Improved Risk Prediction Using a Refined European Guidelines Instrument in Pulmonary Arterial Hypertension Related to Congenital Heart Disease.

The European guidelines advocate a goal-oriented treatment approach in pulmonary arterial hypertension (PAH), based on a comprehensive risk assessment instrument, which has been validated in several PAH subgroups. We investigated its discriminatory ability and explored tricuspid annular plane systolic excursion and revised thresholds to improve its predictability within the adult congenital heart disease (CHD) population. In total, 223 adults (42 ± 16 years, 66% women, 68% Eisenmenger) were enrolled from 5 European PAH-CHD expert centers. Patients were classified as low, intermediate, or high risk at the baseline visit and at follow-up within 4 to 18 months. By the general PAH guidelines instrument, survival did not differ between the risk groups (p-value not significant), mostly because of the skewed group distribution. Reclassifying patients using revised thresholds for N-terminal pro-brain natriuretic peptide and 6-minute walk distance (i.e., low, intermediate, and high as <500, 500 to 1,400, >1,400 ng/L and >400, and 165 to 400 and <165 m, respectively) and use of tricuspid annular plane systolic excursion (low, intermediate, and high as >20, 16 to 20, and <16 mm, respectively) significantly improved the discrimination between the risk groups at baseline and follow-up (p = 0.001, receiver operating characteristic increase from 0.648 to 0.701), reclassifying 64 patients (29%). Irrespective of follow-up risk group, survival was better for patients with higher proportions of low-risk variables. Improvement to a low-risk profile at a median of 9 months of follow-up provided improved survival compared with the survival of patients who remained in the low-risk group. In conclusion, the external validity of general risk instrument for PAH appeared to be of limited discriminatory value in patients with PAH-CHD. We propose a refined risk instrument with improved discrimination for PAH-CHD.

Clinical Course of TGA After Arterial Switch Operation in the Current Era.

Background: The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available regarding the clinical course in the current era. Objectives: The purpose was to describe clinical outcome late after ASO in a national cohort, including survival, rates of (re-)interventions, and clinical events. Methods: A total of 1,061 TGA-ASO patients (median age 10.7 years [IQR: 2.0-18.2 years]) from a nationwide prospective registry with a median follow-up of 8.0 years (IQR: 5.4-8.8 years) were included. Using an analysis with age as the primary time scale, cumulative incidence of survival, (re)interventions, and clinical events were determined. Results: At the age of 35 years, late survival was 93% (95% CI: 88%-98%). The cumulative re-intervention rate at the right ventricular outflow tract and pulmonary branches was 36% (95% CI: 31%-41%). Other cumulative re-intervention rates at 35 years were on the left ventricular outflow tract (neo-aortic root and valve) 16% (95% CI: 10%-22%), aortic arch 9% (95% CI: 5%-13%), and coronary arteries 3% (95% CI: 1%-6%). Furthermore, 11% (95% CI: 6%-16%) of the patients required electrophysiological interventions. Clinical events, including heart failure, endocarditis, and myocardial infarction occurred in 8% (95% CI: 5%-11%). Independent risk factors for any (re-)intervention were TGA morphological subtype (Taussig-Bing double outlet right ventricle [HR: 4.9, 95% CI: 2.9-8.1]) and previous pulmonary artery banding (HR: 1.6, 95% CI: 1.0-2.2). Conclusions: TGA-ASO patients have an excellent survival. However, their clinical course is characterized by an ongoing need for (re-)interventions, especially on the right ventricular outflow tract and the left ventricular outflow tract indicating a strict lifelong surveillance, also in adulthood.

Decreased clinical performance in TGA-ASO patients after RVOT interventions; a multicenter European collaboration.

BACKGROUND: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions. OBJECTIVES: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. METHODS: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP). RESULTS: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029). CONCLUSIONS: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions.

Resveratrol-Loaded Polydimethylsiloxane-Silica Hybrid Materials: Synthesis, Characterization, and Antitumoral Activity.

