bluuebunny/crossref_metadata_2025 huggingface dataset:
Wear debris analysis of Al-Si/MWCNT nanocomposite during dry sliding wear tests
Authors: T Shivaramu H , U Vignesh Nayak , K S Umashankar
Published: May 2024

This study demonstrates the enhancement of wear resistance achieved by incorporating multi-walled carbon nanotubes (MWCNTs) in LM6 aluminum alloy to form nanocomposites. Experiments on wear resistance study were performed at different test parameters for various compositions of MWCNT in LM6 alloy. The size and nature of debris obtained post experiments were significantly dependent on the MWCNT contents. Wear resistance was found to increase with increase in the MWCNT fraction in the nanocomposite. The worn surface and the shape as well as the size of the debris were studied under scanning electron microscopy (SEM). Energy-dispersive spectroscopy (EDS) analysis of the worn surfaces was used to detect and measure the constituents present in the debris. SEM micrographs of the nanocomposites show that the features of the wear debris are completely altered when MWCNT was added. Further the wear mechanism underwent a change from oxidative in LM6 to that of ploughing in LM6 nanocomposite. The recorded surface roughness values also confirm the above findings and show significantly reduced surface roughness (∼82%, 0.75 wt% MWCNT). These results clearly demonstrate the advantage of addition of MWCNT for enhancing resistance to wear in LM6 alloys.
Network intrusion classification for IoT networks using an extreme learning machine
Authors: Akuthota Uday Chandra , Bhargava Lava
Published: May 2024

The detection of intrusions has a significant impact on providing information security, and it is an essential technology to recognize diverse network threats effectively. This work proposes a machine learning technique to perform intrusion detection and classification using multiple feature extraction and testing using an Extreme learning machine (ELM). The model is evaluated on the two network intrusion datasets (NSL-KDD and UNSW-NB15), which consist of real-time network traffic. The arithmetic, gradient, and statistical features were extracted and evaluated with the proposed model. The method’s efficacy is assessed using accuracy, sensitivity, specificity, precision, and F1-score. The proposed method achieves 94.5%, 97.61%, 96.91%, 96.51%, and 97.05% accuracy, sensitivity, specificity, precision, and F1-score for NSL-KDD and 94.3%, 98,36%, 99.31%, 99.67% and 99.01% of accuracy, sensitivity, specificity, precision and F1-score for the UNSWNB-15 dataset respectively, which is better performance outcomes when compared to other existing works.
Is hepatic GABA transaminase a promising target for obesity and epilepsy treatments?
Authors: Kumrungsee Thanutchaporn
Published: May 2024

γ-Aminobutyric acid (GABA) transaminase (GABA-T) is a GABA-degrading enzyme that plays an essential role in regulating GABA levels and maintaining supplies of GABA. Although GABA in the mammalian brain was discovered 70 years ago, research on GABA and GABA-T has predominantly focused on the brain. Notwithstanding the high activity and expression of GABA-T in the liver, the exact functions of GABA-T in the liver remain unknown. This article reviews the up-to-date information on GABA-T in the liver. It presents recent findings on the role of liver GABA-T in food intake suppression and appetite regulation. Finally, the potential functions of liver GABA-T in other neurological diseases, natural GABA-T inhibitors, and future perspectives in this research area are discussed.
SGCLDGA: unveiling drug–gene associations through simple graph contrastive learning
Authors: Fan Yanhao , Zhang Che , Hu Xiaowen , Huang Zhijian , Xue Jiameng , Deng Lei
Published: May 2024

Drug repurposing offers a viable strategy for discovering new drugs and therapeutic targets through the analysis of drug–gene interactions. However, traditional experimental methods are plagued by their costliness and inefficiency. Despite graph convolutional network (GCN)-based models’ state-of-the-art performance in prediction, their reliance on supervised learning makes them vulnerable to data sparsity, a common challenge in drug discovery, further complicating model development. In this study, we propose SGCLDGA, a novel computational model leveraging graph neural networks and contrastive learning to predict unknown drug–gene associations. SGCLDGA employs GCNs to extract vector representations of drugs and genes from the original bipartite graph. Subsequently, singular value decomposition (SVD) is employed to enhance the graph and generate multiple views. The model performs contrastive learning across these views, optimizing vector representations through a contrastive loss function to better distinguish positive and negative samples. The final step involves utilizing inner product calculations to determine association scores between drugs and genes. Experimental results on the DGIdb4.0 dataset demonstrate SGCLDGA’s superior performance compared with six state-of-the-art methods. Ablation studies and case analyses validate the significance of contrastive learning and SVD, highlighting SGCLDGA’s potential in discovering new drug–gene associations. The code and dataset for SGCLDGA are freely available at https://github.com/one-melon/SGCLDGA.
‘Violence is completely normal’: Managing Violence Through Narrative Normalization
Authors: Storm-Mathisen Frøja
Published: May 2024

