KDM1A maintains genome-wide homeostasis of transcriptional enhancers.

Transcriptional enhancers enable exquisite spatiotemporal control of gene expression in metazoans. Enrichment of monomethylation of histone H3 lysine 4 (H3K4me1) is a major chromatin signature of transcriptional enhancers. Lysine (K)-specific demethylase 1A (KDM1A, also known as LSD1), an H3K4me2/me1 demethylase, inactivates stem-cell enhancers during the differentiation of mouse embryonic stem cells (mESCs). However, its role in undifferentiated mESCs remains obscure. Here, we show that KDM1A actively maintains the optimal enhancer status in both undifferentiated and lineage-committed cells. KDM1A occupies a majority of enhancers in undifferentiated mESCs. KDM1A levels at enhancers exhibit clear positive correlations with its substrate H3K4me2, H3K27ac, and transcription at enhancers. In Kdm1a-deficient mESCs, a large fraction of these enhancers gains additional H3K4 methylation, which is accompanied by increases in H3K27 acetylation and increased expression of both enhancer RNAs (eRNAs) and target genes. In postmitotic neurons, loss of KDM1A leads to premature activation of neuronal activity-dependent enhancers and genes. Taken together, these results suggest that KDM1A is a versatile regulator of enhancers and acts as a rheostat to maintain optimal enhancer activity by counterbalancing H3K4 methylation at enhancers.

Can incorrect artificial intelligence (AI) results impact radiologists, and if so, what can we do about it? A multi-reader pilot study of lung cancer detection with chest radiography.

OBJECTIVE: To examine whether incorrect AI results impact radiologist performance, and if so, whether human factors can be optimized to reduce error. METHODS: Multi-reader design, 6 radiologists interpreted 90 identical chest radiographs (follow-up CT needed: yes/no) on four occasions (09/20-01/22). No AI result was provided for session 1. Sham AI results were provided for sessions 2-4, and AI for 12 cases were manipulated to be incorrect (8 false positives (FP), 4 false negatives (FN)) (0.87 ROC-AUC). In the Delete AI (No Box) condition, radiologists were told AI results would not be saved for the evaluation. In Keep AI (No Box) and Keep AI (Box), radiologists were told results would be saved. In Keep AI (Box), the ostensible AI program visually outlined the region of suspicion. AI results were constant between conditions. RESULTS: Relative to the No AI condition (FN = 2.7%, FP = 51.4%), FN and FPs were higher in the Keep AI (No Box) (FN = 33.0%, FP = 86.0%), Delete AI (No Box) (FN = 26.7%, FP = 80.5%), and Keep AI (Box) (FN = to 20.7%, FP = 80.5%) conditions (all ps < 0.05). FNs were higher in the Keep AI (No Box) condition (33.0%) than in the Keep AI (Box) condition (20.7%) (p = 0.04). FPs were higher in the Keep AI (No Box) (86.0%) condition than in the Delete AI (No Box) condition (80.5%) (p = 0.03). CONCLUSION: Incorrect AI causes radiologists to make incorrect follow-up decisions when they were correct without AI. This effect is mitigated when radiologists believe AI will be deleted from the patient's file or a box is provided around the region of interest. CLINICAL RELEVANCE STATEMENT: When AI is wrong, radiologists make more errors than they would have without AI. Based on human factors psychology, our manuscript provides evidence for two AI implementation strategies that reduce the deleterious effects of incorrect AI. KEY POINTS: • When AI provided incorrect results, false negative and false positive rates among the radiologists increased. • False positives decreased when AI results were deleted, versus kept, in the patient's record. • False negatives and false positives decreased when AI visually outlined the region of suspicion.

Exploring Amodiaquine's Repurposing Potential in Breast Cancer Treatment-Assessment of In-Vitro Efficacy & Mechanism of Action.