In this work, hybrid materials within the polydimethylsiloxane-silica (PDMS-SiO2) system, synthesized via the sol-gel method, were developed and characterized for their potential to incorporate and release the bioactive compound resveratrol (RES). RES was incorporated into the materials with a high loading efficiency (>75%) using the rotary evaporator technique. This incorporation induced the amorphization of RES, resulting in enhanced solubility and in vitro release when compared to the free polyphenolic compound. The release profiles displayed pH dependence, exhibiting notably faster release at pH 5.2 compared to pH 7.4. The gradual release of RES over time demonstrated an initial time lag of approximately 4 h, being well described by the Weibull model. In vitro cytotoxicity studies were conducted on human osteosarcoma cells (MG-63), revealing a concentration-dependent decrease in cell viability for RES-loaded samples (for concentrations >50 µg mL-1).

Morin Hydrate Encapsulation and Release from Mesoporous Silica Nanoparticles for Melanoma Therapy.

Melanoma incidence, a type of skin cancer, has been increasing worldwide. There is a strong need to develop new therapeutic strategies to improve melanoma treatment. Morin is a bioflavonoid with the potential for use in the treatment of cancer, including melanoma. However, therapeutic applications of morin are restrained owing to its low aqueous solubility and limited bioavailability. This work investigates morin hydrate (MH) encapsulation in mesoporous silica nanoparticles (MSNs) to enhance morin bioavailability and consequently increase the antitumor effects in melanoma cells. Spheroidal MSNs with a mean size of 56.3 ± 6.5 nm and a specific surface area of 816 m2/g were synthesized. MH was successfully loaded (MH-MSN) using the evaporation method, with a loading capacity of 28.3% and loading efficiency of 99.1%. In vitro release studies showed that morin release from MH-MSNs was enhanced at pH 5.2, indicating increased flavonoid solubility. The in vitro cytotoxicity of MH and MH-MSNs on human A375, MNT-1 and SK-MEL-28 melanoma cell lines was investigated. Exposure to MSNs did not affect the cell viability of any of the cell lines tested, suggesting that the nanoparticles are biocompatible. The effect of MH and MH-MSNs on reducing cell viability was time- and concentration-dependent in all melanoma cell lines. The A375 and SK-MEL-28 cell lines were slightly more sensitive than MNT-1 cells in both the MH and MH-MSN treatments. Our findings suggest that MH-MSNs are a promising delivery system for the treatment of melanoma.

Infections in Biological and Targeted Synthetic Drug Use in Rheumatoid Arthritis: Where do We Stand? A Scoping Review and Meta-analysis.

INTRODUCTION: The advent of biological and targeted synthetic therapies has revolutionized rheumatoid arthritis (RA) treatment. However, this has come at the price of an increased risk of infections. The aim of this study was to present an integrated overview of both serious and non-serious infections, and to identify potential predictors of infection risk in RA patients using biological or targeted synthetic drugs. METHODS: We systematically reviewed available literature from PubMed and Cochrane and performed multivariate meta-analysis with meta-regression on the reported infections. Randomized controlled trials and prospective and retrospective observational studies including patient registry studies were analyzed, combined as well as separately. We excluded studies focusing on viral infections only. RESULTS: Infections were not reported in a standardized manner. Meta-analysis showed significant heterogeneity that persisted after forming subgroups by study design and follow-up duration. Overall, the pooled proportions of patients experiencing an infection during a study were 0.30 (95% CI, 0.28-0.33) and 0.03 (95% CI, 0.028-0.035) for any kind of infections or serious infections only, respectively. We found no potential predictors that were consistent across all study subgroups. CONCLUSIONS: The high heterogeneity and the inconsistency of potential predictors between studies show that we do not yet have a complete picture of infection risk in RA patients using biological or targeted synthetic drugs. Besides, we found non-serious infections outnumbered serious infections by a factor 10:1, but only a few studies have focused on their occurrence. Future studies should apply a uniform method of infectious adverse event reporting and also focus on non-serious infections and their impact on treatment decisions and quality of life.

Improved Outcomes After Pulmonary Valve Replacement in Repaired Tetralogy of Fallot.