This article introduces the concept ‘narrative normalization of violence’ as a theoretical framework for exploring the interplay between crime and marginality in street culture. Drawing from 4 months of ethnographic observations and 24 qualitative interviews with young men involved in a violent street culture in Oslo, Norway, the study identifies three prevalent narratives. The first, ‘Part of the game’, minimizes the danger of violence; the second, ‘It’s all about respect’, internalizes violence as part of a desired subcultural identity; and the third, ‘We come from concrete’, emphasizes the importance of belonging. In distinctive and important ways these narratives shape collective energies that influence beliefs, attitudes and aspirations, which work to narratively render the exceptional nature of violence manageable and mundane.
Data-Driven Patient clusters of Type 2 Diabetes May Help to Identify Patients at Risk and Predict Metabolic Surgery Outcomes on Diabetes Remission and NAFLD Pregression
Authors: Poljo A , Klasen J M , Süsstrunk J , Kraljević M , Peterli R , Müller-Stich B P , Billeter A T
Published: May 2024

Background

Precision medicine and customized medicine have gained enormous attention in recent years, especially in the treatment of type 2 diabetes (T2D). Different subgroups of diabetes have been identified by research employing data-driven cluster analysis, each with a unique diabetes progression and complication risk (Ahlqvist et al., Lancet Diabetes Endocrinol. 2018).

Aims

We aimed to apply the proposed cluster analysis to a patent population post metabolic surgery and investigate the association with T2D remission and presence of NAFLD.

Methods

We retrospectively linked newly defined clusters to metabolic surgery outcomes in 53 T2D patients. Utilizing k-means and hierarchical clustering, three clusters emerged based on glutamate decarboxylase antibodies, age, BMI, HbA1c, and homoeostatic model assessment estimates of β-cell function (HOMA2-B%) and insulin resistance (HOMA2-IR). Intraoperative liver biopsies assessed nonalcoholic fatty liver disease (NAFLD) presence differentiating between simple steatosis (NAFL) and steatohepatitis (NASH). Clinical and biochemical data were collected over two years, focusing on T2D remission and NAFLD improvement.

Results

Cluster 1, characterized by the lowest BMI, highest NASH rate, impaired beta-cell function, and increased insulin resistance, displayed a favorable response to surgery, indicating robust regeneration of beta-cells. Despite increased insulin production, T2D remission was surprisingly low at 44.0% after one year, in contrast to 75.00% in Cluster 2 and 100.00% in Cluster 3. Metabolic surgery notably reduced insulin resistance and promoted NASH remission, evidenced by a significant reduction in a non-invasive NASH detection score and liver enzyme levels across all three clusters.

Conclusion

Our findings suggest that patients in Cluster 1 already show a lack of beta-cell compensation being associated with a higher prevalence of NAFLD and poorer diabetic control and therefore especially might benefit from an earlier intervention. Data-driven classification might help to customize treatment plans and identify patients at higher risk of problems at diagnosis.
Characterization of Colon Anastomosis Healing in Obese Mice
Authors: Delaune V , Lacotte S , Bouroumeau A , Bornand A , Slits F , Gex Q , Buchs N C , Toso C
Published: May 2024

Background

Colon anastomosis leak is the most feared complication in colorectal surgery, with high morbidity and mortality. Despite the identification of correctible risk factors, its incidence has remained stable for the past 50 years. One of the risk factors is obesity, a systemic disease whose prevalence is continuously increasing worldwide. To understand the implicated mechanisms, and to develop therapeutic strategies, characterization of colon anastomosis healing in obese subjects is mandatory.

Aims

We aimed to describe the colon anastomotic healing process in obese mice, with a secondary aim to identify potential targets to decrease post-operative leaks.

Methods

Three groups of mice were fed different diets for 16 weeks: normal diet only (ND), high-fat diet reverted to normal diet on day of surgery (HF-ND), or high-fat diet only (HF-HF). Surgery consisted of left colon hemi-transection on the anti-mesenteric wall, and subsequent anastomosis with separate stitches. N=5 mice from each group were sacrificed at days 3, 5, 7, 10 and 14 after surgery.

Results

HF-HF mice had diarrhea and lost weight up to day 10 after surgery, compared to day 1 for ND mice. Overall, abscess rate was 4% in ND and HF-ND, and 8% in HF-HF mice. Free leak rate was 0% in ND and HF-ND, and 16% in HF-HF mice (p=0.03). Angiogenesis was decreased in HF-HF mice at day 5 compared to ND mice (p=0.02).

Conclusion

Obese mice undergoing continued high-fat diet (HF-HF) globally demonstrated worst outcomes after colon anastomosis with increased leak rates, and decreased angiogenesis. Despite having similarly low angiogenesis, these results seem to be mitigated in high-fat diet fed mice reverting to normal diet on day of surgery (HF-ND), hinting towards an involvement of gut microbiota. Further analysis of gut microbiota and angiogenesis pathways are warranted in order to determine therapeutic strategies.
Circumscribed Thinning of the Calvaria - A Long-Term Sequela After Vacuum Extraction Delivery
Authors: Liniger B
Published: May 2024

Background

Vacuum extraction deliveries are associated with a number of complications like injuries to the skin, subperiosteal, subgaleal and intracranial hemorrhages. Even skull fractures have been described, but data on persistent changes in the bone structure of the skull like thinning of the calvaria is lacking in the literature.

Aims

We describe a previously unreported long-term sequela of vacuum extraction delivery.

