bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint analysis of multiple phenotypes for extremely unbalanced case–control association studies using multi-layer network
Authors: Xie Hongjing , Cao Xuewei , Zhang Shuanglin , Sha Qiuying
Published: November 2023

Motivation

Genome-wide association studies is an essential tool for analyzing associations between phenotypes and single nucleotide polymorphisms (SNPs). Most of binary phenotypes in large biobanks are extremely unbalanced, which leads to inflated type I error rates for many widely used association tests for joint analysis of multiple phenotypes. In this article, we first propose a novel method to construct a Multi-Layer Network (MLN) using individuals with at least one case status among all phenotypes. Then, we introduce a computationally efficient community detection method to group phenotypes into disjoint clusters based on the MLN. Finally, we propose a novel approach, MLN with Omnibus (MLN-O), to jointly analyse the association between phenotypes and a SNP. MLN-O uses the score test to test the association of each merged phenotype in a cluster and a SNP, then uses the Omnibus test to obtain an overall test statistic to test the association between all phenotypes and a SNP.

Results

We conduct extensive simulation studies to reveal that the proposed approach can control type I error rates and is more powerful than some existing methods. Meanwhile, we apply the proposed method to a real data set in the UK Biobank. Using phenotypes in Chapter XIII (Diseases of the musculoskeletal system and connective tissue) in the UK Biobank, we find that MLN-O identifies more significant SNPs than other methods we compare with.

Availability and implementation

https://github.com/Hongjing-Xie/Multi-Layer-Network-with-Omnibus-MLN-O.
CSF 14-3-3β is associated with progressive cognitive decline in Alzheimer’s disease
Authors: Qiang Qiang , Skudder-Hill Loren , Toyota Tomoko , Huang Zhe , Wei Wenshi , Adachi Hiroaki ,   Alzheimer’s Disease Neuroimaging Initiative
Published: November 2023

Alzheimer’s disease is a neurodegenerative disorder characterized pathologically by amyloid-beta plaques, tau tangles and neuronal loss. In clinical practice, the 14-3-3 isoform beta (β) is a biomarker that aids in the diagnosis of sporadic Creutzfeldt–Jakob disease. Recently, a proteomics study found increased CSF 14-3-3β levels in Alzheimer’s disease patients, suggesting a potential link between CSF 14-3-3β and Alzheimer’s disease. Our present study aimed to further investigate the role of CSF 14-3-3β in Alzheimer’s disease by analysing the data of 719 participants with available CSF 14-3-3β measurements from the Alzheimer’s Disease Neuroimaging Initiative. Higher CSF 14-3-3β levels were observed in the mild cognitive impairment group compared to the cognitively normal group, with the highest CSF 14-3-3β levels in the Alzheimer’s disease dementia group. This study also found significant associations between CSF 14-3-3β levels and CSF biomarkers of p-tau, t-tau, pTau/Aβ42 ratios and GAP-43, as well as other Alzheimer’s disease biomarkers such as Aβ-PET. An early increase in CSF 14-3-3β levels was observed prior to Aβ-PET–positive status, and CSF 14-3-3β levels continued to rise after crossing the Aβ-PET positivity threshold before reaching a plateau. The diagnostic accuracy of CSF 14-3-3β (area under the receiver operating characteristic curve = 0.819) was moderate compared to other established Alzheimer’s disease biomarkers in distinguishing cognitively normal Aβ pathology–negative individuals from Alzheimer’s disease Aβ pathology–positive individuals. Higher baseline CSF 14-3-3β levels were associated with accelerated cognitive decline, reduced hippocampus volumes and declining fluorodeoxyglucose-PET values over a 4-year follow-up period. Patients with mild cognitive impairment and high CSF 14-3-3β levels at baseline had a significantly increased risk [hazard ratio = 2.894 (1.599–5.238), P < 0.001] of progression to Alzheimer’s disease dementia during follow-up. These findings indicate that CSF 14-3-3β may be a potential biomarker for Alzheimer’s disease and could provide a more comprehensive understanding of the underlying pathological changes of Alzheimer’s disease, as well as aid in the diagnosis and monitoring of disease progression.
Functional hub disruption emphasizes consciousness recovery in severe traumatic brain injury
Authors: Oujamaa Lydia , Delon-Martin Chantal , Jaroszynski Chloé , Termenon Maite , Silva Stein , Payen Jean-François , Achard Sophie
Published: November 2023