BACKGROUND: The impact of pulmonary valve replacement (PVR) on major adverse clinical outcomes in patients with repaired tetralogy of Fallot (rTOF) is unknown. OBJECTIVES: The purpose of this study was to determine whether PVR is associated with improved survival and freedom from sustained ventricular tachycardia (VT) in rTOF. METHODS: A PVR propensity score was created to adjust for baseline differences between PVR and non-PVR patients enrolled in INDICATOR (International Multicenter TOF Registry). The primary outcome was time to the earliest occurrence of death or sustained VT. PVR and non-PVR patients were matched 1:1 on PVR propensity score (matched cohort) and in the full cohort, modeling was performed with propensity score as a covariate adjustment. RESULTS: Among 1,143 patients with rTOF (age 27 ± 14 years, 47% PVR, follow-up 8.3 ± 5.2 years), the primary outcome occurred in 82. The adjusted HR for the primary outcome for PVR vs no-PVR (matched cohort n = 524) was 0.41 (95% CI: 0.21-0.81; multivariable model P = 0.010). Full cohort analysis revealed similar results. Subgroup analysis suggested beneficial effects in patients with advanced right ventricular (RV) dilatation (interaction P = 0.046; full cohort). In patients with RV end-systolic volume index >80 mL/m2, PVR was associated with a lower primary outcome risk (HR: 0.32; 95% CI: 0.16-0.62; P < 0.001). There was no association between PVR and the primary outcome in patients with RV end-systolic volume index ≤80 mL/m2 (HR: 0.86; 95% CI: 0.38-1.92; P = 0.70). CONCLUSIONS: Compared with rTOF patients who did not receive PVR, propensity score-matched individuals receiving PVR had lower risk of a composite endpoint of death or sustained VT.

Cardiac Fibrosis and Innervation State in Uncorrected and Corrected Transposition of the Great Arteries: A Postmortem Histological Analysis and Systematic Review.

In the transposition of the great arteries (TGA), alterations in hemodynamics and oxygen saturation could result in fibrotic remodeling, but histological studies are scarce. We aimed to investigate fibrosis and innervation state in the full spectrum of TGA and correlate findings to clinical literature. Twenty-two human postmortem TGA hearts, including TGA without surgical correction (n = 8), after Mustard/Senning (n = 6), and arterial switch operation (ASO, n = 8), were studied. In newborn uncorrected TGA specimens (1 day-1.5 months), significantly more interstitial fibrosis (8.6% ± 3.0) was observed compared to control hearts (5.4% ± 0.8, p = 0.016). After the Mustard/Senning procedure, the amount of interstitial fibrosis was significantly higher (19.8% ± 5.1, p = 0.002), remarkably more in the subpulmonary left ventricle (LV) than in the systemic right ventricle (RV). In TGA-ASO, an increased amount of fibrosis was found in one adult specimen. The amount of innervation was diminished from 3 days after ASO (0.034% ± 0.017) compared to uncorrected TGA (0.082% ± 0.026, p = 0.036). In conclusion, in these selected postmortem TGA specimens, diffuse interstitial fibrosis was already present in newborn hearts, suggesting that altered oxygen saturations may already impact myocardial structure in the fetal phase. TGA-Mustard/Senning specimens showed diffuse myocardial fibrosis in the systemic RV and, remarkably, in the LV. Post-ASO, decreased uptake of nerve staining was observed, implicating (partial) myocardial denervation after ASO.

Common genetic variants improve risk stratification after the atrial switch operation for transposition of the great arteries.

