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Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children and adolescents, increasing the risk of its progression toward nonalcoholic steatohepatitis (NASH), cirrhosis, and cancer. There is an urgent need for noninvasive early diagnostic and prognostic tools such as epigenetic marks (epimarks), which would replace liver biopsy in the future. We used plasma samples from 67 children with biopsy-proven NAFLD, and as controls we used samples from 20 children negative for steatosis by ultrasound. All patients were genotyped for patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane bound O-acyltransferase domain containing 7 (MBOAT7), and klotho-β (KLB) gene variants, and data on anthropometric and biochemical parameters were collected. Furthermore, plasma cell-free DNA (cfDNA) methylation was quantified using a commercially available kit, and ImageStream(X) was used for the detection of free circulating histone complexes and variants. We found a significant enrichment of the levels of histone macroH2A1.2 in the plasma of children with NAFLD compared to controls, and a strong correlation between cfDNA methylation levels and NASH. Receiver operating characteristic curve analysis demonstrated that combination of cfDNA methylation, PNPLA3 rs738409 variant, coupled with either high-density lipoprotein cholesterol or alanine aminotransferase levels can strongly predict the progression of pediatric NAFLD to NASH with area under the curve >0.87. Conclusion: Our pilot study combined epimarks and genetic and metabolic markers for a robust risk assessment of NAFLD development and progression in children, offering a promising noninvasive tool for the consistent diagnosis and prognosis of pediatric NAFLD. Further studies are necessary to identify their pathogenic origin and function.

Incident HIV infections occurring in people on PrEP may have delayed seroconversion. New CDC guidelines recommend the addition of HIV-1 viral load for screening for all on PrEP. We believe antigen/antibody screening should continue for tenofovir-based PrEP at this time.

Recent advances in digital breast tomosynthesis (DBT) technology were focused on the reconstruction of 2D "Synthesized Mammograms" (SMs) from DBT dataset. The introduction of SMs could avoid an additional digital mammography (DM) which is often required in complement to DBT examinations. Therefore, breast absorbed dose and compression time can be significantly reduced in DBT+SM procedures with respect to DBT+DM modality. However, to date, a limited number of studies have objectively characterised the image quality of SMs with respect to DM images. Therefore, the aim of this phantom study was to comprehensively compare SMs and DM images in terms of several image quality parameters. A Selenia Dimensions system (Hologic, Bedford, Mass, USA) was employed in this work. Five different phantoms were adopted to study noise, contrast and spatial resolution properties of the images. Specifically, noise power spectrum (NPS), maps of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), modulation transfer function (MTF) and contrast-detail (CD) thresholds were evaluated both for SM and DM modalities. SMs were characterised by different texture, noise and SNR spatial distribution properties with respect to DM images. Additionally, while in some conditions SM provides higher CNR than DM, lower overall performances in terms spatial resolution and CD curves were found in comparison to DM images. Therefore, given the great benefits of SMs in terms of dose and compression time saving, further clinical investigations on SMs image quality properties could be of practical interest to integrate our findings.

INTRODUCTION: Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality. METHODS: Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage. RESULTS: A total of 852 (79% male, age 66 [37-85] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1-30.7) Kg/m2 and 13 (7-22) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18-1.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI - 0.591 to - 0.964; p = 0.64]). CONCLUSIONS: In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed., SCOPUS: ar.j, info:eu-repo/semantics/published

X-ray breast imaging techniques are an essential part of breast cancer screening programs and their improvements lead to gain in performance and accuracy. Radiation dose estimate and control play an important role in digital mammography and digital breast tomosynthesis investigations, since the risk of radioinduced cancer to the gland must be contained and dose delivered to the gland must be declared in the medical report. The actual dosimetric protocols suggest the assessment of radiation dose by means of Monte Carlo calculation on digital breast phantoms, providing the assumption of the homogeneous mixture of glandular and adipose tissues within the breast organ, leading to a drastic approximation. In line with the trend of other research groups, with the aim of improving the Monte Carlo model, in the current work a new heterogeneous digital breast model is proposed, involving a voxelized approach and disengaging from the concept of homogeneous phantom. The proposed model is based on new findings in the literature and after a validation process, the model is adopted to evaluate mean glandular dose discrepancies with the traditional model which is adopted in clinic for decades.

Digital breast tomosynthesis (DBT) has recently gained interest both for breast cancer screening and diagnosis. Its employment has increased also in conjunction with digital mammography (DM), to improve cancer detection and reduce false positive recall rate. Synthetic mammograms (SMs) reconstructed from DBT data have been introduced to replace DM in the DBT + DM approach, for preserving the benefits of the dual-acquisition modality whilst reducing radiation dose and compression time. Therefore, different DBT models have been commercialized and the effective potential of each system has been investigated. In particular, wide-angle DBT was shown to provide better depth resolution than narrow-angle DBT, while narrow-angle DBT allows better identification of microcalcifications compared to wide-angle DBT. Given the increasing employment of SMs as supplement to DBT, a comparison of image quality between SMs obtained in narrow-angle and wide-angle DBT is of practical interest. Therefore, the aim of this phantom study was to evaluate and compare the image quality of SMs reconstructed from 15° (SM15) and 40° (SM40) DBT in a commercial system. Spatial resolution, noise and contrast properties were evaluated through the modulation transfer function (MTF), noise power spectrum, maps of signal-to-noise ratio (SNR), image contrast, contrast-to-noise ratio (CNR) and contrast-detail (CD) thresholds. SM40 expressed higher MTF than SM15, but also lower SNR and CNR levels. SM15 and SM40 were characterized by slight different texture, and a different behavior in terms of contrast was found. SM15 provided better CD performances than SM40. These results suggest that the employment of wide/narrow-angle DBT + SM images should be optimized based on the specific image task.