Methods

We present a series of 8 children, who were referred because of an irregularity of the cranial surface without other symptoms. The investigations revealed a circumscribed thinning of the calvaria in all 8 cases. Detailed history and the specific clinical findings were crucial in the assessment. Various imaging techniques were used to visualize the lesions and rule out some differential diagnoses.

Results

All children had undergone a vacuum-assisted delivery. All irregularities of the cranial surface were discovered incidentally. Clinical examination revealed a round (6) or linear (1) channel-shaped indentation of the calvaria in 7 cases. The shape and size of the annular thinning of the calvaria matched devices commonly used in vacuum extraction very well. In one patient, a localized protrusion of the calvaria was investigated, but an indentation more posteriorly was detected in the CT scan. CT scan was performed in 6 patients, in 2, parents refused this examination. In the follow-up, no progression or symptoms was observed in any of the patients.

Conclusion

Such long-term sequelae after vacuum-assisted delivery have not been reported yet and the underlying mechanism is unclear. In children who present with irregularities of the cranium, an accurate history, including the mode of birth, and detailed clinical examination should be performed. Knowledge about the presented pathology may help to avoid extensive investigations, particularly CT scan. The publication of further cases could help to propagate the circumscribed thinning of the calvaria after vacuum extraction as a distinctive clinical entity.
New Diagnostic-Based Systematic Classification for Skier's Thumb Injuries: A Revision That is Needed
Authors: Strohmaier A , Wirtz C , Krafft L , Häfeli M
Published: May 2024

Background

Acute injuries to the ulnar collateral ligament (UCL) of the first metacarpophalangeal joint (MCPj), commonly referred to as Skier’s thumb injuries, can be further categorized into different types based on bone lesions and joint instability. However, none of the existing classifications encompasses all types and combinations of injuries. A unified classification system that provides direct treatment recommendations for each type is required, particularly for cases with no clear indications.

Aims

To develop a new classification system for acute UCL injuries of the first MCPj that comprehensively defines all possible combinations and types of injuries and facilitates treatment decision-making for each specific type in daily clinical practice.

Methods

The retrospective study included patients with acute UCL lesions who underwent conservative or operative treatment at our clinic between 2018 and 2023. This classification addresses ligamentous or osseous lesions, fracture fragment size and dislocation, ligament configuration (e.g. Stener lesions), and joint stability. Correlated radiography, ultrasonography, MRI, and intraoperative findings were used to define all combinations and variants of skier`s thumb injuries. Pre-therapeutic joint stability was characterized according to the criteria established in the literature. Dislocation criteria for bone lesions were defined in a preliminary observer trial. The classification was applied by three hand surgeons with different training levels. Treatment applied and a 3-months follow-up was documented.

Results

In 213 patients with acute UCL tears, the new classification was consistently applied, and the treatment derived was largely aligned with the recommendations in the literature for both absolute and relative indications for splint or operative therapy. The vast majority of the patients were stable after 3 months.

Conclusion

This new classification is the first to combine the clinical and radiological aspects of skier`s thumb injuries into one classification and encompasses all variants. It is comprehensive, can be easily applied retrospectively, and provides clear treatment recommendations in most cases.
Decoding the Clavien-Dindo Classification: Artificial Intelligence (AI) as a Novel Tool to Grade Postoperative Complications
Authors: Staubli S , Walker H L , Saner F , Salinas C H , Broering D C , Malago M , Spiro M , Raptis D A
Published: May 2024

Background

The CDC standardizes grading of postoperative complications. However, consistent, and precise application in dynamic clinical settings is challenging. AI offers a potential solution for efficient automated grading.

Aims

To assess ChatGPT’s capability of grading postoperative complications using the Clavien-Dindo classification (CDC) via Artificial Intelligence (AI) with Natural Language Processing (NLP).

Methods

ChatGPT's accuracy in defining the CDC, generating clinical examples, grading complications from existing scenarios, and interpreting complications from fictional clinical summaries, was tested.

Results

ChatGPT 4 precisely mirrored the CDC, outperforming version 3.5. In generating clinical examples, ChatGPT 4 showcased 99% agreement with minor errors in urinary catheterization. For single complications, it achieved 97% accuracy. ChatGPT was able to accurately extract, grade, and analyze complications from free text fictional discharge summaries.

Conclusion

ChatGPT 4 demonstrates promising proficiency and accuracy in applying the CDC. In the future, AI has the potential to become the mainstay tool to accurately capture, extract, and analyze CDC data from clinical datasets.
New Generation Superior Single Plating versus Low-Profile Dual Mini-Fragment Plating of Diaphyseal Clavicle Fractures - A Biomechanical Study
Authors: Pastor T , Pastor T , Zderic I , Berk T , Souleiman F , Vögelin E , Beeres F , Gueorguiev B
Published: May 2024

Background

Recently, a new generation of superior clavicle plates was developed featuring the variable-angle locking technology for enhanced screw positioning and optimized plate-to-bone fit design. On the other hand, mini-fragment plates used in dual plating mode have demonstrated promising clinical results. However, these two bone-implant constructs have not been investigated biomechanically in a human cadaveric model.

Aims

To compare the biomechanical competence of single superior plating using the new generation plate versus dual plating with low-profile mini-fragment plates.

