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Background Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. Objective The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. Methods A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010–2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. Results From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015–2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. Conclusion The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010–2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-021-00498-3.

A one-year-old, French Bulldog was referred for the management of a severe form of pulmonary valve stenosis (PS) complicated by right-sided congestive heart failure. Echocardiography showed severe valvular PS with right ventricular concentric hypertrophy, dilatation and severe right atrial enlargement. A pulmonary balloon valvuloplasty (PBV) was performed with a balloon-to-pulmonary annulus ratio of 1.36. Echocardiography immediately after PBV showed a significant reduction in right atrial and ventricular size, improved opening and mobility of the pulmonary valve leaflets, and a 75% reduction in the pulmonary pressure gradient from 158 mmHg pre-operative to 40 mmHg post-operative. The dog recovered well from anesthesia, but two hours later suddenly showed severe respiratory distress. Focus cardiac ultrasound showed increased left cardiac size with echocardiographic signs of high left ventricular filling pressure. Bedside lung ultrasound showed diffuse numerous-to-confluent B lines, compatible with severe alveolar-interstitial syndrome. The dog was treated with furosemide, helmet continuous positive airway pressure and then mechanical ventilation but without success. At post-mortem evaluation, histological examination of the lung showed diffuse, severe broncho-alveolar edema with mixed leukocyte, fibrin and red blood cell infiltrate. Moreover, severe congestion and multifocal alveolar hemorrhages were evident. All findings were compatible with fatal acute lung injury after PBV secondary to pulmonary reperfusion-ischemia injury and increased pulmonary capillary hydrostatic pressure. Based on the present case, acute lung injury should be considered as a rare but serious complication of PBV.

Objective To synthesize the growing body of literature on the role of social determinants of health (SDoH) in asthma and asthma disparities. Data Sources A pubmed.gov search was performed to identify published literature on SDoH, asthma, asthma disparities, and race and ethnicity. Current asthma statistics of the Centers for Disease Control and Prevention were reviewed. Study Selections Relevant articles on SDoH, asthma, asthma disparities, and race and ethnicity were reviewed in detail. Results Black and Latinx Americans have a higher asthma prevalence and greater asthma morbidity than White Americans and also bear a disproportionate burden of SDoH. Inequities in SDoH are rooted in structural racism and population-level injustices that affect the socioeconomic status, physical environment, and health care access/quality of Black and Latinx Americans. There is evidence that racial/ethnic inequities in SDoH, such as socioeconomic status, neighborhood environment, housing, environmental exposures, and health care access/quality, contribute to excess burden of asthma prevalence/incidence, morbidity, exacerbations, and abnormal lung function among certain racial/ethnic populations. In addition, Black and Latinx communities experience high levels of long-term stress, which may increase asthma risk through direct effects on the immune system and hypothalamic-pituitary-adrenocortical activation. Long-term stress may also mediate the effects of SDoH on asthma. Conclusion Although there is clear evidence linking SDoH to excess asthma risk and implicating SDoH in asthma disparities, the extent to which asthma disparities are explained by inequities in SDoH and the relative contributions of each of these SDoH to asthma disparities remain unclear. This knowledge is needed to effectively develop and test systems-level interventions targeting SDoH, with the ultimate goal of meaningfully reducing racial/ethnic asthma disparities.

Congenital anomalies may have an increased risk of noncommunicable diseases (NCDs) We performed a clinical exome analysis in an infant affected by “Vertebral, Anorectal, Cardiac, Tracheoesophageal, Genitourinary, and Limb” (VACTERL) malformation association to identify potential biomarkers that may be helpful for preventing malignancy risk or other chronic processes. Among the variants, six variants that may be linked with VACTERL were identified in the exome analysis. The variants c.501G>C on OLR1 and c.-8C>G on PSMA6 were previously associated with myocardial infarction. The variants c.1936A>G on AKAP10 and c.575A>G on PON1 are linked to defects in cardiac conduction and artery disease, respectively. Alterations in metabolism were also suggested by the variants c.860G>A on EPHX2 and c.214C>A on GHRL. In addition, three variants associated with colon cancer were discovered. Specifically, the reported variants were c.723G>A on CCND1 and c.91T>A on AURKA proto-oncogenes as well as c.827A>C in the tumor suppressor PTPRJ. A further inspection identified 15 rare variants carried by cancer genes. Specifically, these mutations are located on five tumor suppressors (SDHA, RB1CC1, PTCH1, DMBT1, BCR) and eight proto-oncogenes (MERTK, CSF1R, MYB, ROS1, PCM1, FGFR2, MYH11, BRCC3) and have an allele frequency lower than 0.01 in the Genome Aggregation Database (GnomAD). We observed that the cardiac and metabolic phenotypic traits are linked with the genotype of the patient. In addition, the risk of developing neoplasia cannot be excluded a priori. Long-term surgical issues of patients with VATER syndrome could benefit from the clinical exome sequencing of a personalized risk assessment for the appearance of further disease in pubertal timing and adult age.

Emerging technologies, such as self-driving cars and 5G communications, are raising new mobility and transportation possibilities in smart and sustainable cities, bringing to a new echo-system often referred to as Internet of Vehicles (IoV). In order to efficiently operate, an IoV system should take into account more stringent requirements with respect to traditional IoT systems, e.g., ultra-broadband connections, high-speed mobility, high-energy efficiency and requires efficient real-time algorithms. This paper proposes an energy and communication driven model for IoV scenarios, where roadside units (RSUs) need to be frequently assigned and re-assigned to the operating vehicles. The problem has been formulated as an Uncapacitated Facility Location Problem (UFLP) for jointly solving the RSU-to-vehicle allocation problem while managing the RSUs switch-on and -off processes. Differently from traditional UFLP approaches, based on static solutions, we propose here a fast-heuristic approach, based on a dynamic multi-period time scale mapping: the proposed algorithm is able to efficiently manage in real-time the RSUs, selecting at each period those to be activated and those to be switched off. The resulting methodology is tested against a set of benchmark instances, which allows us to illustrate its potential. Results, in terms of overall cost–mapping both energy consumption and transmission delays–, number of active RSUs, and convergence speed, are compared with static approaches, showing the effectiveness of the proposed dynamic solution. It is noticeable a gain of up to 11% in terms of overall cost with respect to the static approaches, with a moderate additional delay for finding the solution, around 0.8 s, while the overall number of RSUs to be switched on is sensibly reduced up to a fraction of 15% of the overall number of deployed RSUs, in the most convenient scenario.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Objective To determine the predictive power for seizure-freedom of 19-channels EEG, measured both before and after three months the initiation of the use of Levetiracetam (LEV), in a cohort of people after a new diagnosis of temporal-lobe epilepsy (TLE) using a machine-learning approach. Methods Twenty-three individuals with TLE were examined. We dichotomized clinical outcome into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG effective power in different frequency bands was compared using baseline EEG (T0) and the EEG after three months of LEV therapy (T1) between SF and NSF patients. Partial Least Square (PLS) analysis was used to test and validate the prediction of the model for clinical outcome. Results A total of 152 features were extracted from the EEG recordings. When considering only the features calculated at T1, a predictive power for seizure-freedom (AUC = 0.750) was obtained. When employing both T0 and T1 features, an AUC = 0.800 was obtained. Conclusions This study provides a proof-of-concept pipeline for predicting the clinical response to anti-seizure medications in people with epilepsy. Significance Future studies may benefit from the pipeline proposed in this study in order to develop a model that can match each patient to the most effective anti-seizure medication.

