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IntroductionHIV-exposed uninfected (HEU) infants exhibit elevated pro-inflammatory biomarkers that persist after birth. However, comprehensive assessments of bioprofiles associated with immune regulation and development in pregnant women with HIV (PWH) and HEU infants has not been performed. Maternal immunity in PWH may be imprinted on their HEU newborns, altering immune bioprofiles during early immune development.MethodsCryopreserved paired plasma samples from 46 HEU infants and their mothers enrolled in PACTG 316, a clinical trial to prevent perinatal HIV-1 transmission were analyzed. PWH received antiretrovirals (ARV) and had either fully suppressed or unsuppressed viral replication. Maternal blood samples obtained during labor and infant samples at birth and 6 months were measured for 21 biomarkers associated with germinal centers (GC), macrophage activation, T-cell activation, interferon gamma (IFN-γ)-inducible chemokines, and immune regulatory cytokines using Mesoscale assays. Pregnant women without HIV (PWOH) and their HIV unexposed uninfected (HUU) newborns and non-pregnant women without HIV (NPWOH) served as reference groups. Linear regression analysis fitted for comparison among groups and adjusted for covariant(s) along with principal component analysis performed to assess differences among groups.ResultsCompared with NPWOH, PWOH displayed higher levels of GC, macrophage, and regulatory biomarkers. PWH compared to PWOH displayed elevated GC, T cell activation, and IFN-γ-inducible chemokines biomarkers at delivery. Similar to their mothers, HEU infants had elevated GC, macrophage, and IFN-γ-inducible chemokines, as well as elevated anti-inflammatory cytokines, IL-10 and IL-1RA. Across all mother/newborn dyads, multiple biomarkers positively correlated, providing further evidence that maternal inflammation imprints on newborn bioprofiles. By 6 months, many HEU biomarkers normalized to levels similar to HUU infants, but some GC and inflammatory biomarkers remained perturbed. Bioprofiles in PWH and HEU infants were similar regardless of the extent of maternal viral suppression by ARV.ConclusionsGC immune pathways are perturbed in HEU newborns, but immune regulatory responses down regulate inflammation during early infancy, indicating a transient inflammatory effect. However, several GC biomarkers that may alter immune development remain perturbed.

Abstract Background The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. Methods Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). Results Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value

Heart failure (HF) is a chronic and progressive disease that often progresses to an advanced stage where conventional therapy is insufficient to relieve patients' symptoms. Despite the availability of advanced therapies such as mechanical circulatory support or heart transplantation, the complexity of defining advanced HF, which requires multiple parameters and multimodality assessment, often leads to delays in referral to dedicated specialists with the result of a worsening prognosis. In this review, we aim to explore the role of cardiac magnetic resonance (CMR) in advanced HF by showing how CMR is useful at every step in managing these patients: from diagnosis to prognostic stratification, hemodynamic evaluation, follow-up and advanced therapies such as heart transplantation. The technical challenges of scanning advanced HF patients, which often require troubleshooting of intracardiac devices and dedicated scans, will be also discussed., (© 2024 The Author(s). Echocardiography published by Wiley Periodicals LLC.)

IntroductionFactors influencing vaccine immune priming in the first year of life involve both innate and adaptive immunity but there are gaps in understanding how these factors sustain vaccine antibody levels in healthy infants. The hypothesis was that bioprofiles associated with B cell survival best predict sustained vaccine IgG levels at one year.MethodsLongitudinal study of plasma bioprofiles in 82 term, healthy infants, who received standard recommended immunizations in the United States, with changes in 15 plasma biomarker concentrations and B cell subsets associated with germinal center development monitored at birth, soon after completion of the initial vaccine series at 6 months, and prior to the 12-month vaccinations. Post vaccination antibody IgG levels to Bordetella pertussis, tetanus toxoid, and conjugated Haemophilus influenzae type B (HiB) were outcome measures.ResultsUsing a least absolute shrinkage and selection operator (lasso) regression model, cord blood (CB) plasma IL-2, IL-17A, IL-31, and soluble CD14 (sCD14) were positively associated with pertussis IgG levels at 12 months, while CB plasma concentrations of APRIL and IL-33 were negatively associated. In contrast, CB concentrations of sCD14 and APRIL were positively associated with sustained tetanus IgG levels. A separate cross-sectional analysis of 18 mother/newborn pairs indicated that CB biomarkers were not due to transplacental transfer, but rather due to immune activation at the fetal/maternal interface. Elevated percentages of cord blood switched memory B cells were positively associated with 12-month HiB IgG levels. BAFF concentrations at 6 and 12 months were positively associated with pertussis and HiB IgG levels respectively.DiscussionSustained B cell immunity is highly influenced by early life immune dynamics beginning prior to birth. The findings provide important insights into how germinal center development shapes vaccine responses in healthy infants and provide a foundation for studies of conditions that impair infant immune development.

