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The presence of wireless and mobile technologies in developing countries, the availability of low-cost, miniaturized wireless sensors, as well as the cost-efficient services provided by new hardware infrastructures have enabled new healthcare services, or new levels of quality and cost-efficiency in established ones. One crucial aspect of Healthcare 4.0 is the concept of P4 in Medicine: predictive, preventive, personalized and participatory. This approach, based on a comprehensive understanding of each patient biology, opposite to clustering patients into treatment groups, is being applied to reduce global health budgets by minimizing unnecessary use of drugs and procedures. These innovations come from the broad set of ICTs, and among them, the pillars of HC4.0 for their importance: IoT, Cloud Computing, and Big Data. Health 4.0 is used to improve the efficiency of physicians by enabling them to optimize resources and data availability. The future of health management will become timesaving and personalized as new technologies will empower individuals to conduct their health monitoring by using cyber–physical systems. Thanks to IoT, Cloud and Fog, as well as Big Data, researchers are allowed to design novel solutions, which are able to efficiently and effectively renew consolidated healthcare practices. [ABSTRACT FROM AUTHOR]

An increasing amount of evidence suggests that migraine is a response to cerebral energy deficiencies or oxidative stress levels that exceed antioxidant capacity. Current pharmacological options are inadequate in treating patients with chronic migraine, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. The ketogenic diet, mimicking fasting that leads to an elevation of ketone bodies, is a therapeutic intervention targeting cerebral metabolism that has recently shown great promise in the prevention of migraines. Moreover, Mediterranean elements like vegetables, nuts, herbs, spices, and olive oil that are sources of anti-inflammatory elements (omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics) may create a positive brain environment by reducing imbalance in the gut microbiome. On the basis of these indications, a combined Mediterranean-ketogenic diet was administered to chronic migraine patients for 4 (T1) and 8 weeks (T2), and anthropometric estimations were collected at T1 and T2 while biochemical parameters at only T2. A significant reduction (p < 0.01) in migraine frequency and intensity was detected as early as 4 weeks of dietary intervention, which was associated with a reduced fat mass (p < 0.001) as well as Homa index (p < 0.05) and insulin levels (p < 0.01) after 8 weeks. Overall, Mediterranean-ketogenic diet may be considered an effective non-pharmacological intervention for migraine, with positive outcomes on body composition. [ABSTRACT FROM AUTHOR]

Cell culture on soft matrix, either in 2D and 3D, preserves the characteristics of progenitors. However, the mechanism by which the mechanical microenvironment determines progenitor phenotype, and its relevance to human biology, remains poorly described. Here we designed multi-well hydrogel plates with a high degree of physico-chemical uniformity to reliably address the molecular mechanism underlying cell state modification driven by physiological stiffness. Cell cycle, differentiation and metabolic activity could be studied in parallel assays, showing that the soft environment promotes an atypical S-phase quiescence and prevents cell drift, while preserving the differentiation capacities of human bronchoepithelial cells. These softness-sensitive responses are associated with calcium leakage from the endoplasmic reticulum (ER) and defects in proteostasis and enhanced basal ER stress. The analysis of available single cell data of the human lung also showed that this non-conventional state coming from the soft extracellular environment is indeed consistent with molecular feature of pulmonary basal cells. Overall, this study demonstrates that mechanical mimicry in 2D culture supports allows to maintain progenitor cells in a state of high physiological relevance for characterizing the molecular events that govern progenitor biology in human tissues. This study focuses on the molecular mechanism behind the progenitor state induced by a soft environment. Using innovative hydrogel supports mimicking normal human lung stiffness, the data presented demonstrate that lung mechanics prevent drift while preserving the differentiation capabilities of lung epithelial cells. Furthermore, we show that the cells are positioned in a quiescent state in the atypical S phase. Mechanistically, we demonstrate that this quiescence: i) is driven by calcium leakage from the endoplasmic reticulum (ER) and basal activation of the PERK branch of ER stress signalling, and ii) protects cells from lethal ER stress caused by metabolic stress. Finally, we validate using human single-cell data that these molecular features identified on the soft matrix are found in basal lung cells. Our results reveal original and relevant molecular mechanisms orchestrating cell fate in a soft environment and resistance to exogenous stresses, thus providing new fundamental and clinical insights into basal cell biology. [Display omitted] [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to an open surgical aortic valve replacement (SAVR) for treating severe symptomatic aortic stenosis. Despite gaining widespread acceptance and approval for use in patients with high, moderate, and low surgical risk, the increasing use of TAVR has raised concerns about potential short- and long-term complications. We present the case of a 69-year-old female who underwent TAVR and subsequently presented to our outpatient cardiology clinic with progressively worsening dyspnea, orthopnea, and paroxysmal nocturnal dyspnea two years after the procedure. Echocardiography and stress testing revealed a recurrence of aortic stenosis, leading to a diagnosis of structural valve deterioration. The patient was subsequently scheduled for SAVR, which revealed commissural fusion, scarring, and unusual pannus formation that significantly narrowed the effective valve area, necessitating valve replacement. Despite requiring SAVR, two years after TAVR, the patient had a favorable postoperative course and outcome on follow-up. This case underscores the importance of continued surveillance and evaluation of patients who undergo TAVR, as they remain at risk for long-term complications such as structural valve deterioration. Proper management, including timely diagnosis and intervention, can lead to successful outcomes in such patients. This case underscores the importance of continued surveillance and evaluation of patients who undergo transcatheter aortic valve replacement, as they remain at risk for long-term complications such as structural valve deterioration. Proper management, including timely diagnosis and intervention, can lead to successful outcomes in such patients. [ABSTRACT FROM AUTHOR]

Previous studies find kidney stone formers (KSF) are at greater risk of developing cardiovascular disease (CVD). The underlying mechanisms are poorly understood, and many clinicians are unaware of this connection. We will: 1 Provide an up-to-date review of epidemiological data. 2 Clearly define CVD outcomes to understand conditions associated with kidney stone formation (KSF). 3 Review hypothesised biological pathways to further understand the relationship. Our systematic review is registered with PROSPERO (ID CRD42021251477). We searched epidemiological and biological data. The epidemiological search generated 669 papers, narrowed down to 15. There were 4,259,869 participants (230,720 KSFs). KSF was associated with 25% higher risk of coronary artery disease (CAD) (95% confidence interval (CI): 15, 35%), 17% higher risk of stroke/transient ischemic attacks (TIA) (CI:10, 25%) and 39% higher risk of arterial disease (AD) (CI: 17 65%). Significant heterogeneity was found. Female-identifying KSFs had a higher risk of stroke (ratio = 1.10) and CAD (1.20). The biological search generated 125 papers, narrowed down to 14. Potential underlying mechanisms were extracted and discussed, including intimal/medial vascular calcification, oxidative stress via osteopontin (OPN), cholesterol-induced pathology, and endothelial dysfunction. There is a significant association between KSF and CVD, supporting the consideration of KSF as a systemic, calcium-mediated disease. Clinicians will benefit from being aware of this connection. [Display omitted] • Largest systematic review on the topic of cardiovascular disease and kidney stones. • Increased risk of coronary artery disease, stroke, and peripheral arterial disease. • Relationship was stronger for female-identifying kidney stone formers. • First time epidemiological and biological review have been combined in this field. • Strengthened a poorly understood, clinically relevant relationship. [ABSTRACT FROM AUTHOR]