Echinobase (www.echinobase.org) is a third generation web resource supporting genomic research on echinoderms. The new version was built by cloning the mature Xenopus model organism knowledgebase, Xenbase, refactoring data ingestion pipelines and modifying the user interface to adapt to multispecies echinoderm content. This approach leveraged over 15 years of previous database and web application development to generate a new fully featured informatics resource in a single year. In addition to the software stack, Echinobase uses the private cloud and physical hosts that support Xenbase. Echinobase currently supports six echinoderm species, focused on those used for genomics, developmental biology and gene regulatory network analyses. Over 38 000 gene pages, 18 000 publications, new improved genome assemblies, JBrowse genome browser and BLAST + services are available and supported by the development of a new echinoderm anatomical ontology, uniformly applied formal gene nomenclature, and consistent orthology predictions. A novel feature of Echinobase is integrating support for multiple, disparate species. New genomes from the diverse echinoderm phylum will be added and supported as data becomes available. The common code development design of the integrated knowledgebases ensures parallel improvements as each resource evolves. This approach is widely applicable for developing new model organism informatics resources.

The Hyperspectral X-ray Imaging (HXI) project will enable non-destructive chemical-state determination of nano-scale samples in the electron microscope for nuclear safeguards applications. To efficiently measure chemical state through electron-excited X-ray emission requires a combination of wide spectral bandwidth, high resolution, and high count rate capability. We are building a next-generation X-ray detector based on an array of transition edge sensors (TESs) to make these measurements possible and routine in the scanning electron microscope (SEM). Leveraging the large pixel densities afforded by microwave multiplexing readout and continuous, uninterrupted operation of a cryogen-free dilution refrigerator, this instrument will have efficiency to allow chemical species identification of nano-scale samples in hours instead of days to weeks. We describe prototype pixel designs for this HXI instrument, comprising three pixel types that will make up the hybrid TES array. Engineering design of the integrated HXI cryostat and SEM system is in progress, with full detector commissioning expected in Spring 2021 followed closely by full-scale integration with the SEM. We also report on the commissioning of a complementary TES-based X-ray emission spectroscopy platform for bulk samples to build a spectral library for HXI sample identification.

We describe 22 examples of a novel, usually paratubal, adnexal tumor associated with Peutz-Jeghers syndrome in nearly 50% of cases that harbored STK11 alterations in all tested (n=21). The patients ranged from 17 to 66 (median 39) years and the tumors from 4.5 to 25.5 (median 11) cm. Most (n=18) were paratubal, with metastases noted in 11/22 (50%) and recurrences in 12/15 (80%). Morphologically, they were characterized by interanastomosing cords and trabeculae of predominantly epithelioid cells, set in a variably prominent myxoid to focally edematous stroma, that often merged to form tubular, cystic, cribriform, and microacinar formations, reminiscent of salivary gland-type tumors. The tumor cells were uniformly atypical, often with prominent nucleoli and a variable mitotic index (median 9 per 10 high-power fields). The tumors were usually positive to a variable extent for epithelial (CAM5.2, AE1/AE3, cytokeratin 7), sex cord (calretinin, inhibin, WT1), and mesothelial (calretinin, D2–40) markers, as well as hormone receptors. PAX8, SF1, and GATA-3 were rarely positive while claudin-4, FOXL2, and TTF-1 were consistently negative. All sequenced tumors (n=21) harbored alterations in STK11, often with a loss of heterozygosity event. There were no other recurrently mutated genes. Recurrent copy number alterations included loss of 1p and 11q, and gain of 1q, 15q, and 15p. Despite an extensive morphological, immunohistochemical, and molecular evaluation, we are unable to determine with certainty the histogenesis of this unique tumor. Wolffian, sex cord stromal, epithelial, and mesothelial origins were considered. We propose the term STK11 adnexal tumor to describe this novel entity and emphasize the importance of genetic counseling in these patients as a significant number of neoplasms occur in association with Peutz-Jeghers syndrome.

BACKGROUND: Most atopic dermatitis (AD) patients are managed by primary care providers (PCPs). PCP discomfort diagnosing and managing AD leads to suboptimal patient outcomes. OBJECTIVE: To determine the efficacy of interventions aimed at improving PCP management of AD. METHODS: A systematic literature review was performed for interventions to improve primary care management of AD. PubMed, MEDLINE, Embase, Scopus, LILACS, Cochrane, GREAT, and CINAHL were searched from database origin to February 24, 2020. Two reviewers independently performed the title/abstract and full-text review, and data extraction. RESULTS: Overall, 3,009 non-duplicate articles were screened; 145 full-text articles were assessed. Thirteen studies met inclusion criteria, including 8 randomized controlled trials, 2 cohorts, 2 qualitative studies, and 1 unspecified design. Seven interventions (53.8%) significantly improved PCP knowledge/ability and/or a patient outcome, including patients consulting with a dermatology-trained nurse, pairing clinical education with expert consultation, pairing trainees with clinical mentors, giving clinicians a treatment guide, pairing clinical education with a treatment guide, and providing an eczema action plan. LIMITATIONS: Studies had moderate-high risk-of-bias, moderate quality, and heterogeneous designs. CONCLUSIONS: There are few studies published and little evidence supporting the efficacy of interventions aimed at improving primary care management of AD. Further research is required to develop and implement effective interventions to improve primary care management of AD.