Due to the heterogeneity of breast cancer, current available treatment options are moderately effective at best. Hence, it is highly recommended to comprehend different subtypes, understand pathogenic mechanisms involved, and develop treatment modalities. The repurposing of an old FDA approved anti-malarial drug, amodiaquine (AQ) presents an outstanding opportunity to explore its efficacy in treating majority of breast cancer subtypes. Cytotoxicity, scratch assay, vasculogenic mimicry study, and clonogenic assay were employed to determine AQ's ability to inhibit cell viability, cell migration, vascular formation, and colony growth. 3D Spheroid cell culture studies were performed to identify tumor growth inhibition potential of AQ in MCF-7 and MDAMB-231 cell lines. Apoptosis assays, cell cycle analysis, RT-qPCR assays, and Western blot studies were performed to determine AQ's ability to induce apoptosis, cell cycle changes, gene expression changes, and induction of autophagy marker proteins. The results from in-vitro studies confirmed the potential of AQ as an anti-cancer drug. In different breast cancer cell lines tested, AQ significantly induces cytotoxicity, inhibit colony formation, inhibit cell migration, reduces 3D spheroid volume, induces apoptosis, blocks cell cycle progression, inhibit expression of cancer related genes, and induces LC3BII protein to inhibit autophagy. Our results demonstrate that amodiaquine is a promising drug to repurpose for breast cancer treatment, which needs numerous efforts from further studies.

Nascent Transcriptomics Reveal Cellular Prolytic Factors Upregulated Upstream of the Latent-to-Lytic Switch Protein of Epstein-Barr Virus.

Lytic activation from latency is a key transition point in the life cycle of herpesviruses. Epstein-Barr virus (EBV) is a human herpesvirus that can cause lymphomas, epithelial cancers, and other diseases, most of which require the lytic cycle. While the lytic cycle of EBV can be triggered by chemicals and immunologic ligands, the lytic cascade is activated only when expression of the EBV latent-to-lytic switch protein ZEBRA is turned on. ZEBRA then transcriptionally activates other EBV genes and, together with some of those gene products, ensures completion of the lytic cycle. However, not every latently infected cell exposed to a lytic trigger turns on the expression of ZEBRA, resulting in responsive and refractory subpopulations. What governs this dichotomy? By examining the nascent transcriptome following exposure to a lytic trigger, we find that several cellular genes are transcriptionally upregulated temporally upstream of ZEBRA. These genes regulate lytic susceptibility to various degrees in latently infected cells that respond to mechanistically distinct lytic triggers. While increased expression of these cellular genes defines a prolytic state, such upregulation also runs counter to the well-known mechanism of viral-nuclease-mediated host shutoff that is activated downstream of ZEBRA. Furthermore, a subset of upregulated cellular genes is transcriptionally repressed temporally downstream of ZEBRA, indicating an additional mode of virus-mediated host shutoff through transcriptional repression. Thus, increased transcription of a set of host genes contributes to a prolytic state that allows a subpopulation of cells to support the EBV lytic cycle.IMPORTANCE Transition from latency to the lytic phase is necessary for herpesvirus-mediated pathology as well as viral spread and persistence in the population at large. Yet, viral genomes in only some cells in a population of latently infected cells respond to lytic triggers, resulting in subpopulations of responsive/lytic and refractory cells. Our investigations into this partially permissive phenotype of the herpesvirus Epstein-Barr virus (EBV) indicate that upon exposure to lytic triggers, certain cellular genes are transcriptionally upregulated, while viral latency genes are downregulated ahead of expression of the viral latent-to-lytic switch protein. These cellular genes contribute to lytic susceptibility to various degrees. Apart from indicating that there may be a cellular "prolytic" state, our findings indicate that (i) early transcriptional upregulation of cellular genes counters the well-known viral-nuclease-mediated host shutoff and (ii) subsequent transcriptional downregulation of a subset of early upregulated cellular genes is a previously undescribed mode of host shutoff.

Cardiovascular magnetic resonance findings in young adult patients with acute myocarditis following mRNA COVID-19 vaccination: a case series.

BACKGROUND: Messenger RNA (mRNA) coronavirus disease of 2019 (COVID-19) vaccine are known to cause minor side effects at the injection site and mild global systemic symptoms in first 24-48 h. Recently published case series have reported a possible association between acute myocarditis and COVID-19 vaccination, predominantly in young males. METHODS: We report a case series of 5 young male patients with cardiovascular magnetic resonance (CMR)-confirmed acute myocarditis within 72 h after receiving a dose of an mRNA-based COVID-19 vaccine. RESULTS: Our case series suggests that myocarditis in this setting is characterized by myocardial edema and late gadolinium enhancement in the lateral wall of the left ventricular (LV) myocardium, reduced global LV longitudinal strain, and preserved LV ejection fraction. All patients in our series remained clinically stable during a relatively short inpatient hospital stay. CONCLUSIONS: In conjunction with other recently published case series and national vaccine safety surveillance data, this case series suggests a possible association between acute myocarditis and COVID-19 vaccination in young males and highlights a potential pattern in accompanying CMR abnormalities.

