Semi-automated reproducible target transfer for cardiac radioablation - A multi-center cross-validation study within the RAVENTA trial.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is a therapeutic option for ventricular tachycardia (VT) where catheter-based ablation is not feasible or has previously failed. Target definition and its transfer from electro-anatomic maps (EAM) to radiotherapy treatment planning systems (TPS) is challenging and operator-dependent. Software solutions have been developed to register EAM with cardiac CT and semi-automatically transfer 2D target surface data into 3D CT volume coordinates. Results of a cross-validation study of two conceptually different software solutions using data from the RAVENTA trial (NCT03867747) are reported. METHODS: Clinical Target Volumes (CTVs) were created from target regions delineated on EAM using two conceptually different approaches by separate investigators on data of 10 patients, blinded to each other's results. Targets were transferred using 3D-3D registration and 2D-3D registration, respectively. The resulting CTVs were compared in a core-lab using two complementary analysis software packages for structure similarity and geometric characteristics. RESULTS: Volumes and surface areas of the CTVs created by both methods were comparable: 14.88 ± 11.72 ml versus 15.15 ± 11.35 ml and 44.29 ± 33.63 cm2 versus 46.43 ± 35.13 cm2. The Dice-coefficient was 0.84 ± 0.04; median surface-distance and Hausdorff-distance were 0.53 ± 0.37 mm and 6.91 ± 2.26 mm, respectively. The 3D-center-of-mass difference was 3.62 ± 0.99 mm. Geometrical volume similarity was 0.94 ± 0.05 %. CONCLUSION: The STAR targets transferred from EAM to TPS using both software solutions resulted in nearly identical 3D structures. Both solutions can be used for QA (quality assurance) and EAM-to-TPS transfer of STAR-targets. Semi-automated methods could potentially help to avoid mistargeting in STAR and offer standardized workflows for methodically harmonized treatments.

Long-Term Health-Related Quality of Life following Acute Type A Aortic Dissection with a Focus on Male-Female Differences: A Cross Sectional Study.

Objectives: Acute type A aortic dissection (ATAAD) is a life-threatening cardiovascular emergency, of which the long-term impact on health-related quality of life (HRQoL) and male-female-specific insights remain inadequately clarified. Methods: Consecutive adult ATAAD patients who underwent surgery were retrospectively included between 2007 and 2017 in four referral centers in the Netherlands, and baseline data were collected. The 36-Item Short-Form (SF-36) Health Survey was sent to all survivors between 2019 and 2021 and compared to validated SF-36 scores of the Dutch general population stratified by age group and sex. Results: In total, 324/555 surviving patients returned the SF-36 questionnaire (response rate 58%), of which 40.0% were female; the median follow-up was 6.5 years (range: 1.7-13.9, IQR: 4.0-9.4) after surgery for ATAAD. In comparison to the general population, ATAAD patients scored significantly lower on 6/8 SF-36 subdomains and higher on bodily pain. Differences in HRQoL domains compared to the sex-matched data were largely comparable between sexes, apart from bodily pain. In the age-matched subgroups impaired HRQoL was most pronounced in younger patients aged 41-60 (5/8 impaired domains). Female ATAAD patients scored significantly worse on 5/8 SF-36 subdomains and the physical component summary (PCS) scores than male patients. Age at ATAAD, female sex, hypertension, COPD, and prior thoracic aortic aneurysm were associated with worse PCS scores. Conclusions: Long-term HRQoL was impaired in both male and female ATAAD patients when compared to the general population. Further studies on the nature of this impairment and on interventions to improve HRQoL after ATAAD are clearly warranted, with special attention to females and younger patients.

Guidelines for Specialized Epilepsy Centers: Executive Summary of the Report of the National Association of Epilepsy Centers Guideline Panel.

