Survey on the approach to antibiotic prophylaxis in liver and kidney transplant recipients colonized with "difficult to treat" Gram-negative bacteria.

BACKGROUND: Performance of active screening for multidrug-resistant Gram-negative bacteria (MDR-GNB) and administration of targeted antibiotic prophylaxis (TAP) in colonized patients undergoing liver (LT) and/or kidney transplantation (KT) are controversial issues. METHODS: Self-administered electronic cross-sectional survey disseminated from January to February 2022. Questionnaire consisted of four parts: hospital/transplant program characteristics, standard screening and antibiotic prophylaxis, clinical vignettes asking for TAP in patients undergoing LT and KT with prior infection/colonization with four different MDR-GNB (extended-spectrum cephalosporin-resistant Enterobacterales [ESCR-E], carbapenem-resistant Enterobacterales [CRE], multidrug-resistant Pseudomonas aeruginosa [MDR-Pa], and carbapenem-resistant Acinetobacter baumannii [CRAb]). RESULTS: Fifty-five respondents participated from 14 countries, mostly infectious disease specialists (69%) with active transplant programs (>100 procedures/year for 34.5% KT and 23.6% LT), and heterogeneous local MDR-GNB prevalence from <15% (30.9%), 15%-30% (43.6%) to >30% (16.4%). The frequency of screening for ESCR-E, CRE, MDR-Pa, and CRAb was 22%, 54%, 17%, and 24% for LT, respectively, and 18%, 36%, 16%, and 11% for KT. Screening time-points were mainly at transplantation 100%, only one-third following transplantation. Screening was always based on rectal swab cultures (100%); multi-site sampling was reported in 40% of KT and 35% of LT. In LT clinical cases, 84%, 58%, 84%, and 40% of respondents reported TAP for prior infection/colonization with ESCR-E, CRE, MDR-Pa, and CRAb, respectively. In KT clinical cases, 55%, 39%, 87%, and 42% of respondents reported TAP use for prior infection/colonization with ESCR-E, CRE, MDR-Pa, and CRAb, respectively. CONCLUSION: There is a large heterogeneity in screening and management of MDR-GNB carriage in LT and KT.

Open-Source Image-Based Tool to Experimentally Evaluate Blood Residence Time in Clinical Devices.

This article introduces an open-source tool to experimentally compare blood residence time in biomedical devices using an image-based method. The experimental setup and the postprocessing workflow are comprehensively elucidated in a detailed report that conducts a thorough comparison of the residence times of a blood analog within three distinct blood oxygenator prototypes. To enable widespread accessibility and ease of use, the user-friendly MATLAB App developed for the analysis is available on the Mathworks repository: https://www.mathworks.com/matlabcentral/fileexchange/135156 .

Clinical efficacy of cefiderocol-based regimens in patients with carbapenem-resistant Acinetobacter baumannii infections: A systematic review with meta-analysis.

OBJECTIVES: To perform a systematic review with meta-analysis to assess the clinical efficacy of cefiderocol-based regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. METHODS: Two authors independently searched PubMed-MEDLINE, Scopus, and Cochrane databases, from inception to 02 July 2023, for randomised controlled trials (RCTs) or observational studies comparing clinical efficacy of cefiderocol-based vs. non-cefiderocol-based regimens in patients with CRAB infections. Data were extracted by the two authors independently, and the quality of included studies was independently assessed using ROB 2.0 or ROBINS-I tools. Primary outcome was mortality rate. Meta-analysis was performed by pooling odds ratios (ORs) retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity. RESULTS: A total of 530 articles were screened, and 6 studies (1 RCT and 5 observational; N=561; 247 cefiderocol-based vs. 314 non-cefiderocol-based regimens) were included. Cefiderocol did not significantly reduce in-hospital mortality compared to alternative therapies (predominantly colistin-based), but the confidence intervals around the effect estimate included clinically important benefit (N=5; OR 0.64; 95%CI 0.40-1.04; I2=57.5%). When only observational studies providing adjustment for confounders were considered, a lower risk of mortality was found in patients treated with cefiderocol-based regimens (N=4; OR 0.53; 95%CI 0.39-0.71; I2=0.0%). CONCLUSIONS: Cefiderocol-based regimens were associated with a significantly lower risk of mortality in patients with CRAB infections in observational studies providing proper adjustment for confounders.

