Deep-Learning-Based Group Pointwise Spatial Mapping of Structure to Function in Glaucoma.

Purpose: To establish generalizable pointwise spatial relationship between structure and function through occlusion analysis of a deep-learning (DL) model for predicting the visual field (VF) sensitivities from 3-dimensional (3D) OCT scan. Design: Retrospective cross-sectional study. Participants: A total of 2151 eyes from 1129 patients. Methods: A DL model was trained to predict 52 VF sensitivities of 24-2 standard automated perimetry from 3D spectral-domain OCT images of the optic nerve head (ONH) with 12 915 OCT-VF pairs. Using occlusion analysis, the contribution of each individual cube covering a 240 × 240 × 31.25 µm region of the ONH to the model's prediction was systematically evaluated for each OCT-VF pair in a separate test set that consisted of 996 OCT-VF pairs. After simple translation (shifting in x- and y-axes to match the ONH center), group t-statistic maps were derived to visualize statistically significant ONH regions for each VF test point within a group. This analysis allowed for understanding the importance of each super voxel (240 × 240 × 31.25 µm covering the entire 4.32 × 4.32 × 1.125 mm ONH cube) in predicting VF test points for specific patient groups. Main Outcome Measures: The region at the ONH corresponding to each VF test point and the effect of the former on the latter. Results: The test set was divided to 2 groups, the healthy-to-early-glaucoma group (792 OCT-VF pairs, VF mean deviation [MD]: -1.32 ± 1.90 decibels [dB]) and the moderate-to-advanced-glaucoma group (204 OCT-VF pairs, VF MD: -17.93 ± 7.68 dB). Two-dimensional group t-statistic maps (x, y projection) were generated for both groups, assigning related ONH regions to visual field test points. The identified influential structural locations for VF sensitivity prediction at each test point aligned well with existing knowledge and understanding of structure-function spatial relationships. Conclusions: This study successfully visualized the global trend of point-by-point spatial relationships between OCT-based structure and VF-based function without the need for prior knowledge or segmentation of OCTs. The revealed spatial correlations were consistent with previously published mappings. This presents possibilities of learning from trained machine learning models without applying any prior knowledge, potentially robust, and free from bias. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Sex differences in achieving guideline-recommended heart rate control among a large sample of patients at risk for sudden cardiac arrest.

Background: Despite known clinical benefits, guideline-recommended heart rate (HR) control is not achieved for a significant proportion of patients with HF with reduced ejection fraction. The wearable cardioverter-defibrillator (WCD) provides continuous HR monitoring and alerts that could aid medication titration. Objective: This study sought to evaluate sex differences in achieving guideline-recommended HR control during a period of WCD use. Methods: Data from patients fitted with a WCD from 2015 to 2018 were obtained from the manufacturer's database (ZOLL). The proportion of patients with adequate nighttime resting HR control at the beginning of use (BOU) and at the end of use (EOU) were compared by sex. Adequate HR control was defined as having a nighttime median HR <70 beats/min. Results: A total of 21,440 women and a comparative sample of 17,328 men (median 90 [IQR 59-116] days of WCD wear) were included in the final dataset. Among patients who did not receive a shock, over half had insufficient HR control at BOU (59% of women, 53% of men). Although the proportion of patients with resting HR ≥70 beats/min improved by EOU, 43% of women and 36% of men did not achieve guideline-recommended HR control. Conclusion: A significant proportion of women and men did not achieve adequate HR control during a period of medical therapy optimization. Compared with men, a greater proportion of women receiving WCD shocks had insufficiently controlled HR in the week preceding ventricular tachyarrhythmia/ventricular fibrillation and 43% of nonshocked women, compared with 36% of men, did not reach adequate HR control during the study period. The WCD can be utilized as a remote monitoring tool to record HR and inform adequate uptitration of beta-blockers, with particular focus on reducing the treatment gap in women.