BACKGROUND: Clinical factors are used to estimate late complication risk in adults after atrial switch operation (AtrSO) for transposition of the great arteries (TGA), but heterogeneity in clinical course remains. We studied whether common genetic variants are associated with outcome and add value to a clinical risk score in TGA-AtrSO patients. METHODS AND RESULTS: This multicenter study followed 133 TGA-AtrSO patients (aged 28 [IQR 24-35] years) for 13 (IQR 9-16) years and examined the association of genome-wide single-nucleotide polymorphisms (SNPs) with a composite endpoint of symptomatic ventricular arrhythmia, heart failure hospitalization, ventricular assist device implantation, heart transplantation, or mortality. Thirty-two patients (24%) reached the endpoint. The genome-wide association study yielded one genome-wide significant (p < 1 × 10-8) locus and 18 suggestive loci (p < 1 × 10-5). A genetic risk score constructed on the basis of independent SNPs with p < 1 × 10-5 was associated with outcome after correction for the clinical risk score (HR = 1.26/point increase [95%CI 1.17-1.35]). Risk stratification improved with a combined risk score (clinical score + genetic score) compared to the clinical score alone (p = 2 × 10-16, C-statistic 0.95 vs 0.85). In 51 patients with a clinical intermediate (5-20%) 5-year risk of events, the combined score reclassified 32 patients to low (<5%) and 5 to high (>20%) risk. Stratified by the combined score, observed 5-year event-free survival was 100%, 79% and 31% for low, intermediate, and high-risk patients, respectively. CONCLUSIONS: Common genetic variants may explain some variation in the clinical course in TGA-AtrSO and improve risk stratification over clinical factors alone, especially in patients at intermediate clinical risk. These findings support the hypothesis that including genetic variants in risk assessment may be beneficial.

Polymeric Materials as Indispensable Tools to Fight RNA Viruses: SARS-CoV-2 and Influenza A.

Towards the end of 2019 in Wuhan, suspicions of a new dangerous virus circulating in the air began to arise. It was the start of the world pandemic coronavirus disease 2019 (COVID-19). Since then, considerable research data and review papers about this virus have been published. Hundreds of researchers have shared their work in order to achieve a better comprehension of this disease, all with the common goal of overcoming this pandemic. The coronavirus is structurally similar to influenza A. Both are RNA viruses and normally associated with comparable infection symptoms. In this review, different case studies targeting polymeric materials were appraised to highlight them as an indispensable tool to fight these RNA viruses. In particular, the main focus was how polymeric materials, and their versatile features could be applied in different stages of viral disease, i.e., in protection, detection and treatment.

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.

Tracking Emergence and Spread of SARS-CoV-2 Omicron Variant in Large and Small Communities by Wastewater Monitoring in Alberta, Canada.

Wastewater monitoring of SARS-CoV-2 enables early detection and monitoring of the COVID-19 disease burden in communities and can track specific variants of concern. We determined proportions of the Omicron and Delta variants across 30 municipalities covering >75% of the province of Alberta (population 4.5 million), Canada, during November 2021-January 2022. Larger cities Calgary and Edmonton exhibited more rapid emergence of Omicron than did smaller and more remote municipalities. Notable exceptions were Banff, a small international resort town, and Fort McMurray, a medium-sized northern community that has many workers who fly in and out regularly. The integrated wastewater signal revealed that the Omicron variant represented close to 100% of SARS-CoV-2 burden by late December, before the peak in newly diagnosed clinical cases throughout Alberta in mid-January. These findings demonstrate that wastewater monitoring offers early and reliable population-level results for establishing the extent and spread of SARS-CoV-2 variants.

NSAID-Based Coordination Compounds for Biomedical Applications: Recent Advances and Developments.

After the serendipitous discovery of cisplatin, a platinum-based drug with chemotherapeutic effects, an incredible amount of research in the area of coordination chemistry has been produced. Other transition metal compounds were studied, and several new relevant metallodrugs have been synthetized in the past few years. This review is focused on coordination compounds with first-row transition metals, namely, copper, cobalt, nickel or manganese, or with zinc, which have potential or effective pharmacological properties. It is known that metal complexes, once bound to organic drugs, can enhance the drugs' biological activities, such as anticancer, antimicrobial or anti-inflammatory ones. NSAIDs are a class of compounds with anti-inflammatory properties used to treat pain or fever. NSAIDs' properties can be strongly improved when included in complexes using their compositional N and O donor atoms, which facilitate their coordination to metal ions. This review focuses on the research on this topic and on the promising or effective results that complexes of first-row transition metals and NSAIDs can exhibit.

Eisenmenger Syndrome: JACC State-of-the-Art Review.