MDR/XDR/PDR or DTR? Which definition best fits the resistance profile of Pseudomonas aeruginosa?

PURPOSE OF REVIEW: The aim of this narrative review is to compare the prognostic utility of the new definition of difficult-to-treat resistance (DTR) vs. established definitions in patients with Pseudomonas aeruginosa infection to understand the therapeutic implications of resistance classification and its impact on clinical outcome. RECENT FINDINGS: Among Gram-negative bacteria (GNB), P. aeruginosa (PA) is associated with high rates of morbidity and mortality, mostly related to its intrinsic capacity of developing antibiotic resistance. Several classifications of antibiotic resistance have been proposed in the last 15 years. The most common used is that from Magiorakos et al. including multidrug resistance (MDR), extensively drug-resistant (XDR) and pan drug resistance (PDR) according to the number of antibiotic classes showing in vitro activity. A further classification based on the resistance to specific antibiotic classes (i.e. fluoroquinolones, cephalosporins, carbapenem resistance) was also proposed. However, both of them have been criticized because of limited usefulness in clinical practice and for poor correlation with patient outcome, mainly in infections due to PA. More recently the new definition of difficult-to-treat resistance (DTR) has been proposed referring to nonsusceptibility to all first-line agents showing high-efficacy and low-toxicity (i.e. carbapenems, ß-lactam-ß-lactamase inhibitor combinations, and fluoroquinolones). Studies including large cohorts of patients with GNB bloodstream infections have confirmed the prognostic value of DTR classification and its clinical usefulness mainly in infections due to PA. Indeed, in the recent documents from the Infectious Diseases Society of America (IDSA) on the management of antibiotic resistant GNB infections, the DTR classification was applied to PA. SUMMARY: DTR definition seems to identify better than MDR/XDR/PDR and single class resistant categories the cases of PA with limited treatment options. It requires periodic revision in order to remain up-to-date with the introduction of new antibiotics and the evolving pattern of resistance.

Ceftazidime/Avibactam and Meropenem/Vaborbactam for the Management of Enterobacterales Infections: A Narrative Review, Clinical Considerations, and Expert Opinion.

This comprehensive review examines the unique attributes, distinctions, and clinical implications of ceftazidime-avibactam (CAZ-AVI) and meropenem-vaborbactam (MEM-VAB) against difficult-to-treat Enterobacterales infections. Our manuscript explores these antibiotics' pharmacokinetic and pharmacodynamic properties, antimicrobial activities, in vitro susceptibility testing, and clinical data. Moreover, it includes a meticulous examination of comparative clinical and microbiological studies, assessed and presented to provide clarity in making informed treatment choices for clinicians. Finally, we propose an expert opinion from a microbiological and a clinical point of view about their use in appropriate clinical settings. This is the first review aiming to provide healthcare professionals with valuable insights for making informed treatment decisions when combating carbapenem-resistant pathogens.

Regional biomechanical characterization of human ascending aortic aneurysms: Microstructure and biaxial mechanical response.

The ascending thoracic aortic aneurysm (ATAA) is a permanent dilatation of the vessel with a high risk of adverse events, and shows heterogeneous properties. To investigate regional differences in the biomechanical properties of ATAAs, tissue samples were collected from 10 patients with tricuspid aortic valve phenotype and specimens from minor, anterior, major, and posterior regions were subjected to multi-ratio planar biaxial extension tests and second-harmonic generation (SHG) imaging. Using the data, parameters of a microstructure-motivated constitutive model were obtained considering fiber dispersion. SHG imaging showed disruptions in the organization of the layers. Structural and material parameters did not differ significantly between regions. The non-symmetric fiber dispersion model proposed by Holzapfel et al. [25] was used to fit the data. The mean angle of collagen fibers was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. The experimental data collected in this study contribute to the biomechanical data available in the literature on human ATAAs. Region-specific parameters for the constitutive models are fundamental to improve the current risk stratification strategies, which are mainly based on aortic size. Such investigations can facilitate the development of more advanced finite element models capable of capturing the regional heterogeneity of pathological tissues. STATEMENT OF SIGNIFICANCE: Tissue samples of human ascending thoracic aortic aneurysms (ATAA) were collected. Samples from four regions underwent multi-ratio planar biaxial extension tests and second-harmonic generation imaging. Region-specific parameters of a microstructure-motivated model considering fiber dispersion were obtained. Structural and material parameters did not differ significantly between regions, however, the mean fiber angle was negatively correlated between minor and anterior regions, and the parameter associated with collagen fiber stiffness was positively correlated between minor and major regions. Furthermore, correlations were found between the stiffness of the ground matrix and the mean fiber angle, and between the parameter associated with the collagen fiber stiffness and the out-of-plane dispersion parameter in the posterior and minor regions, respectively. This study provides a unique set of mechanical and structural data, supporting the microstructural influence on the tissue response. It may facilitate the development of better finite element models capable of capturing the regional tissue heterogeneity.