Cultural heritage information systems, such as H-BIM, are becoming more and more widespread today, thanks to their potential to bring together, around a 3D representation, the wealth of knowledge related to a given object of study. However, the reconstruction of such tools starting from 3D architectural surveying is still largely deemed as a lengthy and time-consuming process, with inherent complexities related to managing and interpreting unstructured and unorganized data derived, e.g., from laser scanning or photogrammetry. Tackling this issue and starting from reality-based surveying, the purpose of this paper is to semi-automatically reconstruct parametric representations for H-BIM-related uses, by means of the most recent 3D data classification techniques that exploit Artificial Intelligence (AI). The presented methodology consists of a first semantic segmentation phase, aiming at the automatic recognition through AI of architectural elements of historic buildings within points clouds; a Random Forest classifier is used for the classification task, evaluating each time the performance of the predictive model. At a second stage, visual programming techniques are applied to the reconstruction of a conceptual mock-up of each detected element and to the subsequent propagation of the 3D information to other objects with similar characteristics. The resulting parametric model can be used for heritage preservation and dissemination purposes, as common practices implemented in modern H-BIM documentation systems. The methodology is tailored to representative case studies related to the typology of the medieval cloister and scattered over the Tuscan territory.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11–34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7–16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9–25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14–29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15–23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17–48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20–41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20–34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20–33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21–46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

Small cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of

Contains fulltext : 238527.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is not clear how specific gait measures reflect disease severity across the disease spectrum in Parkinson's disease (PD). OBJECTIVE: To identify the gait and mobility measures that are most sensitive and reflective of PD motor stages and determine the optimal sensor location in each disease stage. METHODS: Cross-sectional wearable-sensor records were collected in 332 patients with PD (Hoehn and Yahr scale I-III) and 100 age-matched healthy controls. Sensors were adhered to the participant's lower back, bilateral ankles, and wrists. Study participants walked in a ~15-meter corridor for 1 minute under two walking conditions: (1) preferred, usual walking speed and (2) walking while engaging in a cognitive task (dual-task). A subgroup (n = 303, 67% PD) also performed the Timed Up and Go test. Multiple machine-learning feature selection and classification algorithms were applied to discriminate between controls and PD and between the different PD severity stages. RESULTS: High discriminatory values were found between motor disease stages with mean sensitivity in the range 72%-83%, specificity 69%-80%, and area under the curve (AUC) 0.76-0.90. Measures from upper-limb sensors best discriminated controls from early PD, turning measures obtained from the trunk sensor were prominent in mid-stage PD, and stride timing and regularity were discriminative in more advanced stages. CONCLUSIONS: Applying machine-learning to multiple, wearable-derived features reveals that different measures of gait and mobility are associated with and discriminate distinct stages of PD. These disparate feature sets can augment the objective monitoring of disease progression and may be useful for cohort selection and power analyses in clinical trials of PD. © 2021 International Parkinson and Movement Disorder Society.

Background Change is an ongoing process in any organizations. Over years, healthcare organizations have been exposed to multiple external stimuli to change (eg, ageing population, increasing incidence of chronic diseases, ongoing Sars-Cov-2 pandemic) that pointed out the need to convert the current healthcare organizational model. Nowadays, the topic is extremely relevant, rendering organizational change an urgency. The work is structured on a double level of analysis. In the beginning, the paper collects the overall literature on the topic of organisational change in order to identify, on the basis of the citation network, the main existing theoretical approaches. Secondly, the analysis attempts to isolate the scientific production related to the healthcare context, by analysing the body of literature outside the identified citation network, divided by clusters of related studies. Methodology This review adopted a quantitative-based method that employs jointly systematic literature review and bibliographic network analysis. Specifically, the study applied a citation network analysis (CNA) and a co-occurrence keywords analysis. The CNA allowed detecting the most relevant papers published over time, identifying the research streams in literature. Results The study showed four main findings. Firstly, consistent with past studies, works reviewed pointed out a convergence on the micro-level perspective for change's analysis. Secondly, an organic viewpoint whereby individual, organization and change's outcome contribute to any organizational change's action has been found in its early stage. Thirdly, works reported change combined with innovation's concept, although the structure of the relationship has not been outlined. Fourth, interestingly, contributions have been limited within the healthcare context. Conclusion Human dimension is the primary criticality to be managed to impede failure of the re-organizational path. Individuals are not passive recipients of change: individual change acceptance has been found a key input. Few papers discussed healthcare professionals' behaviour, and those available focused on technology-led changes perspective. In this view, individual acceptance of change within the healthcare context resulted being undeveloped and offers rooms for further analyses.

Background Blunt aortic injury (BAI) and traumatic brain injury (TBI) represent the 2 leading causes of death after blunt trauma. The goal of this study was to examine the impact of TBI and use of thoracic endovascular aortic repair (TEVAR) on patients with BAI, using a large, national dataset. Study Design Patients with BAI were identified from the Trauma Quality Improvement Program (TQIP) database over 10 years, ending in 2016. Patients with BAI were stratified by the presence of concomitant TBI and compared. Multivariable logistic regression (MLR) analysis was performed to determine independent predictors of mortality in BAI patients with and without TBI. Youden’s index was used to identify the optimal time to TEVAR in these patients. Results 17,040 patients with BAI were identified, with 4,748 (28%) having a TBI. Patients with BAI and TBI were predominantly male, with a higher injury burden and greater severity of shock at presentation, underwent fewer TEVAR procedures, and had increased mortality compared with BAI patients without TBI. The optimal time for TEVAR was 9 hours. Mortality was significantly increased in patients undergoing TEVAR before 9 hours (12.9% vs 6.5%, p = 0.003). For BAI patients with and without TBI, MLR identified use of TEVAR as the only modifiable risk factor significantly associated with reduced mortality (odds ratio [OR] 0.41; 95%CI 0.32–0.54, p Conclusions TBI significantly increases mortality in BAI patients. TEVAR and delayed repair both significantly reduced mortality. So, for patients with both BAI and TBI, an endovascular repair performed in a delayed fashion should be the preferred approach.

Background Treatment beyond progression with immunotherapy may be appropriate in selected patients based on the potential for late responses. The aim of this systematic review was to explore the impact of treatment beyond progression in patients receiving an anti-PD-1/PD-L1 based regimen for an advanced solid tumor. Methods A systematic literature search was performed to identify prospective clinical trials reporting data on overall response rate by immune-related criteria and/or the number of patients treated beyond conventional criteria-defined PD and/or the number of patients achieving a clinical benefit after an initial PD with regimens including an anti-PD-1/PD-L1 agent which received the FDA approval for the treatment of an advanced solid tumor. Results 254 (4.6%) responses after an initial RECIST-defined progressive disease were observed among 5588 patients, based on 35 trials included in our analysis reporting this information. The overall rate of patients receiving treatment beyond progressive disease was 30.2%, based on data on 5334 patients enrolled in 36 trials, and the rate of patients who achieved an unconventional response among those treated beyond progressive disease was 19.7% (based on 25 trials for a total of 853 patients). Conclusion The results of our systematic review support the clinical relevance of unconventional responses to anti-PD-1/PD-L1-based regimens; however, most publications provided only partial information regarding immune-related clinical activity, or did not provide any information at all, highlighting the need of a more comprehensive report of such data in trials investigating immunotherapy for the treatment of patients with advanced tumors.