Methods

Sixteen paired human cadaveric clavicles were assigned pairwise to two groups for instrumentation with either a 2.7 mm Variable Angle Locking Compression Plate placed superiorly (Group 1), or with one 2.5 mm anterior plate combined with one 2.0 mm superior matrix mandible plate (Group 2). An unstable clavicle shaft fracture AO/OTA15.2C was simulated by means of a 5 mm osteotomy gap. All specimens were cyclically tested to failure under craniocaudal cantilever bending, superimposed with bidirectional torsion around the shaft axis and monitored via motion tracking.

Results

Initial stiffness was significantly higher in Group 2 (9.28±4.40 N/mm) compared to Group 1 (3.68±1.08 N/mm), p=0.003. The amplitudes of interfragmentary motions in terms of craniocaudal and shear displacement, fracture gap opening, and torsion were significantly bigger over the course of 12500 cycles in Group 1 compared to Group 2; p≤0.038. Cycles to 2 mm shear displacement were significantly lower in Group 1 (22792±4346) compared to Group 2 (27437±1877), p=0.047.

Conclusion

From a biomechanical perspective, low-profile 2.5/2.0 dual plates demonstrated significantly higher initial stiffness, less interfragmentary movements, and higher resistance to failure compared to 2.7 single superior variable-angle locking plates and can therefore be considered as a useful alternative for diaphyseal clavicle fracture fixation especially in unstable fracture configurations.
Reconstruction Techniques and Associated Morbidity after Minimally Invasive Gastrectomy for Cancer – Insights from the GastroBenchmark and GASTRODATA databases
Authors: Schneider M , Kim J , Berlth F , Sugita Y , Grimminger P , Baiocchi G L , de Manzoni G , Bencivenga M , Nunobe S , Consortium T G , Consortium T G , Yang H K , Gutschow C A
Published: May 2024

Background

Various anastomotic and reconstruction techniques are used to restore intestinal continuity after minimally invasive total (TG) and subtotal distal gastrectomy (DG).

Aims

Their effects on anastomotic leakage and postoperative morbidity have not been extensively studied.

Methods

Patients after minimally invasive TG and DG were selected from a cohort of 9356 oncological gastrectomies performed between 2017-2021 in 44 specialized centers.

Results

Three anastomotic techniques (circular stapled (CS, 3.7%); linear stapled (LS, 93.8%); hand sewn (HS, 2.5%)) and three types of bowel reconstruction (Roux (RX, 51.5%); Billroth I (BI, 23.1%); Billroth II (BII, 25.4%)) were identified after TG (n=878) and DG (n=3334). Postoperative morbidity was higher after TG compared to DG (AL 5.2% vs. 1.1%, p≤0.001; 90-day mortality 1.6% vs. 0.4%, p≤0.001; overall morbidity 28.6% vs. 16.3%, p≤0.001; major morbidity 15.4% vs. 8.0%, p≤0.001).

Anastomotic leakage rate in the TG cohort was higher after CS (13.1%) and HS (7.9%) than after LS anastomoses (1.9%, p<0.001). Similarly, overall (CS: 43.9%, HS: 28.6%, LS: 23.1%) and major complications rates (CS: 25.2%, HS: 11.1%, LS: 12.0%) as well as mortality (CS: 4.7%, HS: 2.2%, LS: 0.8%) were higher after CS. Multivariate analysis confirmed anastomotic technique as a predictive factor for anastomotic leakage (Fig. 1), but not for occurrence of mortality, overall and major complications.

In the DG cohort, most (98.7%), outcomes were similar for all types of bowel reconstruction: Anastomotic leakage (BI: 1.4%, BII 0.8%, RX 1.2%, p=0.440), 90-day mortality (BI: 0%, BII 0.1%, RY: 1.1%%, p=0.109), overall (BI: 14.5%, BII: 15.0%, RX: 18.7%, p=0.208) and major morbidity (BI: 7.9%, BII: 9.1%, RX: 7.2%, p=0.219).

Conclusion

In suitable situations, DG should be preferred to TG, as postoperative morbidity is significantly lower. In addition, LS should be the preferred method of anastomosis after TG. Conversely, the techniques for bowel reconstruction can be chosen according to the surgeon's preference.
Endovascular Treatment of Complex Aortic Aneurysms Using Inner Branch Device (IBEVAR): A Single Center Experience
Authors: Déglise S , Longchamp J , Ricciardi P , Côté E , Trunfio R , Deslarzes-Dubuis C
Published: May 2024

Background

Due to advances in devices and techniques, the endovascular approach using fenestrated or branched endografts has emerged as a valid and safe alternative for patients with complex aortic aneurysms, especially if considered at high risk for surgery. The use of inner branch devices (iBEVAR) combining benefits of fenestrations and outer branches could offer an ideal configuration in this context.

Aims

The aim of our study was to report our monocentric experience with iBEVAR in the treatment of complex aortic aneurysms.

Methods

A retrospective analysis of prospective data retrieved from 1 center between January 2020 and January 2024 was done. Endpoints were immediate technical success, postoperative morbidity, rate of re-intervention and mortality.

