2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.

Computational methods meet in vitro techniques: A case study on fusaric acid and its possible detoxification through cytochrome P450 enzymes.

Mycotoxins are known environmental pollutants that may contaminate food and feed chains. Some mycotoxins are regulated in many countries to limit the trading of contaminated and harmful commodities. However, the so-called emerging mycotoxins are poorly understood and need to be investigated further. Fusaric acid is an emerging mycotoxin, noxious to plants and animals, but is known to be less toxic to plants when hydroxylated. The detoxification routes effective in animals have not been elucidated yet. In this context, this study integrated in silico and in vitro techniques to discover potential bioremediation routes to turn fusaric acid to its less toxic metabolites. The toxicodynamics of these forms in humans have also been addressed. An in silico screening process, followed by molecular docking and dynamics studies, identified CYP199A4 from the bacterium Rhodopseudomonas palustris HaA2 as a potential fusaric acid biotransforming enzyme. Its activity was confirmed in vitro. However, the effect of hydroxylation seemed to have a limited impact on the modelled toxicodynamics against human targets. This study represents a starting point to develop a hybrid in silico/in vitro pipeline to find bioremediation agents for other food, feed and environmental contaminants.

Duct Stenting in Duct-Dependent Systemic Blood Flow, Past, Present, and Future.

Arterial duct stenting, pioneered in the early 1990s for newborns with a duct-dependent pulmonary and systemic circulation, has evolved significantly over the past decades. This progressive technique has led to the development of novel therapeutic strategies, including the Hybrid approach introduced three decades ago, and more recently, a complete transcatheter approach for treating newborns with hypoplastic left heart syndrome (HLHS). Subsequently, the transcatheter method has been extended to bi-ventricular lesions and patients with pulmonary hypertension, establishing a reverse Potts-shunt pathophysiology. Considering current experiences, this review aims to assess the strengths, weaknesses, and complications associated with ductal stenting, which represents a critical component of these complex treatment strategies. Despite advancements, the mortality rate of Norwood and Hybrid stage-1 procedures has plateaued, underscoring the importance of enhancing the quality of life of affected patients as the primary therapeutic goal. The prerequisite is a gentle, almost atraumatic medicine, particularly during the newborn period. It is essential to recognize that both the Hybrid and total transcatheter approaches demand comparable experience to Norwood surgery. Successful outcomes hinge on much more than merely inserting a stent into the duct; they require meticulous attention to detail and comprehensive management strategies.

Hybrid Dorsal Preservation Rhinoplasty: Reediting an Aesthetic Dorsum.

BACKGROUND: The prerequisite of a well-shaped dorsum with proper dorsal aesthetic lines that needs no modifications in its width and symmetry is key to letdown and push-down techniques as classically described. The common current concept is that total preservation of the middle vault is obligatory. This, however, obviously limits the indications, since nasal dorsum with natural aesthetic dorsal lines per se is relatively few. The recent, impressive, revival of letdown and push-down procedures has progressively generated numerous technical variations, but all those essentially still left the middle vault unmodified. The concept of splitting the middle vault and modifying its width and symmetry, while leaving the crucial dorsal (central) and lateral Keystone area intact, represents a new hybrid approach to the nasal dorsum. The structural benefits of classical component separation are combined with the major advantage of preserving the flexible chondro-osseous joint at the keystone junction. Osteotomies and/or osteoplasty can be done as necessary to modify the bony dorsum and at the same time any type of septal deformity can be addressed according to the time-tested L-strut principle, a Cottle septoplasty included. This hybrid approach expands indications beyond those of the conventional push-down/letdown technique, including moderate asymmetries of the bony and cartilaginous dorsum. Although splitting the middle vault along the septal T will also facilitate middle vault reshaping in cases where a full letdown procedure is indicated, this paper will clarity address only those instances where no circumferential osteotomy is done. METHODS AND MATERIALS: The dorsal bony nasal pyramid is always addressed first by rhinosculpture (osteoplasty) with piezoelectric inserts and/or burrs, in combination with different types of osteotomies as needed. This will allow narrowing of the bridge and correction of bony asymmetries. The osseous-cartilaginous connection of the central dorsal keystone area (DKA) is totally preserved. At this point, three main variations are possible: Type 1) preservation of the septal T and push-down by a high-middle septal strip resection, two different variations (1A and 1B) are possible here, Type 2) reduction in width of the septal T-segment and middle vault restoration by spreader flaps without any push-down of the septal T and Type 3) preservation of the septal T and letdown by low strip resection. CONCLUSION: Hybrid Dorsal Preservation involves concepts of Structure and Preservation Rhinoplasty. Dorsal and lateral keystone area are preserved, and the middle vault could be modified splitting the septal T in the anatomical plane, expanding patient indications and improve outcomes. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A hybrid approach for fatigue life prediction of in-service asphalt pavement.