Severe traumatic brain injury can lead to transient or even chronic disorder of consciousness. To increase diagnosis and prognosis accuracy of disorder of consciousness, functional neuroimaging is recommended 1 month post-injury. Here, we investigated brain networks remodelling on longitudinal data between 1 and 3 months post severe traumatic brain injury related to change of consciousness. Thirty-four severe traumatic brain-injured patients were included in a cross-sectional and longitudinal clinical study, and their MRI data were compared to those of 20 healthy subjects. Long duration resting-state functional MRI were acquired in minimally conscious and conscious patients at two time points after their brain injury. The first time corresponds to the exit from intensive care unit and the second one to the discharge from post-intensive care rehabilitation ward. Brain networks data were extracted using graph analysis and metrics at each node quantifying local (clustering) and global (degree) connectivity characteristics. Comparison with brain networks of healthy subjects revealed patterns of hyper- and hypo-connectivity that characterize brain networks reorganization through the hub disruption index, a value quantifying the functional disruption in each individual severe traumatic brain injury graph. At discharge from intensive care unit, 24 patients’ graphs (9 minimally conscious and 15 conscious) were fully analysed and demonstrated significant network disruption. Clustering and degree nodal metrics, respectively, related to segregation and integration properties of the network, were relevant to distinguish minimally conscious and conscious groups. At discharge from post-intensive care rehabilitation unit, 15 patients’ graphs (2 minimally conscious, 13 conscious) were fully analysed. The conscious group still presented a significant difference with healthy subjects. Using mixed effects models, we showed that consciousness state, rather than time, explained the hub disruption index differences between minimally conscious and conscious groups. While severe traumatic brain-injured patients recovered full consciousness, regional functional connectivity evolved towards a healthy pattern. More specifically, the restoration of a healthy brain functional segregation could be necessary for consciousness recovery after severe traumatic brain injury. For the first time, extracting the hub disruption index directly from each patient’s graph, we were able to track the clinical alteration and subsequent recovery of consciousness during the first 3 months following a severe traumatic brain injury.
Classifying real-world macroscopic images in the primary–secondary care interface using transfer learning: implications for development of artificial intelligence solutions using nondermoscopic images
Authors: Carse Jacob , Süveges Tamás , Chin Gillian , Muthiah Shareen , Morton Colin , Proby Charlotte , Trucco Emanuele , Fleming Colin , McKenna Stephen
Published: November 2023

Background

The application of deep learning (DL) to diagnostic dermatology has been the subject of numerous studies, with some reporting skin lesion classification performance on curated datasets comparable to that of experienced dermatologists. Most skin disease images encountered in clinical settings are macroscopic, without dermoscopic information, and exhibit considerable variability. Further research is necessary to determine the generalizability of DL algorithms across populations and acquisition settings.

Objectives

To assess the extent to which DL can generalize to nondermoscopic datasets acquired at the primary–secondary care interface in the National Health Service (NHS); to explore how to obtain a clinically satisfactory performance on nonstandardized, real-world local data without the availability of large diagnostically labelled local datasets; and to measure the impact of pretraining DL algorithms on external, public datasets.

Methods

Diagnostic macroscopic image datasets were created from previous referrals from primary to secondary care. These included 2213 images referred from primary care practitioners in NHS Tayside and 1510 images from NHS Forth Valley acquired by medical photographers. Two further datasets with identical diagnostic labels were obtained from sources in the public domain, namely the International Skin Imaging Collaboration (ISIC) dermoscopic dataset and the SD-260 nondermoscopic dataset. DL algorithms, specifically EfficientNets and Self-attention with Window-wise Inner-product based Network (SWIN) transformers, were trained using data from each of these datasets. Algorithms were also fine-tuned on images from the NHS datasets after pretraining on different data combinations, including the larger public-domain datasets. Receiver operating characteristic curves and the area under such curves (AUC) were used to assess performance.

Results

SWIN transformers tested on Forth Valley data had AUCs of 0.85 and 0.89 when trained on SD-260 and Forth Valley data, respectively. Training on SD-260 followed by fine tuning of Forth Valley data gave an AUC of 0.91. Similar effects of pretraining and tuning on local data were observed using Tayside data and EfficientNets. Pretraining on the larger dermoscopic image dataset (ISIC 2019) provided no additional benefit.

Conclusions

Pretraining on public macroscopic images followed by tuning to local data gave promising results. Further improvements are needed to afford deployment in real clinical pathways. Larger datasets local to the target domain might be expected to yield further improved performance.
The “microcephalic hydrocephalus” paradox as a paradigm of altered neural stem cell biology
Authors: Duy Phan Q , Mehta Neel H , Kahle Kristopher T
Published: November 2023

Characterized by enlarged brain ventricles, hydrocephalus is a common neurological disorder classically attributed to a primary defect in cerebrospinal fluid (CSF) homeostasis. Microcephaly (“small head”) and hydrocephalus are typically viewed as two mutually exclusive phenomenon, since hydrocephalus is thought of as a fluid “plumbing” disorder leading to CSF accumulation, ventricular dilatation, and resultant macrocephaly. However, some cases of hydrocephalus can be associated with microcephaly. Recent work in the genomics of congenital hydrocephalus (CH) and an improved understanding of the tropism of certain viruses such as Zika and cytomegalovirus are beginning to shed light into the paradox “microcephalic hydrocephalus” by defining prenatal neural stem cells (NSC) as the spatiotemporal “scene of the crime.” In some forms of CH and viral brain infections, impaired fetal NSC proliferation leads to decreased neurogenesis, cortical hypoplasia and impaired biomechanical interactions at the CSF–brain interface that collectively engender ventriculomegaly despite an overall and often striking decrease in head circumference. The coexistence of microcephaly and hydrocephalus suggests that these two phenotypes may overlap more than previously appreciated. Continued study of both conditions may be unexpectedly fertile ground for providing new insights into human NSC biology and our understanding of neurodevelopmental disorders.
Resting-state neural correlates of individual differences in ignored experience and its deleterious effect
Authors: Cen Yu-Shan , Li Wei , Xia Ling-Xiang
Published: November 2023