Landiolol for refractory ventricular fibrillation in out-of-hospital cardiac arrest: A randomized, double-blind, placebo-controlled, pilot trial.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) complicated by refractory ventricular fibrillation (VF) is associated with poor outcome. Beta-1-receptor selective blockade might overcome refractory VF and improve survival. This trial investigates the efficacy and safety of prehospital landiolol in OHCA and refractory VF. METHODS: In this randomized, double-blind, placebo-controlled pilot trial, patients with OHCA and recurrent or refractory VF (at least 3 defibrillation attempts and last rhythm shockable), pretreated with epinephrine and amiodarone, were allocated to receive add-on treatment with landiolol or placebo. Landiolol was given as a 20 mg bolus infusion. The primary efficacy outcome was time from trial drug infusion to sustained return of spontaneous circulation (ROSC). Safety outcomes included the onset of bradycardia and asystole. RESULTS: A total of 36 patients were enrolled, 19 were allocated to the landiolol group and 17 to the placebo group. Time from trial drug infusion to sustained ROSC was similar between treatment groups (39 min [landiolol] versus 41 min [placebo]). Sustained ROSC was numerically lower in the landiolol group compared with the placebo group (7 patients [36.8%] versus 11 patients [64.7%], respectively). Asystole within 15 min of trial drug infusion occurred significantly more often in the landiolol group than in the placebo group (7 patients [36.8%] and 0 patients [0.0%], respectively). CONCLUSION: In patients with OHCA and refractory VF who are pretreated with epinephrine and amiodarone, add-on bolus infusion of landiolol 20 mg did not lead to a shorter time to sustained ROSC compared with placebo. Landiolol might be associated with bradycardia and asystole.

Competing risks of monomorphic vs. non-monomorphic ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: Global Electrical Heterogeneity and Clinical Outcomes (GEHCO) study.

AIMS: Ablation of monomorphic ventricular tachycardia (MMVT) has been shown to reduce shock frequency and improve survival. We aimed to compare cause-specific risk factors for MMVT and polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) and to develop predictive models. METHODS AND RESULTS: The multicentre retrospective cohort study included 2668 patients (age 63.1 ± 13.0 years; 23% female; 78% white; 43% non-ischaemic cardiomyopathy; left ventricular ejection fraction 28.2 ± 11.1%). Cox models were adjusted for demographic characteristics, heart failure severity and treatment, device programming, and electrocardiogram metrics. Global electrical heterogeneity was measured by spatial QRS-T angle (QRSTa), spatial ventricular gradient elevation (SVGel), azimuth, magnitude (SVGmag), and sum absolute QRST integral (SAIQRST). We compared the out-of-sample performance of the lasso and elastic net for Cox proportional hazards and the Fine-Gray competing risk model. During a median follow-up of 4 years, 359 patients experienced their first sustained MMVT with appropriate implantable cardioverter-defibrillator (ICD) therapy, and 129 patients had their first PVT/VF with appropriate ICD shock. The risk of MMVT was associated with wider QRSTa [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.01-1.34], larger SVGel (HR 1.17; 95% CI 1.05-1.30), and smaller SVGmag (HR 0.74; 95% CI 0.63-0.86) and SAIQRST (HR 0.84; 95% CI 0.71-0.99). The best-performing 3-year competing risk Fine-Gray model for MMVT [time-dependent area under the receiver operating characteristic curve (ROC(t)AUC) 0.728; 95% CI 0.668-0.788] identified high-risk (> 50%) patients with 75% sensitivity and 65% specificity, and PVT/VF prediction model had ROC(t)AUC 0.915 (95% CI 0.868-0.962), both satisfactory calibration. CONCLUSION: We developed and validated models to predict the competing risks of MMVT or PVT/VF that could inform procedural planning and future randomized controlled trials of prophylactic ventricular tachycardia ablation. CLINICAL TRIAL REGISTRATION: URL:www.clinicaltrials.gov Unique identifier:NCT03210883.