Long-Term Survivors in a Cohort of People Living with HIV Diagnosed between 1985 and 1994: Predictive Factors Associated with More Than 25 Years of Survival.

Although the mortality rate among individuals diagnosed during the pre-Highly Active Antiretroviral Treatment era has been substantial, a considerable number of them survived. Our study aimed to evaluate the prevalence of HIV long-term survivors in a cohort of People Living with HIV diagnosed between 1985 and 1994 and to speculate about potential predictive factors associated to long survival. This is a retrospective single-center study. Subjects surviving more than 300 months (25 years) from HIV diagnosis were defined as Long Term Survivors. Overall, 210 subjects were enrolled. More than 75.24% of the included people living with HIV were males, with a median age of 28 years (IQR 25-34). The prevalent risk factors for HIV infection were injection drug use (47.62%), followed by unprotected sex among heterosexual individuals (23.81%). Ninety-three individuals (44.29%) could be defined as LTS with a median (IQR) survival of 333 (312-377) months. A hazard ratio of 12.45 (95% CI 7.91-19.59) was found between individuals who were exposed to Highly Active AntiRetroviral Treatment (HAART) and individuals who were not, with the latter being at greater risk of death. The availability and accessibility of effective antiretroviral therapy for people living with HIV remain the cornerstone of survival.

Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Quantitative Measurement of Swallowing Performance Using Iowa Oral Performance Instrument: A Systematic Review and Meta-Analysis.

Swallowing is a complex but stereotyped motor activity aimed at serving two vital purposes: alimentary function and the protection of upper airways. Therefore, any impairment of the swallowing act can represent a significant clinical and personal problem that needs an accurate diagnosis by means of reliable and non-invasive techniques. Thus, a systematic review and meta-analysis was performed to investigate the reliability of the Iowa Oral Pressure Instrument (IOPI) in distinguishing healthy controls (HC) from patients affected by swallowing disorders or pathologies and conditions that imply dysphagia. A comprehensive search was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and using PubMed, Scopus, Web of Science, Cochrane, and Lilacs databases. Overall, 271 articles were identified and, after a three-step screening, 33 case-control and interventional studies reporting IOPI measurements were included. The methodological quality of the retrieved studies resulted in being at a low risk of bias. The meta-analysis on case-control studies showed that maximum tongue pressure (MIP) values were always higher in HC than in patients, with an overall effect of the MIP difference of 18.2 KPa (17.7-18.7 KPa CI). This result was also confirmed when the sample was split into adults and children, although the MIP difference between HC and patients was greater in children than in adults (21.0 vs. 15.4 KPa in the MIP mean difference overall effect, respectively). Tongue endurance (TE) showed conflicting results among studies, with an overall effect among studies near zero (0.7 s, 0.2-1.1 s CI) and a slight tendency toward higher TE values in HC than in patients. Among the intervention studies, MIP values were higher after treatment than before, with a better outcome after the experimental tongue training exercise than traditional treatments (the MIP mean difference overall effect was 10.8 and 2.3 KPa, respectively). In conclusion, MIP values can be considered as a reliable measure of swallowing function in adults and in children, with a more marked MIP difference between HC and patients for the children population. MIP measures in patients are also able to detect the best outcome on the tongue function after the training exercise compared to traditional training.

Possible role of low dose dexamethasone administration in listeria monocytogenes meningoencephalitis: A case series.