Objectives: No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD., Methods: Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA., Results: In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3 years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively., Conclusions: The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD., Clinical Relevance Statement: The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies., Key Points: • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Incomplete atrial lesions resulting in pulmonary vein-left atrium reconnection after pulmonary vein antrum isolation (PVAI), are related to atrial fibrillation (AF) recurrence. Unfortunately, during the PVAI procedure, fluoroscopy and electroanatomic mapping cannot accurately determine the location and size of the ablation lesions in the atrial wall and this can result in incomplete PVAI lesions (PVAI-L) after radiofrequency catheter ablation (RFCA)., Aim: We seek to evaluate whether cardiac magnetic resonance (CMR), immediately after RFCA of AF, can identify PVAI-L by characterizing the left atrial tissue., Methods: Ten patients (63.1 ± 5.7 years old, 80% male) receiving a RFCA for paroxysmal AF underwent a CMR before (<1 week) and after (<1 h) the PVAI. Two-dimensional dark-blood T2-weighted short tau inversion recovery (DB-STIR), Three-dimensional inversion-recovery prepared long inversion time (3D-TWILITE) and three-dimensional late gadolinium enhancement (3D-LGE) images were performed to visualize PVAI-L., Results: The PVAI-L was visible in 10 patients (100%) using 3D-TWILITE and 3D-LGE. Conversely, On DB-STIR, the ablation core of the PAVI-L could not be identified because of a diffuse high signal of the atrial wall post-PVAI. Microvascular obstruction was identified in 7 (70%) patients using 3D-LGE., Conclusion: CMR can visualize PVAI-L immediately after the RFCA of AF even without the use of contrast agents. Future studies are needed to understand if the use of CMR for PVAI-L detection after RFCA can improve the results of ablation procedures., (© 2023 Wiley Periodicals LLC.)

In this prospective observational cohort study, we provide preliminary findings from a same-day multidisciplinary fast-tracked normal pressure hydrocephalus (NPH) clinic; incorporating the expertise of movement disorders neurologists, emphasizing the clinical characteristics, consensus classification, and management of patients referred for suspected NPH. We evaluated 111 patients (male/female: 67/44) from April 2022 to May 2023. Based on the multidisciplinary team consensus, 52 (46.8%) were classified as "probable" idiopathic NPH (iNPH), 14 (12.6%) as "possible" NPH, 42 (37.8%) as "unlikely" NPH, and three (2.7%) as secondary NPH. While parkinsonian syndromes were recognized in 19.2% of "probable" iNPH patients (vs. 7.1% in "possible" and 26.2% in "unlikely" NPH), no significant group differences were noted in the scores of the UPDRS-III scale. Degenerative spine pathologies were prevalent across all NPH categories, affecting at least 50% of patients. In the "probable" iNPH group, 78.8% received programmable ventriculoperitoneal shunts, with clinical improvement identified in 87.8% at 12-month follow-up. Our findings underscore the high prevalence of overlapping and competing movement and spinal disorders in patients with suspected NPH. Further, our novel approach, incorporating movement disorder neurologists in NPH multidisciplinary evaluation, improved diagnostic precision and streamlined personalized plans, including further neurological workups, necessary spinal interventions, and medical management or rehabilitation.