Fatigue cracking is one of the main pavement failures, which makes accurate fatigue life prediction for the design and maintenance of asphalt pavements crucial. The majority of traditional prediction methods are based entirely on the laboratory fatigue test, without considering the field condition and maintenance data. This paper aims to propose a hybrid approach to fill this gap. The key idea is that the damage condition is back-calculated by an artificial intelligence-based finite-element (FE) model updating using field-monitoring information (data-driven component), which is used to update the parameters in the mechanistic composition-specific fatigue life prediction equation (model-driven component). The laboratory test of field cores gives the material non-destructive properties. The simulated pavement response subjected to truck loading shows good agreement with measured values, which indicates that the verified constitutive relationship could be used in the data-driven component. Furthermore, in view that the fatigue test is time- and money-consuming, this paper proposes a non-test estimation of the fatigue characteristic curve based on FE simulation of a repeated direct tension test. Three test pavement sections were employed as case studies. Results showed that the predicted fatigue life changes with the service time. At the early age, semi-rigid pavement has a larger fatigue life than flexible and inverted pavements. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.

Drug-coated balloon combined with drug-eluting stent for the treatment of coronary bifurcation lesions: insights from the HYPER study.

True coronary bifurcation lesions (CBL) represent a challenging scenario for percutaneous coronary interventions (PCI), and are associated with a higher risk of target lesion failure (TLF), particularly when two stents are implanted. A hybrid strategy combining a drug-eluting stent (DES) in the main branch, and a drug-coated balloon in the side branch may improve outcomes by reducing the total stent length while maintaining an effective anti-prolipherative action. In this sub-study of the HYPER trial, 50 patients with true CBL were treated with a hybrid strategy: procedural success was 96%, one case of peri-procedural myocardial infarction and one case of TLF (in a DES-treated segment) at 1 year were reported. This study suggests that such a hybrid strategy may be a safe and effective option for true CBL PCI, and warrants additional investigations to compare outcomes with standard of care strategies.

Successful Hybrid Approach Treatment of a Large Persistent Sciatic Artery Aneurysm-A Case Report.

Background and Objectives: Persistent sciatic artery (PSA) is a rare congenital vascular anomaly that is often asymptomatic, but can be associated with aneurysm formation and potential complications, such as thromboembolism or aneurysm rupture in some cases. We present a case of a 75-year-old woman with a symptomatic thrombus-containing aneurysm of the left PSA. Materials and Methods: The treatment of the PSA aneurysm involved a successful hybrid approach, which included open surgical bypass and endovascular embolization. The open surgical bypass was performed from the left common femoral artery to the left above-the-knee popliteal artery using a synthetic graft, while the aneurysm exclusion was achieved through endovascular plug embolization. Results: Control angiography revealed complete exclusion of the PSA aneurysm. At the 1-month follow-up, there were no palpable pulsatile masses in the left gluteal region, and the patient reported no symptoms. Conclusions: Given the high incidence of limb- and life-threatening complications associated with a PSA aneurysm, accurate diagnosis and appropriate treatment are crucial. In this case, a combination of open surgical and endovascular techniques resulted in a favorable outcome for the patient, highlighting the effectiveness of the hybrid approach in managing PSA aneurysms. Further studies are warranted to explore and refine treatment strategies for these complex vascular anomalies.

Tropicalisation of epidemiological models in Africa: A mixed and hybrid approach to better predict COVID-19 indicators.