The National Association of Epilepsy Centers first published the guidelines for epilepsy centers in 1990, which were last updated in 2010. Since that update, epilepsy care and the science of guideline development have advanced significantly, including the importance of incorporating a diversity of stakeholder perspectives such as those of patients and their caregivers. Currently, despite extensive published data examining the efficacy of treatments and diagnostic testing for epilepsy, there remain significant gaps in data identifying the essential services needed for a comprehensive epilepsy center and the optimal manner for their delivery. The trustworthy consensus-based statements (TCBS) process produces unbiased, scientifically valid guidelines through a transparent process that incorporates available evidence and expert opinion. A systematic literature search returned 5937 relevant studies from which 197 articles were retained for data extraction. A panel of 41 stakeholders with diverse expertise evaluated this evidence and drafted recommendations following the TCBS process. The panel reached consensus on 52 recommendations covering services provided by specialized epilepsy centers in both the inpatient and outpatient settings in major topic areas including epilepsy monitoring unit care, surgery, neuroimaging, neuropsychology, genetics, and outpatient care. Recommendations were informed by the evidence review and reflect the consensus of a broad panel of expert opinions.

Health-related quality of life in patients with aortic dissection: An unmet need.

Knowledge about the Health-related Quality of Life (HR-QoL) after Type A (TA-AAD) and Type B acute aortic dissection (TB-AAD) is still insufficient. Through this systematic review, including 22 studies (16 for TA-AAD and 6 TB-AAD -1998-2023), the entire literature on HR-QoL after surgical and/or endovascular and/or medical interventions has been investigated. In TA-AAD patients, despite overall SF-36 score was similar to the standard population, with > 80 years patients displaying a better emotional domain, the SF-12 was significant lower to controls in physical and mental well-being domains. Exercise-based cardiac rehabilitation improved HR-QoL. In TB-AAD, vitality and mental health SF-36 scores improved after thoracic endovascular aortic repair (TEVAR); long-term QoL was similar in the open surgery group compared to TEVAR. Overall, HR-QoL after AAD seems adequate irrespective of age or sex, except for some specific domains. Physical exercise and cardiac rehabilitation may improve HR-QoL in these patients. PROSPERO registry ID: CRD42023421130.

Non-Markovian Modeling of Nonequilibrium Fluctuations and Dissipation in Active Viscoelastic Biomatter.

Based on a Hamiltonian that incorporates the elastic coupling between a tracer particle and the embedding active viscoelastic biomatter, we derive a generalized non-Markovian Langevin model for the nonequilibrium mechanical tracer response. Our analytical expressions for the frequency-dependent tracer response function and the tracer positional autocorrelation function agree quantitatively with experimental data for red blood cells and actomyosin networks with and without adenosine triphosphate over the entire frequency range and in particular reproduce the low-frequency violation of the fluctuation-dissipation theorem. The viscoelastic power laws, the elastic constants and effective friction coefficients extracted from the experimental data allow straightforward physical interpretation.

Enhanced interfacial water dissociation on a hydrated iron porphyrin single-atom catalyst in graphene.

Single Atom Catalysis (SAC) is an expanding field of heterogeneous catalysis in which single metallic atoms embedded in different materials catalyze a chemical reaction, but these new catalytic materials still lack fundamental understanding when used in electrochemical environments. Recent characterizations of non-noble metals like Fe deposited on N-doped graphitic materials have evidenced two types of Fe-N4 fourfold coordination, either of pyridine type or of porphyrin type. Here, we study these defects embedded in a graphene sheet and immersed in an explicit aqueous medium at the quantum level. While the Fe-pyridine SAC model is clear cut and widely studied, it is not the case for the Fe-porphyrin SAC that remains ill-defined, because of the necessary embedding of odd-membered rings in graphene. We first propose an atomistic model for the Fe-porphyrin SAC. Using spin-polarized ab initio molecular dynamics, we show that both Fe SACs spontaneously adsorb two interfacial water molecules from the solvent on opposite sides. Interestingly, we unveil a different catalytic reactivity of the two hydrated SAC motives: while the Fe-porphyrin defect eventually dissociates an adsorbed water molecule under a moderate external electric field, the Fe-pyridine defect does not convey water dissociation.