The effect that pathologic and radiologic interpretation of invasive and non-invasive areas in lung adenocarcinoma has on T-stage and treatment.

Lung adenocarcinoma is currently staged based on invasive tumor size, excluding areas of lepidic (in situ) growth. Invasive tumor size may be determined by pathologic assessment of a surgical specimen or radiographic assessment on computerized tomography (CT) scan. When invasive tumor size is the primary stage determinate, radiographic-pathologic discordance or discordant interpretation among pathologists may alter tumor stage and treatment. We reviewed 40 cases of non-mucinous pulmonary adenocarcinoma in which tumor size was the only stage-determinant. We determined the inter-observer variability when microscopically assessing architectural patterns and its effect on pathologic stage and treatment. Additionally, we correlated pathologic and radiographic assessment of invasive tumor size and its effect on tumor stage and treatment. The intraclass correlation among three pathologists was 0.9879; all three pathologists agreed on T-stage in 75% of cases. Four cases of pathologic disagreement had the potential to alter therapy. Intraclass correlation between the pathologists and invasive tumor size determined by CT scan was 0.8482. In 23 cases (57.5%) the pathologic T-stage differed (it increased >90% of the time) from clinical T-stage (determined by CT scan) based on invasive tumor size. Five of the radiographically-pathologically discrepant cases resulted in a stage change that had the potential to alter adjuvant therapy. Our findings suggest the stage differences in pathologic staging are prognostically relevant, but unlikely to impact routine selection of adjuvant therapy, and the observed variability in clinical stage tends to select against overuse of neoadjuvant therapy when invasive tumor size is the primary stage-determinant.

Performance of Radiologists in Differentiating COVID-19 from Non-COVID-19 Viral Pneumonia at Chest CT.

Background Despite its high sensitivity in diagnosing coronavirus disease 2019 (COVID-19) in a screening population, the chest CT appearance of COVID-19 pneumonia is thought to be nonspecific. Purpose To assess the performance of radiologists in the United States and China in differentiating COVID-19 from viral pneumonia at chest CT. Materials and Methods In this study, 219 patients with positive COVID-19, as determined with reverse-transcription polymerase chain reaction (RT-PCR) and abnormal chest CT findings, were retrospectively identified from seven Chinese hospitals in Hunan Province, China, from January 6 to February 20, 2020. Two hundred five patients with positive respiratory pathogen panel results for viral pneumonia and CT findings consistent with or highly suspicious for pneumonia, according to original radiologic interpretation within 7 days of each other, were identified from Rhode Island Hospital in Providence, RI. Three radiologists from China reviewed all chest CT scans (n = 424) blinded to RT-PCR findings to differentiate COVID-19 from viral pneumonia. A sample of 58 age-matched patients was randomly selected and evaluated by four radiologists from the United States in a similar fashion. Different CT features were recorded and compared between the two groups. Results For all chest CT scans (n = 424), the accuracy of the three radiologists from China in differentiating COVID-19 from non-COVID-19 viral pneumonia was 83% (350 of 424), 80% (338 of 424), and 60% (255 of 424). In the randomly selected sample (n = 58), the sensitivities of three radiologists from China and four radiologists from the United States were 80%, 67%, 97%, 93%, 83%, 73%, and 70%, respectively. The corresponding specificities of the same readers were 100%, 93%, 7%, 100%, 93%, 93%, and 100%, respectively. Compared with non-COVID-19 pneumonia, COVID-19 pneumonia was more likely to have a peripheral distribution (80% vs 57%, P < .001), ground-glass opacity (91% vs 68%, P < .001), fine reticular opacity (56% vs 22%, P < .001), and vascular thickening (59% vs 22%, P < .001), but it was less likely to have a central and peripheral distribution (14% vs 35%, P < .001), pleural effusion (4% vs 39%, P < .001), or lymphadenopathy (3% vs 10%, P = .002). Conclusion Radiologists in China and in the United States distinguished coronavirus disease 2019 from viral pneumonia at chest CT with moderate to high accuracy. © RSNA, 2020 Online supplemental material is available for this article. A translation of this abstract in Farsi is available in the supplement. ترجمه چکیده این مقاله به فارسی، در ضمیمه موجود است.

Cardiothoracic Complications of Immune Checkpoint Inhibitor Therapy: An Imaging Review.