Cardiac amyloidosis (CA) is a cardiac storage disease caused by the progressive extracellular deposition of misfolded proteins in the myocardium. Despite the increasing interest in this pathology, it remains an underdiagnosed condition. Non-invasive diagnostic techniques play a central role in the suspicion and detection of CA, also thanks to the continuous scientific and technological advances in these tools. The 12-lead electrocardiography is an inexpensive and reproducible test with a diagnostic accuracy that, in some cases, exceeds that of imaging techniques, as recent studies have shown. Echocardiography is the first-line imaging modality, although none of its parameters are pathognomonic. According to the 2023 ESC Guidelines, a left ventricular wall thickness ≥ 12 mm is mandatory for the suspicion of CA, making this technique crucial. Cardiac magnetic resonance provides high-resolution images associated with tissue characterization. The use of contrast and non-contrast sequences enhances the diagnostic power of this imaging modality. Nuclear imaging techniques, including bone scintigraphy and positron emission tomography, allow the detection of amyloid deposition in the heart, and their role is also central in assessing the prognosis and response to therapy. The role of computed tomography was recently evaluated by several studies, above in population affected by aortic stenosis undergoing transcatheter aortic valve replacement, with promising results. Finally, machine learning and artificial intelligence-derived algorithms are gaining ground in this scenario and provide the basis for future research. Understanding the new insights into non-invasive diagnostic techniques is critical to better diagnose and manage patients with CA and improve their survival.

Background and Aims: This study investigated the additional prognostic value of epicardial adipose tissue (EAT) volume for major adverse cardiovascular events (MACE) in patients undergoing stress cardiac magnetic resonance (CMR) imaging., Methods: 730 consecutive patients [mean age: 63 ± 10 years; 616 men] who underwent stress CMR for known or suspected coronary artery disease were randomly divided into derivation (n = 365) and validation (n = 365) cohorts. MACE was defined as non-fatal myocardial infarction and cardiac deaths. A deep learning algorithm was developed and trained to quantify EAT volume from CMR. EAT volume was adjusted for height (EAT volume index). A composite CMR-based risk score by Cox analysis of the risk of MACE was created., Results: In the derivation cohort, 32 patients (8.7 %) developed MACE during a follow-up of 2103 days. Left ventricular ejection fraction (LVEF) < 35 % (HR 4.407 [95 % CI 1.903-10.202]; p<0.001), stress perfusion defect (HR 3.550 [95 % CI 1.765-7.138]; p<0.001), late gadolinium enhancement (LGE) (HR 4.428 [95%CI 1.822-10.759]; p = 0.001) and EAT volume index (HR 1.082 [95 % CI 1.045-1.120]; p<0.001) were independent predictors of MACE. In a multivariate Cox regression analysis, adding EAT volume index to a composite risk score including LVEF, stress perfusion defect and LGE provided additional value in MACE prediction, with a net reclassification improvement of 0.683 (95%CI, 0.336-1.03; p<0.001). The combined evaluation of risk score and EAT volume index showed a higher Harrel C statistic as compared to risk score (0.85 vs. 0.76; p<0.001) and EAT volume index alone (0.85 vs.0.74; p<0.001). These findings were confirmed in the validation cohort., Conclusions: In patients with clinically indicated stress CMR, fully automated EAT volume measured by deep learning can provide additional prognostic information on top of standard clinical and imaging parameters., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gianluca Pontone reports a relationship with G.E. Healthcare, Bracco, Heartflow, Boheringher that includes: funding grants and speaking and lecture fees. The other authors have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: We aimed to investigate the role of feature-tracking (FT) strain in long-term risk stratification of patients with known or suspected coronary artery disease (CAD) who underwent stress cardiac MRI with dipyridamole; to determine if contrast-free stress cardiac MRI with strain measurements could provide comparable prognostic value to myocardial perfusion., Materials and Methods: This retrospective study included consecutive patients with stable symptoms suggesting possible cardiac ischemia who underwent stress cardiac MRI with dipyridamole. The mean follow-up period was 5.8 years ±1.2 [SD]. FT cardiac MRI analysis was performed for each patient to obtain 2D global peak circumferential strain (GCS). The primary outcome measure was major adverse cardiac events (MACE), defined as nonfatal myocardial infarction and cardiac death., Results: A total of 729 patients (mean age, 63 years ±10 [SD]; 616 males) were included. MACE occurred in 70 (9.6%) patients. The presence of late gadolinium enhancement (LGE) ([HR] 2.74, [95% CI: 1.53, 4.88]; P < .001) and stress GCS (HR, 1.06 [95% CI: 1.01, 1.12]; P = .016) were independently associated with MACE. A model based on contrast-free assessment of LVEF and stress GCS showed similar performance for predicting MACE than LVEF and perfusion (P = .056)., Conclusions: In patients with known or suspected CAD undergoing stress cardiac MRI with dipyridamole, GCS and LGE presence were independent predictors of MACE. Contrast-free stress cardiac MRI with stress GCS measurement offered prognostic value akin to myocardial perfusion assessment., Clinical Relevance Statement: Stress global circumferential strain represented an additional method to predict major adverse cardiac events in patients undergoing stress cardiac MRI, even without the use of contrast agents. This would be of particular significance in patients with severe renal impairment., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Conflict of interest: The authors declare no conflict of interest.