Listeria (L.) monocytogenes is a gram-positive, non-sporulating, facultatively anaerobic bacillus transmitted to humans through ingestion of contaminated foods. Listeriosis represents the third most common cause of death from foodborne illness, with a mortality rate of 20-30%, especially for patients affected by an invasive disease, which typically affects immunocompromised patients, pregnant women, the elderly, and neonates. It causes several clinical syndromes, of which meningitis, meningoencephalitis, and sepsis are the most challenging to deal with. Here, five cases of L. monocytogenes meningitis/meningoencephalitis affecting two previously healthy immunocompetent and three immunocompromised adult patients treated with ampicillin plus gentamicin are reported. In addition, all the patients described in this report received a low dose of intravenous dexamethasone; four of them made a full recovery. Additionally, a literature search was performed to better explain the appropriate clinical and therapeutic management approaches for these patients, highlighting the value of dexamethasone administration as part of the therapy.

Clinical characteristics and predictors of death among hospitalized patients infected with SARS-CoV-2 in Sicily, Italy: A retrospective observational study.

Since late December 2019, severe acute respiratory syndrome coronavirus 2 has spread across the world, which resulted in the World Health Organization declaring a global pandemic. Coronavirus disease 2019 (COVID-19) presents a highly variable spectrum with regard to the severity of illness. Most infected individuals exhibit a mild to moderate illness (81%); however, 14% have a serious disease and 5% develop severe acute respiratory distress syndrome (ARDS), requiring intensive care support. The mortality rate of COVID-19 continues to rise across the world. Data regarding predictors of mortality in patients with COVID 19 are still scarce but are being actively investigated. The present multicenter retrospective observational study provides a complete description of the demographic and clinical characteristics, comorbidities and laboratory abnormalities in a population of 421 hospitalized patients recruited across eight infectious disease units in Southern Italy (Sicily) with the aim of identifying the baseline characteristics predisposing COVID-19 patients to critical illness or death. In this study, older age, pre-existing comorbidities and certain changes in laboratory markers (such as neutrophilia, lymphocytopenia and increased C-reactive protein levels) at the time of admission were associated with a higher risk of mortality. Male sex, on the other hand, was not significantly associated with increased risk of mortality. Symptoms such as fatigue, older age, a number of co-pathologies and use of continuous positive airway pressure were the most significant contributors in the estimation of clinical prognosis. Further research is required to better characterize the epidemiological features of COVID-19, to understand the related predictors of death and to develop new effective therapeutic strategies.

Ampicillin plus ceftriaxone therapy against Enterococcus faecalis endocarditis: A case report, guidelines considerations, and literature review.

Enterococcus faecalis infective endocarditis (EFIE) continues to be a very serious disease, showing considerable morbidity and mortality rates which are influenced by the spread of multi-drug resistant strains occurred in the last decades. Although aminoglycosides were considered the treatment of choice of EIFE, in recent years several studies have investigated alternative therapeutic approaches, including combinations of beta-lactams, mainly because of the aminoglycoside-renowned nephrotoxicity and the widespread development of high-level aminoglycosides resistance (HLAR). In this scenario, we reported a case involving a prosthetic valve infective endocarditis caused by an aminoglycoside-resistant E. faecalis strain which was successfully treated with ampicillin plus ceftriaxone despite the presence of artificial heart valve and the patient's severe clinical conditions.

Engineering in-plane mechanics of electrospun polyurethane scaffolds for cardiovascular tissue applications.

Effective cardiovascular tissue surrogates require high control of scaffold structural and mechanical features to match native tissue properties, which are dependent on tissue-specific mechanics, function heterogenicity, and morphology. Bridging scaffold processing variables with native tissue properties is recognized as a priority for advancing biomechanical performance of biomedical materials and, when translated to the clinical practice, their efficacy. Accordingly, this study selected electrospinning on a rotating cylindrical target as an apparatus of broad application and mapped the relationship between key processing variables and scaffold mechanics and structure. This information was combined with mechanical anisotropy ranges of interest for the three main categories of tissue surrogated in cardiovascular tissue engineering: heart valve leaflets, ventricle wall, and large diameter blood vessels. Specifically, three processing variables have been considered: the rotational velocity and the rastering velocity of the mandrel and the dry (single nozzle - polymer only) vs wet (double nozzle - polymer plus phosphate buffer saline solution) fabrication configuration. While the dry configuration is generally utilized to obtain micro-fiber based polymeric mats, the wet fabrication is representative of processing conditions utilized to incorporate cells, growth factors, or micro-particles within the fibrous scaffold matrix. Dry and wet processed electrospun mats were fabricated with tangential and rastering velocities within the 0.3-9.0 m/s and 0.16-8 cm/s range respectively. Biaxial mechanics, fiber network, and pore micro-architectures were measured for each combination of velocities and for each fabrication modality (dry and wet). Results allowed identification of the precise combination of rotational and rastering velocities, for both dry and wet conditions, that is able to recapitulate the native cardiovascular tissue anisotropy ratio. By adopting a simple and broadly utilized electrospinning layout, this study is meant to provide a repeatable and easy to access methodology to improve biomimicry of the in plane-mechanics of heart valve leaflets, ventricular wall, and large diameter blood vessels.

