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Palpable thyroid nodules are present in approximately 5–7% of the adult population, and of these, only a small percentage (5–10%) harbor malignancy. Ultrasound (US) imaging of the neck is typically used to characterize thyroid nodules in order to triage lesions with the highest risk of malignancy. Fine needle aspiration (FNA) is recommended for thyroid lesions with radiographically suspicious features (as outlined below). FNA biopsy of the thyroid gland is an increasingly common procedure, with approximately 300,000–500,000 biopsies performed annually in the United States. The 2015 American Thyroid Association management guidelines underscore the importance of radiologic risk stratification.

Background: Frontotemporal dementia (FTD) describes a cluster of neurocognitive syndromes that present with impairment of executive functioning, changes in behavior, and a decrease in language proficiency. FTD is the second most common form of dementia in those younger than 65 years and is expected to increase in prevalence as the population ages. This goal in our review is to describe advances in the understanding of neurobiological pathology, classification, assessment, and treatment of FTD syndromes. Methods: PubMed was searched to obtain reviews and studies that pertain to advancements in genetics, neurobiology, neuroimaging, classification, and treatment of FTD syndromes. Articles were chosen with a predilection to more recent preclinical/clinical trials and systematic reviews. Results: Recent reviews and trials indicate a significant advancement in the understanding of molecular and neurobiological clinical correlates to variants of FTD. Genetic and histopathologic markers have only recently been discovered in the past decade. Current therapeutic modalities are limited, with most studies reporting improvement in symptoms with nonpharmacological interventions. However, a small number of studies have reported improvement of behavioral symptoms with selective serotonin reuptake inhibitor (SSRI) treatment. Stimulants may help with disinhibition, apathy, and risk-taking behavior. Memantine and cholinesterase inhibitors have not demonstrated efficacy in ameliorating FTD symptoms. Antipsychotics have been used to treat agitation and psychosis, but safety concerns and side effect profiles limit utilization in the general FTD population. Nevertheless, recent breakthroughs in the understanding of FTD pathology have led to developments in pharmacological interventions that focus on producing treatments with autoimmune, genetic, and molecular targets. Conclusion: FTD is an underdiagnosed group of neurological syndromes comprising multiple variants with distinct neurobiological profiles and presentations. Recent advances suggest there is an array of potential novel therapeutic targets, although data concerning their effectiveness are still preliminary or preclinical. Further studies are required to develop pharmacological interventions, as there are currently no US Food and Drug administration approved treatments to manage FTD syndromes.

Lewy body dementia (LBD) is an umbrella term for major neurocognitive disorders caused by Lewy body pathology. Parkinson's disease dementia (PDD) and Dementia with Lewy bodies (DLB) are the two main syndromes in LBD. LBDs typically present with cognitive impairment, cholinergic deficiency, neuropsychiatric symptoms such as visual hallucinations and paranoid delusions, as well as parkinsonian symptoms. Due to the urgency in diagnosing LBD early in the disease course to provide the most optimal management of these syndromes, it is important that clinicians elicit the most clinically significant symptoms during patient encounters. The focus of this chapter is to discuss current LBD classification systems and assessments, neuropathology of LBDs, behavioral symptomatology, contemporary management options, and possible future targets of treatment. PubMed was searched to obtain reviews and studies that pertain to classification, behavioral symptomatology, neurobiology, neuroimaging, and treatment of LBDs. Articles were chosen with a predilection to more recent clinical trials and systematic reviews or meta-analyses. Updates to diagnostic criteria have increased clinical diagnostic sensitivity and specificity. Current therapeutic modalities are limited as there is no current disease-modifying drug available. Cholinesterase inhibitors have been reported to be effective in decreasing neuropsychiatric and cognitive symptoms. Neuroleptics should be avoided unless clinically indicated. There is a paucity of studies investigating treatment options for mood symptoms. Current novel targets of treatment focus on decreasing α-synuclein burden. LBDs are a group of dementia syndromes that affect a significant portion of the elderly population. Early diagnosis and treatment is necessary to improve patient quality of life with current treatment options more focused on alleviating severe symptomatology rather than modifying disease pathology.