Background: This study looks at the clinical applications of nanotechnology in dentistry, with an emphasis on implantology, preventive care, orthodontics, restorative dentistry, and endodontics. Methods: Following PRISMA criteria and registered in PROSPERO (ID: CRD 564245), a PubMed, Scopus, and Web of Science search was conducted for studies from January 2014 to April 2024. The criteria were English-language research on nanotechnology in dental coatings, with a focus on clinical trials and observational studies. The electronic database search yielded 8881 publications. Following the screening process, 17 records were selected for qualitative analysis. Results: Nanotechnology has revolutionized dentistry. In orthodontics, nanoparticles improve antibacterial characteristics, durability, and biocompatibility, lowering bacterial colonization and plaque. In preventative care, Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) combined with stannous fluoride (SnF 2 ) and nano-sized sodium trimetaphosphate (TMPnano) substantially remineralizes enamel. Nanostructured surfaces in dental implants, particularly those containing calcium, improve osseointegration and stability. Nanoparticles in restorative dentistry improve composite and adhesive strength, aesthetics, and longevity. Conclusions: Nanotechnology improves dental materials and equipment, resulting in better treatment outcomes and increased patient comfort. Its integration provides more effective treatments, which improves dental care and patient outcomes. More research is needed to overcome present problems and expand nanotechnology's medicinal applications.

Background: Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction-associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N-acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) in children with obesity and biopsy-confirmed MASLD., Methods: Thirteen children (n = 13; age: 13.6 ± 2.8 years; NAS score >2) underwent a double-blind, placebo-controlled trial of NAC (either 600 or 1200 mg NAC/day) or placebo for 16 weeks. Measurements included LFF (magnetic resonance imaging), LS (ultrasound elastography), and body composition. Erythrocyte glutathione (GSH), liver enzymes, insulin, glucose, adiponectin, high-sensitivity c-reactive protein (hs-CRP), and interleukin-6 (IL-6) were also measured. homeostasis model assessment for insulin resistance (HOMA-IR) was calculated., Results: Sixteen-week NAC treatment improved (baseline adjusted between-group p < .05 for all) markers of inflammation (IL-6 and hs-CRP), oxidative stress (GSH), and IR (HOMA-IR) and reduced liver enzymes, LFF and LS. Body weight and body composition did not show beneficial changes., Conclusions: Sixteen-week NAC treatment was well tolerated in children with obesity and MASLD and led to improvements in oxidative stress, inflammation and IR and liver outcomes. The results from this pilot study support further investigation of NAC as a therapeutic agent in children with MASLD., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. Methods and results This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). Conclusion A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay. [ABSTRACT FROM AUTHOR]