Results

During this period, 72 patients with a mean age of 68.5 years (range 41-88) were identified. The maximum preoperative mean aortic diameter was 56 mm (44-71 mm). The majority of patients was asymptomatic. For diffuse thoraco-abdominal aortic aneurysms, a 2-steps procedure was used. There were 34 off-the-shelf E-nside (47%) and the remaining 38 patients were treated with a custom-made Extra-Design graft (53%). Despite successful endograft deployment in all patients and branch catheterization in 69/72 cases (96%), the technical success was 94% due to an additional open conversion for ilio-mesenteric bypass. The 30-days mortality was 5.5%.

During the post-operative period, 19% of patients presented complications with 1 case of mesenteric ischaemia requiring a visceral resection and 2 cases of paralytic ileus, treated conservatively. 5 cases (6.9) of spinal cord ischemia were observed. During the median follow-up, 22 patients (31%) had a re-intervention, for endoleaks, bridging-stent events or limbs problems. The overall target vessel patency was 94%.

Conclusion

The use of iBEVAR appears to be safe and effective for the treatment of complex aortic aneurysms with an acceptable rate of complications. Strict follow-up is mandatory and about one-third of patients required a re-intervention. Further patients and longer follow-up are needed.
The implications of amyloid-β pathology: only time will tell
Authors: Coomans Emma M , Ossenkoppele Rik
Published: May 2024

This scientific commentary refers to ‘Characterizing brain tau and cognitive decline along the amyloid timeline in Alzheimer’s disease’ by Cody et al. (https://doi.org/10.1093/brain/awae116).
Breakthrough Invasive Fungal Infections in Patients With High-Risk Hematological Disorders Receiving Voriconazole and Posaconazole Prophylaxis: A Systematic Review
Authors: Boutin Catherine-Audrey , Durocher Florence , Beauchemin Stéphanie , Ziegler Daniela , Abou Chakra Claire Nour , Dufresne Simon Frédéric
Published: May 2024

Background

Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis.

Methods

We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023.

Results

We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%.

Conclusions

In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management.
Degenerative mitral regurgitation due to flail leaflet: sex-related differences in presentation, management, and outcomes
Authors: Avierinos Jean-Fançois , Tribouilloy Christophe , Bursi Francesca , Grigioni Francesco , Vanoverschelde Jean-Louis , Resseguier Noémie , Théron Alexis , Pasquet Agnes , Pradier Julie , Biagini Elena , Barbieri Andrea , Michelena Hector , Benfari Giovanni , Rusinaru Dan , Zaffran Stéphane , Vancraeynest David , Collart Fréderic , Bohbot Yohann , Essayagh Benjamin , Enriquez-Sarano Maurice
Published: May 2024

Background and Aims

Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes.

Methods

In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up.

Results

At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27–1.65), P < .001] but was higher in females [SMR 2.00 (1.67–2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04–1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14–2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02–1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16–1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85–0.99), P = .036].

Conclusions

Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.
ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events
Authors: De Luca Leonardo , Pugliese Francesco Rocco , Susi Beniamino , Navazio Alessandro , Corda Marco , Fabbri Andrea , Scicchitano Pietro , Voza Antonio , Vanni Simone , Bilato Claudio , Geraci Giovanna , Gabrielli Domenico , Grimaldi Massimo , Colivicchi Furio , De Iaco Fabio , Oliva Fabrizio
Published: May 2024

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists (Associazione Nazionale Medici Cardiologi Ospedalieri) and the Italian Society of Emergency Medicine (Società Italiana di Medicina d’Emergenza-Urgenza) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events.
PREVALENCE OF WILD–TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS IN ELDERLY SUBJECTS FROM THE GENERAL POPULATION
Authors: Aimo A , Vergaro G , Castiglione V , Fabiani I , Barison A , Gentile F , Ferrari Chen Y , Giorgetti A , Genovesi D , Buda G , Franzini M , Moscardini S , Rapezzi C , Fontana M , Passino C , Emdin M
Published: May 2024

Background

Wild–type transthyretin cardiac amyloidosis (ATTRwt–CA) affects older adults, and is currently considered as a rare disorder.

Objective

We investigated for the first time the prevalence of ATTRwt–CA in elderly individuals from the general population.

Methods

General practitioners from Pisa, Italy, proposed a screening for ATTRwt–CA to all their patients aged 65–90 years, until 1,000 accepted. The following red flags were searched: interventricular septal thickness ≥12 mm, any echocardiographic, ECG or clinical hallmark of CA, or high sensitivity–troponin T ≥14 ng/L. Individuals with at least one red flag (n=346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted.

Results

Four patients received a non–invasive diagnosis of ATTRwt–CA. All complained of dyspnoea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (grade 3), left ventricular (LV) wall thickening, grade 2 to 3 diastolic dysfunction, and N–terminal pro–B–type natriuretic peptide (NT–proBNP) >1,000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT–proBNP <300 ng/L. The prevalence of ATTR–CA in subjects ≥65 years was calculated as 0.46% (i.e., 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2).