Immune checkpoint inhibitor therapy has revolutionized the treatment of many different types of cancer. However, despite dramatic improvements in tumor oncologic response and patient outcomes, immune checkpoint blockade has been associated with multiple distinctive side-effects termed immune-related adverse events. These often have important clinical implications because these can vary in severity, sometimes even resulting in death. Therefore, it is important for both radiologists and clinicians to recognize and be aware of these reactions to help appropriately guide patient management. This article specifically highlights imaging manifestations of the most common cardiothoracic toxicities of these agents, including pneumonitis, sarcoid-like granulomatosis and lymphadenopathy, and myocarditis.

Augmenting performance of a MEMS cantilever-based photonic crystal waveguide for switching applications.

In this paper, a micro-electro-mechanical system-based cantilever is integrated as a line defect on a photonic crystal silicon slab for optical switching applications. The elliptical holes are etched in the photonic crystal waveguide that result in wide transmission bandwidth of 56 nm in comparison to etched circular holes in the structure with a footprint of only ${12.5}\,\,{\unicode{x00B5}{\rm m}} \times {8}\,\,{\unicode{x00B5}{\rm m}}$12.5µm×8µm. The device is optimized for variation in height, the lattice constant, and semi-major and semi-minor axes in the optical range of the S-C-L band. It is shown that the response rise time of the device is 21 µs with very high extinction ratio of 30.4 dB and low insertion loss of 0.32 dB.

Molecular epidemiology & therapeutic options of carbapenem-resistant Gram-negative bacteria.

Background & objectives: The growing incidence and the wide diversity of carbapenemase-producing bacterial strains is a major concern as only a few antimicrobial agents are active on carbapenem-resistant bacteria. This study was designed to study molecular epidemiology of carbapenem-resistant Gram-negative bacterial (GNB) isolates from the community and hospital settings. Methods: In this study, non-duplicate GNB were isolated from clinical specimens, and phenotypic test such as modified Hodge test, metallo ß-lactamase E-strip test, etc. were performed on carbapenem-resistant bacteria. Multiplex PCR was performed to identify the presence of blaIMP, blaVIM, blaKPC, blaOXA48, blaOXA23, blaSPM, blaGIM, blaSIM and blaNDM. Minimum inhibitory concentration (MIC) of colistin, fosfomycin, minocycline, chloramphenicol and tigecycline was also determined. Results: Of the 3414 GNB studied, carbapenem resistance was 9.20 per cent and maximum resistance (11.2%) was present at tertiary care centre, followed by secondary care (4%) and primary centre (2.1%). Among the carbapenem-resistant bacteria, overall, the most common isolate was Pseudomonas aeruginosa (24%). On multiplex PCR 90.3 per cent carbapenem-resistant isolates were positive for carbapenemase gene. The blaNDM(63%) was the most prevalent gene followed by blaVIM(18.4%). MIC results showed that 88 per cent carbapenem-resistant Enterobacteriaceae were sensitive to fosfomycin, whereas 78 per cent of P. aeruginosa and 85 per cent Acinetobacter spp. were sensitive to colistin. Interpretation & conclusions: Carbapenem resistance in GNB isolates from the community and hospital settings was found to be on the rise and should be closely monitored. In the absence of new antibiotics in pipeline and limited therapeutic options, prudent use of antibiotics and strict infection control practices should be followed in hospital to limit the emergence and spread of multidrug-resistant bacteria.

Generalizable Inter-Institutional Classification of Abnormal Chest Radiographs Using Efficient Convolutional Neural Networks.

Our objective is to evaluate the effectiveness of efficient convolutional neural networks (CNNs) for abnormality detection in chest radiographs and investigate the generalizability of our models on data from independent sources. We used the National Institutes of Health ChestX-ray14 (NIH-CXR) and the Rhode Island Hospital chest radiograph (RIH-CXR) datasets in this study. Both datasets were split into training, validation, and test sets. The DenseNet and MobileNetV2 CNN architectures were used to train models on each dataset to classify chest radiographs into normal or abnormal categories; models trained on NIH-CXR were designed to also predict the presence of 14 different pathological findings. Models were evaluated on both NIH-CXR and RIH-CXR test sets based on the area under the receiver operating characteristic curve (AUROC). DenseNet and MobileNetV2 models achieved AUROCs of 0.900 and 0.893 for normal versus abnormal classification on NIH-CXR and AUROCs of 0.960 and 0.951 on RIH-CXR. For the 14 pathological findings in NIH-CXR, MobileNetV2 achieved an AUROC within 0.03 of DenseNet for each finding, with an average difference of 0.01. When externally validated on independently collected data (e.g., RIH-CXR-trained models on NIH-CXR), model AUROCs decreased by 3.6-5.2% relative to their locally trained counterparts. MobileNetV2 achieved comparable performance to DenseNet in our analysis, demonstrating the efficacy of efficient CNNs for chest radiograph abnormality detection. In addition, models were able to generalize to external data albeit with performance decreases that should be taken into consideration when applying models on data from different institutions.