[Lead extraction in cardiac implantable electronic devices]. / Sondenextraktionen bei implantierbaren kardialen Devices.

Lead extraction due to infection or lead dysfunction has become more important in recent years. Patients with high risk of severe and life-threatening complications should only undergo surgery in experienced centers where appropriate personnel and equipment are available. In this review, different techniques and methods to safely and successfully perform transvenous lead extraction are summarized.

Long Term Health Related Quality of Life After Acute Type B Aortic Dissection: a Cross Sectional Survey Study.

OBJECTIVE: Acute type B aortic dissection (ATBD) is a rare yet serious cardiovascular event that potentially has an impact on health related quality of life (HRQoL). However, long term follow up data on this topic are scarce. This study aimed to review the long term HRQoL among patients treated for ATBD. METHODS: In this multicentre, cross sectional survey study, consecutive treated patients with ATBD between 2007 and 2017 in four referral centres in the Netherlands were retrospectively included and baseline data were collected. Between 2019 and 2021 the 36 Item Short Form Survey (SF-36) was sent to all surviving patients (n = 263) and was compared with validated SF-36 scores in the Dutch general population stratified by age and sex. RESULTS: In total, 144 of 263 surviving patients completed the SF-36 (response rate 55%). Median (IQR) age was 68 (61, 76) years at completion of the questionnaire, and 40% (n = 58) were female. Initial treatment was medical in 55% (n = 79), endovascular in 41% (n = 59), and surgical in 4% (n = 6) of ATBD patients. Median follow up time was 6.1 (range 1.7-13.9; IQR 4.0, 9.0) years. Compared with the general population, patients scored significantly worse on six of eight SF-36 subdomains, particularly physical domains. Apart from bodily pain, there were no substantial differences in HRQoL between male and female ATBD patients. Compared with sex matched normative data, females scored significantly worse on five of eight subdomains, whereas males scored significantly lower on six subdomains. Younger patients aged 41-60 years seemed more severely impaired in HRQoL compared with the age matched general population. Treatment strategy did not influence HRQoL outcomes. Follow up time was associated with better Physical and Mental Component Summary scores. CONCLUSION: Long term HRQoL was impaired in ATBD patients compared with the Dutch general population, especially regarding physical status. This warrants more attention for HRQoL during clinical follow up. Rehabilitation programmes including exercise and physical support might improve HRQoL and increase patients' health understanding.

Elective Ascending Aortic Aneurysm Surgery in the Elderly.

BACKGROUND: No clear guidelines exist for performing preventive surgery for ascending aortic (AA) aneurysm in elderly patients. This study aims to provide insights by: (1) evaluating patient and procedural characteristics and (2) comparing early outcomes and long-term mortality after surgery between elderly and non-elderly patients. METHODS: A multicenter retrospective observational cohort-study was performed. Data was collected on patients who underwent elective AA surgery in three institutions (2006-2017). Clinical presentation, outcomes, and mortality were compared between elderly (≥70 years) and non-elderly patients. RESULTS: In total, 724 non-elderly and 231 elderly patients were operated upon. Elderly patients had larger aortic diameters (57.0 mm (IQR 53-63) vs. 53.0 mm (IQR 49-58), p < 0.001) and more cardiovascular risk factors at the time of surgery than non-elderly patients. Elderly females had significantly larger aortic diameters than elderly males (59.5 mm (55-65) vs. 56.0 mm (51-60), p < 0.001). Short-term mortality was comparable between elderly and non-elderly patients (3.0% vs. 1.5%, p = 0.16). Five-year survival was 93.9% in non-elderly patients and 81.4% in elderly patients (p < 0.001), which are both lower than that of the age-matched general Dutch population. CONCLUSION: This study showed that in elderly patients, a higher threshold exists to undergo surgery, especially in elderly females. Despite these differences, short-term outcomes were comparable between 'relatively healthy' elderly and non-elderly patients.

Outcomes after cardiac rehabilitation in patients following repair of thoracic aortic aneurysm or dissection: a protocol for a systematic review and meta-analysis.