Evaluating the clinical benefit of pembrolizumab as a first-line agent in advanced solid tumors: A comprehensive review.

INTRODUCTION: The study evaluates the first-line application of pembrolizumab in metastatic non-small-cell lung cancer (mNSCLC), head and neck squamous cell cancer (HNSCC), gastric cancer, and renal cell carcinoma. Utilizing the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the American Society of Clinical Oncology Value Framework (ASCO-VF), the analysis incorporates data from pivotal KEYNOTE trials. METHODS: The study systematically assessed the clinical benefit of pembrolizumab in advanced solid malignancies through nine randomized controlled trials, one of which comprised two experimental arms. Data extraction from primary sources was conducted from PubMed, ASCO, and ESMO publications. Utilizing ESMO-MCBS and ASCO-VF forms, the evaluation focused on clinical benefit, toxicity, and bonus points, with discrepancies resolved through consensus discussions. RESULTS: Nine first-line indications for pembrolizumab received Food and Drug Administration approval for metastatic solid tumors between 2018 and 2023. Notable distinctions in ESMO-MCBS grades revealed seven trials with substantial clinical benefit (grades 5 to 4) and three with moderate to negligible benefit (grades 3 to 1). Bonus points, primarily based on the tail of the curve, were allocated to three trials for overall survival, one for progression-free survival, and one for a significant improvement in quality of life. CONCLUSIONS: Our evaluation of pembrolizumab across diverse cancers, especially in mNSCLC and HNSCC, revealed varied outcomes and challenges in clinical benefit interpretation. The assessment of clinical benefit, incorporating quantitative and qualitative endpoints, underscores the need to consider survivorship outcomes and patient perspectives for a comprehensive understanding.

Investigating a novel surrogate indicator of adipose accumulation in relation to erectile dysfunction.

INTRODUCTION: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction. METHODS: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction. RESULTS: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively. CONCLUSION: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction.

"Empty Cyst Sign" Appearance of CSF-Venous Fistula on Digital Spinal Myelography.

Cerebrospinal fluid venous fistulas (CSF-VFs) are an uncommon, yet increasingly recognized, cause of spontaneous intracranial hypotension.1-5 The workup involves magnetic resonance imaging (MRI) of the brain with and without contrast and MRI of the neuroaxis without contrast before dynamic myelography, either computed tomography or digital subtraction.6 The present case of an older woman with symptomatic intracranial hypotension is notable for the specific appearance of CSF-VFs on digital spinal myelography (Video 1). Among her numerous perineural cysts, it was the "disappearing" or "empty" cyst from which the fistula originated. The diagnosis was made using a second lateral fluoroscopy view, not typically used in digital spinal myelography, which demonstrated emptying of contrast from the T6 perineural cyst into the segmental vein at this level, or the "empty cyst sign." The patient then underwent transvenous onyx embolization with resolution of her orthostatic headaches and improvement of contrast-enhanced MRI of the brain with the Bern score decreasing from 7 to 0 at 3 months of follow-up.7 Because transvenous embolization of CSF-VFs is a relatively new procedure, the long-term outcomes of the procedure are not yet known.

Association between Metabolic Score for Visceral Fat and the risk of hypertension in different ethnic groups: a prospective cohort study in Southwest China.