Foreign body ingestion (FBI) in children requires early identification to prevent adverse outcomes and may necessitate endoscopic or surgical intervention. This study aims to develop a nomogram that identifies children who require urgent surgical or endoscopic intervention by using the patient's medical history and clinical parameters collected at admission. This study is a retrospective review (01/2015–12/2020) of a multicenter case series of children admitted for FBI. Data from 5864 records from 24 hospitals in Italy were analyzed. Logistic regression models were used to establish the probability of requiring surgical or endoscopic intervention based on patient history and clinical characteristics. The nomogram representing the results from the multivariable model was reported to examine the propensity for surgery/endoscopy. The study identified a significant association between intervention and various factors, including type of foreign body (blunt: reference category, disk battery (odds ratio OR:4.89), food bolus (OR:1.88), magnets (OR:2.61), sharp-pointed (OR:1.65), unknown (OR:1.02)), pre-existing diseases or conditions (OR 3.42), drooling (OR 10.91), dysphagia (OR 5.58), vomiting (OR 3.30), retrosternal pain (OR 5.59), abdominal pain (OR 1.58), hematemesis (OR 2.82), food refusal/poor feeding (OR 2.99), and unexplained crying (OR 2.01). The multivariable regression model showed good calibration and discrimination ability, with an area under the ROC curve of 0.77. This study developed the first nomogram to predict the probability of the need for surgical or endoscopic intervention in children with FBI, based on the information collected at admission. The nomogram will aid clinicians in identifying children who require early intervention to prevent adverse outcomes. [ABSTRACT FROM AUTHOR]

In the backdrop of telemedicine's rise, this review explores its integration into oral and maxillofacial surgery (OMFS), especially given the healthcare access challenges faced by nearly 20% of the rural population in the United States of America. The study underscores the potential of telemedicine to address disparities in access to OMFS care, particularly in rural areas, by improving patient care, reducing travel needs, and fostering collaborative diagnosis and treatment. The findings advocate for broader adoption of telemedicine in OMFS, contingent upon supportive policy and infrastructure changes. [ABSTRACT FROM AUTHOR]

Echocardiographic diagnosis of pulmonary hypertension (PH) in horses is usually based on Doppler interrogation of tricuspid (TR) or pulmonic regurgitation (PR). This study aimed at investigating two-dimensional echocardiographic (2DE) variables, including pulmonary artery diameter (PAD) and pulmonary artery distensibility index (PADI), to diagnose PH. 41 healthy horses; 82 horses with TR or PR and normal intracardiac pressure gradients; and 35 horses with TR or PR velocities indicating PH. The 2DE variables were compared between groups, cut-offs for the diagnosis of PH were determined, and conditional inference trees served to identify the variable best predicting PH in the absence of TR or PR. Horses with PH had larger end-diastolic cross-sectional (short-axis) PAD (PAD ed-sx) (5.8 ± 1.0 cm; mean ± SD) and smaller PADI [/PADps] (15.4 ± 7.7%) than healthy horses (5.0 ± 0.6 cm, P<0.0001; 20.5 ± 4.4%, P<0.001) and horses with TR or PR but no PH (5.3 ± 0.6 cm, P=0.003; 18.8 ± 4.2%, P=0.005). PAD ed-sx predicted PH with sensitivity (Se) = 36% and specificity (Sp) = 94% (cut-off 6.0 cm, AUC = 0.668, P=0.002), while PADI [/PADps] predicted PH with Se = 43% and Sp = 92% (cut-off 13.7%, AUC = 0.662, P=0.004). In the absence of TR, PAD ed-sx and the end-diastolic long-axis aortic diameter-to-PAD ed-sx ratio (AoD ed-lx /PAD ed-sx) were most suitable to diagnose PH. Pulmonary artery crosssectional (short-axis) diameter at end-diastole measured in a right-parasternal long axis view of the left ventricular outflow tract and Pulmonary artery distensibility index were moderately specific but not very sensitive to diagnosing PH. Nonetheless, they may be used as complementary indices suggesting PH in the absence of TR or PR. [ABSTRACT FROM AUTHOR]

What are the smallest worthwhile effects of nonsteroidal anti-inflammatory drugs (NSAIDs) for people with acute and chronic low back pain (LBP)? What is the smallest worthwhile effect of individualised exercise for people with chronic LBP compared with no intervention? Benefit-harm trade-off study. Participants were recruited by advertisement on social media and included if they were English-speaking adults in Australia who had non-specific LBP. Pain intensity. A total of 116 people with acute LBP and 230 people with chronic LBP were recruited. For acute LBP, the smallest worthwhile effect of NSAIDs additional to no intervention was a 30% (IQR 10 to 40%) reduction in pain intensity. For chronic LBP, the smallest worthwhile effect of NSAIDs additional to no intervention was a 27.5% (IQR 10 to 50%) reduction in pain intensity. For chronic LBP, the smallest worthwhile effect of exercise additional to no intervention was a 20% (IQR 10 to 40%) reduction in pain intensity. There were small associations between baseline pain, duration of pain and level of exercise and the smallest worthwhile effect of NSAIDs for acute LBP. There were no other clear associations. For people with LBP, the smallest worthwhile effect of exercise and NSAIDs additional to no intervention is approximately a 20 to 30% reduction in pain. These results can inform the interpretation of the effects of NSAIDs and exercise in randomised trials and meta-analyses, incorporating consumers' perspectives. Further research on comparisons between different interventions and on other core LBP outcomes may inform decision-making. OSF osf.io/3erjx/. [ABSTRACT FROM AUTHOR]

In this work, large-eddy simulation (LES) is conducted for a turbulent pulverized coal flame with a detailed phenomenological model to characterize the soot evolution and a flamelet model to describe the detailed gas phase kinetics. In particular, a quadrature-based moment method (QBMM) is adopted to describe the soot statistics with the physicochemical processes of soot particle nucleation, condensation, coagulation, chemical surface growth and oxidization being considered. The simulation results are compared to the experimental data, including the direct photograph images, particle velocities, laser induced fluorescence (LIF) for polycyclic aromatic hydrocarbons (PAHs), laser induced incandescence (LII) for soot, scanning electron microscope (SEM) with the thermophoretic sampling (TS), and the time-resolved LII (TiRe-LII) for spatial soot particle size distribution. The comparisons show that the ignition position and the mean velocity of the coal particles can be accurately predicted with the proposed flamelet/QBMM/LES method, and an overall good agreement is also obtained when comparing against the PAHs-LIF, soot-LII and SEM images. The importance of the contributions of the different physicochemical processes to the soot particle volume growth is quantified by analyzing the corresponding moment source terms. It is found that for the pulverized coal flame studied, the chemical surface growth is the most important contribution to the soot volume growth at different locations along the streamwise direction. Although the nucleation does not make a significant contribution to soot volume growth, it determines the number density of the primary soot particles formed in the main flow region. [ABSTRACT FROM AUTHOR]

A combined experimental and numerical investigation of partially premixed laminar methane-air flames undergoing side-wall quenching (SWQ) is performed. A well-established SWQ burner is adapted to allow the seeding of the main flow with additional gaseous products issued from a (secondary) wall inlet close to the flame's quenching point. First, the characteristics of the partially premixed flame that quenches at the wall are assessed using planar laser-induced fluorescence measurements of the OH radical, and a corresponding numerical simulation with fully-resolved transport and chemistry is conducted. A boundary layer of enriched mixture is formed at the wall, leading to a reaction zone parallel to the wall for high injection rates from the wall inlet. Subsequently, in a numerical study, the wall inflow is mixed with dimethylmethylphosphonat (DMMP), a phosphor-based flame retardant. The DMMP addition allows the assessment of the combined effects of heat loss and flame retardants on the flame structure during flame-wall interaction. With an increasing amount of DMMP in the injected mixture, the flame stabilizes further away from the wall and shows a decrease in the local heat-release rate. Thereby, the maximum wall heat flux is significantly reduced. That results in a lower thermal load on the quenching wall. The flame structure analysis shows an accumulation of the intermediate species HOPO at the wall similar to the CO accumulation during the quenching of premixed flames without flame retardant addition. The study shows how the structure of a partially premixed flame is influenced by a wall that releases either additional fuel or a mixture of fuel and flame retardant. The insights gained from the canonical configuration can lead to a better understanding of the combined effects of flame retardants and heat losses in near-wall flames. [ABSTRACT FROM AUTHOR]

Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM. We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint. 7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine. The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies. [Display omitted] • Meta-analysis of HER2-targeted therapies for breast cancer leptomeningeal metastases. • Intrathecal trastuzumab is not superior to intravenous or oral anti-HER2 therapies. • Trastuzumab deruxtecan demonstrates impressive efficacy in this setting. [ABSTRACT FROM AUTHOR]

We report a case of a 58-year-old male suffering from primary pulmonary arterial hypertension (PH), Eisenmenger's syndrome (ES) and ischemic heart disease who has already undergone multiple revascularizations and is a candidate for en bloc heart-lung transplantation. The patient acceded to our center with pneumonia and consequent worsening of respiratory symptoms and asthenia. The echocardiogram demonstrated a severely dilated and hypokinetic right ventricle with a systolic-diastolic D-shape and massive tricuspid regurgitation besides a dilated and fixed inferior vena cava. Considering the clinical worsening with advanced cardiorespiratory failure and the lability of hemodynamic compensation, hospitalization in cardiac intensive care was proposed. Upon admission, the patient presented a picture of predominantly right-sided SCAI D cardiogenic shock in type I PH and severe hypoxia. Initially, the hemodynamic instability was successfully medically managed with epinephrine intravenous (IV) infusion, a combination of multiple pulmonary vasodilators (Milrinone EV, Epoprostenol EV, Treprostinil continuous SC infusion and iNO) and Non-Invasive Ventilation (NIV). The patient was then included in the emergency transplantation list. Unfortunately, pneumonia severely worsened the pulmonary oxygenation with subsequent right ventricle de-compensation, increasing the right-to-left shunt and precipitating the cardiorespiratory equilibrium. We discussed the possibility of supporting the patient with veno-venous (VV) ECMO, but the RV failure was too severe (TAPSE 11 mm, FAC 20%, PAPs 92 mmHg, CVP 18 mmHg) and unresponsive to maximal medical therapy to allow the venous-venous support adequate effectiveness. Therefore, we decided to assist the patient with an awake femoral-femoral veno-arterial (VA) ECMO bridge-to-transplantation. As expected, it was not a simple mechanical circulatory support (MCS) management: the good LV function and the severe RV dilation made it impossible to obtain full drainage of the heart, which continued to eject de-oxygenated blood in ascending aorta. Veno-arterial-venous (VAV) ECMO was considered, but the incomplete RV drainage made it impossible to avoid liver stasis and a VAV configuration was considered inapplicable to manage the Harlequin Syndrome which occurred. Therefore, to improve the oxygenation in the "upper circulation" and, at the same time, to maintain the patient awake and able to prosecute physiotherapy, we assisted the patient with High-Flow Nasal Cannula (HFNC 50 L/min FiO2 100%) connected to an inhaled Nitric Oxide circuit (iNO 20ppm). In this way, we managed to assist the patient for 10 days, up to organs arrival, and the the patient was successfully transplanted. This case highlights the complexity and still the feasibility of VA ECMO support, complicated by Harlequin Syndrome, as a bridge to heart-lung transplantation in acutely decompensated patients with ES, in which the conditions of the right heart could not tolerate the VV ECMO solution. [ABSTRACT FROM AUTHOR]

In this study, the thermochemical state during turbulent flame-wall interaction of a stoichiometric methane-air flame is investigated using a fully resolved simulation with detailed chemistry. The turbulent side-wall quenching flame shows both head-on quenching and side-wall quenching-like behavior that significantly affects the CO formation in the near-wall region. The detailed insights from the simulation are used to evaluate a recently proposed flame (tip) vortex interaction mechanism identified from experiments on turbulent side-wall quenching. It describes the entrainment of burnt gases into the fresh gas mixture near the flame's quenching point. The flame behavior and thermochemical states observed in the simulation are similar to the phenomena observed in the experiments. A novel chemistry manifold is presented that accounts for both the effects of flame dilution due to exhaust gas recirculation in the flame vortex interaction area and enthalpy losses to the wall. The manifold is validated in an a-priori analysis using the simulation results as a reference. The incorporation of exhaust gas recirculation effects in the manifold leads to a significantly increased prediction accuracy in the near-wall regions of flame-vortex interactions. [ABSTRACT FROM AUTHOR]

This study investigates the effects of curvature on the local heat release rate and mixture fraction during turbulent flame-wall interaction of a lean dimethyl ether/air flame using a fully resolved simulation with a reduced skeletal chemical reaction mechanism and mixture-averaged transport. The region in which turbulent flame-wall interaction affects the flame is found to be restricted to a wall distance less than twice the laminar flame thickness. In regions without heat losses, heat release rate and curvature, as well as mixture fraction and curvature, are negatively correlated, which is in accordance with experimental findings. Flame-wall interaction alters the correlation between heat release rate and curvature. An inversion in the sign of the correlation from negative to positive is observed as the flame starts to experience heat losses to the wall. The correlation between mixture fraction and curvature, however, is unaffected by flame-wall interactions and remains negative. Similarly to experimental findings, the investigated turbulent side-wall quenching flame shows both head-on quenching and side-wall quenching-like behavior. The different quenching events are associated with different curvature values in the near-wall region. Furthermore, for medium heat loss, the correlations between heat release rate and curvature are sensitive to the quenching scenario. [ABSTRACT FROM AUTHOR]

In premixed flame propagation of lean hydrogen or hydrogen-enriched blends, both hydrodynamic and thermo-diffusive instabilities are governing the flame front shape and affect its propagation velocity. As a result, different types of cellular patterns can occur along the flame front in a laminar scenario. In this context, an interesting phenomenon is the formation of polyhedral flames which can be observed in a Bunsen burner. It is the objective of this work to systematically characterize the polyhedral structures of premixed methane/hydrogen Bunsen flames in a combined experimental and numerical study. A series of lean flames with hydrogen content varying between 20 and 85% at two equivalence ratios is investigated. The experiments encompass chemiluminescence imaging together with Planar Laser-induced Fluorescence (PLIF) measurements of the OH radical. Characteristic cell sizes are quantified from the experiments and related to the characteristic length scales obtained from a linear stability analysis. In the experiments, it is observed that the cell sizes at the base of the polyhedral Bunsen flames decrease almost linearly with hydrogen addition and only a weak dependence on the equivalence ratio is noted. These trends are well reflected in the numerical results and the length scale comparison further shows that the wavelength with the maximum growth rate predicted by the linear stability analysis is comparable to the cell size obtained from the experiment. The correlation between the experimental findings and the linear stability analysis is discussed from multiple perspectives considering the governing time and length scales, furthermore drawing relations to previous studies on cellular flames. [ABSTRACT FROM AUTHOR]