BACKGROUND: Patients receiving thoracic aortic repair suffer from long-term impairment in daily functioning and quality of life following intervention due to a combination of their life-threatening condition (i.e. aortic aneurysm or dissection), undergoing major surgery, as well as long-term exercise restrictions thereafter. Despite the known risks of exercise, it is vital that patients regain physical activity in order to recover their daily functioning and quality of life. Cardiac rehabilitation could be a safe and effective treatment to support patients to become physically active by providing exercise training, comprehensive rehabilitation services, and safety recommendations. Despite new insights in recent literature and clinical practice, international guidelines do not recommend cardiac rehabilitation due to limited evidence. We aim to fill this knowledge gap by performing a systematic review and meta-analysis on the effectiveness of cardiac rehabilitation in patients following thoracic aortic repair. METHODS: This protocol has been developed following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). MEDLINE, Embase, and CINAHL will be searched for eligible observational and interventional studies from inception up to April 2022. Screening (title/abstract and full text), data extraction, risk of bias assessment, and therapeutic validity rating will be conducted by two independent reviewers. A random-effects model will be used to meta-analyse performance-based outcomes, patient-reported outcomes, clinician-reported outcomes, and researcher-reported outcomes. Subsequently, meta-bias and confidence in evidence will be analysed by two independent reviewers. DISCUSSION: To exercise or not to exercise in patients following thoracic aortic repair has been a topic of discussion for years. The intended systematic review and meta-analysis will provide comprehensive evidence on the effectiveness of phase III outpatient exercise-based cardiac rehabilitation in patients following thoracic aortic repair. Findings from this review may inform future guidelines for the management of patients with thoracic aortic disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022301204.

Novel biomarkers associated with thoracic aortic disease.

BACKGROUND: Biomarkers might help to improve diagnosis, surveillance and risk stratification of thoracic aortic disease (TAD). We explored the association between a broad spectrum of cardiovascular biomarkers with clinical characteristics and thoracic aortic diameter in TAD patients. METHODS: Venous blood-samples were obtained in 158 clinically stable TAD patients visiting our outpatient clinic (2017-2020). TAD was defined as a thoracic aortic diameter ≥ 40 mm, or genetic confirmation (hereditary TAD). The cardiovascular panel III of the Olink multiplex platform was used for batch analysis of 92 proteins. A comparison was made between biomarker levels in patients with and without previous aortic dissection and/or surgery, and with and without hereditary TAD. Linear regression analyses were applied to identify (relative, normalized) biomarker concentrations associated with the absolute thoracic aortic diameter (ADmax), and thoracic aortic diameter indexed for body surface area (IDmax). RESULTS: Median age of study patients was 61.0 (IQR 50.3-68.8) years, 37.3% females. Mean ADmax and IDmax were 43.3 ± 5.4 mm and 21.3 ± 3.3 mm/m2. After multivariable adjustment, Matrix Metalloproteinase-3 (MMP-3) and Insulin-like growth factor binding protein 2 (IGFBP-2) showed a significant positive association with ADmax and IDmax, respectively. Patients with previous aortic surgery/dissection had higher N-terminal-pro hormone BNP (NTproBNP) (median 3.67 [IQR 3.01-3.99] vs 2.84 [2.32-3.26], p ≤0.001). Patients with hereditary TAD had higher Trem-like transcript protein 2 (TLT-2) (median 4.64 [IQR 4.45-4.84]) than those with non-heriditary TAD (4.40 [4.17-4.64]; p = 0.00042). CONCLUSIONS: Among a broad range of biomarkers, MMP-3 and IGFBP-2 were associated with disease severity in TAD patients. The pathophysiological pathways uncovered by these biomarkers, and their potential clinical use warrants further research.

Electrophysiology lab efficiency comparison between cryoballoon and point-by-point radiofrequency ablation: a German sub-analysis of the FREEZE Cohort study.