CONTEXT: Since the outbreak of the SARS-COV2 epidemic turned into a COVID-19 pandemic, international bodies such as the WHO as well as governments have announced projections for morbidity and mortality indicators related to COVID-19. Most of them indicated that the health situation would be worrying. Although using artificial intelligence with mathematical algorithms and/or neural networks, the results of the SIR models were poorly performing and not very accurate in relation to the observed reality in the African states in general and in Senegal in particular. Hence the imperative need to configure the modelling process and approach considering local contexts. METHOD: The model implemented is a mixed prediction model based on the Bucky model developed by OCHA and adapted to the context. The construction of the mixed model was done in two steps (basic model with publicly available data, such as those from United Nations-like organisations such as OCHA or WHO for Senegal), (adding more specific data collected through the mixed epidemiological survey). This survey was conducted in Senegal in six localities (Dakar, Thies, Diourbel, Kedougou, Saint-Louis and Ziguinchor) chosen according to the number of confirmed cases of COVID-19. In total, 1000 individuals distributed in proportion to the size of the regions were interviewed in April 2021. RESULTS: The projected cases in the baseline model were already considerably higher than the cases reported in April. This may be plausible, given the low detection rates throughout Senegal during this period. However, the hybrid model predicted an even higher infection rate than the baseline, perhaps mainly due to vulnerability related to food insecurity and solid cooking fuels. This may mean that there would be more unreported cases than reported. Overall, the mortality rate of both models would be considerably lower than the government-reported mortality rate, even though the number of confirmed cases remains high. This may be an underestimate of the death rate. CONCLUSION: An accurate and reliable prediction in times of epidemics and/or pandemics, such as COVID-19, should be based on mixed or hybrid data integrating a quantitative and qualitative approach to enable better policymaking. The projections resulting from this approach would still be effective and would take better account of local realities and contexts, especially for developing countries.

BepFAMN: A Method for Linear B-Cell Epitope Predictions Based on Fuzzy-ARTMAP Artificial Neural Network.

The public health system is extremely dependent on the use of vaccines to immunize the population from a series of infectious and dangerous diseases, preventing the system from collapsing and millions of people dying every year. However, to develop these vaccines and effectively monitor these diseases, it is necessary to use accurate diagnostic methods capable of identifying highly immunogenic regions within a given pathogenic protein. Existing experimental methods are expensive, time-consuming, and require arduous laboratory work, as they require the screening of a large number of potential candidate epitopes, making the methods extremely laborious, especially for application to larger microorganisms. In the last decades, researchers have developed in silico prediction methods, based on machine learning, to identify these markers, to drastically reduce the list of potential candidate epitopes for experimental tests, and, consequently, to reduce the laborious task associated with their mapping. Despite these efforts, the tools and methods still have low accuracy, slow diagnosis, and offline training. Thus, we develop a method to predict B-cell linear epitopes which are based on a Fuzzy-ARTMAP neural network architecture, called BepFAMN (B Epitope Prediction Fuzzy ARTMAP Artificial Neural Network). This was trained using a linear averaging scheme on 15 properties that include an amino acid ratio scale and a set of 14 physicochemical scales. The database used was obtained from the IEDB website, from which the amino acid sequences with the annotations of their positive and negative epitopes were taken. To train and validate the knowledge models, five-fold cross-validation and competition techniques were used. The BepiPred-2.0 database, an independent database, was used for the tests. In our experiment, the validation dataset reached sensitivity = 91.50%, specificity = 91.49%, accuracy = 91.49%, MCC = 0.83, and an area under the curve (AUC) ROC of approximately 0.9289. The result in the testing dataset achieves a significant improvement, with sensitivity = 81.87%, specificity = 74.75%, accuracy = 78.27%, MCC = 0.56, and AOC = 0.7831. These achieved values demonstrate that BepFAMN outperforms all other linear B-cell epitope prediction tools currently used. In addition, the architecture provides mechanisms for online training, which allow the user to find a new B-cell linear epitope, and to improve the model without need to re-train itself with the whole dataset. This fact contributes to a considerable reduction in the number of potential linear epitopes to be experimentally validated, reducing laboratory time and accelerating the development of diagnostic tests, vaccines, and immunotherapeutic approaches.