The variation and accuracy of computed tomography angiography (CTA) features of anomalous aortic origin of a coronary artery (AAOCA) have not been completely characterized. We evaluated anomalous right (AAORCA) and left (AAOLCA) coronary arteries by CTA, with an emphasis on reproducibility, comparison with surgical measurements, and effect of nitroglycerin. CTAs were interpreted for location of coronary origin & exit from the aorta, course, and dominance; minor & major diameters of the proximal & distal coronaries; shape of orifice; and intramural length. Relationships between vessel measurements, body surface area (BSA), and nitroglycerin use were evaluated. Comparisons between CTA and surgical measurements included intramural length, surgical probe size pre-intervention vs. CTA proximal AAOCA diameter, and surgical probe size post-intervention vs. CTA distal AAOCA diameter. Of 104 patients [81 (78%) AAORCA], all but 1 were intramural. Compared to AAOLCA, AAORCA patients were more likely to have a high origin (91% vs. 31%, p ​< ​0.01), and slit-like orifice (58% vs. 26%, p ​< ​0.01). When CTAs with nitroglycerin were compared to those without, no difference in proximal AAOCA dimensions was identified; however distal AAOCA and normal-origin coronary dimensions were larger in scans with nitroglycerin. Aside from slit-like orifice, reliability of coronary CTA measurements, including proximal AAOCA minor diameter and intramural length, was moderate to good between readers. In a subgroup of 54 patients, proximal AAOCA minor diameter and intramural length had good agreement and correlation with surgery. Proximal AAOCA dimensions and intramural length are reproducible variables. The lack of difference in proximal AAOCA dimensions with nitroglycerin may reflect abnormal vessel mechanics. Multicenter studies are an important next step in understanding the generalizability of our findings. Table of Contents Summary: In this study we evaluated 104 CT angiograms on patients with anomalous origin of the coronary arteries (AAOCA; 81 right and 23 left), with an emphasis on clinically useful measurements that have high reliability (intra-rater, inter-rater, and comparison with surgical measurements). We found that measurements of the intramural segment (e.g., proximal AAOCA dimensions and intramural length) had moderate-good reliability. The lack of difference in these measurements with/without nitroglycerin at the time of CTA (versus evidence of dilation in the non-intramural vessel) supports their clinical utility as measures of potential ischemic risk. [ABSTRACT FROM AUTHOR]

To compare post-operative outcomes associated with thymectomy performed using either open or robotic approaches. Retrospective cohort study from a single-center prospective registry consisting of patients undergoing thymectomy between 2000 and 2020. Patients were grouped according to surgical approach (open vs robotic). A propensity-score matching analysis was performed in a 2:1 open to robotic ratio, and surgical outcomes were evaluated. We analyzed 234 thymectomies (155 open; 79 robotic). Myasthenia gravis was present in 23.2% and 32.9% (P = 0.249) in the open and in the robotic group, respectively. All covariates were balanced in the matched groups (open n = 114; robotic n =5 9), except lesion size. The robotic approach was significantly associated with shorter surgical time (median 95 vs 65 minutes, P < 0.001), lesser clinical (21.1% vs 6.8%, P = 0.016) and surgical (11.4% vs 1.7%, P = 0.036) complications during the same hospitalization, less Clavien-Dindo grade 2 or higher complication rates (28.1 vs 15.3%, P = 0.048), chest tube duration (median: 3 vs 0 days, P < 0.001) and in-hospital length of stay (median: 5 vs 0 days, P < 0.001). Bleeding (P = 0.214), ICU length of stay (P = 0.167), reoperation rate (open, 1.8% vs robotic 0%), 90-day mortality (P = 0.341) and readmission rate post discharge (P = 0.277) were similar between the groups. In the matched population with primary thymic epithelial tumors, the completeness of resection rate was similar (open, 92.1% vs robotic 96.8%, P = 0.66.). Robotic thymectomy is associated with improved post-operative outcomes when compared to open thymectomy, without compromising the goals of oncologic surgery. Longer follow-up is needed to ensure oncologic equivalence. [Display omitted] [ABSTRACT FROM AUTHOR]

A quiz concerning the Douleur Neuropathique 4 (DN4) questionnaire for neuropathic pain assessment evaluates pain characteristics, associated symptoms, and sensory examination findings, emphasizing a score ≥ 4/10 as indicative of neuropathic pain.

• Optimization of a quality control routine across sites in a 3T multicentric study. • More than 80% of ACR quality control measures were within the acceptance ranges. • All measures demonstrated good reproducibility over time. • Inter-vendor differences were observed in the uniformity and geometric metrics. • The automated analysis allows each site to independently monitor scanner performance. Generating big-data is becoming imperative with the advent of machine learning. RIN-Neuroimaging Network addresses this need by developing harmonized protocols for multisite studies to identify quantitative MRI (qMRI) biomarkers for neurological diseases. In this context, image quality control (QC) is essential. Here, we present methods and results of how the RIN performs intra- and inter-site reproducibility of geometrical and image contrast parameters, demonstrating the relevance of such QC practice. American College of Radiology (ACR) large and small phantoms were selected. Eighteen sites were equipped with a 3T scanner that differed by vendor, hardware/software versions, and receiver coils. The standard ACR protocol was optimized (in-plane voxel, post-processing filters, receiver bandwidth) and repeated monthly. Uniformity, ghosting, geometric accuracy, ellipse's ratio, slice thickness, and high-contrast detectability tests were performed using an automatic QC script. Measures were mostly within the ACR tolerance ranges for both T1- and T2-weighted acquisitions, for all scanners, regardless of vendor, coil, and signal transmission chain type. All measurements showed good reproducibility over time. Uniformity and slice thickness failed at some sites. Scanners that upgraded the signal transmission chain showed a decrease in geometric distortion along the slice encoding direction. Inter-vendor differences were observed in uniformity and geometric measurements along the slice encoding direction (i.e. ellipse's ratio). Use of the ACR phantoms highlighted issues that triggered interventions to correct performance at some sites and to improve the longitudinal stability of the scanners. This is relevant for establishing precision levels for future multisite studies of qMRI biomarkers. [ABSTRACT FROM AUTHOR]

A need exists for a unified curriculum framework for nurse educators, recognizing racism as a central driver of health inequities. This paper provides nurse educators with a unifying curriculum framework that centers racism as a root cause of health inequity shaping SSDH. A critical examination of the social and structural determinants of health (SSDH) and Yob's (2018) Framework for a Curriculum in Social Change was conducted, to develop a curriculum framework tailored to the intersection of SSDH and social change within nursing education. The "Nursing Education Integrating Social Change for Health Equity (NISCHE)" framework was developed as a comprehensive curriculum framework for SSDH and social change specifically tailored for nursing education. Practical examples of curricular activities across various settings are offered, thus illustrating implementation and potential impact. By centering racism in the curriculum framework and emphasizing its role in perpetuating health inequities, this paper advances a crucial agenda in nursing education. • Presents the NISCHE framework to address racism as a root cause of health inequity. • Aligns SSDH with Yob's social change curriculum framework for nursing education. • Provides exemplars to integrate SSDH and social change across nursing programs. • Supports policy implications for advancing health equity through nursing education. [ABSTRACT FROM AUTHOR]

Purpose: Triple X syndrome, is an often undiagnosed chromosomal abnormality with an incidence of 1/1000 females. Main associated disorders are urogenital malformations, premature ovarian failure or primary amenorrhea, gastrointestinal problems, psychiatric disorders and epilepsy. To date, triple X is not related to a specific epileptic syndrome. Therefore, the purpose of this clinical series is to analyze seizure semiology, electroencephalogram features and the long-term outcome of 13 patients with epilepsy and triple X syndrome.Methods: We retrospectively evaluated the long-term seizure outcome in patients with triple X syndrome who had been referred to 11 Epilepsy Centers in Italy. A close electroclinical follow-up was made for at least 2 years and outcomes were reported.Results: Our case series confirms that epilepsy is not an occasional finding but part of the phenotypic spectrum of this syndrome. The seizure semiology shows an higher prevalence of focal seizures in 62% of patients. EEG findings of focal epileptic activity were reported in 85% of patients. Anti-seizure medications were successful in all our patients whom in most cases were responsive to monotherapy.Conclusion: According to our case series most successful drugs were VPA and LEV. Long term prognosis of epilepsy in our case series was good. Our experience suggests that all triple X patients achieve good seizure control and in 69% of cases normalization of the EEG. [ABSTRACT FROM AUTHOR]

