Analysis of N- and O-linked site-specific glycosylation by ion mobility mass spectrometry: State of the art and future directions.

Glycosylation, the major post-translational modification of proteins, significantly increases the diversity of proteoforms. Glycans are involved in a variety of pivotal structural and functional roles of proteins, and changes in glycosylation are profoundly connected to the progression of numerous diseases. Mass spectrometry (MS) has emerged as the gold standard for glycan and glycopeptide analysis because of its high sensitivity and the wealth of fragmentation information that can be obtained. Various separation techniques have been employed to resolve glycan and glycopeptide isomers at the front end of the MS. However, differentiating structures of isobaric and isomeric glycopeptides constitutes a challenge in MS-based characterization. Many reports described the use of various ion mobility-mass spectrometry (IM-MS) techniques for glycomic analyses. Nevertheless, very few studies have focused on N- and O-linked site-specific glycopeptidomic analysis. Unlike glycomics, glycoproteomics presents a multitude of inherent challenges in microheterogeneity, which are further exacerbated by the lack of dedicated bioinformatics tools. In this review, we cover recent advances made towards the growing field of site-specific glycosylation analysis using IM-MS with a specific emphasis on the MS techniques and capabilities in resolving isomeric peptidoglycan structures. Furthermore, we discuss commonly used software that supports IM-MS data analysis of glycopeptides.

Chromosomal instability in aneuploid acute lymphoblastic leukemia associates with disease progression.

Chromosomal instability (CIN) lies at the core of cancer development leading to aneuploidy, chromosomal copy-number heterogeneity (chr-CNH) and ultimately, unfavorable clinical outcomes. Despite its ubiquity in cancer, the presence of CIN in childhood B-cell acute lymphoblastic leukemia (cB-ALL), the most frequent pediatric cancer showing high frequencies of aneuploidy, remains unknown. Here, we elucidate the presence of CIN in aneuploid cB-ALL subtypes using single-cell whole-genome sequencing of primary cB-ALL samples and by generating and functionally characterizing patient-derived xenograft models (cB-ALL-PDX). We report higher rates of CIN across aneuploid than in euploid cB-ALL that strongly correlate with intraclonal chr-CNH and overall survival in mice. This association was further supported by in silico mathematical modeling. Moreover, mass-spectrometry analyses of cB-ALL-PDX revealed a "CIN signature" enriched in mitotic-spindle regulatory pathways, which was confirmed by RNA-sequencing of a large cohort of cB-ALL samples. The link between the presence of CIN in aneuploid cB-ALL and disease progression opens new possibilities for patient stratification and offers a promising new avenue as a therapeutic target in cB-ALL treatment.

Torque Teno Virus plasma DNA load: a novel prognostic biomarker in CAR-T therapy.

Torque Teno Virus (TTV) is a single-stranded circular DNA virus which has been identified as a surrogate marker of immune competence in transplantation. In this study we investigated the dynamics of plasma TTV DNAemia in 79 adult patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory large B-cell lymphoma, also evaluating the impact of TTV on immunotoxicities, response and survival outcomes. After lymphodepleting therapy, TTV DNA load was found to decrease slightly until reaching nadir around day 10, after which it increased steadily until reaching maximum load around day 90. TTV DNA load < 4.05 log10 copies/ml at immune effector cell-associated neurotoxicity syndrome (ICANS) onset identified patients at risk of progressing to severe forms of ICANS (OR 16.68, P = 0.048). Finally, patients who experienced falling or stable TTV DNA load between lymphodepletion and CAR-T infusion had better progression-free survival than those with ascending TTV DNA load (HR 0.31, P = 0.006). These findings suggest that TTV monitoring could serve as a surrogate marker of immune competence, enabling predictions of CAR-T efficacy and toxicity. This could pave the way for the development of TTV-guided therapeutic strategies that modulate clinical patient management based on plasma TTV load, similar to suggested strategies in solid organ transplant recipients.