Machine Learning Methods for Multiscale Physics and Urban Engineering Problems.

We present an overview of four challenging research areas in multiscale physics and engineering as well as four data science topics that may be developed for addressing these challenges. We focus on multiscale spatiotemporal problems in light of the importance of understanding the accompanying scientific processes and engineering ideas, where "multiscale" refers to concurrent, non-trivial and coupled models over scales separated by orders of magnitude in either space, time, energy, momenta, or any other relevant parameter. Specifically, we consider problems where the data may be obtained at various resolutions; analyzing such data and constructing coupled models led to open research questions in various applications of data science. Numeric studies are reported for one of the data science techniques discussed here for illustration, namely, on approximate Bayesian computations.

A systematic review and meta-analysis of combined carotid endarterectomy with ipsilateral proximal intervention (hybrid approach) for tandem carotid artery lesions.

OBJECTIVE: The safety and effectiveness of using the hybrid approach to treat tandem carotid lesions is controversial, and the clinical significance of the technical variants on the perioperative outcomes has not been evaluated. The present meta-analysis was performed to evaluate the technique, safety, effectiveness, and long-term outcomes of the hybrid approach. METHODS: The PubMed, Embase, and Cochrane Library databases were searched to identify studies from January 1, 1996 to January 11, 2020. The baseline patient characteristics, comorbidities, procedural details, and perioperative and long-term outcomes were collected and analyzed. A pooled overall survival curve was drawn. Univariate analysis was performed to compare the perioperative stroke risk between subgroups. RESULTS: Overall, 275 patients (mean age, 66.94 years) from 15 studies were included. All the patients had presented with tandem stenosis of ≥50%, and 67.2% were symptomatic. The overall technical success rate was 99.8% (95% confidence interval [CI], 98.0%-100.0%). The pooled perioperative complications rates were as follows: death, 1.5% (95% CI, 0.0%-2.9%); stroke, 2.6% (95% CI, 0.7%-4.4%); combined stroke/death, 3.3% (95% CI, 1.2%-5.4%); and myocardial infarction, 3.2% (95% CI, 0.7%-9.1%). The overall primary patency rates were 99.2% (95% CI, 96.0%-100.0%) and 88.2% (95% CI, 78.8%-95.4%) at 1 and 2 years, respectively. Reintervention was performed in 6.6% of the patients (95% CI, 3.0%-11.2%). The pooled overall survival rates were 89.9% (95% CI, 83.7%-96.7%), 83.7% (95% CI, 75.9%-92.2%), and 75.9% (95% CI, 66.5%-86.7%) at 1, 3, and 5 years, respectively. Operations in which carotid endarterectomy was performed first carried a significantly greater risk of perioperative stroke compared with those in which proximal intervention had been performed first (5.7% vs 0.0%; P = .01). No difference was found in perioperative stroke risk between the subgroups of baseline symptomatic status (asymptomatic, 5.1%; symptomatic, 1.9%; P = .32), preoperative antiplatelet therapy (dual, 3.6%; single, 5.8%; P = .79), and carotid clamping during intervention (clamping, 2.8%; unclamping, 6.3%; P = .40). CONCLUSIONS: For patients with a presumed high risk of neurologic events because of carotid tandem lesions, the hybrid approach could be considered a reasonable option with high technical success and acceptable perioperative and long-term results. Performing carotid artery stenting before carotid endarterectomy and administering perioperative dual antiplatelet therapy should be considered to promote technical success and better outcomes. Prospective and randomized controlled studies are needed to confirm the results and provide recommendations on patient selection for the hybrid approach.

Left ventricular surgical remodeling 2.0.