Uncovering the neural mechanisms of ostracism experience (including its subclasses of excluded and ignored experiences) is important. However, the resting-state functional brain substrates responsible for individual differences in ostracism experience and its negative effects remain largely undefined. This study explored these issues in a sample of 198 Chinese college students by assessing the amplitude of low-frequency fluctuations and functional connectivity. The findings indicated a positive correlation between ignored experience and the amplitude of low-frequency fluctuations in the right superior frontal gyrus and the functional connectivity between the right superior frontal gyrus and left cerebellum posterior lobe. Additionally, a negative correlation was found between ignored experience and the functional connectivity between the right superior frontal gyrus and the bilateral insula as well as the bilateral inferior parietal lobule. Moreover, the mediation analysis demonstrated that the effects of the functional connectivities of right superior frontal gyrus–left cerebellum posterior lobe and right superior frontal gyrus–right inferior parietal lobule on revenge intention were mediated by ignored experience. Our study offers novel insights into the neural correlates of both individual variations in ignored experience and its typical deleterious effect. These results could deepen our understanding of individual differences in negative experiences and inspire the development of targeted interventions for social stress from the perspective of the brain.
Thalamic connectivity topography in newborns with spina bifida: association with neurological functional level but not developmental outcome at 2 years
Authors: Ji Hui , Payette Kelly , Speckert Anna , Tuura Ruth , Grehten Patrice , Kottke Raimund , Ochseinbein-Kölble Nicole , Hagmann Cornelia , Mazzone Luca , Meuli Martin , Padden Beth , Hackenberg Annette , Wille David-Alexander , Moehrlen Ueli , Latal Beatrice , SPINA BIFIDA STUDY GROUP ZURICH  , Jakab Andras
Published: November 2023

Spina bifida affects spinal cord and cerebral development, leading to motor and cognitive delay. We investigated whether there are associations between thalamocortical connectivity topography, neurological function, and developmental outcomes in open spina bifida. Diffusion tensor MRI was used to assess thalamocortical connectivity in 44 newborns with open spina bifida who underwent prenatal surgical repair. We quantified the volume of clusters formed based on the strongest probabilistic connectivity to the frontal, parietal, and temporal cortex. Developmental outcomes were assessed using the Bayley III Scales, while the functional level of the lesion was assessed by neurological examination at 2 years of age. Higher functional level was associated with smaller thalamo-parietal, while lower functional level was associated with smaller thalamo-temporal connectivity clusters (Bonferroni-corrected P < 0.05). Lower functional levels were associated with weaker thalamic temporal connectivity, particularly in the ventrolateral and ventral anterior nuclei. No associations were found between thalamocortical connectivity and developmental outcomes. Our findings suggest that altered thalamocortical circuitry development in open spina bifida may contribute to impaired lower extremity function, impacting motor function and independent ambulation. We hypothesize that the neurologic function might not merely be caused by the spinal cord lesion, but further impacted by the disruption of cerebral neuronal circuitry.
A 1-month-old infant with pulmonary hypertensive crisis after cardiac surgery was successfully rescued with connection of left atrial and right ventricular pressure measurement tubes: a case report
Authors: Zhang Huijun , Song Hailong
Published: November 2023

Background

Pulmonary hypertensive crisis is a complication with extremely high mortality after surgery of congenital heart disease. However, there are still no treatment guidelines or expert consensus on the standard treatment of pulmonary hypertensive crisis, and the effect of conventional treatment is still unsatisfactory. We present a case of a patient who developed pulmonary hypertensive crisis after cardiac surgery, and was successfully rescued with a pioneering method, which has never been reported so far.

Case summary

An infant with congenital heart disease had undergone cardiac surgery successfully. Due to obvious myocardial oedema, sternal closure was delayed. The left atrial and right ventricular pressure monitoring tubes, both of which were connected through a triplet, were inserted into right pulmonary vein and pulmonary artery, respectively, and the triplet was in closed condition. On the night of the surgery, pulmonary hypertensive crisis occurred. Emergency bedside thoracotomy was given, and the triplet was turned on urgently to make the left atrial and right ventricular pressure monitoring tubes connected. Meantime, conventional treatment was performed. Eventually, the pulmonary hypertensive crisis was quickly relieved, and the infant was discharged 9 days later.

Discussion

The left atrial and right ventricular pressure monitoring tubes are placed intraoperatively in patients who both need delayed sternal closure and have high risk factors for pulmonary hypertensive crisis, by which could not only monitor the pressure of left atrium and right ventricle in real time but also effectively relieve the right ventricular pressure instantaneously when pulmonary hypertensive crisis occurs, as well as remedy ischaemia of systemic and coronary circulation.
Left atrial appendage occlusion guided by intracardiac echocardiography in a patient with a 34 mm atrial septal defect occluder: a case report
Authors: Korsholm Kasper , Jensen Jesper Møller , Nielsen-Kudsk Jens Erik
Published: November 2023

Background

Intracardiac echocardiography (ICE)–guided left atrial appendage occlusion (LAAO) is increasingly common. Patients with previous atrial septal defect closure constitute a significant challenge for transseptal access.

Case summary

A 49-year-old man with persistent atrial fibrillation, hypertension, and reduced left ventricular function was considered for LAAO after a life-threatening intrathoracic bleeding while on oral anticoagulation. Percutaneous atrial septal defect closure was performed 15 years before with a 34 mm Amplatzer Septal Occluder. Preprocedural cardiac computed tomography demonstrated the atrial septal occluder device with a small native interatrial septum at the inferior margin. The left atrial appendage landing zone measured 17 × 22 mm. The LAAO was performed under local analgesia. A steerable sheath was used to guide the transseptal puncture, and the ICE probe was traced along a guidewire across the atrial septum. A 12-F Amulet delivery sheath was advanced through the same transseptal hole. Under ICE and fluoroscopy guidance, a 25 mm Amplatzer Amulet was deployed. Follow-up imaging showed a well-positioned device with a small peridevice leak at the disc.