Responses of Mytilus galloprovincialis in a Multi-Stressor Scenario: Effects of an Invasive Seaweed Exudate and Microplastic Pollution under Ocean Warming.

Microplastic pollution, global warming, and invasive species are known threats to marine biota, but the impact of their simultaneous exposure is still not well understood. This study investigated whether the toxic effects posed by the invasive red seaweed Asparagopsis armata exudate (2%) to the mussel Mytilus galloprovincialis are amplified by a 96 h exposure to increased temperature (24 °C) and polyethylene microplastics (PE-MPs, 1 mg/L). Biochemical (neurotoxicity, energy metabolism, oxidative stress, and damage) and physiological (byssal thread production) responses were evaluated. The number of produced byssus greatly decreased under concomitant exposure to all stressors. The antioxidant defences were depleted in the gills of mussels exposed to temperature rises and PE-MPs, regardless of exudate exposure, preventing oxidative damage. Moreover, the heat shock protein content tended to decrease in all treatments relative to the control. The increased total glutathione in the mussels' digestive gland exposed to 24 °C, exudate, and PE-MPs avoided oxidative damage. Neurotoxicity was observed in the same treatment. In contrast, the energy metabolism remained unaltered. In conclusion, depending on the endpoint, simultaneous exposure to A. armata exudate, PE-MPs, and warming does not necessarily mean an amplification of their single effects. Studies focusing on the impact of multiple stressors are imperative to better understand the underlying mechanisms of this chronic exposure.

Remdesivir or Nirmatrelvir/Ritonavir Therapy for Omicron SARS-CoV-2 Infection in Hematological Patients and Cell Therapy Recipients.

BACKGROUND: Scarce data exist that analyze the outcomes of hematological patients with SARS-CoV-2 infection during the Omicron variant period who received treatment with remdesivir or nirmatrelvir/ritonavir. METHODS: This study aims to address this issue by using a retrospective observational registry, created by the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group, spanning from 27 December 2021 to 30 April 2023. RESULTS: This study included 466 patients, 243 (52%) who were treated with remdesivir and 223 (48%) with nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir was primarily used for mild cases, resulting in a lower COVID-19-related mortality rate (1.3%), while remdesivir was preferred for moderate to severe cases (40%), exhibiting a higher mortality rate (9%). A multivariate analysis in the remdesivir cohort showed that male gender (odds ratio (OR) 0.35, p = 0.042) correlated with a lower mortality risk, while corticosteroid use (OR 9.4, p < 0.001) and co-infection (OR 2.8, p = 0.047) were linked to a higher mortality risk. Prolonged virus shedding was common, with 52% of patients shedding the virus for more than 25 days. In patients treated with remdesivir, factors associated with prolonged shedding included B-cell malignancy as well as underlying disease, severe disease, a later onset of and shorter duration of remdesivir treatment and a higher baseline viral load. Nirmatrelvir/ritonavir demonstrated a comparable safety profile to remdesivir, despite a higher risk of drug interactions. CONCLUSIONS: Nirmatrelvir/ritonavir proved to be a safe and effective option for treating mild cases in the outpatient setting, while remdesivir was preferred for severe cases, where corticosteroids and co-infection significantly predicted worse outcomes. Despite antiviral therapy, prolonged shedding remains a matter of concern.

"Ghost" fragment ions in structure and site-specific glycoproteomics analysis.

Mass spectrometry (MS) can unlock crucial insights into the intricate world of glycosylation analysis. Despite its immense potential, the qualitative and quantitative analysis of isobaric glycopeptide structures remains one of the most daunting hurdles in the field of glycoproteomics. The ability to distinguish between these complex glycan structures poses a significant challenge, hindering our ability to accurately measure and understand the role of glycoproteins in biological systems. A few recent publications described the use of collision energy (CE) modulation to improve structural elucidation, especially for qualitative purposes. Different linkages of glycan units usually demonstrate different stabilities under CID/HCD fragmentation conditions. Fragmentation of the glycan moiety produces low molecular weight ions (oxonium ions) that can serve as a structure-specific signature for specific glycan moieties, however, specificity of these fragments has never been examined closely. Here, we investigated fragmentation specificity using synthetic stable isotope-labelled glycopeptide standards. These standards were isotopically labelled at the reducing terminal GlcNAc, which allowed us to resolve fragments produced by oligomannose core moiety and fragments generated from outer antennary structures. Our research identified the potential for false positive structure assignments due to the occurrence of "Ghost" fragments resulting from single glyco unit rearrangement or mannose core fragmentation within the collision cell. To mitigate this issue, we have established a minimal intensity threshold for these fragments to prevent the misidentification of structure-specific fragments in glycoproteomics analysis. Our findings provide a crucial step forward in the quest for more accurate and reliable glycoproteomics measurements.