Endogenous retroviruses and neighboring genes are coordinately repressed by LSD1/KDM1A.

Endogenous retroviruses (ERVs) constitute a substantial portion of mammalian genomes, and their retrotransposition activity helped to drive genetic variation, yet their expression is tightly regulated to prevent unchecked amplification. We generated a series of mouse mutants and embryonic stem (ES) cell lines carrying "deletable" and "rescuable" alleles of the lysine-specific demethylase LSD1/KDM1A. In the absence of KDM1A, the murine endogenous retrovirus MuERV-L/MERVL becomes overexpressed and embryonic development arrests at gastrulation. A number of cellular genes normally restricted to the zygotic genome activation (ZGA) period also become up-regulated in Kdm1a mutants. Strikingly, many of these cellular genes are flanked by MERVL sequences or have cryptic LTRs as promoters that are targets of KDM1A repression. Using genome-wide epigenetic profiling of Kdm1a mutant ES cells, we demonstrate that this subset of ZGA genes and MERVL elements displays increased methylation of histone H3K4, increased acetylation of H3K27, and decreased methylation of H3K9. As a consequence, Kdm1a mutant ES cells exhibit an unusual propensity to generate extraembryonic tissues. Our findings suggest that ancient retroviral insertions were used to co-opt regulatory sequences targeted by KDM1A for epigenetic silencing of cell fate genes during early mammalian embryonic development.

Correction to: Hemiarthroplasty for neck of femur fractures: to cement or not? A systematic review of literature and meta-analysis.

The original version of this article unfortunately contained a mistake. The correct information is given below. In abstract, the last sentence of the "Primary outcomes" section should read as: Mortality at 1 year was the same in both the groups.

Hemiarthroplasty for neck of femur fractures: to cement or not? A systematic review of literature and meta-analysis.

BACKGROUND: Management of fractures of neck of femur in the elderly is largely joint sacrificing, with hemiarthroplasties being the most common entity used. Cemented and uncemented, both the techniques, are universally accepted; however, the former has been more time tested, despite its theoretical disadvantage in the form of cement embolism leading to intra-operative complications. Uncemented stems have been ever evolving with newer designs to increase incorporation, stability and durability. They have their own reported sets of disadvantages like subsidence and fractures. However, overall there is no established gold standard out of the two. OBJECTIVE: The present systematic review and meta-analysis of current literature was conducted, so as to determine the superiority of one technique over the other by comparing the primary outcomes like hip function, residual pain, local and general complications and mortality. Additionally secondary outcomes like duration of surgery, blood loss and re-operations were analysed as well. METHODOLOGY: Three databases of PubMed, EMBASE and SCOPUS were searched for relevant articles of last 10 years that directly compare uncemented and cemented hemiarthroplasties, and based on our inclusion and exclusion criteria, article selection was done. RESULTS: We analysed a total of six randomised controlled studies dated from 2008 to 2017. PRIMARY OUTCOMES: There was a significant difference in post-operative ability to ambulate at 1 year, between 2 groups with odds ratio 0.45 (95% CI 0.29-0.67, p = 0.0001) favouring cemented hemiarthroplasty. Prosthesis-related complications like fractures and subsidence and general complications like lung complications were more in uncemented group. Mortality at 1 year was more in cemented group. SECONDARY OUTCOMES: Mean surgical time was lesser in uncemented cases. There was no difference in blood loss and re-operation rates. CONCLUSION: Cementing techniques are here to stay, until a better, durable and more stable uncemented stem evolves, that could lessen the complications related to uncemented surgeries and match the cemented implants in pain relief and ambulation.

Neuroblastoma pathogenesis: deregulation of embryonic neural crest development.