T1 Magnetization Prepared Two Rapid Acquisition Gradient Echo (MP2RAGE) with compress sensing (CS) has been proposed as an improvement of the standard MPRAGE sequence with multiple advantages including reduced acquisition time needed to provide a quantitative 3D anatomical image coupled with T1-map. Here we investigated the agreement between FreeSurfer-derived volume measurements obtained from MPRAGE and CS MP2RAGE acquisitions. MPRAGE and CS MP2RAGE images of 37 subjects (14 patients with neurodegenerative disorders and 23 healthy controls) were acquired on a 3 T MR scanner and grey matter volumes were extracted using standard FreeSurfer parcellation. Lin's concordance correlation coefficient (Lin's CCC), Bland-Altman analysis, Passing-Bablok regression and DICE similarity coefficient were calculated to assess the agreement between the two. We found a good correspondence for most of the regions examined, with 93.5 % of them showing a mean DICE index >0.70. Poorer results were found with Lin's CCC especially for subcortical labels across patients. The Bland-Altman analysis showed CS MP2RAGE tended to measure lower cortical volumes compared to MPRAGE but in most cases the difference wasn't statistically relevant. The Passing-Bablock regression indicated overall an absence of systematic constant and proportional bias when CS MP2RAGE was used instead of MPRAGE. We found a good concordance for volumes obtained from MPRAGE and CS MP2RAGE images using FreeSurfer, suggesting a possible role of CS MP2RAGE for structural analysis with significant advantages like shorter acquisition time and the possibility to simultaneously obtain quantitative T1-maps of the brain enriching the diagnostic power of this technique. [ABSTRACT FROM AUTHOR]

[Display omitted] • Reproducibility of harmonized QSM protocol at 3T was tested in a multicentric study. • The traveling brain study yielded optimal structural similarity and reproducibility. • ROI-dependent χ quantification errors were 0.001–0.017 ppm for traveling brains. • In healthy subjects, ROI-dependent χ variability of 0.005–0.025 ppm can be expected. • The harmonized protocol yields reliable χ and it is ready for multicentric studies. Quantitative Susceptibility Mapping (QSM) is an MRI-based technique allowing the non-invasive quantification of iron content and myelination in the brain. The RIN – Neuroimaging Network established an optimized and harmonized protocol for QSM across ten sites with 3T MRI systems from three different vendors to enable multicentric studies. The assessment of the reproducibility of this protocol is crucial to establish susceptibility as a quantitative biomarker. In this work, we evaluated cross-vendor reproducibility in a group of six traveling brains. Then, we recruited fifty-one volunteers and measured the variability of QSM values in a cohort of healthy subjects scanned at different sites, simulating a multicentric study. Both voxelwise and Region of Interest (ROI)-based analysis on cortical and subcortical gray matter were performed. The traveling brain study yielded high structural similarity (∼0.8) and excellent reproducibility comparing maps acquired on scanners from two different vendors. Depending on the ROI, we reported a quantification error ranging from 0.001 to 0.017 ppm for the traveling brains. In the cohort of fifty-one healthy subjects scanned at nine different sites, the ROI-dependent variability of susceptibility values, of the order of 0.005–0.025 ppm, was comparable to the result of the traveling brain experiment. The harmonized QSM protocol of the RIN – Neuroimaging Network provides a reliable quantification of susceptibility in both cortical and subcortical gray matter regions and it is ready for multicentric and longitudinal clinical studies in neurological and pychiatric diseases. [ABSTRACT FROM AUTHOR]

There is a literature gap for hospitals in single-payer health care systems quantifying the influence of hospital volume on outcomes after major lung cancer resection. We aimed to determine the effect of hospital volume on mortality and length of stay. A retrospective cohort study using administrative, population-based data from a single-payer universal health care system was performed in adults with non-small cell lung cancer who underwent lobectomy or pneumonectomy between 2008 and 2017. Hospital volume was defined as the average annual number of major lung resections performed at each institution. Length of stay and postoperative mortality were compared using multivariable linear and nonlinear regression between hospital volume categories and continuously. Adjusted association between hospital volume and postoperative mortality was determined by multivariable logistic regression. In all, 10 831 lung resections were performed: 1237 pneumonectomies and 9594 lobectomies. Patients undergoing lobectomy at high-volume hospitals had shorter median length of stay (6 vs 8 days, P =.001) compared with low-volume hospitals. After adjusting for confounders, surgery at a high-volume center was significantly associated with shorter length of stay after lobectomy and overall resections (P ≤.001), but not after pneumonectomy (P =.787). Surgery at a high-volume center was positively associated with improved 90-day mortality in lobectomy and overall procedures (odds ratio 0.607 [95% confidence interval, 0.399 to 0.925], and 0.632 [95% confidence interval, 0.441 to 0.904], respectively). Volume was not a predictor of 90-day mortality after pneumonectomy (odds ratio 0.533 [95% confidence interval, 0.257 to 1.104], P =.090). Surgery at a high-volume center was positively correlated with improved 90-day survival and shorter hospital length of stay. The results support regionalized lung cancer care in a single-payer health care system. [Display omitted] [ABSTRACT FROM AUTHOR]

Direct Acting Antivirals(DAAs) achieve the highest rate of sustained viral response(SVR) in patients with genotype-1b(G1b) Hepatitis C virus(HCV) infection. Reducing treatment duration can simplify the management and improve adherence of therapy. The study evaluates the efficacy of 8 weeks of elbasvir/grazoprevir regimen in 75 treatment-naïve(TN), G1b patients with mild-moderate fibrosis(Liver Stiffness by Fibroscan® <9.0 kPa). Viral load(VL) has been evaluated by Roche TaqMan RT-PCR(LLOQ<15 IU/ml). Mean age was 61.0 ± 14.2 years, 44% were male, mean LS by Fibroscan® was 6.1 ± 1.8 kPa. Twenty-eight patients(37.3%) had an HOMA>2.5. Two patients were excluded from analysis(one dropped out and the other one had diagnosed genotype 2c at genotyping by sequencing performed after relapse). At 8 weeks(EOT), 71 out of 73 patients(97.3%) had undetectable HCV-RNA, while in two cases HCV-RNA was detectable but with VL<15 IU/ml. Both of them achieved SVR. Two G1b patients relapsed at 12 weeks of follow-up, both with baseline VL>800,000 IU/ml and HOMA score 1.3 and 3.8 respectively. Both had undetectable HCV VL at 4th week and at the EOT. Modified intention-to-treat SVR12 for G1b patients was 71/73(97.3%). In naïve, genotype-1b HCV-infected patients with mild/moderate liver fibrosis, short course of 8 weeks of EBR/GZR appears to achieve high efficacy regardless of features of insulin resistance. [ABSTRACT FROM AUTHOR]

Previous studies reported a poor outcome in patients with coronavirus 2019 (COVID-19) undergoing cardiac surgery. Complications most frequently described were respiratory failure, renal failure, and thromboembolic events. In their recent experience, the authors observed a very high incidence of bleeding complications. The purpose of the study was to investigate a possible significant correlation between perioperative COVID-19 infection and hemorrhagic complications compared to non-COVID-19 patients. Single-center, observational, retrospective, matched case-control (1:2) study involving patients who underwent open-heart cardiac surgery from February 2020 and March 2021 with positive perioperative diagnosis of COVID-19 infection, matched with patients without COVID-19 infection. Cardiac surgery unit and intensive care unit of a university tertiary center in a metropolitan area. In the study period, 773 patients underwent cardiac surgery on cardiopulmonary bypass (CPB). Among them, 23 consecutive patients had perioperative diagnosis of COVID-19 infection (study group). These patients were compared with 46 corresponding controls (control group) that matched for age, sex, body mass index, and Society of Thoracic Surgeons score. Open-heart cardiac surgery on CPB. In the study group, 2 patients (9%) died in the intensive care unit from severe respiratory failure, shock, and multiple organ failure. In the study group, patients showed a significantly higher incidence of bleeding complications (48% v 2%, p = 0.0001) and cases of surgical reexploration for bleeding (35% v 2%, p = 0.0001), a higher incidence of severe postoperative thrombocytopenia (39% v 6%, p = 0.0007), and a higher need of blood components transfusions (74% v 30%, p = 0.0006). Chest tubes blood loss and surgical hemostasis time were markedly prolonged (p = 0.02 and p = 0.003, respectively). A worrisome increased risk of early and late bleeding complications in COVID-19 patients was observed, and it should be considered when assessing the operative risk. CPB-related inflammatory reaction could exacerbate the deleterious effect of COVID-19 on the coagulation system and likely deviate it toward a hemorrhagic pattern. [Display omitted] • Coronavirus infection is confirmed to markedly increase the postoperative risk. • A higher rate of hemorrhagic complications and surgical reexplorations for bleeding was observed. • Coronavirus infection should be taken in account as a risk factor for postoperative bleeding. [ABSTRACT FROM AUTHOR]