Objective: Visceral adipose tissue assessment holds significant importance in hypertension prevention. This study aimed to explore the association between the Metabolic Score for Visceral Fat (METS-VF), a new indicator based on laboratory and anthropometry measures, and hypertension risk and to further investigate the association between the METS-VF and the risk of hypertension in different ethnic groups. Methods: In this study, a total of 9,280 people from 48 townships in 12 districts (counties) of Guizhou Province were selected for the survey using a multistage cluster random sampling method, and 5,127 cases were finally included in the analysis after excluding those with missing relevant data, losing visits, dying at follow-up, those who suffered from hypertension at baseline, and those whose information on the outcome of hypertension was not clear. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) between METS-VF and incident hypertension, and an accelerated failure time (AFT) model was applied to analyze the association between METS-VF and the onset time of hypertension. Results: The total person-years (PYs) of the 5,127 subjects were 36,188.52 years, and the median follow-up time was 6.64 years. During follow-up, 1,127 patients were newly diagnosed with hypertension, and the incidence density was 31.14/1,000 PYs. After adjusting for multivariables, compared with the METS-VF first (Q1), the third (Q3) and fourth (Q4) groups of the METS-VF increased by 29.9% and 61.5%, respectively (HR = 1.299 [1.061, 1.590] and 1.615 [1.280, 2.036]). The risk of hypertension increased with higher METS-VF values (HR = 1.323 [1.167, 1.500], ptrend < 0.001). In the Han Chinese population, Q2 and Q3 increased the risk of hypertension (HR = 1.459 [1.111, 1.917], 1.999 [1.417, 2.718]), and the onset of hypertension was advanced by 0.653 (ß = -0.653 (-0.930, -0.375]) years for per 1 unit increase in METS-VF. However, these associations were not found in ethnic minorities. Conclusion: METS-VF was significantly positively associated with the risk of hypertension, and the association was different among ethnic groups.

Outcome of Darunavir-Cobicistat-Based Regimens in HIV-Infected People Who Have Experienced Virological Failure.

Objective: To evaluate the virological outcome of darunavir-cobicistat (DRVc)-based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination. Methods: This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc-based regimen with HIV-RNA >50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV-RNA <50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA <50 copies/mL, last available visit, or loss to follow-up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS. Results: A total of 176 individuals were included, and 120 (68.2%) achieved <50 HIV-RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004-1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant-bearing protease inhibitor-resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up. Conclusion: Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.

The impact of alternate defibrillation strategies on shock-refractory and recurrent ventricular fibrillation: A secondary analysis of the DOSE VF cluster randomized controlled trial.

BACKGROUND: The DOSE VF randomized controlled trial (RCT) employed a pragmatic definition of refractory ventricular fibrillation (VF after three successive shocks). However, it remains unclear whether the underlying rhythm during the first three shocks was shock-refractory or recurrent VF. OBJECTIVE: To explore the relationship between alternate defibrillation strategies employed during the DOSE VF RCT and the type of VF, either shock-refractory VF or recurrent VF, on patient outcomes. METHODS: We performed a secondary analysis of the DOSE VF RCT. We categorized cases as shock-refractory or recurrent VF based on pre-randomization shocks (shocks 1-3). We then analyzed all subsequent (post-randomization) shocks to assess the impact of standard, vector change (VC) or double sequential external defibrillation (DSED) shocks on clinical outcomes employing logistic regression adjusted for Utstein variables, antiarrhythmics, and epinephrine. RESULTS: We included 345 patients; 60 (17%) shock-refractory VF, and 285 (83%) recurrent VF. Patients in recurrent VF had greater survival than shock-refractory VF (OR: 2.76 95% CI [1.04, 7.27]). DSED was superior to standard defibrillation for survival overall, and for patients with shock-refractory VF (28.6% vs 0%, p = 0.041) but not for those in recurrent VF. DSED was superior to standard defibrillation for return of spontaneous circulation (ROSC) and neurologic survival for shock-refractory and recurrent VF. VC defibrillation was not superior for survival or ROSC overall, for shock-refractory, or recurrent VF groups, but was superior for VF termination across all groups. CONCLUSION: DSED appears to be the superior defibrillation strategy in the DOSE VF trial, irrespective of whether the preceding VF is shock-refractory or recurrent.

Machine learning prediction of refractory ventricular fibrillation in out-of-hospital cardiac arrest using features available to EMS.