Conclusions

ATTRwt–CA has a prevalence of 0.46% in elderly subjects from the general population.
A CASE OF LEFT ACCESSORY PATHWAY ABLATION IN A PATIENT WITH PERSISTENT LEFT SUPERIOR VENA CAVA AND ABSENCE OF RIGHT SUPERIOR VENA CAVA
Authors: Biagi A , Rossi L , Bolognesi M , Aschieri D
Published: May 2024

Introduction

A 31–year old man was admitted in our emergency department for palpitation. A 12–lead electrocardiogram (EKG) showed a well tolerated regular narrow–QRS tachycardia. A bolus of 6mg + 12 mg of adenosine was administered with only temporary resolution of arrhythmia; subsequently an electric cardioversion was performed with restoration of sinus rhythm. A baseline EKG showed no sign of pre–excitation.

Electrophysiological Study

A decapolar magnetic sensor–based catheter integrated with the electroanatomical mapping system was inserted through the right femoral vein and advanced in the right atrium (RA) where geometry reconstruction of this chamber was obtained (Figure 1). The catheter was easily advanced in the coronary sinus that appeared dilatated but failed to progress in the right superior vena cava. A venography was performed and confirmed the diagnosis of persistence left superior vena cava (PLSVC) and absence of right superior vena cava. Two quadripolar catheters were advanced and positioned respectively at His bundle (HIS) and in the right ventricular apex (RVA). During pacing from right ventricular (RV) apex an eccentric retrograde atrial activation was shown. After isoprenaline infusion during atrial programmed stimulation an atrioventricular reentry tachycardia was induced. An intracardiac ecocardiography (ICE) connected with CARTO3 was positioned in the RA. Atrial septal puncture was performed with ICE guidance and an 8.5F sheet was advanced in left atrium. Activation mapping during pacing from RVA showed maximum VA fusion at the postero–lateral localization. An open–irrigate contact force catheter (Smartouch SF; Biosense Webster, Inc., Irvine, California, USA) was inserted; multiple radiofrequency application with 30–35W were applied with resolution of the accessory pathway (Figure 2).

Conclusion

PLSVC is the most frequent congenital abnormality of the thoracic venous system. The prevalence of this condition is variable and range between a 0.2% and a 3% in the general population. This condition is generally asymptomatic and is accidentally found during procedure. In up to 90% of the cases, the right superior vena cava (RSVC) accompanies PLSVC. In a minority of cases RSVC failed to developed resulting in isolated PLSV. The identification of PLSVC and the absence of RSVC during electrophysical study is crucial. For the purpose of a correct and safe transeptal puncture the use of intracardiac ultrasound is mandatory.
VALIDATION OF QUANTITATIVE FLOW RATIO DERIVED VIRTUAL ANGIOPLASTY WITH POST–ANGIOPLASTY FRACTIONAL FLOW RESERVE. THE QIMERA–I STUDY
Authors: Marengo G , Amat Santos I , Cortes Villar C , Doronzo M , De Benedictis M , Barbero U , Moncalvo C
Published: May 2024

Backgroud

Quantitative flow ratio (QFR) virtual angioplasty with pre–PCI residual QFR showed better results compared with angiographic approach to assess post–PCI functional results. However correlation with pre–PCI residual QFR and post–PCI fractional flow reserve (FFR) is lacking.

Methods

Multicenter prospective study including consecutive patientswith angiographically 50–90% coronary lesions and positive QFR result. All patients were evaluated with QFR, hyperemic and non–hyperemic pressure ratios (NHPR) before and after the index PCI. Pre–PCI residual QFR (virtual angioplasty) was calculated and compared with post–PCI fractional flow reserve (FFR), QFR and NHPR.

Results

A total of 84 patients with 92 treated coronary lesions were included, with a mean age of 65.5±10.9 years and 59% of single vessel lesion being the left anterior descending artery in 69%. The mean vessel diameter was 2.82±0.41 mm. Procedural success was achieved in all cases, with a mean number of implanted stents of 1.17±0.46. Baseline QFR value was 0.69 ± 0.12 and baseline FFR and NHPR were 0.73 + 0.08 and 0.82 + 0.11, respectively. Mean post–PCI FFR increased to 0.87 ±0.05 whereas residual QFR had been estimated as 0.95 ± 0.05 showing poor correlation with post–PCI FFR (0.163; 95%CI:0.078–0.386) and a low diagnostic accuracy (30.9%, 95%CI:20–43%).

Conclusions

In this analysis, the results of QFR–based virtual angioplasty did not seem to accurately correlate with post–PCI FFR.
AORTIC PERIVASCULAR ATTENUATION ON CHEST COMPUTED TOMOGRAPHY ANGIOGRAPHY AND MARFAN SYNDROME
Authors: Tuttolomondo D , Gaibazzi N , Pini A , Secchi F
Published: May 2024

Introduction

Marfan syndrome (MFS, OMIM #154700) is an autosomal dominant inherited disorder with a prevalence in the general population of about 3/10,000. It mainly affects connective tissue due to mutations in the FBN1 gene (15q21.1) that codes for fibrillin–1. The prognosis of patients with MFS is dominated by the high risk of aortic dissection or rupture. Peri–vascular adipose tissue attenuation (PVAT) applied to thoracic angioTC (CTA) is a marker of localised vascular inflammation that is greater in ascending aortic aneurysm than in healthy controls and is associated with in–situ increase of fibrotic tissue. In patients with MFS there is excessive deposition of collagen and proteoglycans with increased wall stiffness that could be identified by PVAT analysis prior to aneurysm development.