Neuroblastoma (NB) is an aggressive pediatric cancer that originates from neural crest tissues of the sympathetic nervous system. NB is highly heterogeneous both from a clinical and a molecular perspective. Clinically, this cancer represents a wide range of phenotypes ranging from spontaneous regression of 4S disease to unremitting treatment-refractory progression and death of high-risk metastatic disease. At a cellular level, the heterogeneous behavior of NB likely arises from an arrest and deregulation of normal neural crest development. In the present review, we summarize our current knowledge of neural crest development as it relates to pathways promoting 'stemness' and how deregulation may contribute to the development of tumor-initiating CSCs. There is an emerging consensus that such tumor subpopulations contribute to the evolution of drug resistance, metastasis and relapse in other equally aggressive malignancies. As relapsed, refractory disease remains the primary cause of death for neuroblastoma, the identification and targeting of CSCs or other primary drivers of tumor progression remains a critical, clinically significant goal for neuroblastoma. We will critically review recent and past evidence in the literature supporting the concept of CSCs as drivers of neuroblastoma pathogenesis.

Cancer Yield of Incidental Breast Lesions Detected on Chest Computed Tomography.

OBJECTIVE: This study aimed to determine the cancer yield for abnormal breast findings initially identified on chest computed tomography (CT). MATERIALS AND METHODS: This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study retrospectively reviewed reports of 41,217 consecutive chest CT examinations done from January 1, 2006, to December 31, 2011, to identify those with breast findings noted in the impression of the report. Examinations done for staging of newly diagnosed breast cancer were excluded. The electronic medical record was searched for any subsequent breast imaging and any corresponding pathology results. Cancer yield was calculated. RESULTS: A total of 258 chest CT examinations with abnormal breast findings were identified in 218 unique patients. Average patient age was 65.6 years (range, 30-100 years). There were 207 women and 11 men. Of these, 75 patients had follow-up breast imaging in our system. One hundred forty-three patients did not have follow-up in our system and were excluded for purposes of cancer detection rate calculation. Thirteen of 75 patients were found to have lesions that were malignant: infiltrating ductal carcinoma (8), invasive lobular carcinoma (2), lymphoma (2), and intracystic papillary cancer with atypical features (1). Four of 75 patients underwent further workup and were found to have lesions that were benign: fibroadenoma (3) and benign fibrocystic change (1). The remainder of the 58 of 75 patients had dedicated breast imaging that was classified as either Breast Imaging Reporting and Data System score 1 or 2, and no further workup was performed. Cancer yield from CT findings was 17.3%. CONCLUSIONS: Abnormal CT findings in the breast warrant additional evaluation with dedicated breast imaging to evaluate for a possible underlying malignancy. Cancer yield from CT findings in this study was 17.3%.

Financial Impact of Incentive Spirometry.

Despite largely unproven clinical effectiveness, incentive spirometry (IS) is widely used in an effort to reduce postoperative pulmonary complications. The objective of the study is to evaluate the financial impact of implementing IS. The amount of time nurses and RTs spend each day doing IS-related activities was assessed utilizing an online survey distributed to the relevant national nursing and respiratory therapists (RT) societies along with questionnaire that was prospectively collected every day for 4 weeks at a single 10-bed cardiothoracic surgery step-down unit. Cost of RT time to teach IS use to patients and cost of nurse time spent reeducating and reminding patients to use IS were used to calculate IS implementation cost estimates per patient. Per-patient cost of IS implementation ranged from $65.30 to $240.96 for a mean 9-day step-down stay. For the 566 patients who stayed in the 10-bed step-down in 2016, the total estimated cost of implementing IS ranged from $36 959.80 to $136 383.36. Using national survey workload data, per-patient cost of IS implementation costed $107.36 (95% confidence interval [CI], $97.88-$116.98) for a hospital stay of 4.5 days. For the 9.7 million inpatient surgeries performed annually in the United States, the total annual cost of implementing postoperative IS is estimated to be $1.04 billion (95% CI, $949.4 million-$1.13 billion). The cost of implementing IS is substantial. Further efficacy studies are necessary to determine whether the cost is justifiable.

Association of Piebaldism with Café-au-Lait Macules.