Although major breakthroughs in the field of pediatric cardiology, cardiac surgery, intervention, and overall care improved the outlook of congenital heart disease, Eisenmenger syndrome (ES) is still encountered and remains a complex clinical entity with multisystem involvement, including secondary erythrocytosis, increased thrombotic and bleeding diathesis, high arrhythmogenic risk, progressive heart failure, and premature death. Clearly, care for ES is best delivered in multidisciplinary expert centers. In this review, we discuss the considerable recent progress in understanding the complex pathophysiology of ES, means of prognostication, and improvement in clinical outcomes achieved with pulmonary arterial hypertension-targeted therapies. Additionally, we delineate areas of uncertainty in various aspects of care, discuss gaps in current evidence, and review current status in less privileged countries and propose initiatives to reduce disease burden. Finally, we propose the application of emerging technologies to enhance the delivery and quality of health care related to ES and beyond.

Coagulation and Anticoagulation in Fontan Patients.

Patients with a Fontan circulation for single-ventricle physiology are at increased risk of developing thromboembolic events. Thromboembolic events can lead to failure of the Fontan circulation, chronic sequelae in case of stroke, and early mortality. Controversies exist regarding the substrates, risk factors, and optimal detection methods for thromboembolic events. Despite the major clinical implications, there is currently no consensus regarding the optimal antithrombotic therapy to prevent or treat thromboembolic events after the Fontan procedure. In this review we aimed to untangle the available literature regarding antithrombotic prophylaxis and treatment for pediatric and adult Fontan patients. A decision-tree algorithm for thromboprophylaxis in Fontan patients is proposed. Additionally, the current state of knowledge is reviewed with respect to the epidemiology, pathophysiology, and detection of thromboembolic events in Fontan patients, and important evidence gaps are highlighted.

Hypertensive response to exercise in adult patients with repaired aortic coarctation.

OBJECTIVE: The clinical and prognostic implications of a hypertensive response to exercise after repair of coarctation of the aorta (CoA) remain controversial. We aimed to determine the prevalence of a hypertensive response to exercise, identify factors associated with peak exercise systolic blood pressure (SBP) and explore the association of peak exercise SBP with resting blood pressure and cardiovascular events during follow-up. METHODS: From the Dutch national CONgenital CORvitia (CONCOR) registry, adults with repaired CoA who underwent exercise stress testing were included. A hypertensive response to exercise was defined as a peak exercise SBP ≥210 mm Hg in men and ≥190 mm Hg in women. Cardiovascular events consisted of coronary artery disease, stroke, aortic complications and cardiovascular death. RESULTS: Of the original cohort of 920 adults with repaired CoA, 675 patients (median age 24 years (range 16-72 years)) underwent exercise stress testing. Of these, 299 patients (44%) had a hypertensive response to exercise. Mean follow-up duration was 10.1 years. Male sex, absence of a bicuspid aortic valve and elevated resting SBP were independently associated with increased peak exercise SBP. Peak exercise SBP was positively predictive of office SBP (ß=0.11, p<0.001) and 24-hour SBP (ß=0.05, p=0.03) at follow-up, despite correction for baseline SBP. During follow-up, 100 patients (15%) developed at least 1 cardiovascular event. Peak exercise SBP was not significantly associated with the occurrence of cardiovascular events (HR 0.994 (95% CI 0.987 to 1.001), p=0.11). CONCLUSIONS: A hypertensive response to exercise was present in nearly half of the patients in this large, prospective cohort of adults with repaired CoA. Risk factors for increased peak exercise SBP were male sex, absence of a bicuspid aortic valve and elevated resting SBP. Increased peak exercise SBP independently predicted hypertension at follow-up. These results support close follow-up of patients with a hypertensive response to exercise to ensure timely diagnosis and treatment of future hypertension.

Silica-Based Nanomaterials for Diabetes Mellitus Treatment.

Diabetes mellitus, a chronic metabolic disease with an alarming global prevalence, is associated with several serious health threats, including cardiovascular diseases. Current diabetes treatments have several limitations and disadvantages, creating the need for new effective formulations to combat this disease and its associated complications. This motivated the development of therapeutic strategies to overcome some of these limitations, such as low therapeutic drug bioavailability or poor compliance of patients with current therapeutic methodologies. Taking advantage of silica nanoparticle characteristics such as tuneable particle and pore size, surface chemistry and biocompatibility, silica-based nanocarriers have been developed with the potential to treat diabetes and regulate blood glucose concentration. This review discusses the main topics in the field, such as oral administration of insulin, glucose-responsive devices and innovative administration routes.