Eye tissue engineering is becoming a promising field in the study and treatment of vitreoretinal diseases, and novel hydrogels are under investigation for vitreous body replacement and 3D cell culture applications. In order to handle a not self-standing hydrogel and to provide it with eye shape, a rigid scaffold that is transparent, non-toxic, and easy to move is needed. To this purpose, we produced bowl-shaped samples by stereolithography (SLA) starting from different commercial transparent resins. We optimized the 3D printing protocol by tuning parameters such as exposure time, layer thickness, and light blocker content added to the resins. The specimens that showed the best dimensional accuracy were chosen to perform biocompatibility tests at different time-point and transparency tests under an optical microscope. Preliminary results showed that the cell culture medium conditioned by the first tested resin formulations caused a massive cell death in the MS5 cell line tested, whereas different formulations did not impact on cell viability. Furthermore, the as built resin samples did not allow cell observation under inverted microscope. It was demonstrated that post-processing progressive grinding remarkably improved cell visualization. [ABSTRACT FROM AUTHOR]

Metal-based inks, such as silver nanoparticle (AgNPs) dispersions, are standard solutions in printed electronics (PE) due to their high bulk conductivity, stability, and commercial availability. Conductive functional printed patterns have been exploited for several applications, such as (wearable) sensors, antennas, transistors, batteries. Recently, PE has also been widely investigated for biomedical and bioelectronic interfaces. In this case, the choice of biocompatible materials is crucial to ensure biological activities of the seeded cells. For instance, the release of Ag+ ions in the medium culture in in-vitro cultures, is known to induce cytotoxicity, in a dose-, size-, and time-dependent way, causing oxidative stress and eventually cellular death. Hence, an encapsulation step of the printed pattern is usually performed to reduce such risk, by inducing however additional limitations and complications on the design and production. This work investigates the biocompatibility of a commercial Aerosol Jet® Printed (AJ®P) AgNPs-based ink (Ø avg,particle size = 35 nm, Ag content ~50 wt%) use to print conductive circuits for in-vitro bioelectrical sensing. Particularly, the ink was AJ® printed on the top of stereolithography (SLA) samples coated with Parylene-C, and further encapsulated with polydimethylsiloxane (PDMS). Cell viability assays were evaluated using both in adhesion and suspension cell type, such fibroblasts and B-Lymphoblastoid cell line respectively, at different time points from 7 days till 21 days to verify cellular activity and proliferation for long term usage. This work provides new insights concerning the use of encapsulated conductive AgNPs-based circuits for in-vitro long-term sensing devices. [ABSTRACT FROM AUTHOR]

[Display omitted] • Circadian rhythms influence the intestinal permeability of chlorogenic acid (CGA) • Gallic acid, but not other polyphenols, counteracts the CGA intestinal permeation. • Dopamine released by enteric nervous system increases the CGA intestinal permeation. • Oral absorption of CGA may be optimized at the evening in the absence of gallic acid. Poor oral bioavailability limits chlorogenic acid (CGA) benefits on the gut-brain axis. In this study we demonstrate the existence of an active circadian-dependent efflux for the CGA intestinal permeation, leading to greater bioavailability in the evening rather than in the morning. As therapeutic/nutraceutical polyphenols can mutually influence their intestinal absorption following circadian rhythms, we also evaluated the effects of other polyphenols on CGA permeation/bioavailability. The results indicate that gallic acid reduced in vitro CGA permeation across IEC-6 cell monolayers, as well as rat oral CGA bioavailability. On the contrary, arbutin, caffeic acid and ferulic acid did not modify in vitro CGA permeation. Finally, 60 mM KCl-evoked dopamine release from PC12 cells significantly increased intestinal CGA permeation, likely by downregulating the expression/activity of efflux transporters, as confirmed by western blot analysis. Dopamine released from the enteric nervous system may therefore increase the dependence of oral bioavailability of CGA on circadian rhythms. [ABSTRACT FROM AUTHOR]

The recent economic development of maritime areas has led to the emergence of new approaches to marine governance in many regions. Unfortunately, the complexity of the natural and socio-economic processes that characterise the marine and coastal ecosystems is generally not sufficiently considered by the existing governance mechanisms. This explains that the inclusion of land-sea interactions (LSIs) in marine and coastal governance remains particularly weak and somewhat inadequate to address the current challenges, especially in Europe. The literature review showed that the mechanisms currently in place for this purpose are highly fragmented, even though legislation has been introduced at the EU level. Focusing on the implementation of the Maritime Spatial Planning Directive (MSPD), four types of obstacles to the integration of LSIs into marine and coastal governance have been identified. They are classified as issue-related, institutional, process-related and knowledge-related. To overcome these challenges, three recommendations have been developed in this paper: 1) the effective implementation of EU marine and coastal legislation's fundamental principles related to an integrated approach; 2) the development of new governance mechanisms to enhance policy coordination and 3) the development of collaborative governance processes. The policy recommendations for LSI integration in marine and coastal governance formulated have not been tested through specific case studies. Therefore, the next step would be to create innovative governance mechanisms for a selection of cases. • EU challenges: issue-related, institutional, process-related and knowledge-related. • Land-sea integration in EU marine/coastal governance progresses. • EU can inspire other regions on the first steps of land-sea integration. [ABSTRACT FROM AUTHOR]

Bone is among the main by-products of the meat and dairy livestock. Currently, in many countries, it is valorised in pet food, disposed through incineration or exported. However, thanks to its biological and mechanical properties, it could be used in several bio-based products such as coatings, packaging, phosphorous, calcium and magnesium supply, flame retardants, etc. Successful valorisations routes of discarded bones need a comprehensive characterization of the bone tissue variability with major biological factors such as age of the animal and the anatomy of the bone itself. In this study, this variability was assessed through Terahertz time-domain spectroscopy and energy dispersive X-ray microanalysis. Bones optical properties (refractive index and absorption coefficient) and main minerals (calcium and phosphorous), were determined for adult cows' femurs and tibias, from the same breed and breeding system and in the age range 93–120 months. Clustering analysis was then carried out, by unsupervised statistical tools (Principal Component Analysis and Agglomerative Hierarchical Clustering). Results showed that the bones considered can be grouped in two classes, represented by each anatomy; besides, the anatomy was most significant than age. The refractive index increased with age and was higher for femur; the cluster of tibias was more homogeneous than femurs. The THz radiation showed to be a useful and non-destructive tool to assess bovine bones variability and also their optical properties. This radiation could be applied to the predict animal bone components (collagen and minerals) extractability so as to valorise each cluster according to its potential. [ABSTRACT FROM AUTHOR]