BACKGROUND: Pulmonary vein isolation (PVI) is recommended to treat paroxysmal and persistent atrial fibrillation (AF). This analysis aimed to assess the hospital efficiency of single-shot cryoballoon ablation (CBA) and point-by-point radiofrequency ablation (RFA). METHODS: The discrete event simulation used PVI procedure times from the FREEZE Cohort study to establish the electrophysiology (EP) lab occupancy time. 1000 EP lab days were simulated according to an illustrative German hospital, including 3 PVI cases per day using CBA at one site and RFA at the other. RESULTS: The analysis included 1560 CBA patients and 1344 RFA patients from the FREEZE Cohort. Some baseline patients' characteristics were different between groups (age, AF type, and some concomitant diseases), without being statistically associated to ablation procedure time. Mean procedure time was 122.2 ± 39.4 min for CBA and 160.3 ± 53.5 min for RFA (p < 0.0001). RFA was associated with a more than five-fold increase of cumulative overtime compared to CBA over the simulated period (1285 h with RFA and 253 h with CBA). 70.7% of RFA lab days included overtime versus 25.7% for CBA. CBA was associated with more days with an additional hour at the end of the EP lab shift compared to RFA (47.8% vs 11.5% days with one hour left, respectively). CONCLUSION: CBA is faster and more predictable than point-by-point RFA, and enables improvements in EP lab efficiency, including: fewer cumulative overtime hours, more days where overtime is avoided and more days with remaining time for the staff or for any EP lab usage. Clinical trial registration NCT01360008 (first registration 25/05/2011).

Editor's Choice - Therapeutic Options and Outcomes in Midaortic Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: Midaortic syndrome (MAS) is narrowing of the distal thoracic and or abdominal aorta with congenital, inflammatory, or idiopathic aetiology. If left untreated, the prognosis is poor due to hypertensive complications. Follow up data after treatment are sparse, contrary to aortic coarctation. This study aimed to investigate hypertension during follow up after medical, endovascular, and surgical therapy in juveniles and adults. DATA SOURCES: A meta-analysis of case series and reports was performed, focusing on the incidence of hypertension during the follow up of juvenile (i.e., age 0-17 years) and adult MAS patients after medical, endovascular, or surgical therapy. REVIEW METHODS: Search queries were performed in PubMed, Embase, and Web of Science, and eligible articles underwent quality control. Descriptive statistics were reported based on available data, and individual patient data meta-analyses were performed using a one stage approach, accounting for clustering by case series or decades of reporting for case reports. For the meta-analysis, missing outcome and aetiology data were multiply imputed. RESULTS: The number of juveniles and adults who underwent endovascular therapy (33.7% vs. 27.3%; p = .42) and surgery (52.2% vs. 58.0%; p = .46) was similar. At baseline, 92.4% of juveniles and 87.5% of adults were hypertensive, decreasing to 23.2% and 24.1% during a follow up of 23 months (juveniles) and 18 months (adults), respectively. More hypertension was found compared with surgery in juveniles after endovascular therapy (38.1% vs. 10.8%; p = .020). Meta-analysis also demonstrated a trend for hypertension after endovascular therapy in juveniles, whereas hypertension was more prevalent following surgery in adults compared with endovascular therapy or medication. CONCLUSION: This review and meta-analysis investigated therapeutic options for MAS in juveniles and adults. It found that complications and hypertension during follow up were more common in juveniles after endovascular treatment, whereas surgery in adults was associated with more hypertension.

Abnormal aortic hemodynamics are associated with risk factors for aortic complications in patients with marfan syndrome.