In this paper, we present a system that allows visually impaired people to autonomously navigate in an unknown indoor and outdoor environment. The system, explicitly designed for low vision people, can be generalized to other users in an easy way. We assume that special landmarks are posed for helping the users in the localization of pre-defined paths. Our novel approach exploits the use of both the inertial sensors and the camera integrated into the smartphone as sensors. Such a navigation system can also provide direction estimates to the tracking system to the users. The success of out approach is proved both through experimental tests performed in controlled indoor environments and in real outdoor installations. A comparison with deep learning methods has been presented. © 2013 IEEE.

In this paper we study the capability of LoRa technology in rejecting different interfering LoRa signals and the impact on the cell capacity. First, we analyze experimentally the link-level performance of LoRa and show that collisions between packets modulated with the same Spreading Factor (SF) usually lead to channel captures, while different spreading factors can indeed cause packet loss if the interference power is strong enough. Second, we model the effect of such findings to quantify the achievable capacity in a typical LoRa cell: we show that high SFs, generally seen as more robust, can be severely affected by inter-SF interference and that different criteria for deciding SF allocations within the cell may lead to significantly different results. Moreover, the use of power control and packet fragmentation can be detrimental more than beneficial in many deployment scenarios. Finally, we discuss the capacity improvements that can be achieved by increasing the density of LoRa gateways. Our results have important implications for the design of LoRa networks: for example, allocating high SFs to faraway end devices might not improve the experienced performance in case of congested networks because of the increased transmission time and vulnerability period.

We evaluated the effects of transcranial random noise stimulation (tRNS) on fatigue in 17 subjects with relapsing–remitting multiple sclerosis with low physical disability. Two different patient groups underwent real or sham stimulation for 10days, targeting the primary motor cortex of the dominant side or contralateral to the most compromised limb. In the ‘real group’, beneficial effects were observed using the Modified Fatigue Impact Scale (p = 0.04; physical subscale: p = 0.03), the subscales ‘change in health’ (p = 0.006) and ‘role limitations due to physical problems’ (p = 0.001) of the Multiple Sclerosis Quality of Life-54, and by assessing the patient impression of perceived fatigue (p = 0.005).

Objective: To compare the accuracy of three ultrasound methods to estimate fetal weight within 48 hours before delivery, in order to recognize macrosomia, defined as birth weight greater than 4000 g.Methods: A prospective and ultrasonic study was performed on a sample of singleton pregnancies between 37 weeks and 41 weeks plus 6 days of gestation. Fetal weight was evaluated with Estimated Fetal Weight (EFW) formula, with the measurement of the Abdominal Circumference (AC) and with the assessment of the Abdominal Circumference corrected with the constant “c” (ACc).Results: 1030 patients with single pregnancy were included, 67.28% of them were primiparous, average Body Mass Index (BMI) at birth was 27.37 and macrosomia was found in 77 (8,08%) fetuses. EFW showed a sensitivity of 61.53%, a specificity of 90.72%, a positive predictive value (PPV) of 27.58% and negative predictive value (NPV) of 97.46%, to recognize birth weight of more than 4000 g. AC greater than 375 mm presented a sensitivity of 53.24%, a specificity of 93.21%, a PPV of 41.41% and a NPV of 95.67%, to detect macrosomic fetuses. ACc greater than 375 mm showed a sensitivity of 66.23%, a specificity of 88.65%, a PPV of 34.35% and a NPV of 96.68%, to predict macrosomia. The mean absolute error when the neonatal weight was greater than 4000 g, with EFW was 9,23%, with AC were 11,02% and with ACc was 9,32%.Conclusions: In this study was shown that either EFW, or AC-only, or ACc are useful tools to detect fetal macrosomia. The measurement of AC and Acc seem to be the easiest methods to learn and to be used every time. During the first stage of labor, ultrasound scan associated to clinic evaluation, provides further elements to physician, to allow a better management of delivery. The finding of a NPV greater than 95% with the three methods, leads to exclude macrosomia with a good approximation, even in case of clinic hypothesis.

Background Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP. Methods In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population. Results Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, –1.8%; 95% confidence interval [CI]: –8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, –7.6%; 97.5% CI: –15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively. Conclusions Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated. Clinical Trials Registration NCT02019420.

BACKGROUND The willingness of interventional cardiologists to adopt innovation and implement changes in day-to-day practice has received limited study. METHODS Online-based survey on learning and innovation: 38 questions were distributed via email list to interventional cardiologists. RESULTS The survey was distributed to 8,110 e-mails and completed by 621 (7.7%, 91.8% men, 60% in the 35 to 54-year-old age group). Of the respondents who perform coronary interventions, 45% perform >100 cases of noncomplex percutaneous coronary interventions per year and of the respondents who perform structural interventions, 15% perform more than >100 transcatheter aortic valve replacements per year. Most respondents (86.7%) rate themselves as highly likely/likely to introduce recently approved equipment in everyday practice and 47.5% have tried a new coronary guidewire in the past 6 months. The most common reasons for reluctance to use new equipment were high cost (64%) and uncertainty about whether it provides additional benefits compared with existing equipment (48.5%). Radial access in STEMI cases is always used by 43.6% of the respondents and 55% always use radial access for coronary angiography. Of those who use femoral access, 32% always use ultrasound guidance and 91% have used a closure device in the last 6 months. Most respondents (80%) read journals to keep up with current practice and believe that the most effective way to learn is through attendance of workshops/short courses (77.5%). Most respondents (69%) are involved in research. CONCLUSION Interventional cardiologists who participated in the survey are highly likely to adopt innovation in daily clinical practice.