A significant increase in the prevalence of kidney stones has been observed worldwide. In the past decades, this expansion was more pronounced among women than men. The precise mechanisms involved in the differences in the risk profile of stone disease between men and women have not been fully elucidated. Diet and lifestyle only partially can explain the differences, and the combination of factors such as the influence of sex hormones, genetics, and disorders in acid-base handling and urine pH, as well as differences in calcium tubular reabsorption and stone composition in men and women, may contribute to differences in the risk profile. In this review, we summarize the sex differences in the pathophysiologic basis of kidney stones, which may contribute to a more focused approach. [ABSTRACT FROM AUTHOR]

The characterization of folate status in subjects at risk of deficiency and with altered vitamin homeostasis is crucial to endorse preventive intervention health policies, especially in developed countries. Several physiological changes (i.e. pregnancy), clinical situations and diseases have been associated to increased requirement, impaired intake and absorption of folate. However clinical practice guidelines (CPG) endorse folic acid supplementation generally discarding the use of its determination in serum to assess the risk of deficiency and/or its concentration at baseline. Poor confidence on the diagnostic accuracy of serum folate assays still persists in the current CPGs although recent standardization efforts have greatly improved inter-method variability and precision. In this review we critically appraise the methodological issues concerning laboratory folate determination and the evidence on the potential adverse effects of folic acid exposure. The final aim is to build a sound background to promote serum folate-based cost-effective health care policies by optimizing folic acid supplementation in subjects at risk of deficiency and with altered folate homeostasis. Our first result was to adjust in relation to current serum folate assays the thresholds reported by CPGs as index of folate status, defined on the association with metabolic and hematologic indicators. We identify a statistically significant difference between the estimated thresholds and accordingly show that the assessment of folate status actually changes in relation to the assay employed. The use of the method-dependent thresholds here reported may pragmatically endorse the stewardship of folic acid supplementation in clinical practice and increase the cost-effectiveness of health care policies. [ABSTRACT FROM AUTHOR]

Background and Aims: Childhood obesity is associated to complications such as insulin resistance and dyslipidemia. High density lipoproteins (HDL) constitute the only lipoprotein fraction with ateroprotective properties. The aim of the present study was to analyze inflammatory markers, carbohydrate metabolism, lipid profile and HDL functionality in obese children and adolescents compared to healthy controls.Methods and Results: Twenty obese children and adolescents (Body mass index z score >3.0) (9-15 years old) and 20 age and sex similar controls were included in the study. Triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, apolipoproteins (apo) A-I and B, glucose and insulin levels were quantified. Lipid indexes and HOMA-IR were calculated. Cholesterol efflux (CEC), lipoprotein associated phospholipase A2 (Lp-PLA2), lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein, plus paraoxonase and arylesterase (ARE) activities were evaluated. Obese children and adolescents showed significantly higher TG [69 (45-95) vs 96 (76-121); p < 0.05], non-HDL-C [99 ± 34 vs 128 ± 26; p < 0.01], TC/HDL-C [2.8 ± 0.6 vs 4.7 ± 1.5; p < 0.01], TG/HDL-C [1.1 (1.0-1.8) vs 2,2 (1.4-3.2); p < 0.01], and HOMA-IR [1.5 (1.1-1.9) vs. 2.6 (2.0-4.5); p < 0.01] values, plus Lp-PLA2 activity [8.3 ± 1.9 vs 7.1 ± 1.7 umol/ml.h; p < 0,05] in addition to lower HDL-C [57 ± 10 vs 39 ± 9; p < 0.01], apo A-I [143 ± 25 vs 125 ± 19; p < 0.05], and CEC [6.4 (5.1-6.8) vs. 7.8 (5.7-9.5); p < 0.01] plus LCAT [12.6 ± 3.3 vs 18.7 ± 2.6; p < 0.05] and ARE [96 ± 19 vs. 110 ± 19; p < 0.05] activities. Lp-PLA2 activity correlated with LDL-C (r = 0.72,p < 0.01), non-HDL-C (r = 0.76,p < 0.01), and apo B (r = 0.60,p < 0.01). LCAT activity correlated with triglycerides (r = -0.78,p < 0.01), HDL-C (r = 0.64,p < 0.01), and apo A-I (r = 0.62, p < 0.05). ARE activity correlated with HDL-C (r = 0.32,p < 0.05) and apoA-I (r = 0.43,p < 0.01). CEC was negatively associated with BMI z-score (r = -0.36,p < 0.05), and triglycerides (r = -0.28,p < 0.05), and positively with LCAT activity (r = 0.65,p < 0.05). In multivariate analysis, BMI z-score was the only parameter significantly associated to CEC (r2 = 0.43, beta = -0.38, p < 0.05).Conclusion: The obese group showed alterations in carbohydrate and lipid metabolism, which were associated to the presence of vascular specific inflammation and impairment of HDL atheroprotective capacity. These children and adolescents would present qualitative alterations in their lipoproteins which would determine higher risk of suffering premature cardiovascular disease. [ABSTRACT FROM AUTHOR]

Purpose: The selection of perioperative antibiotics for prevention of surgical site infection (SSI) is often limited by the presence of a reported penicillin allergy. The purpose of this study was to determine if oral and maxillofacial surgery patients who report allergy to penicillin are at an increased risk of developing SSI.Methods: A retrospective cohort study was performed of patients who underwent oral and maxillofacial surgical procedures in the operating room setting at a single institution between 2011 and 2018. The following categories of procedures were investigated: dentoalveolar, orthognathic, orthognathic with third molar extraction, pathology and reconstruction, and temporomandibular joint. The primary predictor and outcome variables were reported penicillin allergy and surgical site infection, respectively. Bivariate and multiple logistic regression analysis were performed. P < .05 was considered to be significant.Results: The cohort was composed of 2,058 patients of which 318 (15.5%) reported allergy to penicillin. Beta-lactam antibiotics were administered less frequently to penicillin allergic patients perioperatively compared with those without penicillin allergy (7.9 vs 97.1%, P < .001), while clindamycin was more commonly administered (76.4 vs 2.5%, P < .001). Clindamycin was associated with a higher SSI rate compared with beta-lactam antibiotics (5.6 vs 1.4%, P < .001). Penicillin allergy was significantly associated with SSI at an adjusted odds ratio of 2.61 (95% CI 1.51 to 4.49, P = .001). After holding perioperative antibiotic usage equal between the 2 groups, penicillin allergy per se was no longer associated with SSI (P = .901), suggesting that the outcome was mediated by antibiotic selection.Conclusions: Penicillin allergy was associated with development of SSI due to receipt of non-beta-lactam antibiotics as perioperative prophylaxis. Formal allergy evaluation should be considered for patients with putative penicillin allergy. [ABSTRACT FROM AUTHOR]

Introduction: The association between the level of physical activity and quality of cardio-pulmonary resuscitation (CPR) performed by laypeople is unclear. The aim of this study was to evaluate the associations between physical activity level and laypeople performance during an eight-minute scenario of CPR.Materials and Methods: This study was a secondary analysis of the MANI-CPR Trial. The entire cohort of participants was grouped based on the level of physical activity assessed using the International Physical Activity Questionnaire (IPAQ) into a "low-moderate" level group and a "high" level group. Descriptive statistics were used for unadjusted analysis and multivariate logistic and linear regression models were also performed.Results: A total of 492 participants who reached the score of "Advanced CPR performer" at the 1-min final test monitored by Laerdal Resusci Anne QCPR were included in this analysis; 224 with a low-moderate level and 268 with a high level of physical activity. A statistically significant difference was found for the outcome of percentage of compressions with adequate depth (low-moderate group: 87.8% [41·4%-99·3%], high group: 97% [63·2%-100%]; P = 0·003). No associations remained significant after controlling for biometric characteristics of the participants, compression protocols and sex.Conclusion: Adequate quality CPR may not need high baseline level of physical activity to be performed by a lay rescuer. [ABSTRACT FROM AUTHOR]