Toxicity assessment of binary mixtures of BP3 with 4-MBC (UV-filters), and BP3 with DEET (insect repellent) using the aquatic midge Chironomus riparius.

Personal care products have various organic ultraviolet filters (UV filters) in their composition to increase protection against ultraviolet radiation. Some of these products also contain insect repellents in their formulations. Consequently, these compounds reach freshwater ecosystems, exposing aquatic organisms to a cocktail of anthropogenic contaminants. In this study, the joint effects of two most frequently detected UV filters (Benzophenone - 3 (BP3) and Enzacamene (4-MBC)) and joint effects of BP3 combined with an insect repellent (N, N diethyl-3-methylbenzamide - DEET) were evaluated using life-history traits of the aquatic midge Chironomus riparius such as emergence rate, time to emergence and imagoes body weight. The results showed synergistic effects between BP3 and 4-MBC for C. riparius emergence rate. Regarding the effects of BP3 and DEET mixture, our analysis suggests synergism in the case of males but antagonism in the case of females' time to emergence. Our results imply that the effects of UV filters present in sediments within chemical mixtures are complex and that the evaluation of effects using different life-history traits can yield different patterns of responses. This study demonstrates the importance of assessing the combined effects of pollutants used/found concomitantly in aquatic systems for a more accurate risk assessment, as individual chemical testing can underestimate the toxicity of organic UV filters.

Nanoplastic exposure inhibits feeding and delays regeneration in a freshwater planarian.

The concentration of nanoplastics (NPs) is expected to increase in aquatic environments thus potentially threatening freshwater organisms through interactions with plastic particles that variously float, circulate in the water column or sink into the benthos. Studies into the mechanisms of any NP effects are still scarce, particularly with respect to the regenerative ability of biota for which there is no recognised model organism. The present study therefore aimed to investigate behavioural and regeneration responses of the freshwater planarian Girardia tigrina after 10 days exposed to along a gradient 0.01-10 mg/L of poly (styrene-co-methyl methacrylate) NPs (∼426 ± 175 nm). Exposure to NPs induced a significant reduction in planarian feeding rate even at low concentrations (LOEC of 0.01 mg/L), while head regeneration was delayed in a clear dose response way (LOEC of 0.1 mg/L for blastema length). Planaria locomotion assessed was not affected. Our results highlight the potential adverse effects of exposure to poly (styrene-co-methyl methacrylate) NPs and show that feeding behaviour and regeneration of a freshwater benthic organism can be indicators of the resulting toxicity. Planarians are becoming widely used model organisms in ecotoxicology and can help to address potential effects of plastic polymers on regeneration.

"Ghost" Fragment Ions in Structure and Site-Specific Glycoproteomics Analysis.