Bladder pressure measurements (BPMs) are considered a key component in the diagnosis of abdominal compartment syndrome (ACS). The purpose of this observational review was to determine risk factors of ACS and associated mortality with particular focus on the role of BPM. A retrospective trauma registry and chart review was performed on trauma patients from January 2003 through December 2010. Comparisons were made between patients with and without ACS. There were 3172 patients included in the study of whom 46 had ACS. Patients with ACS were younger, more severely injured, with longer lengths of stay. Logistic regression determined Injury Severity Score (ISS) and urinary catheter days as independent predictors of ACS, whereas independent predictors of mortality included age, ISS, and ACS. Subset analysis demonstrated no association between BPM 20 mmHg or greater and diagnosis of ACS versus no ACS. Logistic regression indicated independent predictors of mortality were number of BPM 20 mmHg or greater and age. Patients with ACS are more severely injured with worse outcomes. An isolated BPM 20 mmHg or greater was not associated with ACS and may be inadequate to independently diagnose ACS. These findings suggest the need for repeat measurements with early intervention if they remain elevated in an effort to decrease mortality associated with ACS.

Our goal was to determine the characteristics of trauma transfer patients with repeat imaging. A retrospective trauma registry review was performed to evaluate trauma patients who were transferred from referring institutions between January 2005 and December 2009. Patients were divided into those who had a duplicate computed tomography (CT) scan versus those who did not. There were 2678 patients included of whom 559 (21%) had at least one repeat CT scan, whereas 2119 (79%) did not have any repeat CT scans. Those with repeat CT scans were older (42.3 ± 27.3 years vs 37.3 ± 25.6 years), had a higher Injury Severity Score (ISS) (13.7 ± 8.7 vs 11.9 ± 8.8), and more likely to have blunt trauma (odds ratio, 4.7; confidence interval, 2.3 to 9.6) (P for all < 0.0007). Those with CT scans done only at the referring facility were younger, had a lower ISS, and shorter lengths of stay (P for all < 0.0003). ISS and age were independent predictors for repeat CT scans. Transfer patients had imaging repeated one-fifth of the time. The younger, less injured patient went without repeat imaging suggesting that they may have been adequately cared for at the outside institution.

Tumor growth and metastasis require that tumor cells must have either the potential to shift genetically or epigenetically between proliferative and invasive phenotypes or both phenotypes simultaneously. In the present study, we demonstrated that neuroblastoma growth and invasion were distinct processes that were carried out by proliferative and invasive phenotypes of tumor cells, respectively. Two subpopulations from human neuroblastoma cell line were isolated: highly invasive (HI) cells and low-invasive (LI) cells. HI and LI cells had different proliferative rate and metastatic ability in vitro and in vivo. In addition, they had distinct activated signal pathways and sensitivities to chemotherapy drugs. Affymetrix microarray and quantitative reverse transcriptase-polymerase chain reaction revealed that visinin-like protein-1 (VSNL-1) mRNA in HI cells was significantly higher than that in LI cells. We also observed that VSNL-1 was over-expressed in tumor specimens from patients with distant organ metastases compared with those without metastases. Furthermore, the invasive and proliferative phenotypes of neuroblastoma cells could be exchanged by regulation of VSNL-1 expression in vitro and in vivo. Up-regulation of VSNL-1 potentiated the anoikis-resistant ability of neuroblastoma cell. The expression of anoikis inhibitor TrkB, intracellular adhesion molecule 1, major histocompatibility complex class I, CD44 and CD44v6 was associated with VSNL-1 level. These results suggested that distinct roles of proliferative and invasive phenotypes contributed to neuroblastoma progression and strongly demonstrated that VSNL-1 played a very important role in neuroblastoma metastasis.

