, and saliva IL1-beta levels, with p-values of 0.038, 0.011, 0.008, <0.001, and 0.010, while MMSE was associated with Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, serum MCP 1 levels, RNA IL1-beta regulation and G6PD serum activity (p = 0.036, 0.003, 0.045, <0.001, and 0.021). Cognitive and motor skills seem to be important as representative tests are associated with periodontal pathogens and oral/general inflammation, wherein G6PD-saliva dysfunction might be involved.
CLINICAL TRIAL REGISTRATION
https://www.bfarm.de/DE/Das-BfArM/Aufgaben/Deutsches-Register-Klinischer-Studien/_node.html, identifier DRKS00005388
BET-inhibitor DYB-41 reduces pulmonary inflammation and local and systemic cytokine levels in LPS-induced acute respiratory distress syndrome: an experimental rodent study.
Get PDFBACKGROUND
Acute respiratory distress syndrome (ARDS) is a form of respiratory failure stemming from various underlying conditions that ultimately lead to inflammation and lung fibrosis. Bromodomain and Extra-Terminal motif (BET) inhibitors are a class of medications that selectively bind to the bromodomains of BET motif proteins, effectively reducing inflammation. However, the use of BET inhibitors in ARDS treatment has not been previously investigated. In our study, we induced ARDS in rats using endotoxin and administered a BET inhibitor. We evaluated the outcomes by examining inflammation markers and lung histopathology.
RESULTS
Nine animals received treatment, while 12 served as controls. In the lung tissue of treated animals, we observed a significant reduction in TNFα levels (549 [149-977] pg/mg vs. 3010 [396-5529] pg/mg; p = 0.009) and IL-1β levels (447 [369-580] pg/mg vs. 662 [523-924] pg/mg; p = 0.012), although IL-6 and IL-10 levels showed no significant differences. In the blood, treated animals exhibited a reduced TNFα level (25 [25-424] pg/ml vs. 900 [285-1744] pg/ml, p = 0.016), but IL-1β levels were significantly higher (1254 [435-2474] pg/ml vs. 384 [213-907] pg/ml, p = 0.049). No differences were observed in IL-6 and IL-10 levels. There were no significant variations in lung tissue levels of TGF-β, SP-D, or RAGE. Histopathological analysis revealed substantial damage, with notably less perivascular edema (3 vs 2; p = 0.0046) and visually more inflammatory cells. However, two semi-quantitative histopathologic scoring systems did not indicate significant differences.
CONCLUSIONS
These preliminary findings suggest a potential beneficial effect of BET inhibitors in the treatment of acute lung injury and ARDS. Further validation and replication of these results with a larger cohort of animals, in diverse models, and using different BET inhibitors are needed to explore their clinical implications
Impact of Left Atrial Posterior Wall Ablation During Pulsed-Field Ablation for Persistent Atrial Fibrillation.
No full textBACKGROUND
Pulmonary vein isolation (PVI) alone is insufficient to treat many patients with persistent atrial fibrillation (PersAF). Adjunctive left atrial posterior wall (LAPW) ablation with thermal technologies has revealed lack of efficacy, perhaps limited by the difficulty in achieving lesion durability amid concerns of esophageal injury.
OBJECTIVES
This study aims to compare the safety and effectiveness of PVI + LAPW ablation vs PVI in patients with PersAF using pulsed-field ablation (PFA).
METHODS
In a retrospective analysis of the MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-approval Clinical Use of Pulsed Field Ablation) registry, we studied consecutive PersAF patients undergoing post-approval treatment with a pentaspline PFA catheter. The primary effectiveness outcome was freedom from any atrial arrhythmia of ≥30 seconds. Safety outcomes included the composite of acute and chronic major adverse events.
RESULTS
Of the 547 patients with PersAF who underwent PFA, 131 (24%) received adjunctive LAPW ablation. Compared to PVI-alone, patients receiving adjunctive LAPW ablation were younger (65 vs 67 years of age, P = 0.08), had a lower CHA2DS2-VASc score (2.3 ± 1.6 vs 2.6 ± 1.6, P = 0.08), and were more likely to receive electroanatomical mapping (48.1% vs 39.0%, P = 0.07) and intracardiac echocardiography imaging (46.1% vs 17.1%, P < 0.001). The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmias was not statistically different between groups in the full (PVI + LAPW: 66.4%; 95% CI: 57.6%-74.4% vs PVI: 73.1%; 95% CI: 68.5%-77.2%; P = 0.68) and propensity-matched cohorts (PVI + LAPW: 71.7% vs PVI: 68.5%; P = 0.34). There was also no significant difference in major adverse events between the groups (2.2% vs 1.4%, respectively, P = 0.51).
CONCLUSIONS
In patients with PersAF undergoing PFA, as compared to PVI-alone, adjunctive LAPW ablation did not improve freedom from atrial arrhythmia at 12 months
MR-based Bony 3D models enable radiation-free preoperative patient-specific analysis and 3D printing for SCFE patients
Get PDFCLINICAL FEATURES AND SURGICAL OUTCOMES OF SCLERAL BUCKLE SURGERY FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: MOORFIELDS BUCKLE STUDY.
No full textPURPOSE
Long-term study to evaluate the clinical and surgical outcomes of SB surgery for primary rhegmatogenous retinal detachment (RRD) at a large tertiary eye center.
METHODS
Non-comparative, retrospective case series of 589 eyes of 569 patients with primary RRD who underwent SB surgery between 2004 and 2022 with median follow-up of 6 months. Main outcome measures were best-corrected visual acuity (BCVA), surgical outcomes, complications, and classification of RRD.