Mass spectrometry (MS) can unlock crucial insights into the intricate world of glycosylation analysis. Despite its immense potential, the qualitative and quantitative analysis of isobaric glycopeptide structures remains one of the most daunting hurdles in the field of glycoproteomics. The ability to distinguish between these complex glycan structures poses a significant challenge, hindering our ability to accurately measure and understand the role of glycoproteins in biological systems. A few recent publications described the use of collision energy (CE) modulation to improve structural elucidation, especially for qualitative purposes. Different linkages of glycan units usually demonstrate different stabilities under CID/HCD fragmentation conditions. Fragmentation of the glycan moiety produces low molecular weight ions (oxonium ions) that can serve as a structure-specific signature for specific glycan moieties; however, the specificity of these fragments has never been examined closely. Here, we particularly focused on N-glycoproteomics analysis and investigated fragmentation specificity using synthetic stable isotope-labeled N-glycopeptide standards. These standards were isotopically labeled at the reducing terminal GlcNAc, which allowed us to resolve fragments produced by the oligomannose core moiety and fragments generated from outer antennary structures. Our research identified the potential for false-positive structure assignments due to the occurrence of "Ghost" fragments resulting from single glyco unit rearrangement or mannose core fragmentation within the collision cell. To mitigate this issue, we have established a minimal intensity threshold for these fragments to prevent misidentification of structure-specific fragments in glycoproteomics analysis. Our findings provide a crucial step forward in the quest for more accurate and reliable glycoproteomics measurements.

Magnetized vermiculite as a tool for the treatment of produced water generated by oil companies: Effects on aquatic organisms before and after treatment.

Produced water (PW) generated by oil companies is a highly impacting waste that contains chemicals such as metals and organic and inorganic compounds. Given its polluting potential, PW requires effective treatment before being discharged into the environment. Conventional treatments have limited efficiency in removing PW toxicity, so alternative approaches must be developed and standardized. In this context, treatment with adsorbent materials like magnetized vermiculite (VMT-mag) is highlighted. This work aimed to evaluate the efficiency of treatment with VMT-mag in reducing PW toxicity to aquatic biota. For this purpose, three aquatic species (the midge Chironomus riparius, the planarian Girardia tigrina, and the crustacean Daphnia magna) were exposed to untreated PW and to PW treated with VMT-mag at laboratory conditions. The assessed endpoints included mortality, growth, emergence, and developmental time of C. riparius; mortality, locomotion, feeding, and head regeneration of G. tigrina; and intrinsic population growth rate (r) and reproductive output of D. magna. The results showed that all the species exposed to raw PW were impaired: C. riparius had delayed development, G. tigrina had reduced locomotor activity and delayed head regeneration, and D. magna had reduced reproduction and delayed intrinsic population growth rate (r). Most of the analyzed parameters showed that treatment with VMT-mag diminished PW toxicity. Therefore, using VMT-mag to treat PW may be the key to reducing the PW effects on aquatic organisms.

Glycoprotein IIb/IIIa inhibitor use in cardiogenic shock complicating myocardial infarction: The Portuguese Registry of Acute Coronary Syndromes.

INTRODUCTION AND OBJECTIVES: Cardiogenic shock (CS) complicates 5-10% of cases of myocardial infarction (MI). Whether glycoprotein IIb/IIIa inhibitors (GPIs) are beneficial in these patients is controversial. Our aim is to assess the prognostic impact of GPI use on in-hospital mortality and outcomes in patients with MI and CS undergoing percutaneous coronary intervention (PCI). METHODS: Between October 2010 and December 2019, 27578 acute coronary syndrome (ACS) patients were included in the multicenter Portuguese Registry of Acute Coronary Syndromes. Of these, 357 with an MI complicated by CS were included in the analysis and grouped based on whether they received GPI therapy (with GPI, n=107 and without GPI, n=250). The primary endpoint was in-hospital mortality. Secondary endpoints included successful PCI and in-hospital reinfarction and major bleeding. RESULTS: Demographics and cardiovascular risk factors did not differ between groups. ST-elevation MI patients were more likely to receive GPIs (95% vs. 83%, p=0.002). In-hospital mortality was similar between groups (OR 1.80, 95% CI 0.96-3.37). Only age and the use of inotropes or intra-aortic balloon pump were predictors of mortality. Also, no differences between groups were noted for successful PCI (OR 0.33, 95% CI 0.62-4.06), reinfarction (OR 0.77, 95% CI 0.15-3.90), or major bleeding (OR 1.68, 95% CI 0.75-3.74). CONCLUSION: The use of GPIs in the context of MI with CS did not significantly impact in-hospital outcomes.