Background COVID-19 is now a worldwide pandemic. Among the many extra-pulmonary manifestations of COVID-19, recent evidence suggested a possible occurrence of thyroid dysfunction. Purpose The Aim of the present review is to summarize available studies regarding thyroid function alterations in patients with COVID-19 and to overview the possible physio-pathological explanations. Conclusions The repercussions of the thyroid of COVID-19 seem to be related, in part, with the occurrence of a “cytokine storm” that would, in turn, induce a “non-thyroidal illness”. Some specific cytokines and chemokines appear to have a direct role on the hypothalamus–pituitary–thyroid axis. On the other hand, some authors have observed an increased incidence of a destructive thyroiditis, either subacute or painless, in patients with COVID-19. The hypothesis of a direct infection of the thyroid by SARS-Cov-2 stems from the observation that its receptor, ACE2, is strongly expressed in thyroid tissue. Lastly, it is highly probable that some pharmaceutical agents largely used for the treatment of COVID-19 can act as confounding factors in the laboratory evaluation of thyroid function parameters.

BackgroundOne-third of the U.S. population has prediabetes, but 90% remain undiagnosed because healthcare providers are not screening for this condition.ObjectiveThe purpose of this quality improvement project was to monitor prediabetes screening and identification, and implement evidence-based recommendations including registered dietician referral.MethodsThis project involved using an evidence-based screening tool to measure individual risk of prediabetes. Aggregate data was collected to evaluate screening implementation, evidence-based recommendations offered by providers, and assess patient risk factors.ResultsThe percentage of patients at risk for prediabetes was 41.3% (n = 111). The most frequent risks were identified as overweight, history of hypertension, family history of type 2 diabetes mellitus (T2DM), and older age. Providers offered education on weight loss 68.5% (n = 76) and exercise 76.6% (n = 85) but referred 33.3% (n = 37) patients for nutrition education. The screening rates were 52.3% (n = 176) and 72.5% (n = 244) in clinics A and B respectively.ConclusionsA gap remains in using evidence-based recommendations to decrease risk of prediabetes. Prediabetes screening identified a greater percentage of persons in this population.Implications for NursingThere is a need for consistent practice of evidence-based recommendations. This project set the benchmark for future efforts to educate, encourage, and measure providers successes.

INTRODUCTION Publicly available firearm data are difficult to access. Trauma registry data are excellent at documenting patterns of firearm-related injury. Law enforcement data excel at capturing national violence trends to include both circumstances and firearm involvement. The goal of this study was to use publicly available law enforcement data from all 50 states to better define patterns of firearm-related homicides in the young. METHODS All homicides in individuals 25 years or younger in the United States over a 37-year period ending in 2016 were analyzed: infant, 1 year or younger; child, 1 to 9 years old; adolescent, 10 to 19 years old; and young adult, 20 to 25 years old. Primary data files were obtained from the Federal Bureau of Investigation and comprised the database. Data analyzed included homicide type, situation, circumstance, month, firearm type, and demographics. Rates of all homicides and firearm-related homicides per 1 million population and the proportion of firearm-related homicides (out of all homicides) were stratified by year and compared over time using simple linear regression. RESULTS A total of 171,113 incidents of firearm-related homicide were analyzed (69% of 246,437 total homicides): 5,313 infants, 2,332 children, 59,777 adolescents, and 103,691 young adults. Most (88%) were male and Black (59%) with a median age of 20 years. Firearm-related homicides peaked during the summer months of June, July, and August (median, 1,156 per year; p = 0.0032). Rates of all homicides (89 to 53 per 1 million population) and firearm-related homicides (56 to 41 per 1 million population) decreased significantly from 1980 to 2016 (β = -1.12, p < 0.0001 and β = -0.57, p = 0.0039, respectively). However, linear regression analysis identified a significant increase in the proportion of firearm-related homicides (out of all homicides) from 63% in 1980 to 76% in 2016 (β = 0.33, p < 0.0001). CONCLUSION For those 25 years or younger, the proportion of firearm-related homicides has steadily and significantly increased over the past 37 years, with 3 of 4 homicides firearm related in the modern era. Despite focused efforts, reductions in the rate of firearm-related homicides still lag behind those for all other methods of homicide by nearly 50%. That is, while the young are less likely to die from homicide, for those unfortunate victims, it is more likely to be due to a firearm. This increasing role of firearms in youth homicides underscores the desperate need to better direct prevention efforts and firearm policy if we hope to further reduce firearm-related deaths in the young. LEVEL OF EVIDENCE Epidemiological study, level III.

Patients with Coronavirus-associated disease-2019 (COVID-19) display alterations of the hemostatic system and the presence of a prothrombotic status frequently leading to vascular complications. However, the impact of COVID-19 on platelet activity, aggregation and agglutination still needs to be clarified. We measured total levels of von Willebrand factor (vWF) and vWF binding to the platelet glycoprotein (Gp) complex (GPIb-IX-V), in a cohort of COVID-19 patients admitted to the intensive care unit of our Institution. Moreover, we evaluated platelet aggregation in response to agonists (ADP, collagen, arachidonic acid) and platelet agglutination in response to ristocetin. We found that levels of vWF antigen and the active form of vWF binding to platelets (vWF:RCo), were markedly increased in these patients. These results were associated with higher agglutination rates induced by ristocetin, thereby indirectly indicating an increased capability of vWF to bind to platelets. Conversely, we found that platelet aggregation in response to both ADP and collagen was lower in COVID-19 patients compared to healthy volunteers. This study shows that COVID-19 is associated with increased vWF-induced platelet agglutination but reduced platelet responsivity to aggregation stimuli. Our findings have translational relevance since platelet adhesion to vWF may represent a marker to predict possible complications and better delineate therapeutic strategies in COVID-19 patients. Electronic Supplementary Material The online version of this article (10.1007/s11239-020-02339-6) contains supplementary material, which is available to authorized users.

This study investigates whether the individual attributes and investment approaches of business angels (BAs) affect the growth of funded companies by distinguishing between two firm types: gazelles...