Post-infectious ST elevation myocardial infarction following a COVID-19 infection: A case report.

Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has been shown to increase the risk of thrombotic events due to a hypercoagulable state caused by several factors. The case of a 59-year-old woman affected by hypertension and metabolic disorders, treated for a COVID-19 infection who developed cardiac symptoms during the first days of hospitalization is reported. Electrocardiogram analysis and cardiac-ultrasound confirmed ST-segment elevation myocardial infarction (STEMI) diagnosis, thus the patient underwent percutaneous coronary intervention, which was successful. This case highlights a possible association between respiratory infection, particularly SARS-CoV-2 infection, and cardiovascular events, in particular Acute Coronary Syndrome. The association between these phenomena seems related to a range of factors, including a proinflammatory state and the hypoxemia. Moreover, the association amongst SARS-CoV-2 and cardiovascular diseases may be also linked to long-term sequelae. Thus, further studies are required to better understand the multifaceted and severe complications of this disease.

Immunological and Clinical Impact of DAA-Mediated HCV Eradication in a Cohort of HIV/HCV Coinfected Patients: Monocentric Italian Experience.

HCV treatment became available for all infected patients regardless of their comorbidities, especially for HIV coinfected subjects, leading to an improvement in both clinical and immunological conditions. We retrospectively analyzed a cohort of HIV/HCV coinfected patients treated with DAA therapies; data regarding epidemiological, viral-immunological, and hepatic parameters before and after DAA administration have been collected. Drug-drug interactions between DAA and both antiretroviral therapy and non-ART-drugs were also evaluated; the study showed the efficacy of DAA schedules in HCV eradication also for HIV/HCV patients with multiple comorbidities and assuming many different drugs. Principal issues are still represented by drug interactions, pill burden, and patients' compliance. These concerns have to be taken into account, especially in HIV patients for whom the immunological state and ART interactions should always be considered.

Entecavir resistance in a patient with treatment-naïve HBV: A case report.

Among nucleos(t)ide analogue therapies for hepatitis B virus (HBV) treatment, entecavir (ETV) and tenofovir disoproxil fumarate (TDF)/tenofovir alafenamide are associated with the lowest rate of drug resistance. ETV is a drug requiring at least three substitutions in the reverse transcriptase (RT) domain to develop resistance, which is a rare occasion in treatment-naïve patients. However, pre-existing or acquired single mutations in the RT domain could lead to a virological breakthrough, after viral suppression. The present case report describes a 58-year-old female patient with hepatitis B virus (HBV) and high viral load who started HBV treatment with ETV. After 85 weeks of treatment, HBV-DNA declined to 0 IU/ml and remained undetectable for 3 years. However, after that period of time, the HBV-DNA rebounded, followed by the rise of liver enzymes (aspartate aminotransferase and alanine transaminase). Only the substitution M204I was detected in the HBV polymerase region. The patient was then switched to TDF treatment, achieving normalization of the liver enzymes and a decline in HBV-DNA levels. The present case report suggests that nucleoside-naïve patients should be cautiously monitored for resistance, even more than biochemically (transaminases, bilirubin) and virologically (HBV-DNA), even if complete HBV suppression is achieved.

"Diagnosis on the Dock" project: A proactive screening program for diagnosing pulmonary tuberculosis in disembarking refugees and new SEI model.