Objective The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of specific information, like the risk of sudden unexpected death in epilepsy (SUDEP) or the existence of lay associations, which might be of special interest for selected categories of patients. Significance Differences between patients with epilepsy and their caring physicians in terms of needs and priorities and suboptimal communication call for the implementation of programs aimed at addressing the factors deemed most relevant by patients and caregivers for the management of the disease.

Background Since the start of the pandemic there has been limited data on mortality in people living with HIV (PLWH) who have Coronavirus Disease 2019 (COVID-19) in the United States (US). We conducted a retrospective review to investigate potential risk factors associated with survival and need for medical ventilation for PLWH and COVID-19. Methods This is a retrospective observational cohort from a large academic center across three campuses, conducted from January 1, 2020 to April 30, 2020. Thirty day readmissions were observed from January 1, 2020 to May 31, 2020. Our patients were identified by an ICD-10 code (B20) corresponding to HIV and positive SARS-CoV-2 PCR test. As a primary endpoint, we compared survivors vs. non-survivors. As a secondary endpoint, we compared patients who needed mechanical ventilator (MV) vs. those who did not need MV. Results Seventy two PLWH (28 female patients (39%), median [IQR] age was 62 [-/+16] years) had positive SARS-CoV-2 PCR tests during this retrospective review. Median CD4+ count was 235 cells/ul and 11 (15%) had an HIV viral load >200 copies/mL. The median length of stay was 5 days and 6 patients were directly discharged from the emergency department. Ten patients were readmitted within 30 days with SARS-CoV-2 – like symptoms and 2 are still inpatient. Twenty patients (27.8%) have expired. All non-survivors that expired had an undetectable HIV viral load (0%, p=0.02). The 11 patients with unsuppressed HIV viral loads at the start of the study period all survived, p=0.02. Non-survivors were more likely to have chronic kidney disease CKD (p< 0.01) acute kidney injury (p< 0.01), higher absolute neutrophils (p< 0.01), and elevated IL-6 levels (p< 0.01) compared to survivors. Fifteen patients (20.8%) required mechanical ventilation (MV), 3 (4.1%) of those patients survived. Patients that required MV were more likely to be male (p=0.01) obese (p< 0.01) and had higher absolute neutrophil counts (p=0.01) versus those that did not need MV. Patients with lower CD4 counts (< 200 cells/uL) did not require more mechanical ventilation (p=0.04). Table 1: Demographics, Primary and Secondary Outcome Results Conclusion PLWH who had COVID-19 had a high mortality rate. Since all the patients who died had an undetectable HIV viral load across CD4 counts, our study suggests that patients with uncontrolled HIV are not at an increased risk of mortality. Disclosures All Authors: No reported disclosures

In silico reproductions of clinical exams represent an alternative strategy in the research and development of medical devices, which permit to avoid issues and costs related to clinical trials on patient population. In this work, we present a platform for virtual clinical trials in 2D and 3D x-ray breast imaging. The platform, developed by the medical physics team at University of Naples, Italy, permits to simulate digital mammography (DM), digital breast tomosynthesis (DBT) and CT dedicated to the breast (BCT) examinations. It relies on Monte Carlo simulations based on Geant4 toolkit and adopts digital models of patients derived from high-resolution 3D clinical breast images acquired at UC Davis, USA. Uncompressed digital breast models for BCT exam simulations were produced by means of a tissue classification algorithm; the compressed digital breast models for simulating DM and DBT are derived by the uncompressed ones via a simulated tissue compression. For a selected exam, specifications and digital patient, the platform computes breast image projections and glandular dose maps within the organ. Energy integrating a well as photon counting and spectral imaging detection scheme have been simulated. The current version of the software uses the Geant4 standard physics list Option4 and simulates and tracks

Background To propose a practical and simple method to individually evaluate the average absorbed dose for digital breast tomosynthesis. Methods The method is based on the estimate of incident air kerma (k a,i ) on the breast surface. An analytical model was developed to calculate the k a,i from the tube voltage, tube load, breast thickness, x-ray tube yield, and anode-filter combination. A homogeneous phantom was employed to simulate the breast in experimental measurements and to assess the dose-depth relationship. The k a,i values were employed to calculate the “average absorbed breast dose” (2ABD) index. Four mammographic units were used to develop and test our method under many conditions close to clinical settings. The average glandular dose (AGD) calculated following the method described by Dance et al., and the 2ABD computed through our method (i.e., from the exposure parameters) were compared in a number of conditions. Results A good agreement was obtained between the k a,i computed through our model and that measured under different clinical conditions: discrepancies < 6% were found in all conditions. 2ABD matches with a good accuracy the AGD for a 100% glandular-breast: the minimum, maximum, and mean differences were < 0.1%, 7%, and 2.4%, respectively; the discrepancies increase with decreasing breast glandularity. Conclusions The proposed model, based on only few exposure parameters, represents a simple way to individually calculate an index, 2ABD, which can be interpreted as the average absorbed dose in a homogeneous phantom, approximating a 100% glandular breast. The method could be easily implemented in any mammographic device performing DBT.