The objective of this study was to test Prostate Imaging Reporting and Data System (PI-RADS) classification on multiparametric magnetic resonance imaging (mpMRI) and MRI-derived prostate-specific antigen density (PSAD) in predicting the risk of reclassification in men in active surveillance (AS), who underwent confirmatory or per-protocol follow-up biopsy.Three hundred eighty-nine patients in AS underwent mpMRI before confirmatory or follow-up biopsy. Patients with negative (-) mpMRI underwent systematic random biopsy. Patients with positive (+) mpMRI underwent targeted fusion prostate biopsies + systematic random biopsies. Different PSAD cutoff values were tested (0.10, 0.10-0.20, ≥ 0.20). Multivariable analyses assessed the risk of reclassification, defined as clinically significant prostate cancer of grade group 2 or more, during follow-up according to PSAD, after adjusting for covariates.One hundred twenty-seven (32.6%) patients had mpMRI(-); 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. The rate of reclassification to grade group 2 PCa was 16%, 22%, 31%, and 39% for mpMRI(-) and PI-RADS 3, 4, and 5, respectively, in case of PSAD 0.10 ng/mLPSAD ≥ 0.20 ng/mL

Introduction Version 2 of the Needs-Based Assessment of Trauma Systems (NBATS) tool quantifies the impact of an additional trauma center on a region. This study applies NBATS-2 to a system where an additional trauma center was added to compare the tool’s predictions to actual patient volumes. Methods Injury data were collected from the trauma registry of the initial (legacy) center and analyzed geographically using ArcGIS. From 2012 to 2014 (“pre-”period), one Level 1 trauma center existed. From 2016 to 2018 (“post-”period), an additional Level 2 center existed. Emergency medical service (EMS) destination guidelines did not change and favored the legacy center for severely injured patients (Injury Severity Score (ISS) >15). NBATS-2 predicted volume was compared to the actual volume received at the legacy center in the post-period. Results 4068 patients were identified across 14 counties. In the pre-period, 72% of the population and 90% of injuries were within a 45-minute drive of the legacy trauma center. In the post-period, 75% of the total population and 90% of injuries were within 45 minutes of either trauma center. The post-predicted volume of severely injured patients at the legacy center was 434, but the actual number was 809. For minor injuries (ISS £15), NBATS-2 predicted 581 vs. 1677 actual. Conclusion NBATS-2 failed to predict the post-period volume changes. Without a change in EMS destination guidelines, this finding was not surprising for severely injured patients. However, the 288% increase in volume of minor injuries was unexpected. NBATS-2 must be refined to assess the impact of local factors on patient volume.

Background Patients who present at night following penetrating abdominal trauma are thought to have more severe injuries and increased risk for morbidity and mortality. The current literature is at odds regarding this belief. The purpose of this study was to evaluate time of day on outcomes following laparotomy for penetrating abdominal trauma. Methods Patients undergoing laparotomy following penetrating abdominal trauma over a 12-month period at a level I trauma center were stratified by age, sex, severity of shock, injury, operative complexity, and time of day (DAY = 0700–1900, NIGHT = 1901–0659). Outcomes of damage control laparotomy, ventilator days, intensive care unit length of stay, hospital length of stay, morbidity, and mortality were compared between DAY and NIGHT. Results A total of 210 patients were identified: 145 (69%) comprised NIGHT, and 65 (31%) comprised DAY. Overall mortality was 2.9%. Both injury severity and intraoperative transfusions were increased with NIGHT with no difference in morbidity (37% vs 40%, P = 0.63) or mortality (2.1% vs 4.6%, P = 0.31). Adjusting for sex, time of day, injury severity, and operative complexity, only abdominal abbreviated injury severity (odds ratio 1.46; 95% confidence interval 1.07–1.99, P = .019) and operative transfusions (odds ratio 1.18; 95% confidence interval 1.09–1.28, P, Highlights • The majority of operative penetrating abdominal trauma occurs at night. • These patients have increased injury burden, more operative transfusions, and increased use of DCL. • Patients who present to a level 1 trauma center with penetrating abdominal trauma should not have any difference in morbidity and mortality based on time of day at presentation. • There is a significant need to understand and evaluate variations in timing of trauma burdens to appropriately staff and provide adequate resources for optimal outcomes regardless of time at presentation.

PURPOSE OF REVIEW Management of patients with coronary artery disease (CAD) has been based on identification of a coronary obstruction causing ischemia and performing a revascularization procedure to reduce that ischemia, with the goal of thereby preventing subsequent major adverse cardiac events (MACEs) in that vascular territory. Recent investigations demonstrate that preemptive percutaneous coronary intervention (PCI) of nonculprit coronary lesions (NCLs) that may not cause ischemia in patients with ST-segment elevation myocardial infarction (STEMI) reduces MACE. In this review, we focus on preemptive PCI, discuss its mechanistic benefits and speculate on its potential value for other coronary syndromes. RECENT FINDINGS The COMPLETE trial in STEMI patients treated with primary PCI demonstrated that preemptive PCI of NCL obstructions, which may not cause ischemia, but often exhibit high-risk OCT plaque characteristics, reduced cardiovascular death or nonfatal myocardial infarction. Reduction in MACE from preemptive PCI of NCL was similar for lesions confirmed to cause ischemia (fractional flow reserve

Introduction Traumatic brain injury (TBI) remains a significant cause of morbidity and mortality. The purpose of this study is to examine outcomes after discharge and identify factors from the index admission that may contribute to long-term mortality. Methods The study population is composed of patients who survived to discharge from a previously published study examining TBI. Demographics, injury severity, and length of stay were abstracted from the index study. Phone surveys of surviving patients were performed to evaluate each patient’s Glasgow Outcome Scale-Extended (GOSE). Patients who were deceased at the time of the survey were compared with those who were alive. Results 1615 patients were alive at the end of the first study period and 211 (13%) comprised the study population. Overall, the median age was 54 years, and the majority were male (74%). The median time to follow-up was 80 months. The population was severely injured, with a median injury severity score (ISS) of 25 and a median head abbreviated injury score (AIS) of 4. Overall mortality was 57%. The group that survived at the time of the survey was younger, more injured, less likely to have received beta-blockers (BB) during the index admission, and had a longer time to follow-up. After adjusting for ISS, age, base deficit, and BB, age was the only variable predictive of mortality (HR 1.03; HL 1.02-1.04). Conclusion Despite being more severely injured, younger patients were more likely to survive to follow-up. Further investigation is needed to determine if aggressive care in older TBI patients in the acute phase leads to good long-term outcomes.