Left ventricular surgical remodeling has been, for a long time, the procedure applied for large dyskinetic, or akinetic, areas as a consequence of a myocardial infarction, mainly located in the left anterior descending area. Many surgical techniques were developed, aimed to a pure reduction of the volume of the left ventricular (LV) cavity or to add to volume reduction a more physiologic conical shape. The expansion of interventional procedures invaded most of the fields before treated only by cardiac surgeons. In this issue, Pillay describes a hybrid technique, involving both interventional cardiologists and cardiac surgeons, aimed to LV volume reduction after an anterior myocardial infarction. A series of internal (right ventricular septum) and external (anterior wall) anchors are implanted to approximate the LV free wall to the anterior septum, consequently excluding the scarred myocardium. Although some limitations of this study, the authors have to be commended for having revitalized a procedure almost eliminated from the surgical scenario.

A hybrid approach for chronic pancreatitis: combination of laparoscopic assisted distal pancreatectomy and open Frey procedure.

BACKGROUND: The treatment of chronic pancreatitis requires a surgical approach in patients who are refractory to medical therapy. During surgical treatment, ductal decompression is required, but a pancreatectomy is necessary for some patients, such as those with severe stenosis of the pancreatic duct. Indeed, suboptimal procedures lead to recurrent pancreatitis. We used a laparoscopic hybrid approach for patients with severe stenosis of the pancreatic duct. In this report, we present the feasibility and outcomes of our approach. METHODS: We selected a laparoscopic approach for the distal pancreatectomy, which is relatively safe and the effect of reducing the length of the wound is substantial. We selected an open approach for the Frey procedure because complete ductal compression has a high risk for injury to the vessels posterior to the pancreas. We recorded the operative outcomes, postoperative complications, and recurrence of pancreatitis. RESULTS: We performed the laparoscopic hybrid approach on 3patients between January and December 2018. There were no major intraoperative complications (Clavien-Dindo classification IIIa or more) and the postoperative course was uneventful in all patients. There were no recurrences of pancreatitis and no postoperative pain in all patients in > 2 years of follow-up. CONCLUSION: Our hybrid method with a focus on complete ductal compression with safety and minimal invasiveness might be the optimal approach for the surgical treatment of chronic pancreatitis that requires a pancreatectomy with the Frey procedure.

HYBRID MICROSURGICAL AND ENDOVASCULAR APPROACH IN THE TREATMENT OF MULTIPLE CEREBRAL ANEURYSMS: AN ILLUSTRATIVE CASE SERIES IN CORRELATION WITH LITERATURE DATA.

Contemporary cerebral aneurysm treatment has advanced due to the expansion of microsurgical and endovascular techniques having different advantages and restraints. However, some aneurysms cannot be effectively treated by a single method alone due to their specific anatomy, location, complexity, and/or multiplicity. Subsequently, multiple aneurysms sometimes necessitate a hybrid strategy integrating both methods. The study aims were to discuss indications, possibilities, and challenges of a hybrid strategy in the decision making and treatment of multiple intracranial aneurysms. A single-institution illustrative case series of multiple intracranial aneurysm patients treated by a hybrid approach was analyzed and management outcome discussed and correlated with literature data. Following the treatment, both patients from our case series recovered well, having complete and stable aneurysmal occlusion with no relapse and no postoperative procedure-related complications or long-lasting neurological symptoms. In conclusion, a hybrid approach is advised as a treatment option for multiple cerebral aneurysms when a single modality is insufficient to bring satisfactory results. It may be a suitable and safe addition to an assortment of treatments pledging clinical improvement and enabling positive management outcome in patients with ruptured and non-ruptured multiple cerebral aneurysms.

Safety and efficacy of a hybrid approach for repair of complicated aberrant subclavian arteries.