RESULTS
At baseline, 447/589 (76.1%), round hole-RRD and 133/589 (22.7%) retinal dialysis-RRD. Overall primary SB success rate was 83.7% for all RD subtypes, with round hole-RD 84.8% and dialysis-RRD 81.2%. Overall, Baseline BCVA was logMAR 0.42 and final logMAR 0.26 (p<0.0001). In macula-OFF RRD, the BCVA significantly improved from 0.79 to 0.48 logMAR (p<0.0001). Macula-ON RRD patients improved from 0.19 to 0.12 logMAR (p=0.014). Binary logistic regression showed registrar surgeon grade (OR 0.09,95% CI 0.01- 0.55), and partial or complete PVD (OR 0.21,95% CI 0.10 - 0.49) associated with reduced odds of primary success. Higher surgical failure associated with low pre-fellowship SB surgeon experience (p=0.024).
CONCLUSION
We report favourable visual and functional outcomes in a large series of SB for primary retinal detachment, mainly for round hole and retinal dialysis RRD patients
Impact of preprocedural left ventricular systolic function on the safety and durability of percutaneous coronary intervention.
No full textBACKGROUND
Percutaneous coronary intervention (PCI) is considered less safe in patients with reduced ejection fraction (EF), an impression based on older data. Whether the safety and durability of contemporary PCI are different in patients with reduced EF compared with normal EF patients is unknown.
METHODS
Patients from the BIOFLOW II, IV and V clinical trials were grouped as normal EF (≥50%) and reduced EF (30%-50%). Using multivariable logistic regression and cox proportional hazards regression, we determined relations of EF category with procedural safety (a composite of cardiac death, myocardial infarction, stroke and urgent coronary artery bypass grafting within 30 days of PCI) and target lesion failure (TLF; comprising cardiac death, target vessel myocardial infarction, target vessel revascularization within 1 year of PCI) respectively. In sensitivity analyses, we regrouped patients into EF < 45% and ≥55% and repeated the aforementioned analyses.
RESULTS
In 1685 patients with normal EF (mean age 65 years; 27% women; mean EF 61%) and 259 with low EF (mean age 64 years; 17% women; mean EF 41%), 101 safety and 148 TLF events occurred. Compared with patients in the normal EF group, those with reduced EF had neither a statistically significant higher proportion of safety events, nor a higher multivariable-adjusted risk for such events. Similarly, patients with reduced EF and normal EF did not differ in terms of TLF event proportions or multivariable-adjusted risk for TLF. The results were similar in sensitivity analyses with EF groups redefined to create a 10% between-group EF separation.
CONCLUSION
PCI safety and durability outcomes are similar in patients with mild-moderately reduced EF and normal EF
Victim, Violent, Vulnerable. A Feminist Response to the Incel Radicalisation Scale
Get PDFFollowing several deadly attacks in recent years, misogynist incels have piqued
academic interest. However, attempts by terrorism scholars to understand incels’ radicalisation, ideology, and mental health raise concerns. In this article, we illustrate these concerns with the example of the Incel Radicalisation Scale (IRS), which relies on survey data and claims to help identify, measure, and prevent radicalisation among incels. First, drawing on a growing feminist knowledge base on incels and male supremacy, masculinity, and violence, we question the definition of core concepts (radicalisation, violence, misogyny) and incels in the IRS. Second, we criticise the methods used for sampling and concept validation, including reliance on incels’ self-representation and the dismissal of their harmful online activity. Third, we assess what these shortcomings mean for the IRS’ conclusions regarding the violent potential of incels, and the role of mental health and misogyny for male supremacist incel movements.
We argue such conclusions are prone to legitimising misogynist incel narratives of victimhood, and overlooking broader harms such as normalising misogynist violence and male and white supremacism. We therefore caution against using the IRS and emphasise the importance of having a comprehensive picture of incel radicalisation. Future studies must be more rigorous about addressing the problematic effects resulting from research designs of uncritical epistemologies in male supremacist research
Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death.
Get PDFBACKGROUND
Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects.
METHODS AND RESULTS
Using a rat model of donation after circulatory death, hearts underwent in situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω-nitro-L-arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow (P<0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω-nitro-L-arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels.
CONCLUSIONS
HOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts
Physician wellbeing and burnout in emergency medicine in Switzerland.
Get PDFEmergency physicians are the most at-risk medical specialist group for burnout. Given its consequences for patient care and physician health and its resulting increased attrition rates, ensuring the wellbeing of emergency physicians is vital for preserving the integrity of the safety net for the healthcare system that is emergency medicine. In an effort to understand the current state of practicing physicians, this study reviews the results of the first national e-survey on physician wellbeing and burnout in emergency medicine in Switzerland. Addressed to all emergency physicians between March and April 2023, it received 611 complete responses. More than half of respondents met at least one criterion for burnout according to the Maslach Burnout Inventory - Human Services Survey (59.2%) and the Copenhagen Burnout Inventory (54.1%). In addition, more than half reported symptoms suggestive of mild to severe depression, with close to 20% screening positively for moderate to severe depression, nearly 4 times the incidence in the general population, according to the Patient Health Questionnaire-9. We found that 10.8% of respondents reported having considered suicide at some point in their career, with nearly half having considered this in the previous 12 months. The resulting high attrition rates (40.6% of respondents had considered leaving emergency medicine because of their working conditions) call into question the sustainability of the system. Coinciding with trends observed in other international studies on burnout in emergency medicine, this study reinforces the fact that certain factors associated with wellbeing are intrinsic to emergency medicine working conditions
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