Gigantomastia, characterized by excessive breast size (usually heavier than 2.5 kg), can result from various causes and significantly affect patients' lives. Surgical intervention is often required, and over time, several techniques have been developed for its treatment. These techniques aim to address the functional and aesthetic concerns associated with gigantomastia, providing relief to patients and improving their quality of life. A 40-year-old primiparous housewife developed unilateral gigantomastia as a consequence of hormone therapy. To address this, a modified reduction mammoplasty procedure was undertaken, incorporating NAC (Nipple-Areola Complex) grafting. The reduction involved removing 3450 g of tissue, resulting in restored breast symmetry and enabling the patient to reintegrate into normal daily life. Compared to the traditional technique, the introduction of some modifications in the design allowed for the absence of complications such as dehiscence of the scar at the intersection of the T, the failure of the nipple graft attachment, and the maintenance of a conical shape over time, enabling complete symmetrization of the two breasts. The use of a modified version of the Thorek technique allowed for optimal functional and aesthetic restoration even in the case of a significantly disproportionate breast compared to the contralateral one, with no complications. • Gigantomastia is a debilitating condition with multiple potential causes. • It can manifest as either bilateral or unilateral, leading to noticeable asymmetry between the two breasts. • Various approaches can be employed for its treatment, distinguished by the use of pedicled nipple flap or nipple grafting. • In this work we present our experience with a modified Nipple-Areola Complex grafting technique. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a portal natural language processing approach to aid in the identification of postoperative venous thromboembolism events from free-text clinical notes. We abstracted clinical notes from 25,494 operative events from 2 independent health care systems. A venous thromboembolism detected as part of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was used as the reference standard. A natural language processing engine, easy clinical information extractor-pulmonary embolism/deep vein thrombosis (EasyCIE-PEDVT), was trained to detect pulmonary embolism and deep vein thrombosis from clinical notes. International Classification of Diseases (ICD) discharge diagnosis codes for venous thromboembolism were used as baseline comparators. The classification performance of EasyCIE-PEDVT was compared with International Classification of Diseases codes using sensitivity, specificity, area under the receiver operating characteristic curve, using an internal and external validation cohort. To detect pulmonary embolism, EasyCIE-PEDVT had a sensitivity of 0.714 and 0.815 in internal and external validation, respectively. To detect deep vein thrombosis, EasyCIE-PEDVT had a sensitivity of 0.846 and 0.849 in internal and external validation, respectively. EasyCIE-PEDVT had significantly higher discrimination for deep vein thrombosis compared with International Classification of Diseases codes in internal validation (area under the receiver operating characteristic curve: 0.920 vs 0.761; P <.001) and external validation (area under the receiver operating characteristic curve: 0.921 vs 0.794; P <.001). There was no significant difference in the discrimination for pulmonary embolism between EasyCIE-PEDVT and ICD codes. Accurate surveillance of postoperative venous thromboembolism may be achieved using natural language processing on clinical notes in 2 independent health care systems. These findings suggest natural language processing may augment manual chart abstraction for large registries such as NSQIP. [ABSTRACT FROM AUTHOR]

To report outcomes in a pilot study of autologous mitochondrial transplantation (MT) in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI). A single-center retrospective study of patients requiring ECMO for postcardiotomy cardiogenic shock following IRI between May 2002 and December 2018 was performed. Postcardiotomy IRI was defined as coronary artery compromise followed by successful revascularization. Patients undergoing revascularization and subsequent MT were compared with those undergoing revascularization alone (Control). Twenty-four patients were included (MT, n = 10; Control, n = 14). Markers of systemic inflammatory response and organ function measured 1 day before and 7 days following revascularization did not differ between groups. Successful separation from ECMO—defined as freedom from ECMO reinstitution within 1 week after initial separation—was possible for 8 patients in the MT group (80%) and 4 in the Control group (29%) (P =.02). Median circumferential strain immediately following IRI but before therapy was not significantly different between groups. Immediately following separation from ECMO, ventricular strain was significantly better in the MT group (−23.0%; range, −20.0% to −28.8%) compared with the Control group (−16.8%; range, −13.0% to −18.4%) (P =.03). Median time to functional recovery after revascularization was significantly shorter in the MT group (2 days vs 9 days; P =.02). Cardiovascular events were lower in the MT group (20% vs 79%; P <.01). Cox regression analysis showed higher composite estimated risk of cardiovascular events in the Control group (hazard ratio, 4.6; 95% confidence interval, 1.0 to 20.9; P =.04) In this pilot study, MT was associated with successful separation from ECMO and enhanced ventricular strain in patients requiring postcardiotomy ECMO for severe refractory cardiogenic shock after IRI. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Hepatocyte growth factor (HGF) is a cytokine and marker of cardiovascular disease (CVD) risk. Less is known about HGF and incident heart failure (HF). We examined the association of HGF with incident HF and its subtypes in a multiethnic cohort.Methods and Results: We included 6597 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, free of clinical CVD and HF at baseline, with HGF measured at baseline. Incident hospitalized HF was assessed and adjudicated for HF with preserved ejection fracture (HFpEF) vs HF with reduced ejection fraction (HFrEF). Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for HF risk by HGF levels, adjusted for socio-demographics, CVD risk factors and N-terminal pro-B-type natriuretic peptide. The mean age was 62 ± 10 years. The median HGF level was 950 pg/mL (interquartile range, 758-1086 pg/mL); 53% were women. Over 14 years (IQR, 11.5-14.7 years), there were 324 cases of HF (133 HFpEF and 157 HFrEF). For the highest HGF tertile compared with lowest, adjusted HRs were 1.59 (95% CI, 1.10-2.31), 1.90 (95% CI, 1.03-3.51), and 1.09 (95% CI, 0.65-1.82) for overall HF, HFpEF, and HFrEF, respectively. For continuous analysis per 1-standard deviation log-transformed HGF, adjusted HRs were 1.22 (95% CI, 1.06-1.41), 1.35 (95% CI, 1.09-1.69), and 1.00 (95% CI, 0.81-1.24) for HF, HFpEF, and HFrEF, respectively.Conclusions: HGF was independently associated with incident HF. HGF remained significantly associated with HFpEF but not HFrEF upon subtype assessment. Future studies should examine the mechanisms underlying these associations and evaluate whether HGF can be used to improve HF risk prediction or direct therapy. [ABSTRACT FROM AUTHOR]

Background: Occurrence of hepatitis C virus (HCV) infection is reduced by effective risk management procedures, but patient-to-patient transmission continues to be reported in healthcare settings.Aim: To report the use of phylogenetic analysis in the clinical risk management of an HCV outbreak among 128 thalassaemia outpatients followed at a thalassaemia centre of an Italian hospital.Methods: Epidemiological investigation and root-cause analysis were performed. All patients with acute hepatitis and known chronic infection were tested for HCV RNA, HCV genotyping, and NS3, NS5A, and NS5B HCV genomic region sequencing. To identify transmission clusters, phylogenetic trees were built for each gene employing Bayesian methods.Findings: All patients with acute hepatitis were infected with HCV genotype 1b. Root-cause analysis, including a lookback procedure, excluded blood donors as the source of HCV transmission. The phylogenetic analysis, conducted on seven patients with acute infection and eight patients with chronic infection, highlighted four transmission clusters including at least one patient with chronic and one patient with acute HCV infection. All patients in the same cluster received a blood transfusion during the same day. Two patients with acute hepatitis spontaneously cleared HCV within four weeks and nine patients received ledipasvir plus sofosbuvir for six weeks, all achieving a sustained virological response.Conclusion: Combined use of root-cause analysis and molecular epidemiology was effective in ascertaining the origin of the HCV outbreak. Antiviral therapy avoided the chronic progression of the infection and further spread in care units and in the family environment. [ABSTRACT FROM AUTHOR]