A 45-day-old infant was brought by his parents to the dermatology outpatient department with chief complaints of asymptomatic, depigmented lesions that had been present on his skin since birth. On mucocutaneous examination, large rhomboid-shaped depigmented macules were noted on the abdomen and lower extremities bilaterally (Figure 1). A depigmented macule was present on the forehead, with white hair (leukotrichia; a "developing forelock") (Figure 2). Three hyperpigmented lesions (café-au-lait macules [CALMs]) were also noted on the chest (Figure 1a). There was no history of consanguinity, and the family history was negative. The infant was otherwise normal for his age. A diagnosis of "piebaldism with CALMs" was made, and his parents were counseled about the disease and its progression, and possible treatment options as the child grew. They were also informed about a currently unquantifiable risk of future development of Legius syndrome or neurofibromatosis type 1 (NF1), and were counseled for regular follow-up.

Pediatric Emergency CT Scans at a Children's Hospital and at Community Hospitals: Radiation Technical Factors Are an Important Source of Radiation Exposure.

OBJECTIVE: This article compares the technical factors-in particular, tube current and voltage-and the resultant exposure to radiation associated with CT examinations performed at a children's hospital and at more general community hospital emergency departments (EDs). MATERIALS AND METHODS: CT scans obtained at community hospital EDs were retrospectively reviewed and compared with CT scans obtained at a children's hospital, to assess differences in kilovoltage, tube current, and volume CT dose index (CTDIvol) used. The number of scans obtained during the contrast-enhanced phase was also assessed. Parametric and nonparametric statistical analyses were used to test differences. RESULTS: A total of 233 body CT examinations were performed at community hospitals, and 287 were performed at a children's hospital. At both types of hospital, the median patient age was 12 years (p = 0.66). Of the body CT scans obtained at community hospitals that focused on the care of adult patients, 194 of 233 (83%) used a tube voltage of 120 kVp, 29 of 233 (12%) used 100 kVp, and two of 233 (< 1%) used 80 kVp. Of the body CT scans obtained at the children's hospital, 121 of 287 (42%) used a tube voltage of 120 kVp, 129 of 287 (45%) used 100 kVp, and 36 of 287 (13%) used 80 kVp. The median tube current was also lower at the children's hospital (110 vs 125 mA) (p < 0.001). At the community hospitals, 11 of 233 studies were multiphasic, whereas at the children's hospital, there were no multiphasic studies. For all CT types, the median CTDIvol was 4.9 mGy (range, 2.5-8.2 mGy) at the children's hospital and 8.6 mGy (range, 6.0-14.4 mGy) at the community hospitals (p < 0.001). CONCLUSION: The results of this study suggest that a large proportion of children who undergo CT at community hospitals receive relatively higher radiation doses than children who undergo CT at children's hospitals. This finding is related to the higher tube settings (in particular, kilovoltage) used at community hospitals.

The Presence of Portal Vein Thrombosis Alters the Classic Enhancement Associated with Diagnosis of Hepatocellular Carcinoma.

AIMS: To determine whether the presence of portal vein thrombosis (PVT) where venous flow within the liver may be altered may delay the diagnosis of HCC and be associated with more advanced disease. We characterized the incidence and imaging characteristics of patients diagnosed with hepatocellular carcinoma in a cohort of patients with PVT compared with those without PVT. METHODS: This is a single-center retrospective study of a subset of HCC patients who underwent dynamic imaging for HCC screening and were found to have PVT. Data abstracted included demographic data, TNM stage, number/type of scans, AFP level, MELD score, and time to diagnosis. RESULTS: Eighty-two patients newly diagnosed with HCC on screening were reviewed, of which 37 % (30/82) were found to have portal vein thrombosis. Patients with PVT had higher rates of atypical imaging associated with HCC compared with those without PVT (83 vs 56 %, p = 0.01) and had lower rates of portal venous washout (23 % vs 50 %, p = 0.018). Patients with PVT and HCC were also diagnosed at later TNM stage than those without PVT (70 vs 23 %, p < 0.001) and were significantly less likely to receive orthotopic liver transplant (3.6 vs 42 %, p < 0.001). Fourteen patients had preexisting PV clot without HCC; 16 developed PVT during screening or at diagnosis. Those with preexisting PVT were older (63. vs 55 years) and had higher rates of diagnosis of HCC using MRI (79 vs 21 % with CT, p = 0.01), compared with those without preexisting PVT. CONCLUSION: The presence of PVT found on dynamic imaging was associated with advanced stage of HCC at the time of diagnosis. Clinicians should have a high suspicion for HCC diagnosis in new liver lesions with atypical enhancement in the setting of PVT. In this setting, MRI was more frequently associated with HCC diagnosis.