Background: Shock-refractory ventricular fibrillation (VF) or ventricular tachycardia (VT) is a treatment challenge in out-of-hospital cardiac arrest (OHCA). This study aimed to develop and validate machine learning models that could be implemented by emergency medical services (EMS) to predict refractory VF/VT in OHCA patients. Methods: This was a retrospective study examining adult non-traumatic OHCA patients brought into the emergency department by Singapore EMS from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Data from April 2010 to March 2020 were extracted for this study. Refractory VF/VT was defined as VF/VT persisting or recurring after at least one shock. Features were selected based on expert clinical opinion and availability to dispatch prior to arrival at scene. Multivariable logistic regression (MVR), LASSO and random forest (RF) models were investigated. Model performance was evaluated using receiver operator characteristic (ROC) area under curve (AUC) analysis and calibration plots. Results: 20,713 patients were included in this study, of which 860 (4.1%) fulfilled the criteria for refractory VF/VT. All models performed comparably and were moderately well-calibrated. ROC-AUC were 0.732 (95% CI, 0.695 - 0.769) for MVR, 0.738 (95% CI, 0.701 - 0.774) for LASSO, and 0.731 (95% CI, 0.690 - 0.773) for RF. The shared important predictors across all models included male gender and public location. Conclusion: The machine learning models developed have potential clinical utility to improve outcomes in cases of refractory VF/VT OHCA. Prediction of refractory VF/VT prior to arrival at patient's side may allow for increased options for intervention both by EMS and tertiary care centres.

Differences in Vertebral Morphology and bone Mineral Density between Grade 1 Vertebral Fracture and Non-Fractured Participants in the Chinese Population.

PURPOSE: To investigate the difference in vertebral morphology and bone mineral density (BMD) between grade 1 VFs and non-fractured participants in the Chinese population to shed light on the clinical significance of grade 1 VFs from various perspectives. METHODS: This retrospective cohort study included patients who received a chest low-dose computed tomography (LDCT) scan for health examination and visited the First Affiliated Hospital of Zhengzhou University, Henan, China, from October 2019 to August 2022. Data were analyzed from March 2023 to July 2023. The main outcome of this study was the difference in morphological parameters and BMD between grade 1 VFs and non-fractured participants. The prevalence of grade 1 VFs in China populations was calculated. The difference in BMD of three fracture types in the Grade 1 group was also evaluated. RESULTS: A total of 3652 participants (1799 males, 54.85 ± 9.02 years, range, 40-92 years; 1853 females, 56.00 ± 9.08 years, range, 40-93 years) were included. The prevalence of grade 2 and 3 increase with age. The prevalence of grade 1 VFs gradually increases ≤ 50y to 60-69y group, but there is a decrease in the ≥ 70 years male group (6.6%) and a rise in the female group (25.5%). There was no significant statistical difference observed in vertebral shape indices (VSI) and BMD between the Grade 1 group and the no-fractured group aged < 50 years old except the wedge index in male. The biconcavity index did not differ between the non-fractured group and the Grade 1 group in men aged 50-59 years, whereas a significant statistical difference was observed in women. Additionally, the results of BMD were consistent with these findings. For the 40-59 years age group, there were significant differences between the compression deformity group and the other groups. CONCLUSIONS: The grade 1 group had higher VSI and lower BMD than the non-fractured group, suggesting an association between the Grade 1 group and osteoporosis in individuals aged over 50 for women and over 60 for men. Different fracture types have significant variations in BMD among middle-aged people. The prevalence of grade 1 VFs exhibits an age-related increase in both genders, with opposite trends observed between older males and females. We suggested VSI can aid physicians in the diagnosis of grade 1 VFs.

Evaluation of changes in the clinical benefits of oncology drugs over time following reimbursement using the ASCO-VF and the ESMO-MCBS.