Background: It is difficult to assess the risk for aortic dissection beyond the aortic root in patients with Marfan syndrome (MFS). To aid risk assessment in these patients, we investigated aortic flow and wall shear stress (WSS) by 4D flow magnetic resonance imaging (MRI) in patients with MFS and compared the results with healthy volunteers. We hypothesized that MFS patients with a high-risk profile for aortic dissection would show abnormal hemodynamics in aortic regions associated with aortic dissection. Methods: MFS patients (n = 55) and healthy subjects (n = 25), matched for age and sex, prospectively underwent 4D flow MRI. 4D flow maps were constructed to detect elevated (defined as higher than the three-dimensional 95 % confidence interval) and deviant directed (defined as vector angle differences higher than 120°) WSS in MFS patients as compared to the controls. Univariate and multivariate associations with risk factors for aortic dissection in MFS patients were assessed. Results: The maximum incidence for elevated WSS was 20 % (CI 9 %-31 %) and found in the ascending aorta. The maximum for deviant directed WSS was 39 % (CI 26 %-52 %) and found in the inner descending aorta. Significantly more male patients had deviant directed WSS in the inner proximal descending aorta (63 % vs 24 %, p = 0.014). Multivariate analysis showed that deviant directed WSS was associated with male sex (p = 0.019), and a haplo-insufficient FBN1 mutation type (p = 0.040). In 60 % of MFS patients with a previous aortic root replacement surgery, abnormal hemodynamics were found in the ascending aorta. No significant differences between hemodynamics were found in the descending aorta between operated and non-operated patients. Conclusion: Deviant directed WSS in the proximal descending aorta is associated with known risk factors for aortic dissection in MFS patients, namely male sex and a haploinsufficient FBN1 mutation type.

A cross-sectional study on fatigue, anxiety, and symptoms of depression and their relation with medical status in adult patients with Marfan syndrome. Psychological consequences in Marfan syndrome.

Marfan syndrome (MFS) is a connective tissue disorder affecting the cardiovascular, ocular, and skeletal system, which may be accompanied by psychological features. This study aimed to determine the prevalence of fatigue, anxiety, and symptoms of depression in MFS patients, and to assess the degree to which sociodemographic and clinical variables are associated with fatigue and psychological aspects. The prevalence of fatigue, anxiety, and symptoms of depression were assessed in two cohorts of MFS patients and compared with healthy controls. The checklist individual strength (CIS), and hospital anxiety and depression scale (HADS) questionnaires were utilized. Medical status was assessed (family history of MFS, aortic root dilatation >40 mm, previous aortic surgery, aortic dissection, chronic pain, skeletal involvement, and scoliosis). Severe fatigue was experienced by 37% of the total MFS cohort (n = 155). MFS patients scored significantly higher on the CIS questionnaire, concerning severe fatigue, as compared with the general Dutch population (p < 0.0001). There were no differences in HADS anxiety or depression scores. In older MFS patients, with a more severe cardiovascular phenotype, chronic pain, and a higher unemployment rate, significantly more symptoms of depression were observed, when compared with the general population (p = 0.027) or compared with younger MFS patients (p = 0.026). Multivariate analysis, showed that anxiety was associated with chronic pain (p = 0.022) and symptoms of depression with unemployment (p = 0.024). MFS patients report significantly more severe fatigue as compared with the general population. Since the cause of fatigue is unclear, more research may be needed. Psychological intervention, for example, cognitive behavioral therapy, may contribute to a reduction in psychological symptoms.

Novel cryoballoon ablation system for pulmonary vein isolation: multicenter assessment of efficacy and safety-ANTARCTICA study.

AIMS: Pulmonary vein isolation (PVI) either by balloon devices or radiofrequency forms the cornerstone of invasive atrial fibrillation (AF) treatment. Although equally effective cryoballoon (CB)-based PVI offers shorter procedure duration and a better safety profile. Beside the worldwide established Arctic Front Advance system, a novel CB device, POLARx, was recently introduced. This CB incorporates unique features, which may translate into improved efficacy and safety. However, multicentre assessment of periprocedural efficacy and safety is lacking up to date. METHODS AND RESULTS: A total of 317 patients with paroxysmal or persistent AF were included and underwent POLARx CB-based PVI in 6 centres from Germany and Italy. Acute efficacy and safety were assessed in this prospective multicenter observational study. In 317 patients [mean age: 64 ± 12 years, 209 of 317 (66%) paroxysmal AF], a total of 1256 pulmonary veins (PVs) were identified and 1252 (99,7%) PVs were successfully isolated utilizing mainly the short tip POLARx CB (82%). The mean minimal CB temperature was -57.9 ± 7°C. Real-time PVI was registered in 72% of PVs. The rate of serious adverse events was 6.0% which was significantly reduced after a learning curve of 25 cases (9.3% vs. 3.0%, P = 0.018). The rate of recurrence-free survival after mean follow-up of 226 ± 115 days including a 90-day blanking period was 86.1%. CONCLUSION: In this large multicentre assessment, the novel POLARx CB shows a promising efficacy and safety profile after a short learning curve.