Discussion

This case report illustrates the feasibility of LAAO performed with ICE guidance from the left atrium in a patient with a large Amplatzer Septal Occluder with a small native interatrial septum. It demonstrates that prior atrial septal defect closure should not be considered as a contraindication for LAAO but warrants careful preprocedural planning.
Aortic root reinforcement combined with vascular rafts eversion and built-in procedure for Acute Type A Aortic dissection surgery
Authors: Li J , Li B H , Yan Y P , Guo F W , Wang H , Zhang Y J , Li Y X , Ma T , Wang Q , He X , Zheng X L , Yan Y
Published: November 2023

Background

Acute type A aortic dissection (ATAAD) is a life-threatening disease with high mortality. Surgery remains the gold standard for the treatment of ATAAD. However, ATAAD surgery, especially the aortic root reinforcement technique, is still a challenge for surgeons.

Methods

All Stanford type A aortic dissection patients undergoing surgery in our hospital from January 2020 to December 2021 were retrospectively entrolled. These patients were divided into three groups according to the surgical procedures of aortic rot: continuous aortic root suture group (CARS group); "intermittent mattress type built-in skirt forming method" group, which was created by our group (XJ-procedure group), aortic root replacement group (Bentall group). The primary outcomes were 30-day mortality and incidence of recurrent dissection of aortic root (before dis-charge, 3 and 6 months of follow-up). The secondly outcomes were the rate of reoperation for aortic root bleeding, the incidence of pseudoaneurysms and the severe aortic valve regurgitation (the residual aortic valve regurgitation greater than grade 2+) rate before discharge, 3 and 6 months of follow-up.

Results

A total of 221 patients were entrolled in this study, including 69, 114 and 38 in CARS group, XJ-procedure group and Bentall group, respectively. The total operation time in the CARS group, XJ-procedure group and Bentall group were 391.74±74.05 minutes, 371.59±79.36minutes and 427.76±100.78 minutes, respectively (P=0.001, Pa=0.108, Pb=0.001). The overall 30-day mortality rate was 6.8% (15/221), 7.2% (5/69), 7.0% (8/114) and 5.3% (2/38) for all patients, CARS group, XJ-procedure group and Bentall group, respectively. In the CARS group, the incidence of recurrent dissection of aortic root was much lower in the XJ-procedure group than the CARS group before discharge (1.8% versus 10.6%), 3 months (9.4% versus 0%) and 6 months (7.8% vs 0%) follow-up, respectively. The rates of reoperation for aortic root bleeding in the CARS group, XJ-procedure group and Bentall group were 4.3%, 0.9%, and 2.6%, respectively (P=0.306, Pa=0.151, Pb=0.439). In the CARS group, the incidence of pseudoaneurysm was 3.0%,3,1%,3.0% before discharge, at 3 months and 6 months follow-up. In the XJ-procedure group, there was no reported pseudoaneurysm. The residual severe aortic valve regurgitation incidence was much lower in the XJ-procedure group than the CARS group at 3 months (0.9% versus 4.7%) and 6 months (0.9% versus 4.7%) follow-up, respectively. Compared with the traditional procedure, the XJ-procedure does not increase the perioperative mortality and reduces the incidence of aortic root complications.

Conclusion

XJ-procedure is a safe and effective aortic root reinforcement technique for ATAAD surgery and reduces aortic root complications by reinforcing the fragile aortic root tissue.
Association of unilateral low ankle-brachial index and bilateral low ankle-brachial index with incident cardiovascular disease and mortality: The Northern Shanghai Study
Authors: Zhao S , Xu C , Xiong J , Tang J M , Yu S K , Maimaitiaili R S T M J , Teliewubai J D L , Chi C , Xu Y W , Zhang Y
Published: November 2023

Background and Aims

Ankle-brachial index (ABI) has been used as a marker for atherosclerosis and a risk factor of cardiovascular disease (CVD). Nevertheless, it is not yet clear whether there is a difference in cardiovascular risk between patients with one leg low ABI (<0.9) (unilateral low ABI) and those with both legs low ABI (bilateral low ABI). Therefore, we investigated the association of target organ damage (TOD) and incident of major cardiovascular events (MACE) in participants with unilateral low ABI and bilateral low ABI.

Methods

We enrolled 3168 participants (mean age 71.3 years, 1361 men) from North Shanghai Study. The participants were divided into 3 groups according to both legs ABI (bilateral low ABI, unilateral low ABI and bilateral normal ABI). TOD, including left ventricular hypertrophy, arterial stiffness, carotid plaque, and renal damage, were measured using standard methods at baseline. MACE was a composite outcome that consisted of nonfatal myocardial infarction, nonfatal stroke and CVD death.

Results

Compared with bilateral normal ABI, bilateral low ABI had higher risk of all TOD, but unilateral low ABI only had higher risk of carotid plaque and renal damage after adjustment covariates. During a median follow-up of 5.4 years, 199 MACE and 192 all-cause mortality occurred. The multivariable-adjusted risk for MACE in individuals with bilateral low ABI (hazard ratio (HR): 1.86; 95% confidence interval (CI), 1.20-2.88) and individuals with unilateral low ABI (HR: 1.58; 95% CI, 1.04-2.41) were higher than individuals with bilateral normal ABI (referent group). Compared with bilateral normal ABI, both unilateral low ABI (hazard ratio: 1.70; 95% CI, 1.13-2.57) and bilateral low ABI (HR: 2.10; 95% CI, 1.39-3.18) had higher risk of all-cause mortality after adjustment covariates.