OBJECTIVE: From 2011 to 2017, the total number of refugees arriving in Europe, particularly in Italy, climbed dramatically. Our aim was to diagnose pulmonary TB in migrants coming from the African coast using a clinical-based port of arrival (PoA) screening program. METHODS: From 2016 to 2018, migrants coming via the Mediterranean Route were screened for body temperature and the presence of cough directly on the dock: if they were feverish with productive cough, their sputum was examined with NAAT; with a dry cough, they underwent Chest-X-ray (CXR). Those migrants with positive NAAT or CXR suggestive for TB were admitted to our ward. In addition, we plotted an SEI simulation of our project to evaluate the epidemiological impact of our screening. RESULTS: Out of 33.676 disembarking migrants, 314 (0.9%) had fever and cough: 80 (25.47%) with productive cough underwent NAAT in sputum, and 16 were positive for TB; 234 (74.52%) with dry cough had a CXR examination, and 39 were suggestive of TB, later confirmed by mycobacterial culture. The SEI-new model analysis demonstrated that our screening program significantly reduced TB spreading all over the country. CONCLUSIONS: For possible future high migrant flows, PoA screening for TB has to be considered feasible and effective in decreasing TB spreading.

Statistical Shape Analysis of Ascending Thoracic Aortic Aneurysm: Correlation between Shape and Biomechanical Descriptors.

An ascending thoracic aortic aneurysm (ATAA) is a heterogeneous disease showing different patterns of aortic dilatation and valve morphologies, each with distinct clinical course. This study aimed to explore the aortic morphology and the associations between shape and function in a population of ATAA, while further assessing novel risk models of aortic surgery not based on aortic size. Shape variability of n = 106 patients with ATAA and different valve morphologies (i.e., bicuspid versus tricuspid aortic valve) was estimated by statistical shape analysis (SSA) to compute a mean aortic shape and its deformation. Once the computational atlas was built, principal component analysis (PCA) allowed to reduce the complex ATAA anatomy to a few shape modes, which were correlated to shear stress and aortic strain, as determined by computational analysis. Findings demonstrated that shape modes are associated to specific morphological features of aneurysmal aorta as the vessel tortuosity and local bulging of the ATAA. A predictive model, built with principal shape modes of the ATAA wall, achieved better performance in stratifying surgically operated ATAAs versus monitored ATAAs, with respect to a baseline model using the maximum aortic diameter. Using current imaging resources, this study demonstrated the potential of SSA to investigate the association between shape and function in ATAAs, with the goal of developing a personalized approach for the treatment of the severity of aneurysmal aorta.

Shear Stress and Aortic Strain Associations With Biomarkers of Ascending Thoracic Aortic Aneurysm.

BACKGROUND: This study aims to investigate the association of wall shear stress (WSS) and aortic strain with circulating biomarkers including matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinase (TIMP), and exosomal level of microRNA (miRNA) in ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valve. METHODS: A total of 76 variables from 125 patients with ascending aortic aneurysms were collected from (1) blood plasma to measure plasma levels of miRNAs and protein activity; (2) computational flow analysis to estimate peak systolic WSS and time-average WSS (TAWSS); and (3) imaging analysis of computed tomography angiography to determine aortic wall strain. Principal component analysis followed by logistic regression allowed the development of a predictive model of aortic surgery by combining biomechanical descriptors and biomarkers. RESULTS: The protein activity of MMP-1, TIMP-1, and MMP-2 was positively correlated to the systolic WSS and TAWSS observed in the proximal ascending aorta (eg, R = 0.52, P < .001, for MMP-1 with TAWSS) where local maxima of WSS were found. For bicuspid patients, aortic wall strain was associated with miR-26a (R = 0.55, P = .041) and miR-320a (R = 0.69, P < .001), which shows a significant difference between bicuspid and tricuspid patients. Receiver-operating characteristics curves revealed that the combination of WSS, MMP-1, TIMP-1, and MMP-12 is predictive of aortic surgery (area under the curve 0.898). CONCLUSIONS: Increased flow-based and structural descriptors of ascending aortic aneurysms are associated with high levels of circulating biomarkers, implicating adverse vascular remodeling in the dilated aorta by mechanotransduction. A combination of shear stress and circulating biomarkers has the potential to improve the decision-making process for ascending aortic aneurysms to a highly individualized level.