PURPOSE: This study aims to estimate changes in the value of oncology drugs over time from initial data of the reimbursement decisions to subsequent publications in Korea, using two value frameworks. METHODS: We retrieved primary publications assessed for reimbursement between 2007 and July 2021 from the decision documents of Health Insurance Review and Assessment and subsequent publications made available following reimbursement decision from ClinicalTrials.Gov and PubMed databases. Changes in the clinical benefit scores were assessed using the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). A paired t test was performed to test whether there was a difference in the scores between primary and subsequent publications. RESULTS: Of 73 anticancer product/indication pairs, 45 (61.6%) had subsequent publications, of which 62.5% were released within 1 year of reimbursement decision. The mean ESMO-MCBS and ASCO-VF Net Health Benefit scores increased from primary to subsequent publications, although the differences were not significant. The mean ASCO-VF bonus score significantly increased from 15.91 to 19.09 (p = 0.05). The ESMO-MCBS and bonus scores increased by 0.25 and 0.21, respectively, and the bonus score had a greater impact on the ESMO-MCBS score than the preliminary score did. CONCLUSION: The value of drugs demonstrated in subsequent publications varies considerably among oncology drugs, depending on uncertainty associated with the initial evidence and the availability of updated evidence. As decision-making in the face of uncertainty becomes more prevalent, the value frameworks can serve as simple screening tools for re-evaluation in these cases.

Could driving help us to "see better"? A comparative assessment of saccadic efficiency, visual speed, and attention.

BACKGROUND: This study aimed at comparing drivers' and non-drivers' results in the Adult Developmental Eye Movement with Distractors test (ADEMd) and the Useful Field of View test (UFOV). METHODS: One hundred and twenty Spaniards (mean age 50.90 ± 17.32 years) without eye disease voluntarily participated in this cross-sectional descriptive study. Participants in a single experimental session completed a questionnaire on sociodemographic, health, eyesight, and driving information. They also performed the ADEMd and UFOV tests randomly following standardized protocols. The ADEMd is a visual-verbal test that measures saccadic efficiency and visual attention. Brown-Forsythe (B-F) tests with Games-Howell post-hoc adjustments were conducted to assess differences between groups. Groups were formed according to sex, age (young adults, adults, and older adults), and driver/non-driver for further analysis. Additionally, associations between dependent variables were assessed through Spearman's correlations. RESULTS: Drivers obtained significantly better results in the ADEMd compared with non-drivers. Non-significant differences between drivers and non-drivers were encountered in the UFOV. Additionally, significant differences were observed between sexes and age groups. It is worth highlighting that non-driver's age significantly correlated with worse ADEMd performance (rho = .637 to .716). This correlation was non-significant in drivers. Similarly, reading hours significantly correlated with better ADEMd performance in non-drivers (rho = - .291 to - .363), but not in drivers. The only significant correlations between ADEMd and UFOV tests were found in drivers (rho = .307 to .410). CONCLUSION: Considering all the discussed results, it could be hypothesized that the driving task promotes abilities, such as oculomotor and cognitive function, which are relevant for the performance in the ADEMd. However, this hypothesis is based on correlational outcomes and further studies should causally assess this possible relation.

Successful ablation of Purkinje ectopy-triggered ventricular fibrillation storm in a patient with orthotopic heart transplantation and severe SARS-CoV-2 pneumonia: a case report.

Background: Catheter ablation is one of the most effective treatment options for patients with drug-refractory, scar-related monomorphic ventricular tachycardia (VT). In selected cases, catheter ablation also plays an important role in treatment of polymorphic VT (PMVT) and/or ventricular fibrillation (VF). Rarely, premature ventricular contractions (PVCs) originating from the Purkinje network can induce PMVT/VF. Ablation and elimination of these PVCs can prevent VF recurrences. Case summary: A 41-year-old patient with a history of orthotopic heart transplantation (HTX) 8 years before admission and newly diagnosed SARS-CoV-2 pneumonia was referred to our centre after experiencing several episodes of drug-refractory VF. An electrophysiological study showed ectopy-triggered VF originating from the anterior and posterior fascicles of the left bundle branch (LBB). Ablation of these PVCs from the LBB led to complete elimination of VF. A subcutaneous implantable cardioverter defibrillator was implanted as secondary prophylaxis. During the observation period of 6 months, no VF recurrence was observed. Conclusion: Identifying and eliminating the trigger (PVCs) can be life-saving and prevent VF in the specific cohort of HTX patients. High-density mapping using multipolar catheters with microelectrodes contributes significantly to our understanding of tachycardia mechanisms.