Conclusion

Both unilateral low ABI and bilateral low ABI are associated with increased CVD risk, but bilateral low ABI with a trend towards increasing CVD risk. More attention should be paid to whether a patient has a unilateral or bilateral low ABI for a more accurate CVD risk assessment.Kaplan-Meier curve for ABI categoriesOR for ABI categories for TOD
Underutilization of guideline-recommended therapy in patients 80 years and older with peripheral artery diseases
Authors: Messiha D , Petrikhovich O , Lortz J , Pinsdorf D , Hogrebe K , Knuschke R , Hering R , Schulz M , Rassaf T , Rammos C
Published: November 2023

Background

Ageing is a major cardiovascular risk factor with detrimental pathophysiological changes that culminate in a high atherosclerotic burden. Peripheral artery disease (PAD) is a major manifestation of atherosclerosis with high mortality. Guideline-recommended treatment is essential, however implementation is inadequate. With an ageing society, age-related inequalities are important and have not been elucidated in a high-risk PAD population on a nation-wide scale. We sought to analyse the outpatient treatment structures and guideline adherence in treatment of PAD patients older than 80 year of age.

Purpose

Aim of the study was to identify age-based inequalities in outpatient treatment care and pharmacotherapy in PAD patients.

Methods

We analyzed age-related differences in prevalence, pharmacotherapy (statins, antiplatelets) and treatment by specialized outpatient care (angiology, vascular surgery, internal medicine, cardiology) in 17,633,970 patients with PAD and statutorily insurance presenting to outpatient care facilities in Germany between 2009 and 2018. The study is based on ambulatory claims data of the panel doctors’ services according to §295 SGB V and drug prescription data according to §300 SGB V, comprising 70.1 million patients per year. Diagnosis of PAD was defined upon medical diagnoses of PAD ICD. Statistical analysis was performed with chi-squared test for trend and two-way Anova.

Results

Of 17,633,970 PAD patients included, 28% were older than 80 years. PAD prevalence increased between 2008 and 2019 (1.85% vs 3.14%), with the proportion of the elderly increasing by a third (24.4% vs 31.2%). Octogenarians were undertreated regarding guideline-recommended statin pharmacotherapy compared to younger patients throughout the observed 10 year time frame (statins 2016: 46.5% vs 52.4%; antiplatelets 2016 30.6% vs 29.3%; p < 0.05). Furthermore, octogenarians received less specialized outpatient care (angiology: 6.4% vs 9.5%, vascular surgery: 8.1% vs 11.8%, cardiology: 25.2% vs 29.2%, p < 0.05).

Conclusions

Our results demonstrate that age-related differences in pharmacotherapy and specialized outpatient care of PAD patients are evident. While overall guideline-recommended outpatient treatment is low, patients 80 years and older are less likely to receive both, leaving age-related health inequalities a challenge of our future.
Effects of PCSK-9 inhibitors on arterial structure and function: preliminary results
Authors: Maloberti A , Vatta A , Grasso A , Garofani I , Morelli M , Giani V , Fortuna M , Gualini E , Giannattasio C
Published: November 2023

Background

One of the latest chapters in the research for new and stronger lipid lowering therapies has led to the development of PCSK9 inhibitors. In addition to the benefit on lipid profile, a limited number of studies have been published showing a possible improvement in vascular function and structure following their administration.

Purpose

To evaluate the effects of PCSK9 inhibitors on structural (via carotid Intima Media Thickness – IMT) and functional (carotid-femoral Pulse Wave Velocity – cf-PWV - and brachial artery Flow Mediated Dilatation - FMD) arterial properties.

Methods

Twenty-two dyslipidemic patients with a clinical indication to PSCK9 inhibitors were prospectively recruited at the cardiology rehabilitation of a hospital. Anthropometric, clinical and therapeutic data were recorded. Each patient underwent instrumental examinations to assess cf-PWV, IMT and FMD at T0 (before the start of therapy), T1 (after 6 months) and T2 (after 12 months).

Results

In the 22 patients who reached 6 months of follow up there was a significant reduction in LDL cholesterol (from 127.8±31.7 to 47.4±29.1 mg/dl, p<0. 0001) while there was no significant difference in arterial parameters (cf-PWV: from 10.5±3.5 to 9.4±2.3 m/s, p=0.092; FMD: from 11.4±8.1 to 9.8±8.3%, p=0.407; IMT: from 775.6±192.8 to 768.7±144.7, microm, p=0.854). Similar results were also obtained in the 12 patients who reached one year of follow-up: LDL from 129.4±29.1 to 48.8±21.9 mg/dl, p<0.0001; cf-PWV from 10.4±3.3 to 10.5±2.9, p=0.874; FMD from 12.0±9.1 to 11.0±5.6%, p=0.930; IMT from 745.1±203.9 to 770.0±127.3 microm, p=0.710.

Conclusion

Our study confirm the strong LDL reduction with PCSK9 inhibitors that are needed in order to reach the targets set by the ESC 2019 guidelines. In contrast, they do not show a significant effect on arterial function and structure in terms of cf-PWV, FMD and carotid IMT.
Acute limb ischemia registry, the forgotten emergency
Authors: Bluro I , Garagoli F , Chiabrando J , Chas J , Valle Raleigh J , Gonzalez N , Fernandez Villar G , Iroulart J , Pellegrini M N , Herzkovich N , Fernandez Recalde M L , Izaguirre A , Rojas Matas C , Kotowicz V , Pizarro R
Published: November 2023

Background

Although acute limb ischemia (ALI) is a leading cause of death and lower limb amputation, knowledge about its epidemiology, presentation, and treatment is limited.