Material

We enrolled 54 consecutive patients with a genetic diagnosis of MFS undergoing control CTA and 43 subjects at low cardiovascular risk undergoing CTA for chest pain.

Exclusion Criteria

Presence of aortic pathology; presence of at least one cardiovascular risk factor; previous vascular surgery/cardiac surgery; ischaemic cardiovascular pathology; presence of significant coronary atherosclerotic pathology; current or previous neoplasm; chronic inflammatory/infectious diseases.

Results

There were no statistically significant differences in age, gender and diameter of the ascending aorta between patients in the MFS group and controls. In contrast, PVAT in the ascending aorta appears greater in patients diagnosed with MFS (p<0.001).

Conclusion

In MFS patients with a normal aortic diameter the degree of vascular fibrosis estimated by PVAT is greater than in healthy controls; PVAT may therefore play a role in the MFS diagnostic process, allowing a potential economic benefit.
INDEPENDENT EFFECT OF SGLT2I ON DIASTOLIC FUNCTION IN HFREF POPULATION
Authors: Stracqualursi M , Nemola G , Moscardelli S , Santangelo G , Buratti S , Losito M , Bursi F , Guazzi M
Published: May 2024

Background

Scientific literature reinforces the role of diastolic dysfunction in patients with heart failure with reduced ejection fraction (HFrEF) as an independent prognostic indicator of all–cause mortality. In this context, E/e’ ratio plays a central role in diastolic dysfunction assessments and diagnosis. Despite the introduction of several novel medical therapies for HFrEF that led to improvement in mortality and HF hospitalization, the effect of the combined treatment with Sacubitril/Valsartan (SV) and Sodium Glucose Transporter 2 inhibitors (SGLT2i) on E/e’ ratio has not been addressed yet.

Aim

We aimed to evaluate the effect of SV alone vs SV+SGLT2i on E/e’ ratio in a real–life population of HFrEF outpatients.

Methods

This is an observational monocentric study including patients treated with either SV alone or with SV+SGLT2i from 2018 to 2023. E/e’ ratio was measured at baseline, at 6 and 12 months.

Results

178 HFrEF patients (mean age 69 years±11, left ventricular ejection fraction (LVEF) 31±6%) in optimal medical therapy were enrolled. 121 of them received SV and 58 received SV+SGLT2i. Baseline E/e’ ratio was similar in the two groups (median value 11,2 [IQR 8;16] in SV group and 10,9 [IQR 8;16] in SV+SGLT2i group, p=0.45). At follow up, only SV+SGLT2i group showed a significative decrease in E/e’ ratio after therapy initiation while SV group showed a E/e’ ratio similar to baseline (E/e’ ratio median value 8,5 [IQR 7;12] vs 11,8 [IQR 8;15] respectively, p=0.035). Moreover, after 12 months most patients receiving SV+SGLT2i didn‘t required diuretic administration compared to those treated with only SV (43% vs 16% respectively; p=0,0002).

Conclusions

Among patients with HFrEF, treatment with SGLT2i+SV was associated with a significative reduction of E/e’ ratio and of diuretic administration. This result might suggest a favorable independent effect of SGLT2i on diastolic function and myocytes relaxation and might provide new evidence on the positive results observed on hard endpoints.
IN–HOSPITAL CHANGES OF PLASMA TRIMETHYLAMINE N–OXIDE (TMAO) LEVELS PREDICTS MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: Aleksova A , Fluca A , Stornaiuolo M , Pani B , Derin A , Pierri A , D‘Errico S , Novellino E , Sinagra G , Janjusevic M
Published: May 2024

Background

Trimethylamine N–oxide (TMAO), a gut microbiota–dependent metabolite, originates from choline, L–carnitine and phosphatidylcholine metabolism. It is abundant in animal–derived foods like red meat, and egg yolk. TMAO plays a crucial role in cardiovascular diseases (CVDs), altering lipid metabolism and endothelial function, inducing oxidative stress, platelet reactivity, inflammation, and arteriosclerosis.

Aim and Methods

Given the high mortality rate of CVDs patients, it is necessary to improve strategies to optimize stratification risk protocols. Previous studies about the impact of TMAO on outcomes relying on a singular measurement had yielded conflicting results. This study aims to assess the impact of in–hospital TMAO fluctuations in individuals with acute myocardial infarction (AMI). Blood samples from AMI survivors were obtained on admission and discharge. The endpoint was a three–point major adverse cardiovascular events (MACE) composed as all–cause mortality, reinfarction and development of heart failure.