Rational design of amphiphilic fluorinated peptides: evaluation of self-assembly properties and hydrogel formation.

Advanced peptide-based nanomaterials composed of self-assembling peptides (SAPs) are of emerging interest in pharmaceutical and biomedical applications. The introduction of fluorine into peptides, in fact, offers unique opportunities to tune their biophysical properties and intermolecular interactions. In particular, the degree of fluorination plays a crucial role in peptide engineering as it can be used to control the characteristics of fluorine-specific interactions and, thus, peptide conformation and self-assembly. Here, we designed and explored a series of amphipathic peptides by incorporating the fluorinated amino acids (2S)-4-monofluoroethylglycine (MfeGly), (2S)-4,4-difluoroethylglycine (DfeGly) and (2S)-4,4,4-trifluoroethylglycine (TfeGly) as hydrophobic components. This approach enabled studying the impact of fluorination on secondary structure formation and peptide self-assembly on a systematic basis. We show that the interplay between polarity and hydrophobicity, both induced differentially by varying degrees of side chain fluorination, does affect peptide folding significantly. A greater degree of fluorination promotes peptide fibrillation and subsequent formation of physical hydrogels in physiological conditions. Molecular simulations revealed the key role played by electrostatically driven intra-chain and inter-chain contact pairs that are modulated by side chain fluorination and give insights into the different self-organization behaviour of selected peptides. Our study provides a systematic report about the distinct features of fluorinated oligomeric peptides with potential applications as peptide-based biomaterials.

Inflammatory biomarkers and risk of cardiovascular events in patients undergoing coronary angiography.

BACKGROUND: Inflammation, measured by traditional biomarkers such as C-reactive protein, has been linked to cardiovascular (CV) events. Recent technological advancement has allowed for measuring larger numbers of inflammatory biomarkers. A contemporary evaluation with established and novel biomarkers of inflammation is needed. METHODS: 1,090 individuals who underwent coronary angiography were enrolled. Twenty-four inflammatory biomarkers were collected prior to angiography. Unsupervised machine learning cluster analyses determined unique patterns of inflammatory biomarkers. Cox proportional hazard regression assessed both association of inflammatory biomarker clusters and individual biomarker associations with major adverse cardiovascular events (MACE; non-fatal myocardial infarction or stroke, and CV death) during a median follow-up of 3.67 years. RESULTS: Four distinct clusters were recognized. Incremental increases in inflammatory biomarkers were observed from cluster 1 to cluster 4. During follow-up, 263 MACE were ascertained. Considering cluster 1 as a reference, study participants with inflammatory cluster 2 (Hazard ratio [HR] 1.55, 95% confidence interval [CI]: 1.01-2.37), cluster 3 (HR 1.89, CI: 1.25-2.85), and cluster 4 (HR 2.93, CI: 1.95-4.42) were at increased risk of MACE. Interleukin (IL)-1α IL-6, IL-8, IL-10, IL-12, Adhesion molecule-1 high-sensitivity C-reactive protein, ferritin, myeloperoxidase, macrophage inflammatory protein (MIP)-1a, MIP 3, and macrophage colony-stimulating factor-1 were independently associated with MACE. CONCLUSIONS: Among persons undergoing coronary angiography procedures, distinct clusters of inflammatory biomarker distributions with significant prognostic meaning may be identified. These results may identify unique targets for anti-inflammatory treatments aimed at CV disease.

Timing of cardiac surgery during pregnancy: a patient-level meta-analysis.

AIMS: To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes. METHODS AND RESULTS: Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06-0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality. CONCLUSION: Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.