Aim

The purpose of this study is to describe patient characteristics, diagnostic approaches taken, modes of presentation, and clinical developments in patients with ALI.

Methods

We prospectively included all ALI outpatients between 2016 and 2022. Patients who had ischemia due to trauma, iatrogenic causes, or those who developed it while in the hospital were excluded. We provide descriptive analysis for our registry, and performed a uni and multivariable regression model in order to identify clinical factors associated with the composite primary endpoint of intrahospital death and limb amputation.

Results

We included 89 consecutive patients with ALI. Table 1 describes the baseline characteristics. The median time from clinical presentation to first medical contact was 24 hours (IQR 4-72 hours). Time between clinical consultation and diagnosis was 1 hours (1.1–7 hours), and time between diagnosis and revascularization was 12 hours (4–36 hours). Although patients with a threatened limb sought treatment sooner than those without (12 hours vs 72 hours, p = 0.001), they had a higher rate of events.

Peripheral thromboembolism was the main cause of ALI and the only etiology associated with death or amputation.

Patients considered candidates for reperfusion therapy comprised 92% of the cohort, while 3 patients were considered candidates for direct amputation and 2 patients were considered candidates for anticoagulation due to the comorbidities they presented. Thirteen patients (21%) died or suffered limb amputations (three suprapatellar, two infrapatellar, and one in the forefoot). One third of the patients suffered a complication during hospitalization. Acute renal failure was the most frequent complication (27%).

In a univariable regression analysis, age, embolic origin, higher levels of lactacidemia, and threatened limb were associated with the composite event of death and limb amputation, whereas in a multivariable regression model, serum lactic acid and have the vitality of the member threatened were independently associated with an increased odds of death or amputation (Tabla 2).

Conclusions

Acute limb ischemia is associated with an increased risk of intrahospital death and limb amputation. Serum lactacidemia and limb threatened at presentation were independently associated with an increased risk of clinical events. Risk of events is associated with the limb clinical condition and not with the delay in revascularization. Even those patients who do not die or are amputated have high morbidity and need for prolonged hospitalization. Increased awareness of the disease are critical for improving survival and limb preservation.
Apolipoprotein C3-rich low-density lipoprotein (AC3RL) increases BBB permeability and deteriorates cerebral ischemic stroke injury
Authors: Tsai P H , Tseng K F , Lin M C , Wang J S , Chang Y H , Chen F Y , Shen M Y
Published: November 2023

Background

Ischaemic stroke causes disability due to brain damage resulting from blood supply obstruction or increased permeability of the blood-brain barrier (BBB) that exposes the blood to toxic substances during reperfusion. Apolipoprotein C3 is a crucial triglyceride transport modulator, and its overexpression raises the risk of dyslipidemia and cardiovascular disease. Clinically, we observed that stroke patients have higher levels of apolipoprotein C3-rich low-density lipoprotein (AC3RL) expression than healthy individuals, and they also have worse prognoses. Simultaneously, we found that an increase in AC3RL is involved in endothelial cell apoptosis and inflammatory response, which may be linked to the occurrence of brain injury after stroke.

Purpose

This study aimed to explore whether the high expression of AC3RL would increase the permeability of the blood-brain barrier, and aggravate brain damage.

Methods

The intraluminal monofilament model of middle cerebral artery occlusion (MCAO) experiment was carried out using C57BL/6 and apolipoprotein E gene knockout mice (ApoE-/-). WT receive an IV injection of AC3RL, which was separate from stroke patients' plasma. APOE-/- was fed a high-fat diet to promote AC3RL higher expression. We performed 60-minute ischaemic and 7-day reperfusion. The modified neurological severity score (mNSS) method was used to assess motor and neurological scores. Evans blue dye was injected through the tail vein one hour before euth

(A) AC3RL, which was separated from stroke patients' plasma. (B) AC3RL concentration in individuals. (C) The white portion of the mice brains TTC stain indicates the site of the injury. (D) Evans blue dye leakage study in mice brains exhibited BBB permeability changes. (E) Assessment of mice's motor and neurological performance using the mNSS. anasia to assess BBB permeability. TTC staining of brain tissue after euthanasia to pinpoint the site of brain damage.

Results

Evans blue dye leakage was observed in the brain tissues of the group with high AC3RL expression, indicating that the BBB permeability has expanded. The mNSS method revealed a significant rise in mice with high levels of AC3RL expression, which suggested a decline in motor and nervous function.

Conclusions

Whether endogenous or exogenous, increased expression of AC3RL leads to more severe cerebral ischemic injury and motor dysfunction, which we believe may be due to increased BBB permeability caused by AC3RL. Therefore, AC3RL can be used as a disease predictor in the future, reducing AC3RL will be the main indicator for reducing severe brain injury.Figure 1.Figure 2.
Long-term incidence of ischemic stroke following transient ischemic attack: a nationwide cohort study during 2014-2020
Authors: Vinding N E , Butt J H , Lauridsen M D , Kristensen S L , Johnsen S P , Kroell J , Graversen P L , Kruuse C , Torp-Pedersen C , Koeber L , Fosboel E L
Published: November 2023

Background

The short-term incidence of ischemic stroke after a transient ischemic attack (TIA) is high. However, data on the long-term incidence are sparse but relevant in order to guide preventive strategies.

Purpose

Estimate 5-year incidence of ischemic stroke after TIA.