OBJECTIVE: Aberrant subclavian artery (ASA), a well-described aortic arch anomaly, is frequently associated with dysphagia and development of Kommerell diverticulum (KD) with aneurysmal degeneration. Historically, open repair has been performed, which can be associated with significant morbidity. More recently, hybrid approaches using different arch vessel revascularization techniques in combination with thoracic endovascular aortic repair (hybrid TEVAR) have been described, but there is a paucity of literature describing outcomes. The objective of this analysis was to describe our experience with management of complicated ASAs using hybrid TEVAR, further adding to the literature describing approaches to and outcomes of hybrid ASA repair. METHODS: A retrospective, single-institution review was performed of all patients treated for ASA complications using hybrid TEVAR (2002-2018). The primary end point was technical success, defined as absence of type I or type III endoleak intraoperatively and within 30 days postoperatively. Secondary end points included complications, reintervention, and survival. Centerline measurement of KD diameters (maximum diameter = opposing aortic outer wall to diverticulum apex) was employed. Kaplan-Meier methodology was used to estimate secondary end points. RESULTS: Eighteen patients (1.4% of 1240 total TEVAR procedures; male, 67%; age, 59 ± 13 years) were identified (left-sided arch and right ASA, 94% [n = 17]; right-sided arch and left ASA, n = 1 [6%]; retroesophageal location and associated KD, 100%); median preoperative KD diameter was 60 mm (interquartile range [IQR], 37-108 mm). Operative indications included diverticulum diameter (61%), dysphagia (17%), rupture (11%), rapid expansion (6%), and endoleak after TEVAR (6%). All procedures used some combination of supraclavicular revascularization and TEVAR (staged, 50% [n = 9]), whereas partial open arch reconstruction was used in 17% (n = 3). There were no perioperative deaths or spinal cord ischemic events. Major complications occurred in 22% (n = 4): nondisabling stroke, one; arm ischemia, one; upper extremity neuropathy, one; and iatrogenic descending thoracic aortic dissection, one. Technical success was 83%, but 44% (n = 8) had an endoleak (type I, n = 3; type II, n = 5 [intercostal, n = 2; aneurysmal subclavian artery origin, n = 3]) during follow-up (median, 4 months; IQR, 1-15 months). Two endoleaks resolved spontaneously, three were treated, and three were observed (1-year freedom from reintervention, 75% ± 10%). Median KD diameter decreased by 7 mm (IQR, 1-12 mm), and 78% (n = 14) experienced diameter reduction or stability in follow-up. The 1- and 3-year survival was 93% ± 6% and 84% ± 10%, respectively. CONCLUSIONS: Hybrid open brachiocephalic artery revascularization with TEVAR appears to be safe and reasonably effective in management of ASA complications as evidenced by a low perioperative complication risk and reasonable positive aortic remodeling. However, endoleak rates raise significant concerns about durability. Therefore, if this technique is employed, the mandatory need for surveillance and high rate of reintervention should be emphasized preoperatively. This analysis represents a relatively large series of a hybrid TEVAR technique to treat ASA complications, but greater patient numbers and longer follow-up are needed to further establish the role of this procedure.

[Hybrid aortic repair in patients with type III aortic dissection and concomitant proximal aortic lesion]. / Gibridnye operatsii u patsientov s rassloeniem aorty III tipa i porazheniem ee proksimal'nogo otdela.

OBJECTIVE: To report our own experience of hybrid treatment using FET technique in patients with type A aortic dissection and concomitant lesion of aortic arch and ascending aorta. MATERIAL AND METHODS: There were 90 (28,3%) FET procedures for the period from January 2010 to August 2019. Type B aortic dissection was diagnosed in 19 (45,2%) patients. Type B aortic dissection combined with aortic arch aneurysm occurred in 11 (58%) cases, ascending aorta aneurysm - 15 (79%) cases. Patients underwent total arch and ascending aorta replacement via median sternotomy (upper partial J-shaped sternotomy in 3 cases). Valve-sparing interventions were performed in 58% of cases (aortic root repair - 6 (32%) patients, David procedure - 5 (26%) cases). Intraoperative features, early postoperative morbidity and in-hospital mortality were retrospectively analyzed. In long-term period, distal aortic remodeling, survival rate and incidence of redo interventions were evaluated. RESULTS: Mean CPB time was 166±27 min, aortic cross-clamping time - 93±23 min, duration of circulatory arrest - 43±11 min. Neurological complications and paraplegia were absent. In-hospital mortality was absent. Reversible acute renal failure without need for hemodialysis developed in 2 cases (11%). Two patients underwent repeated intervention (TEVAR) due to dSINE and negative aortic remodeling. Annual survival rate was 100%. Freedom from redo aortic surgery was 89,5%. CONCLUSION: FET surgery is an adequate alternative treatment for type B aortic dissection combined with lesion of aortic arch and ascending aorta. This approach ensures a one-stage repair in patients with contraindications to TEVAR. Unlike thoracotomy, FET procedure is valuable for simultaneous correction of cardiac and proximal aortic lesion, stabilizing the distal segments of dissected aorta. This is obvious advantage of this technique.