How cognitive performance changes according to the ankle-brachial index score in an elderly cohort? Results from the Toledo Study of Healthy Ageing.

In the ageing process, the vascular system undergoes morphological and functional changes that may condition brain functioning; for this reason, the aims of this study were to assess the effect of vascular function indirectly measured by ankle-brachial index (ABI) on both cognitive performance at baseline and change in cognitive performance at end of follow-up. We developed a prospective, population-based, cohort study with 1147 participants aged > 65 years obtained from the Toledo Study for Healthy Ageing who had cognitive assessment and measured ABI in the first wave (2006-2009) were selected for the cross-sectional analysis. Those participants who also performed the cognitive assessment in the second wave (2011-2013) were selected for the prospective analysis. Cognitive impairment diagnosis and symptoms and/or history of cardio/neurovascular disease were used as exclusion criteria. Multivariate segmented regression model was used to assess the associations between ABI and cognitive performance in both the cross-sectional and prospective analyses. As ABI score decreased from 1.4, the cross-sectional analysis showed a higher decrease in cognitive performance and the prospective analysis showed a higher degree of worsening in cognitive performance. Our findings suggest that the ABI, a widespread measure of vascular health in primary care, may be a useful tool for predicting cognitive performance and its evolution.

Discovery of plasma proteins associated with ventricular fibrillation during first ST-elevation myocardial infarction via proteomics.

AIMS: The underlying biological mechanisms of ventricular fibrillation (VF) during acute myocardial infarction are largely unknown. To our knowledge, this is the first proteomic study for this trait, with the aim to identify and characterize proteins that are associated with VF during first ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: We included 230 participants from a Danish ongoing case-control study on patients with first STEMI with VF (case, n = 110) and without VF (control, n = 120) before guided catheter insertion for primary percutaneous coronary intervention. The plasma proteome was investigated using mass spectrometry-based proteomics on plasma samples collected within 24 h of symptom onset, and one patient was excluded in quality control. In 229 STEMI patients {72% men, median age 62 years [interquartile range (IQR): 54-70]}, a median of 257 proteins (IQR: 244-281) were quantified per patient. A total of 26 proteins were associated with VF; these proteins were involved in several biological processes including blood coagulation, haemostasis, and immunity. After correcting for multiple testing, two up-regulated proteins remained significantly associated with VF, actin beta-like 2 [ACTBL2, fold change (FC) 2.25, P < 0.001, q = 0.023], and coagulation factor XIII-A (F13A1, FC 1.48, P < 0.001, q = 0.023). None of the proteins were correlated with anterior infarct location. CONCLUSION: Ventricular fibrillation due to first STEMI was significantly associated with two up-regulated proteins (ACTBL2 and F13A1), suggesting that they may represent novel underlying molecular VF mechanisms. Further research is needed to determine whether these proteins are predictive biomarkers or acute phase response proteins to VF during acute ischaemia.

Central effects of the serotoninergic, GABAergic, and cholecystokinin systems on neuropeptide VF (NPVF)-induced hypophagia and feeding behavior in neonatal broiler chicken.