Methods

Using the Danish Stroke Registry, patients with first-time TIA during the period September 2014-December 2020 were identified and matched 1:4 with individuals from the background population, and 1:1 with patients with a first-time ischemic stroke, based on age, sex, and calendar year. The cumulative incidences of ischemic stroke and mortality were estimated by the Aalen-Johansen and Kaplan-Meier estimators, respectively, and compared between groups by use of conditional multivariable Cox regression.

Results

After matching, we included 23,244 patients with TIA, 92,976 patients from the background population, and 23,244 patients with ischemic stroke (median age 70 years [25th-75th percentile 60-78]: 53% men). Patients with TIA had more comorbidities than the background population, yet less than the ischemic stroke population. The five-year incidence of ischemic stroke following TIA (6.5% [95% CI 6.1-7.0]) was higher than for the background population (2.3% [95% CI 2.2-2.4], hazard ratio (HR) 3.31 [95% CI 3.04-3.61]), but lower than for the control stroke population (10.3% [95% CI 9.8-10.8], HR 0.60 [95% CI 0.55-0.66]). Five-year mortality for patients with TIA (18.0% [95% CI 17.8-19.1]) was higher than for the background population (15.0% [95% CI 14.7-15.3], HR 1.20 [95% CI 1.14-1.26]), but lower than for the control stroke population (29.9% [95%CI 29.2-30.6], HR 0.41 [95% CI 0.39-0.44]) (Figure 1).

Conclusion

Patients with first-time transient ischemic attach had a 5-year incidence of ischemic stroke of 6.5%. After adjustment for potential confounders, the rate of ischemic stroke was approximately three-fold higher than that of the background population, and 40% lower than that of patients with ischemic stroke.Figure 1.Cumulative incidence of stroke
Risk of delayed intracranial hemorrhage according to antithrombotic treatment in patients with traumatic brain injury: systematic review and meta-analysis
Authors: Cimini L A , Giomi E , Becattini C , Vedovati M C
Published: November 2023

Background

Antithrombotic treatment is a risk factor for the development of delayed (DICH) intracranial hemorrhage after head trauma. However, it is not known whether i) the risk of DICH differs according to antithrombotic treatments and ii) prescription of serial brain-CT after a first normal CT scan is indicated.

Aim

The aims of this study are: i) to evaluate the risk of DICH after traumatic brain injury (TBI) according to different antithrombotic treatments (vitamin K antagonist [VKA], direct oral anticoagulants [DOACs], antiplatelets [AP]); ii) to evaluate the usefulness of serial CT scans vs clinical observation to rule out a DICH.

Methods

Medline and Embase databases were searched from inception up to June 2022 to find studies that met the following characteristics: i) enrolling TBI patients admitted to emergency departments within 24 hours since trauma; ii) enrolling patients were receiving VKA, DOACs or APs at time of TBI; iii) had a normal brain-CT scan at admission. Primary study outcome was DICH, defined as the presence of subdural, epidural or parenchymal haematoma, subarachnoid haemorrhage or cerebral contusion.

Results

3070 records were identified, and 27 observational studies were included. No significant difference in the risk of DICH was observed in patients receiving VKAs or DOACs (23 studies, 6078 patients) at time of TBI: 2.52% vs 2.01%, risk ratio (RR) 1.40, 95% CI 0.91;2.14, : 0% (Fig.1A). Similarly, no difference was observed between patients receiving VKAs or APs (10 studies, 3864 patients): 1.43% vs 1.54%, RR 0.92, CI 95% 0.40;2.14, : 0%; and between DOACs or APs (6 studies, 1916 patients): 0.87% vs AP 1.81 %, RR 0.62, 95% CI 0.10-3.71, = 0% (Fig. 1B). No studies comparing serial brain-CT vs clinical observation were found.

Conclusion

Our study shows that the risk of developing DICH after TBI does not differ across the antithrombotic treatments. Further studies should assess the role of serial brain-CT in this setting.
Validation of the resting full-cycle ratio and diastolic pressure ratio through myocardial perfusion imaging with [15O]H2O positron emission tomography
Authors: Dahdal J , Bakker F , Svanerud J , Danad I , Driessen R , Raijmakers P , Harms H , Lammertsma A , Van De Hoef T , Appelman Y , Van Royen N , Knaapen P , De Waard G
Published: November 2023

Background

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are invasive techniques used to evaluate the hemodynamic significance of coronary artery stenosis. These methods have been validated through perfusion imaging techniques and clinical trials. However, new invasive pressure indices that do not require hyperemia have recently emerged, and it is essential to confirm their diagnostic efficacy.

Purpose

To validate the resting full-cycle ratio (RFR) and the diastolic pressure ratio (dPR), against [15O]H2O positron emission tomography (PET) imaging.

Methods

A total of 129 symptomatic patients with an intermediate risk of coronary artery disease (CAD) were included. All patients underwent cardiac [15O]H2O PET with quantitative assessment of myocardial perfusion, and within 2 weeks coronary angiography was performed. Intracoronary pressure measurements were obtained in 320 vessels and RFR, dPR, and FFR were computed. In the case of RFR and dPR, values ≤ 0.89, and for FFR, values ≤ 0.8 were classified as abnormal. PET myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) served as reference standards. The index tests and gold standard results were evaluated by blinded researchers.

Results

Figure 1 shows the diagnostic performance of each ratio in coronary arteries with stenoses (136 of 320 vessels, 38%). The overall diagnostic accuracies of RFR, dPR and FFR did not differ when PET MBF < 2.3 ml · min-1 and PET MPR < 2.5 were considered as the reference standard. No significant differences were observed in the areas under the receiver-operating-characteristic (ROC) curve among the indices (Figure 2). In addition, the indices demonstrated comparable performance when the analysis included all of the vessels.