Results

The total cohort comprised 149 AMI patients, with 77% males and a mean age of 64(11) years. Main pro–atherosclerotic risk factors included dyslipidaemia (51%) and hypertension (54.4%). Median TMAO values were significantly higher on admission than discharge (7.81[3.47–19.98] vs. 3.45[2.3–4.78] μM, respectively, p<0.01). TMAO measurements on discharge were used to determine the metabolite cut–off through continuous hazard ratio analysis, showing a linear association with values exceeding 3.45 μM and MACE incidence. The cohort was divided into two groups: low–low/high–low (LL/HL), with 75 patients (50.3%) with persistently low or initially higher and decreasing TMAO levels, and high–high/low–high (HH/LH), with 74 patients (49.7%) exhibiting consistently high or initially lower but increasing TMAO levels during hospitalization. Over the 30–months follow–up, 21.5% of patients experienced MACE. Survival analysis revealed that patients in the HH/LH group were more likely to experience the endpoint (p=0.05). Multivariate Cox analysis demonstrated that patients in the HH/LH group faced more than twice the risk of MACE compared to those in the LL/HL group, along with older age and impaired left ventricular systolic function.

Conclusions

AMI patients with consistently high or escalating TMAO levels face unfavourable outcomes. Understanding the dynamics of TMAO throughout hospitalization may be a predictive factor for patient outcomes.
CAROTID–FEMORAL PULSE WAVE VELOCITY PROGRESSION IN HYPERTENSIVE PATIENTS IS ASSOCIATED WITH SUBSEQUENT CV OUTCOMES
Authors: Maloberti A , Rebora P , Occhino G , Andreano A , Rita C , Tognola C , Toscani G , Peraro G , Morelli M , Pezzoli S , Cavalieri D‘Oro L , Russo A , Giannattasio C
Published: May 2024

Objective

Arterial stiffness (Pulse Wave Velocity – PWV) is associated with CV events and mortality. However, little is known on the relationship of its progression (ΔPWV) over time with CV outcomes. The aim of our study was to evaluate the relationship between PWV progression and all–cause mortality and CV events in hypertensive subjects.

Methods

We enrolled 402 consecutive hypertensive outpatients. At baseline anamnestic, clinical, BP, laboratory data and PWV were assessed. We performed a PWV follow–up examination at a median time of 3.7±0.5 years. Patients were subsequently followed for a median time of 10.1 (IQR 9.5 –10.5) years recording all–cause mortality and CV events.

Results

At baseline the mean age was 53.2±13.0 years, SBP and DBP were 141.8±17.5 and 86.8±10.5 mmHg and PWV was 8.5±1.9 m/s. Despite an improvement in BP control (–9.2±19.5 and –8.0±12.3 for SBP and DBP respectively), at follow–up the population showed a PWV increase (ΔPWV +0.6±1.9 m/s). Progressors (ΔPWV ≥ 0.5 m/s, 204 patients, 50.7%) had a significantly lower survival probability and higher cumulative incidence of composite events, while no differences were seen for CV events (unadjusted analysis). At cox multivariable analysis neither ΔPWV ≥ 0.5 m/s (progressors) nor ΔPWV (as a spline function) were associated with CV events and with all–cause mortality. However, the association with survival probability and cumulative incidence of CV events, as a composite outcome, was significant (HR = 2.32, 95% CI: 1.33 – 4.04, p=0.003).

Conclusions

In conclusion, our study shows that PWV progression of at least 0.5 m/s is frequent in hypertensive patients and that it is associated with a significantly higher risk of developing CV events or dying (composite outcome).
NSTEMI OR AL CARDIAC AMYLOIDOSIS: ALL IS NOT AS IT SEEMS
Authors: Starnazzi F , Dei L , Trambaiolo P , D‘Ambrosi A , Granatelli A , Romano S , Sciarra L
Published: May 2024

Background

Light–chain amyloidosis (AL) is caused by misfolded light chains produced by a small B–cell clone in bone marrow, that aggregate in plasma and deposit in various tissue, included the heart. The progressive nature of the disease and the high mortality rate within 6 months of diagnosis makes early diagnosis very important.

Clinical Case

A 64–year–old patient presented to the Emergency Room (ER) with shortness of breath for a month and externally positive exercise test for symptoms without ECG alterations. The ECG performed in the ER diffuse low voltages with no repolarization abnormalities. Laboratory tests showed an increase in Troponin I| from 0.658 to 0.669 ng/ml (normal range <0.012) and elevated NTproBNP at 7080 pg/ml. The electrophoresis profile indicated MGUS, known since 2015.The patient was admitted to the Intensive Cardiac Unit (ICU) with a diagnosis of NSTEMI. The medical history revealed a family history of Chronic Coronary Syndrome (CCS) and hypertension. Home therapy included beta–blockers and Angiotensin Receptor Blockers (ARBs). Upon admission to ICU, the patient was asymptomatic. Coronary angiography revealed dual stenosis of the anterior descending coronary artery and was treated by dual drug eluting stent. The patient‘s symptoms remained unchanged. A single subsequent episode of paroxysmal dyspnea occurred. An echocardiogram conducted in the EchoLab raised suspicion of cardiac amyloidosis. Hematological exams to assess a possible AL type showed positive results. The patient underwent a bone marrow aspirate because the hematologists were unable to perform a biopsy due to the concomitant dual antiplatelet therapy. We are currently waiting for the histological results to start chemotherapy.

Conclusions

An early suspicion of amyloidosis could have aided in established the correct timing for angioplasty and double anti–aggregation. This clinical case requires a multidisciplinary approach between cardiologists and hematologists, especially given the very high mortality within a few months of diagnosis.