Baffle Complications in Adults After Atrial Switch for Transposition of the Great Arteries.

BACKGROUND: Baffle complications, ie, leakage or stenosis, after an atrial switch operation (AtrSO) for transposition of the great arteries (TGA) are difficult to detect with the use of routine transthoracic echocardiography (TTE). We examined baffle interventions and the prevalence of baffle complications. METHODS: This dual-centre study followed TGA-AtrSO patients for the occurrence of baffle interventions. In addition, in 2017-2019, prevalence of baffle complications was determined in patients undergoing routine contrast-enhanced (CE) TTE including various hemodynamic conditions and computed tomography (CT). Baffle leaks were defined as right-to-left shunting on CE-TTE and baffle stenosis as a systemic venous baffle diameter of < 10 mm on CT. RESULTS: In total, 67 TGA-AtrSO patients were followed to a median age of 38 (interquartile range 34-42) years, for a median of 9 (6-13) years. Baffle interventions were documented in 24 patients (36%). Cumulative risk of baffle interventions was 25% after 15 years of follow-up. Prevalence of baffle complications was determined in 29/67 patients. In total, 4 (14%) had patent baffles, 11 (38%) had leakage only, 5 (17%) had stenosis only, and 9 (31%) had both, while 24/29 (84%) were asymptomatic. Although baffle leaks were not associated with clinical characteristics, peak work rate during exercise TTE was lower in patients with vs without stenosis (89 ± 24 W vs 123 ± 21 W; P < 0.001). CONCLUSIONS: Baffle complications are common in TGA-AtrSO. The cumulative risk of baffle interventions was 25% after 15 years of follow-up. CE-TTE uncovered asymptomatic baffle leakage in the majority of patients, especially with examination during exercise. CT revealed baffle stenosis in almost half of the patients, which was associated with decreased exercise tolerance. Awareness of these findings may alter clinical follow-up.

Cardiac MRI predictors of good long-term outcomes in patients with repaired TOF.

BACKGROUND: Risk stratification in patients with repaired tetralogy of Fallot (rTOF) have focused on poor clinical outcomes while predictors of a benign clinical course have not been characterized. OBJECTIVE: The goal of this study was to Identify cardiac magnetic resonance (CMR) markers of a good clinical course late after TOF repair. METHODS: Clinical and CMR data from the International Multicenter TOF Registry (INDICATOR) were analyzed. The primary outcome was time to the earliest occurrence of a composite of death, aborted sudden death, and sustained ventricular tachycardia (VT). The secondary outcome was time to the earliest occurrence of atrial arrhythmia, nonsustained VT, and NYHA class >II. Multinomial regression was used to identify predictors of the 3-category outcome: (a) good outcome, defined as freedom from the primary AND secondary outcomes at age 50 years; (b) poor outcome, defined as presence of the primary outcome before age 50 years; and (c) intermediate outcome, defined as not fulfilling criteria for good or poor outcomes. RESULTS: Among 1088 eligible patients, 96 had good outcome, 60 experienced poor outcome, and 932 had intermediate outcome. Patients were age 25.8±10.8 years at the time of the index CMR. Median follow-up was 5.8 years (IQR 3.0, 9.9) after CMR in event-free patients. By univariate analysis, smaller right ventricular (RV) end-systolic and end-diastolic volume index, smaller left ventricular end-systolic volume index, higher right and left ventricular ejection fraction, lower right and left ventricular mass index, and lower left ventricular mass/volume ratio were associated with good outcome. Multivariable modeling identified higher RV ejection fraction (OR 2.38 per 10% increase, P = .002) and lower RV mass index (OR 1.72, per 10 g/m2 decrease, P = .002) as independently associated with good outcome after adjusting for age at CMR. Classification and regression tree analysis identified important thresholds associated with good outcome that were specific to patients age ≥37 years at the time of CMR; these were RV ejection fraction ≥42% and RV mass index <39 g/m2. CONCLUSIONS: Adults with rTOF and no more than mild RV dysfunction combined with no significant RV hypertrophy are likely to be free from serious adverse clinical events into their sixth decade of life and may require less frequent cardiac testing.