Conclusion

The novel non-hyperemic pressure ratios, RFR and dPR, have a diagnostic performance that is comparable to FFR when using [15O]H2O PET to assess myocardial perfusion abnormalities. These findings suggest that RFR and dPR may be considered for clinical use in symptomatic patients with CAD.Figure 1Diagnostic performance;StenosisFigure 2ROC curve analysis;Stenosis
Efficiency of orbital atherectomy for eccentric calcium in bending vessels: in-vitro vessel models
Authors: Tanaka Y , Mitsui H , Murakami K , Saito S , Iwasaki K
Published: November 2023

Background/Introduction

The mode of action of orbital atherectomy (OA) consists of a fast elliptical rotation of the crown, allowing for focal treatment with slow forward and backward movements. However, reports on the efficiency of OA for eccentric calcium in bending vessels are limited.

Purpose

This study aimed to clarify the mechanism of action of the crown and elucidate the anatomical condition for an efficient OA on eccentric calcium in bending lesions, via in vitro experimental models.

Methods

In total, 40 in vitro stenotic vessel models with eccentric calcium were developed; five models with a combination of two calcium positions (inner or outer side bending), two curvature radiuses (R, 10 or 20 mm), and two bending angles (A, 100º or 60º). Each model was connected to a whole aorta model and the procedures were performed using the Diamondback 360 coronary OA system through a 6F short-tip amplatz 1.0 guiding catheter. The protocol included two 30-second low-speed ablations followed by one 30-second high-speed ablation. Micro-computed tomography analyses of the models were performed before and after ablation to evaluate the ablated calcium volume and maximum depth.

Results

Eccentric calcium at inner side of the bending was more ablated than at outer side (6.6 mm3 vs 2.7 mm3, P < 0.0001). Among the inner side, the ablated calcium volume was higher in the R20/A60 model (8.28 mm3) than in R10/A100 (6.30 mm3; P = 0.14), R10/A60 (5.62 mm3, P = 0.04), and R20/A100 (6.06 mm3, P = 0.09) models (Figure 1A). The ablated maximum depth was also higher in the R20/A60 model (0.98 mm) than in other models (R10/A100: 0.84 mm, R10/A60: 0.90 mm, R20/A100: 0.78 mm); however, there were no significant differences. Moreover, among the outer side, the ablated calcium volume was higher in the R20/A100 model (5.17 mm3) than in the R10/A100 (1.95 mm3, P < 0.001), R10/A60 (2.12 mm3, P = 0.002), and R20/A60 (1.73 mm3, P < 0.001) models (Figure 1B). The ablated maximum depth was also significantly higher in the R20/A100 model (0.47 mm) than in other models (R10/A100: 0.32 mm, P = 0.03; R10/A60: 0.33 mm, P = 0.05; R20/A60: 0.27 mm, P = 0.01).

Conclusions

Curvature radius and bending angles could be associated with efficiency of OA for eccentric calcium in bending vessels. Although small curvature radiuses may be unsuitable for OA in the inner or outer side, it may be effective for inner side lesions with a large curvature radius and low bending angles, and outer side lesions with a large curvature radius and high bending angles.
Twelve-months vessel healing profile following the novel resorbable magnesium scaffold implantation: an intravascular OCT analysis of the BIOMAG-I trial
Authors: Seguchi M , Aytekin A , Xhepa E , Haude M , Wlodarczak A , Van Der Schaaf R J , Torzewski J , Ferdinande B , Escaned J , Iglesias J F , Bennett J , Toth G , Toelg R , Garcia-Garcia H M , Joner M
Published: November 2023

Background

The first-in-human trial of the latest resorbable magnesium scaffold (RMS), DREAMS 3G, showed favorable clinical and angiographic outcomes up to 6-months. An intravascular optical coherence tomography (OCT) assessment of the vascular healing profile at 6 months and 12 months follow-up may serve as additional supportive evidence for device safety and efficacy.

Purpose

The aim of this study was to evaluate the vessel healing process by quantifying the presence of strut protrusion (SP) and strut degradation following DREAMS 3G implantation as per intravascular OCT imaging.

Methods

Patients from the BIOMAG-I trial who underwent OCT imaging at both 6- and 12-months were deemed eligible. This resulted in the inclusion of a total of 51 patients and 52 lesions in the current analysis. The acquired intravascular imaging data were evaluated every 1 mm to visualize and quantify the SP and the number of visible struts at 6- and 12-months. In addition, we investigated the potential impact of SP on mean and minimum lumen area (mm2) at both time point.

Results

At 12 months, the mean SP area was significantly smaller in comparison to 6 months follow-up (1.87±2.22 mm2 at 6 months vs. 0.99±1.27 mm2 at 12 months, p<0.001). There was a positive correlation between SP area and mean lumen area at both 6 months (p<0.001) and 12 months (p=0.014) follow-up. Similarly, a positive correlation was observed between SP area and minimum lumen area up to 6 months (p=0.006 at 6 months, p=0.323 at 12 months). The number of visible struts was 6.44±7.59 at 6 months and 1.79±0.85 at 12 months (p<0.001).

Conclusion

The SP area was larger in lesions with greater lumen area following the implantation of the novel RMS. The observed SP area was significantly smaller at 12 months in comparison to 6 months follow-up. These results suggest that the presence of SP is part of a favorable vascular healing process following the treatment with the latest resorbable magnesium scaffold.