Infective endocarditis complicated with coronary artery septic embolization: is it worth to be mentioned? Case presentation and review of the literature.

Coronary artery septic embolization is a rare, but severe complication of infective endocarditis involving the leftside of the valves. The first case mentioned in the literature was a postmortem finding of a left anterior descending coronary artery occlusion by a vegetation fragment. Since this case, there have been several therapeutic strategies published with this clinical setting including medical treatment, percutaneous coronary angioplasty addressing coronary occlusion, surgical intervention for both the infected valve and coronary embolization, and hybrid procedures with transcatheter septic embolus aspiration followed by surgical valvular interventions. Out of the three interventions mentioned, the latter provided the best results and was in concordance with results observed in a case of mitral valve infected endocarditis complicated with acute occlusion of the left anterior descending coronary artery in patient whose comorbidities included hypertrophic obstructive cardiomyopathy. A transcatheter left anterior descending coronary artery embolus aspiration was performed , followed by a surgical mitral valve replacement and septal myectomy with an uneventful postoperative course. Although rare, this severe complication of infective endocarditis has a specific clinical course and therapeutic strategy, and in our opinion, it could be mentioned as a separate entity among embolic complications of infective endocarditis in future guidelines. Previously published cases suggest that the hybrid intervention might be the therapy of choice for this clinical setting; however, larger studies are necessary for confirmation.

Using a hybrid read-across method to evaluate chemical toxicity based on chemical structure and biological data.

Read-across has become a primary approach to fill data gaps for chemical safety assessments. Chemical similarity based on structure, reactivity, and physic-chemical property information is a traditional approach applied for read-across toxicity studies. However, toxicity mechanisms are usually complicated in a biological system, so only using chemical similarity to perform the read-across for new compounds was not satisfactory for most toxicity endpoints, especially when the chemically similar compounds show dissimilar toxicities. This study aims to develop an enhanced read-across method for chemical toxicity predictions. To this end, we used two large toxicity datasets for read-across purposes. One consists of 3979 compounds with Ames mutagenicity data, and the other contains 7332 compounds with rat acute oral toxicity data. First, biological data for all compounds in these two datasets were obtained by querying thousands of PubChem bioassays. The PubChem bioassays with at least five compounds from either of these two datasets showing active responses were selected to generate comprehensive bioprofiles. The read-across studies were performed by using chemical similarity search only and also by using a hybrid similarity search based on both chemical descriptors and bioprofiles. Compared to traditional read-across based on chemical similarity, the hybrid read-across approach showed improved accuracy of predictions for both Ames mutagenicity and acute oral toxicity. Furthermore, we could illustrate potential toxicity mechanisms by analyzing the bioprofiles used for this hybrid read-across study. The results of this study indicate that the new hybrid read-across approach could be an applicable computational tool for chemical toxicity predictions. In this way, the bottleneck of traditional read-across studies can be overcome by introducing public biological data into the traditional process. The incorporation of bioprofiles generated from the additional biological data for compounds can partially solve the "activity cliff" issue and reveal their potential toxicity mechanisms. This study leads to a promising direction to utilize data-driven approaches for computational toxicology studies in the big data era.

A Review of Recent Advances in Benchmark Dose Methodology.

In this review, recent methodological developments for the benchmark dose (BMD) methodology are summarized. Specifically, we introduce the advances for the main steps in BMD derivation: selecting the procedure for defining a BMD from a predefined benchmark response (BMR), setting a BMR, selecting a dose-response model, and estimating the corresponding BMD lower limit (BMDL). Although the last decade has shown major progress in the development of BMD methodology, there is still room for improvement. Remaining challenges are the implementation of new statistical methods in user-friendly software and the lack of consensus about how to derive the BMDL.