Renal sympathetic denervation in resistant hypertension: The association between vitamin D and positive early response in systolic blood pressure.

AIMS AND OBJECTIVES: Vitamin D deficiency is a common finding and there is a suggested association with hypertension. Resistant hypertension is a clinical problem observed in 5-30% of hypertensive patients. Renal denervation (RDN) has been used for patients with resistant hypertension and has proven to lower blood pressure. Our primary goal was to assess the vitamin D serum concentration as a predictor of blood pressure response to RDN in highly selected patients. METHODS: This prospective, nonrandomized, single-center study included 24 patients treated with RDN. Based on their one-year response after RDN, patients were classified as responders or non-responders at six months or at 12 months. RESULTS: The median follow-up was 52 months (range, 14-91 months). After RDN, 17 patients (70.8%) had a reduction >5 mmHg in the mean systolic blood pressure, at the first six months of follow-up. At 12 months, 20 patients (83.3%) were responders. Vitamin D levels at baseline (15.1±4.8 vs. 24.2±8.8 ng/ml) and at six months (16.6±7.2 vs. 25±9.2 ng/ml) were lower in early non-responders compared to early responders (p=0.008), without significant variation during follow-up. Even though Vitamin D levels were lower in the total responder's group, no statistically significant differences were found (p=ns). CONCLUSION: In patients with resistant hypertension, low vitamin D concentrations were associated with an absence of early response to RDN.

Polymeric nanoparticles targeting Sialyl-Tn in gastric cancer: A live tracking under flow conditions.

Drug delivery using nanoparticles (NPs) represents a potential approach for therapy in cancer, such gastric cancer (GC) due to their targeting ability and controlled release properties. The use of advanced nanosystems that deliver anti-cancer drugs specifically to tumor cells may strongly rely on the expression of cancer-associated targets. Glycans aberrantly expressed by cancer cells are attractive targets for such delivery strategy. Sialylated glycans, such as Sialyl-Tn (STn) are aberrantly expressed in several epithelial tumors, including GC, being a potential target for a delivery nanosystem. The aim of this study was the development of NPs surface-functionalized with a specific antibody targeting the STn glycan and further evaluate this nanosystem effectiveness regarding its specificity and recognition capacity. Our results showed that the NPs surface-functionalized with anti-STn antibody efficiently are recognized by cells displaying the cancer-associated STn antigen under static and live cell monitoring flow conditions. This uncovers the potential use of such NPs for drug delivery in cancer. However, flow exposure was disclosed as an important biomechanical parameter to be taken into consideration. Here we presented an innovative and successful methodology to live track the NPs targeting STn antigen under shear stress, simulating the physiological flow. We demonstrate that unspecific binding of NPs agglomerates did not occur under flow conditions, in contrast with static assays. This robust approach can be applied for in vitro drug studies, giving valuable insights for in vivo studies.

Hand grip strength, standing balance, and rapid foot tapping in relation to the menopausal transition in Campeche, Mexico.

OBJECTIVES: This cross-sectional study investigated menopause status in relation to hand grip strength, standing balance, and rapid foot tapping. A secondary aim was to examine the relationship between physical performance and urban/rural residence with a focus on habitual daily tasks. METHODS: Maya and non-Maya women (40-60 years) were drawn from urban and rural sites in Campeche, Mexico (n = 543). Demographic, reproductive, and lifestyle information was collected in face-to-face interviews along with anthropometric and physical function measures. Linear regression was used to evaluate menopause status in relation to strength, balance, and foot tapping speed while adjusting for residence, ethnicity, and other variables. RESULTS: Hand grip strength was 22.5, 21.6, and 20.0 kg in pre-, peri-, and postmenopausal women, respectively, but menopause status was not significantly related to grip strength in models adjusted for age. Grip strength was negatively associated with age and socioeconomic index, and positively associated with height and weight, self-reported health, and hours/week spent grinding corn/making tortillas. Postural stability was 9.4, 6.9, and 5.6 s across menopause categories; and menopause status remained significant in adjusted models. The number of foot taps in 10 s was 35.7, 33.4, and 33.9 taps in pre-, peri-, and postmenopausal women. Parity was negatively associated with foot tapping in adjusted models. CONCLUSIONS: While age is a key predictor of physical function in women aged 40-60 years, menopausal status appears to have additional influences on postural control beyond age alone. Hours spent grinding corn/making tortillas were significantly associated with grip strength among rural women.