The study was performed to evaluate the role of central serotoninergic, GABAergic, and cholecystokinin systems in neuropeptide VF (NPVF)-induced hypophagia in broiler chickens. In this study, 9 experiments were designed, each with one control and three treatment groups (n = 44 in each experiment). Control chicks of all groups were subjected to normal saline + Evans blue 0.1 % Intracerebroventricular (ICV) injection. In the first experiment, 3 groups of chicks received NPVF (4, 8, and 16 nmol). In experiment 2-9, one group of chicks received NPVF (16 nmol), another received 10 µg fluoxetine (serotonin reuptake inhibitor) (experiment 2), 1.25 µg PCPA (serotonin synthesis inhibitor) (experiment 3), 1.5 µg SB-242,084 (5-HT2C receptor antagonist) (experiment 4), 15.25 nmol 8-OH-DPAT (5-HT1A receptor antagonist) (experiment 5), 0.5 µg picrotoxin (GABAA receptor antagonist) (experiment 6), 20 ng CGP54626 (GABAB receptor antagonist) (experiment 7), 1 nmol devazepide (CCKA receptor antagonist) (experiment 8), and 1 nmol/L-365(-|-),260 (CCKB receptor antagonist) (experiment 9), and another final group received combination of specific neurotransmitter + NPVF Then, the cumulative food intake was measured until 120 min post-injection. ICV injection of NPVF (8 and 16 nmol) significantly decreased food intake (P < 0.05). Simultaneous injection of fluoxetine + NPVF and also picrotoxin + NPVF significantly increased hypophagia caused by NPVF (P < 0.05). However, co-administration of PCPA + NPVF and also SB242084 + NPVF significantly decreased NPVF-induced hypophagia (P < 0.05). Finally, 8-OH-DPAT, CGP54626, devazepide, and L-365,260 had no effect on the hypophagia brought on by NPVF (P > 0.05). Count-type behaviors were dose-dependent and decreased in groups that received NPVF compared to the control group (P < 0.05). Our finding recommended an interconnection between central NPVF and serotoninergic, GABAergic, and cholecystokinin systems in neonatal chickens.

The newly proposed Metabolic Score for Visceral Fat is a reliable tool for identifying non-alcoholic fatty liver disease, requiring attention to age-specific effects in both sexes.

Objective: The newly proposed Metabolic Visceral Fat Score (METS-VF) is considered a more effective measure for visceral adipose tissue (VAT) than other obesity indicators. This study aimed to reveal the association between METS-VF and non-alcoholic fatty liver disease (NAFLD), and its variations across age groups within both sexes. Methods: Data from 14,251 medical examiners in the NAGALA project were employed in this study. 3D fitted surface plots were constructed based on multivariate logistic regression models to visualize the isolated and combined effects of aging and METS-VF on NAFLD. Receiver operating characteristic curve (ROC) analysis was conducted to compare the diagnostic performance of METS-VF with other VAT surrogate markers in predicting NAFLD. Results: The results of multivariate logistic regression analysis showed that each unit increase in METS-VF was independently associated with a 333% and 312% increase in the odds of NAFLD in males and females, respectively. Additionally, the 3D fitted surface plot showed that age significantly influenced the association between METS-VF and the odds of NAFLD in both sexes, as follows: (i) In males, when METS-VF was less than 6.2, the METS-VF-related odds of NAFLD increased gradually with age in the 20-45 age group, reached a plateau in the 45-65 age group, and then decreased in the group above 65 years old; however, when male METS-VF exceeded 6.2, aging and METS-VF combined to further increase the odds of NAFLD in all age groups, particularly in the 45-65 age group. (ii) In females, aging seemed to reduce METS-VF-related odds of NAFLD in the 18-40 age group, but significantly increased it in the 40-60 age group, particularly for those with higher METS-VF levels. Further ROC analysis revealed that compared to other VAT surrogate markers, METS-VF showed the highest diagnostic accuracy for NAFLD in females, especially in those under 45 years of age [area under the curve (AUC) = 0.9256]. Conclusions: This study firstly revealed a significant positive correlation between METS-VF and the odds of NAFLD, with METS-VF surpassing other VAT surrogate markers in NAFLD diagnosis. Moreover, age significantly influenced the METS-VF-related odds of NAFLD and METS-VF's diagnostic efficacy for NAFLD in both sexes.