Adjuvant chemotherapy and/or chemoradiation [chemo(radiation)] is considered the standard of care for resected patients with pancreatic adenocarcinoma. However, invasive carcinoma arising from an intraductal papillary mucinous neoplasm (IPMN) seems to have different biologic behavior and prognosis. Retrospective data suggest a survival benefit of adjuvant chemo(radiation) for resected invasive IPMNs with metastatic nodal disease; however, it is unclear whether this remains valid for node-negative patients. To compare the outcome of patients with invasive IPMNs who received adjuvant chemo(radiation) with that of those treated with surgery alone, we queried the National Cancer Database regarding data of patients who underwent pancreatic resection for invasive IPMN between 2006 and 2015. A propensity score analysis was conducted to balance covariates between treatment groups. For the study, 492 patients were eligible, of whom 267 (54.3%) received adjuvant chemo(radiation). Estimated 1- and 3-year overall survival rates were 88.9% and 73.5% versus 93.2% and 72.8% for patients who did or did not receive adjuvant chemo(radiation), respectively. Among patients with negative nodal stage, there was no difference in overall survival between patients who received versus patients who did not receive adjuvant chemo(radiation) (P = 0.973). In contrast, among patients with positive nodal disease, those who received adjuvant chemo(radiation) had significantly better OS compared with those who did not (P = 0.001). In patients with resected invasive IPMNs, adjuvant chemo(radiation) was associated with significantly improved overall survival only in presence of nodal metastases. This finding can help clinicians to select adjuvant treatment in a patient-tailored fashion.

Background: A growing number of neuroimaging studies have revealed spatial abnormalities of resting-state functional brain network activity in bipolar disorder (BD). Conversely, abnormalities of resting state temporal dynamics have been scarcely investigated so far. The aim of this study was to characterize the EEG microstates activity in BD patients with a history of manic predominant polarity. Patients were euthymic and pharmacologically stabilized. Methods: Nineteen BD patients (mean age 34.4 ± 11.0, 7 female) and 19 healthy controls (HC; mean age 38.2 ± 9.9, 7 female) were recruited. The psychometric evaluation included the Hamilton Depression Scale (HAMD), the Young Mania Rating Scale (YMRS), the Dissociative Experience Scale (DES), and the State-Trait Anxiety Inventory (STAI). Two runs of 2 minutes of EEG activity by a 128-channel system were acquired at rest and analyzed through microstate analysis. Results: We found a reduced presence of microstate B in BD patients compared to HC, since BD patients have a tendency to transit from the microstate B to the microstates C and D significantly more than HC. Furthermore, microstate B features were correlated with DES, state STAI and trait STAI scores. Conclusion: The reduced presence of microstate B might be associated with episodic autobiographic memory deficit, exaggerated self-focusing and states of dissociations characteristic of BD. Strong correlations of microstate B metrics and dynamics with symptoms of dissociation and anxiety across the two groups supported this interpretation.

Inflammatory myofibroblastic tumors (IMT) of the uterus may be underrecognized as their morphology and immunophenotype may overlap with myxoid variants of uterine smooth muscle tumors and endometrial stromal tumors. Although ALK is a helpful biomarker, not all uterine IMTs are ALK-rearranged, and a small subset of myxoid leiomyosarcomas is ALK-positive. Herein, we evaluated a series of 23 IMTs for the novel endometrial stromal markers interferon-inducible transmembrane protein-1 (IFITM1) and BCOR, the novel myoid marker transgelin, and possible predictive markers p16 and p53 by immunohistochemistry to determine their expression profile and potential prognostic value. Patients' ages ranged from 8 to 59 (mean 39) years and tumors from 2 to 20 (mean 8.2) cm. Follow-up was available for 12/23 (52%) patients; 9/12 (75%) without evidence of disease, 2/12 (17%) alive with disease, and 1/12 (8%) dead from disease. Four IMTs were classified as malignant due to extrauterine disease at diagnosis and/or recurrence. IFITM1 was positive (combined score>2) in 19/23 (83%), BCOR in 8/20 (40%), and transgelin in 22/23 (96%) of tumors. IFITM1 and BCOR were more often expressed in the myxoid component, and transgelin in the compact areas. p16 expression was absent in 5/23 (22%) of IMTs, while p53 was wildtype in all tumors. p16-negative IMTs included all 4 classified as malignant and one where the patient was lost to follow-up. Molecular data were available in 2 malignant IMTs, both of which harbored CDKN2A deletions. We conclude that caution is advised when using IFITM1, BCOR, and transgelin as markers for endometrial and smooth muscle tumors, as these are commonly expressed in IMTs. However, we did identify an association among lack of p16 staining, CKDN2A deletions, and aggressive behavior that merits corroboration by other studies. As a result of this finding, we recommend the use of p16 in the diagnostic work-up of uterine IMTs due to its potential prognostic significance.

What is known and objective Stenotrophomonas maltophilia is an intrinsically multidrug-resistant (MDR) organism which commonly presents as a respiratory tract infection. S. maltophilia is typically treated with high-dose sulfamethoxazole/trimethoprim (SMX/TMP). However, SMX/TMP and other treatment options for S. maltophilia can be limited because of resistance, allergy, adverse events or unavailability of the drug; use of novel agents may be necessary to adequately treat this MDR infection and overcome these limitations. Case description This small case series describes two patients who underwent treatment with tigecycline for ventilator-associated pneumonia (VAP) caused by S. maltophilia after admission to a trauma intensive care unit. At the time of admission for the two reported patients, a national drug shortage of intravenous (IV) SMX/TMP prevented its use. Tigecycline was chosen as a novel agent to treat S. maltophilia VAP based on culture and susceptibility data, and it was used successfully. Both patients showed clinical signs of improvement with eventual cure and discharge from the hospital after treatment with tigecycline, and one patient demonstrated confirmed microbiological cure with a negative repeat bronchoscopic bronchoalveolar lavage (BAL). What is new and conclusion To our knowledge, this small case series is the first documentation of utilizing tigecycline to treat S. maltophilia VAP in the United States. Although it likely should not be considered as a first-line agent, tigecycline proved to be an effective treatment option in the two cases described in the setting of a national drug shortage of the drug of choice.

Introduction & objectives: We tested the role of multiparametric magnetic resonance imaging (mpMRI) in disease reclassification and whether the combination of mpMRI and clinicopathological variables could represent the most accurate approach to predict the risk of reclassification during active surveillance. Materials & methods: Three-hundred eighty-nine patients (pts) underwent mpMRI and subsequent confirmatory or follow-up biopsy according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol. Pts with negative (−) mpMRI underwent systematic random biopsy. Pts with positive (+) mpMRI [Prostate Imaging Reporting and Data System, version 2 (PI-RADS-V2) score ≥3] underwent targeted + systematic random biopsies. Multivariate analyses were used to create three models predicting the probability of reclassification [International Society of Urological Pathology ≥ Grade Group 2 (GG2)]: a basic model including only clinical variables (age, prostate-specific antigen density, and number of positive cores at baseline), an Magnetic resonance imaging (MRI) model including only the PI-RADS score, and a full model including both the previous ones. The predictive accuracy (PA) of each model was quantified using the area under the curve. Results: mpMRI negative (−) was recorded in 127 (32.6%) pts; mpMRI positive (+) was recorded in 262 pts: 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. At a median follow-up of 12 months, 125 pts (32%) were reclassified to GG2 prostate cancer. The rate of reclassification to GG2 prostate cancer was 17%, 35%, 38%, and 52% for mpMRI (−), PI-RADS 3, 4, and 5, respectively (P