Editorial for the Special Issue "Microplastics in Aquatic Environments: Occurrence, Distribution and Effects".

The large production and widespread daily consumption of plastic materials-which began in the last century-together with the often-inadequate collection and recycling systems, have made plastics and, consequently, microplastics (MPs) ubiquitous pollutants [...].

Site-specific glycosylation of SARS-CoV-2: Big challenges in mass spectrometry analysis.

Glycosylation of viral proteins is required for the progeny formation and infectivity of virtually all viruses. It is increasingly clear that distinct glycans also play pivotal roles in the virus's ability to shield and evade the host's immune system. Recently, there has been a great advancement in structural identification and quantitation of viral glycosylation, especially spike proteins. Given the ongoing pandemic and the high demand for structure analysis of SARS-CoV-2 densely glycosylated spike protein, mass spectrometry methodologies have been employed to accurately determine glycosylation patterns. There are still many challenges in the determination of site-specific glycosylation of SARS-CoV-2 viral spike protein. This is compounded by some conflicting results regarding glycan site occupancy and glycan structural characterization. These are probably due to differences in the expression systems, form of expressed spike glycoprotein, MS methodologies, and analysis software. In this review, we recap the glycosylation of spike protein and compare among various studies. Also, we describe the most recent advancements in glycosylation analysis in greater detail and we explain some misinterpretation of previously observed data in recent publications. Our study provides a comprehensive view of the spike protein glycosylation and highlights the importance of consistent glycosylation determination.

Combined effects of polyethylene microplastics and natural stressors on Chironomus riparius life-history traits.

Several studies have shown that ingestion of microplastics causes adverse effects in aquatic organisms, including sediment-dwelling invertebrates. Most studies focus on evaluating the effects of plastic particles alone without testing the mediating effects of different natural stressors and thus lacking realistic exposure scenarios. The present study addresses the interactive effects of exposure to polyethylene microplastics (PE-MPs; 2.5 g/kg) in the midge Chironomus riparius life history traits under different temperatures (15, 20 and 25 °C), a salinity gradient (0, 1 and 3 g L-1 sodium chloride - NaCl) and different levels of food (0.5, 0.25 and 0.125 mg macerated fish food larva-1day-1). By the analyses of linear models and independent action models applied to different life-history traits, such as larval growth, development time and imagoes body weight, the present work reveals that under temperatures lower than 20 °C or severe food shortage (<0.25 mg macerated fish food larva-1day-1), microplastics' effects can be stronger than those observed at standard toxicity test conditions (20 °C and 0.5 mg food larva-1day-1). Additionally, we also found that, in general, toxicity induced by PE-MPs to C. riparius larvae was reduced under warmer temperature (25 °C) and salinity. As observed, MPs toxicity can be mediated by natural stressors, which underlines the importance of co-exposure studies. In this sense, these results contribute to a more accurate risk assessment of microplastics. Despite the complex interactions between microplastics and natural factors here tested, were not found evidence that the deleterious effects of PE-MPs on C. riparius life cycle history are aggravated under increased temperature, food shortage, or salinisation of freshwaters.

High-sensitivity Troponin I and Ablation Effectiveness Quotient after Ablation Index-guided pulmonary vein isolation-markers of arrhythmia recurrence?