Purpose. Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment characterized by redetachment of the retina as a result of membrane formation and contraction. A variety of retinal cells, including retinal pigment epithelial (RPE) and Müller glia, and growth factors may be responsible. Platelet-derived growth factor receptor alpha (PDGFRα) is found in large quantities in PVR membranes, and is intrinsic to the development of PVR in rabbit models. This study explores the expression of PDGFR in cocultures of RPE and Müller cells over time to examine how these two cell types may collaborate in the development of PVR. We also examine how changes in PDGFRαexpression alter Müller cell pathogenicity.Methods. Human MIO-M1 Müller progenitor (MPC) and ARPE19 cells were studied in a transmembrane coculture system. Immunocytochemistry and Western blot were used to look at PDGFRα, PDGFRβ, and GFAP expression. A transfected MPC line cell line expressing the PDGFRα(MIO-M1α) was generated, and tested in a rabbit model for its ability to induce PVR.Results. The expression of PDGFRαand PDGFRβwas upregulated in MIO-M1 MPCs cocultured with ARPE19 cells; GFAP was slightly decreased. Increased expression of PDGFRαin the MIO-M1 cell line resulted in increased pathogenicity and enhanced ability to induce PVR in a rabbit model.Conclusions. Müller and RPE cell interaction can lead to upregulation of PDGFRαand increased Müller cell pathogenicity. Müller cells may play a more active role than previously thought in the development of PVR membranes, particularly when stimulated by an RPE-cell-rich environment. Additional studies of human samples and in animal models are warranted.

A 27-year-old male who presented to our clinic with a nine year history of painless hematochezia. Examination was remarkable for right thigh hypertrophy and large varicose veins in the right lateral thigh. His medical history was significant for a port-wine stain on his right thigh noted early in childhood, a right leg venectomy and iron deficiency anemia. Colonoscopy revealed grade I internal hemorrhoids. Prominent rectal veins were also visualized from 10cm to the anal verge. Vascular surgery was consulted and a right leg venogram was obtained demonstrating extensive pelvic venous collaterals and an aberrant sciatic vein. There was also communication from the common femoral vein to the venous collaterals in the knee and thigh. Pathology review from his previous venectomy revealed arteriovenous fistulas. These findings were consistent with the Klippel-Trenauny Weber Syndrome (KTWS). Our patient subsequently underwent endovenous ablation of his right sciatic vein. This was followed by ultrasound-guided foam sclerotherapy. Follow-up sigmoidoscopy revealed complete ablation of his rectal varices. The Klippel-Trenauny syndrome was described in 1900 as a rare, non-hereditary congenital abnormality of obscure etiology characterized by the clinical triad of soft tissue hypertrophy of an extremity, varicosities, and cutaneous hemangiomas or lymphangiomas. Increased venous pressure during defecation and direct mucosal trauma caused by feces can aggravate recurrent hematochezia. Endoscopy may show visible vessels or nodules and bluish angiomatous lesions. Endoscopic recognition of rectal varices, and determination of the etiology of hematochezia is important in guiding appropriate therapy and management. doi:10.4021/gr2009.05.1290 Publish ahead of print May 22, 2009

Background: The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. Methods: Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. Results: Fifteen percent of patients were 55 years of age or older. A similar proportion of patients ≥ 55 went directly to the operating room compared with patients < 55 (41% vs. 38%) but the mortality for patients ≥ 55 was significantly greater than patients < 55 (43% vs. 23%). Patients ≥ 55 failed nonoperative management (NOM) more frequently than patients < 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p < 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women ≥ 55 failed NOM more frequently than women < 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p < 0.05). Conclusion: Patients ≥ 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients < 55. Women ≥ 55 had significantly greater mortality and failure of NOM than women < 55.

[Background and Aims] Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH)., [Methods] PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model., [Results] We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs., [Conclusions] When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking., [Lay summary] Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring., This work has been undertaken as part of the LITMUS (Liver Investigation: Testing Marker Utility in Steatohepatitis) project. The LITMUS project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 777377. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and Europen Federation of Pharmaceutical Industries and Associations (efpia.eu).