Contralateral strength training (CST) is increasingly investigated and employed as a non-conventional way to induce an indirect gain in strength in the weakened untrained limb. However, its effects on gait performance are more controversial.To assess and compare the effects of contralateral (CST) and direct (DST) strength training on spatio-temporal parameters, kinematic and kinetic descriptors of gait in persons with relapsing-remitting multiple sclerosis (PwMS).Twenty-eight PwMS (EDSS 2.0-5.5) with inter-side difference in ankle dorsiflexors' strength ≥ 20 % and moderate gait impairment (walking speed 0.70-0.94 m/s), were randomly assigned to a CST (undergoing training of the less-affected dorsiflexors) or DST group (where the most-affected dorsiflexors were trained). Before and after a 6-week high-intensity resistance training (three 25-minute sessions/week), PwMS underwent bilateral measurements of dorsiflexors' maximal strength and assessment of gait spatio-temporal parameters, lower limb joint kinematics and kinetics.Following the training period, muscle strength increased significantly in both groups (on average, CST + 29.5 %, p 0.0005; DST + 15.7 %, p = 0.001) with no difference between the two interventions. Significant changes in gait speed (+16.5 %; p 0.0001) and stride length (+6.0 %; p = 0.04) were detected only after DST, while no difference was detected in the CST group. Ankle moment and ROM were unaffected by the training. In PwMS with mild to moderate disability and lower limb dorsiflexors' strength asymmetry, CST was not inferior to DST in inducing significant strength gains in the untrained most-affected limb. However, only DST significantly improved gait performance and, specifically, walking speed. Even though CST did not worsen asymmetry, data suggest that contralateral approaches should not be recommended straightaway if the training goal is to improve outcomes other than strength and, specifically, walking speed.

Introduction Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine malignant cancer. It is an epidermal cancer common in the head and neck. Objectives Though there is limited number of cases described in the literature for the treatment difficult to obtain. Our purpose was to present the clinical course and treatment of four patients with MCC. Methods We conducted a retrospective analysis and obtained detailed clinical information for all 4 patients treated for MCC at the ENT Department of the SS Annunziata Hospital in Chieti, Italy, from 2013 through 2015. Results In our study, two patients presented with the tumor in a rare site (lower eyelid). All of the patients underwent surgical treatment: three patients had free excision margins and negative sentinel lymph nodes (SLNs) while 1 patient had free excision margins and positive SLNs. The latter patient underwent ipsilateral neck dissection. In another patient, the fluorodeoxyglucose positron emission topography (FDG PET)/computed tomography (CT) performed 6 months after the surgery has shown high metabolic activity in the left parotid gland, and the patient underwent total parotidectomy and a neck dissection. Conclusion Sentinel lymph node biopsy is a useful technique in small size MCCs of the head and neck. However, the parotid gland should be strictly controlled in patients with lower eyelid tumors.

Bowel and mesenteric injuries are rare in patients following blunt abdominal trauma. Computed tomography (CT) imaging has become a mainstay in the work-up of the stable trauma patient. The purpose of this study was to identify radiographic predictors of therapeutic operative intervention for mesenteric and/or bowel injuries in patients after blunt abdominal trauma. All patients with a discharge diagnosis of bowel and/or mesenteric injury after blunt trauma were identified over a 5-year period. Admission CT scans were reviewed to identify potential predictors of bowel and/or mesenteric injury. Patients were then stratified by operative intervention [therapeutic laparotomy (TL) vs. non-therapeutic laparotomy (NTL)] and compared. All potential predictors included in the initial regression model were assigned one point and a score based on the number of predictors was calculated: the radiographic predictors of therapeutic operative intervention (RAPTOR) score. 151 patients were identified. 114 (76%) patients underwent operative intervention. Of these, 75 patients (66%) underwent TL. Multifocal hematoma, acute arterial extravasation, bowel wall hematoma, bowel devascularization, fecalization, pneumoperitoneum and fat pad injury, identified as potential predictors on univariable analysis, were included in the initial regression model and comprised the RAPTOR score. The optimal RAPTOR score was identified as ≥ 3, with a sensitivity, specificity and positive predictive value of 67%, 85% and 86%, respectively. Acute arterial extravasation (OR 3.8; 95% CI 1.2–4.3), bowel devascularization (OR 14.5; 95% CI 11.8–18.4) and fat pad injury (OR 4.5 95% CI 1.6–6.2) were identified as independent predictors of TL (AUC 0.91). CT imaging remains vital in assessing for potential bowel and/or mesenteric injuries following blunt abdominal trauma. The RAPTOR score provides a simplified approach to predict the need for early therapeutic operative intervention.

Red cell distribution width (RDW) is an unconventional biomarker of inflammation. We aimed to explore its role as a predictor of treatment response in rheumatoid arthritis (RA). Eighty-two RA patients (55 females), median age [interquartile range] 63 years [52-69], were selected by scanning the medical records of a rheumatology clinic, to analyze the associations between baseline RDW, disease activity scores and inflammatory markers, as well as the relationship between RDW changes following methotrexate (MTX) and treatment response. The lower the median baseline RDW, the greater were the chances of a positive EULAR response at three months, 13.5% [13.0-14.4] being among those with good response, vs 14.0% [13.2-14.7] and 14.2% [13.5- 16.0] (p=0.009) among those with moderate and poor response, respectively. MTX treatment was followed by a significant RDW increase (p

We are developing an imaging capability (“Hyperspectral X-ray Imaging”) for mapping chemical information (molecular formula, phase, oxidation state, hydration) that is based on ultra-high-resolution X-ray emission spectroscopy with large transition-edge sensor microcalorimeter arrays in the scanning electron microscope. By combining microcalorimeter arrays with hundreds of pixels, high-bandwidth microwave frequency-division multiplexing, and fast digital electronics for near real-time data processing, our goal is to enable measurements using laboratory-scale instrumentation rather than synchrotron beamlines. Our application focus here is on mapping the chemical form of uranium compounds on the nanoscale. We will present our approach to developing the Hyperspectral X-ray Imaging capability, progress toward a 128-pixel microwave multiplexed X-ray fluorescence instrument at LANL, and the path to high-throughput nanoscale chemical mapping.