BACKGROUND: There are conflicting data regarding the relationship between high-sensitivity cardiac Troponin I (Hs-cTnI) and the ablation effectiveness quotient (AEQ) with arrhythmia recurrence following atrial fibrillation (AF) ablation. Our goals were to evaluate the impact of the Ablation Index (AI) software on Hs-cTnI and AEQ levels and to assess whether these markers are predictors of arrhythmia recurrence. METHODS: Prospective single-center study of 75 consecutive patients referred for paroxysmal AF ablation from October 2017 to January 2019. Procedural endpoints and 2-year outcomes were assessed and compared to those of 75 propensity score-matched patients submitted to non-AI-guided pulmonary vein isolation (PVI) [control group]. RESULTS: Compared to the control group, patients having AI-guided PVI had lower Hs-cTnI values (1580 [IQR 1180-2140] ng/L vs. 2600 [IQR 1840 - 3900], p < 0.001) and a lower AEQ (0.9 [IQR 0.6-1.2] ng/L/s vs. 1.4 [0.8-1.6] ng/L/s, p < 0.001). After a median follow-up of 26 (IQR 20-32) months, there was a significant reduction in arrhythmia recurrence in the AI group (15% vs. 31%, HR 0.67 [95% CI, 0.32-1.40], p = 0.02). However, neither Hs-cTnI nor AEQ was predictors of arrhythmia recurrence in AI-guided PVI. CONCLUSIONS: The use of the AI software led to reduced levels of Hs-cTnI and lower AEQ in AF patients submitted to PVI. However, none of these markers predicted arrhythmia recurrence.

Aortic valve intervention for aortic stenosis and cardiac amyloidosis: a systematic review and meta-analysis.

Aortic stenosis with cardiac amyloidosis (CA-AS) is common in the elderly. We provide an overview and a meta-analysis of outcomes after aortic valve (AV) intervention. The primary end point was all-cause mortality. Weighted pooled analysis showed a non-significant higher risk of death in CA-AS patients following surgical or transcatheter AV replacement. After transcatheter AV replacement, the risk of death in CA-AS patients was comparable to that associated with aortic stenosis alone (risk ratio: 1.23; 95% CI: 0.77-1.96; p = 0.39; I2 = 0%). An AV intervention is possibly not futile in CA-AS and should not be denied to patients with this condition.

Dual presentation of aortic stenosis (AS) and cardiac amyloidosis (CA) is common in the elderly. Patients with CA-AS face a dismal prognosis. Clinical outcomes after an aortic valve intervention are conflicting. Our data showed that there is no increased risk of death in CA-AS patients compared with patients with only AS after an aortic valve replacement. In particular, our analysis unveils that following less invasive percutaneous aortic valve replacement, rates of death of patients with concomitant CA were not significantly different from those in patients who had AS without CA. Based on this data, an aortic valve substitution procedure should not be withheld in patients with CA.

Computed tomography coronary angiography as the noninvasive in stable coronary artery disease? Long-term outcomes meta-analysis.

Aim: To compare outcomes of coronary computed tomography angiography (CCTA) with that of functional testing (FT) in stable coronary artery disease. Methods: We searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs). A random-effects meta-analysis targeting all-cause death and nonfatal acute coronary syndromes was performed. Results: Eight RCTs enrolling 29,579 patients were included. Pooled relative risk (RR) for the primary end point was similar between CCTA and FT (RR = 0.97; 95% CI: 0.76-1.22). CCTA outperformed FT in nonfatal myocardial infarction (MI) (RR = 0.59; 95% CI: 0.41-0.83) and in downstream testing (OR: 0.47; 95% CI: 0.21-1.01). Conclusion: Updated data of stable coronary artery disease suggests that CCTA improved nonfatal MI and downstream testing.

Coronary heart disease (narrowed or blocked arteries) can be diagnosed either by a functional testing or an anatomic testing. In functional testing, we will see if there is some reduced blood flow in the heart. In anatomic testing, a computerized tomography coronary angiogram is performed, to see the presence of atherosclerotic plaque (cholesterol) and the degree of obstruction. In this review, we provide an aerial view of the latest evidence on the best approach to coronary artery disease diagnosis. Updated evidence shows that a computerized tomography coronary angiogram reduced the risk of myocardial infarction and the need of further testing after an initial approach.