Saliva microRNA Biomarkers of Cumulative Concussion.

Recurrent concussions increase risk for persistent post-concussion symptoms, and may lead to chronic neurocognitive deficits. Little is known about the molecular pathways that contribute to persistent concussion symptoms. We hypothesized that salivary measurement of microribonucleic acids (miRNAs), a class of epitranscriptional molecules implicated in concussion pathophysiology, would provide insights about the molecular cascade resulting from recurrent concussions. This hypothesis was tested in a case-control study involving 13 former professional football athletes with a history of recurrent concussion, and 18 age/sex-matched peers. Molecules of interest were further validated in a cross-sectional study of 310 younger individuals with a history of no concussion (n = 230), a single concussion (n = 56), or recurrent concussions (n = 24). There was no difference in neurocognitive performance between the former professional athletes and their peers, or among younger individuals with varying concussion exposures. However, younger individuals without prior concussion outperformed peers with prior concussion on three balance assessments. Twenty salivary miRNAs differed (adj. p < 0.05) between former professional athletes and their peers. Two of these (miR-28-3p and miR-339-3p) demonstrated relationships (p < 0.05) with the number of prior concussions reported by younger individuals. miR-28-3p and miR-339-5p may play a role in the pathophysiologic mechanism involved in cumulative concussion effects.

Infiltrative hepatocellular carcinoma: what radiologists need to know.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The macroscopic growth pattern of HCC is subdivided into three categories: nodular, massive, and infiltrative. Infiltrative HCC accounts for 7%-20% of HCC cases and is confirmed at pathologic analysis on the basis of the spread of minute tumor nodules throughout large regions of the liver. Infiltrative HCC may represent a diagnostic challenge because it is often difficult to distinguish from background changes in cirrhosis at imaging. Infiltrative HCC usually spreads over multiple hepatic segments, occupying an entire hepatic lobe or the entire liver, and it is frequently associated with portal vein tumor thrombosis. The tumor is usually ill defined at ultrasonography and shows minimal and inconsistent arterial enhancement and heterogeneous washout at contrast material-enhanced computed tomography and magnetic resonance (MR) imaging. The tumor may be more visible among the surrounding liver parenchyma at diffusion-, T1-, and T2-weighted MR imaging. Several liver diseases can mimic the infiltrative appearance of this malignancy, including focal confluent fibrosis, hepatic fat deposition, hepatic microabscesses, intrahepatic cholangiocarcinoma, and diffuse metastatic disease (pseudocirrhosis). The prognosis for patients with infiltrative HCC is poor because the tumor is often markedly advanced and associated with vascular invasion at presentation. Survival after surgical resection is decreased; thus, infiltrative HCC is a contraindication for resection and transplantation. Knowledge of the key tumor characteristics and imaging findings will help radiologists formulate a correct and timely diagnosis to improve patient management.

Biliary strictures and masses: an expanded differential diagnosis.

Biliary strictures and masses are commonly a result of cholangiocarcinoma. However, there are several congenital, infectious, inflammatory, autoimmune, iatrogenic, and neoplastic etiologies that should also be considered in the differential diagnosis. Knowledge of the key imaging and clinical findings will aid in facilitating the diagnosis and treatment.

Radiogenomics of clear cell renal cell carcinoma: preliminary findings of The Cancer Genome Atlas-Renal Cell Carcinoma (TCGA-RCC) Imaging Research Group.

PURPOSE: To investigate associations between imaging features and mutational status of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: This multi-institutional, multi-reader study included 103 patients (77 men; median age 59 years, range 34-79) with ccRCC examined with CT in 81 patients, MRI in 19, and both CT and MRI in three; images were downloaded from The Cancer Imaging Archive, an NCI-funded project for genome-mapping and analyses. Imaging features [size (mm), margin (well-defined or ill-defined), composition (solid or cystic), necrosis (for solid tumors: 0%, 1%-33%, 34%-66% or >66%), growth pattern (endophytic, <50% exophytic, or ≥50% exophytic), and calcification (present, absent, or indeterminate)] were reviewed independently by three readers blinded to mutational data. The association of imaging features with mutational status (VHL, BAP1, PBRM1, SETD2, KDM5C, and MUC4) was assessed. RESULTS: Median tumor size was 49 mm (range 14-162 mm), 73 (71%) tumors had well-defined margins, 98 (95%) tumors were solid, 95 (92%) showed presence of necrosis, 46 (45%) had ≥50% exophytic component, and 18 (19.8%) had calcification. VHL (n = 52) and PBRM1 (n = 24) were the most common mutations. BAP1 mutation was associated with ill-defined margin and presence of calcification (p = 0.02 and 0.002, respectively, Pearson's χ (2) test); MUC4 mutation was associated with an exophytic growth pattern (p = 0.002, Mann-Whitney U test). CONCLUSIONS: BAP1 mutation was associated with ill-defined tumor margins and presence of calcification; MUC4 mutation was associated with exophytic growth. Given the known prognostic implications of BAP1 and MUC4 mutations, these results support using radiogenomics to aid in prognostication and management.

Academic portfolio in the digital era: organizing and maintaining a portfolio using reference managers.

The academic portfolio has become an integral part of the promotions process. Creating and maintaining an academic portfolio in paper-based or web-based formats can be a cumbersome and time-consuming task. In this article, we describe an alternative way to efficiently organize an academic portfolio using a reference manager software, and discuss some of the afforded advantages. The reference manager software Papers (Mekentosj, Amsterdam, The Netherlands) was used to create an academic portfolio. The article outlines the key steps in creating and maintaining a digital academic portfolio. Using reference manager software (Papers), we created an academic portfolio that allows the user to digitally organize clinical, teaching, and research accomplishments in an indexed library enabling efficient updating, rapid retrieval, and easy sharing. To our knowledge, this is the first digital portfolio of its kind.

In search of a consensus: evaluation of the patient with hematuria in an era of cost containment.

OBJECTIVE: The purpose of this article is to describe the current consensus guidelines for nonimaging triage and ultimate preferred imaging approach for the patient with unexplained hematuria. CONCLUSION: Numerous consensus guidelines from varying societies have outlined preferred imaging pathways for the patient with unexplained urologic causes of hematuria. Future guidelines will need to take into account disease prevalence, radiation considerations, and cost.

Cystic hepatic lesions: a review and an algorithmic approach.

OBJECTIVE: The purpose of this article is to review the different cystic hepatic lesions, with an emphasis on the imaging features that help to differentiate them, and to propose a practical algorithm for approaching the diagnosis of these lesions. CONCLUSION: The number and morphology of the lesions and determination of whether there is a solid component are key imaging features that are helpful for approaching the diagnosis of cystic hepatic lesions. Familiarity with these features and knowledge of the clinical associations will help the radiologist to establish a definitive diagnosis or provide a reasonable differential diagnosis.

MDCT of acute cecal conditions.

The cecum comprises a relatively short segment of the gastrointestinal tract, but it can be affected by numerous acute conditions. Acute conditions may arise from processes primary to the cecum, such as volvulus, bascule, neoplasm, and trauma. Alternatively, acute conditions can be due to secondary to systemic or nearby pathology, such as infection, inflammatory processes, ischemia, and infarction. While it is common to suspect appendicitis as the etiology of acute right lower quadrant abdominal pain, the cecum should also be considered as a potential cause of pain, especially in the setting of an abnormal or absent appendix. Multi-detector computed tomography (MDCT) has evolved to become the best imaging modality to evaluate patients presenting with right lower quadrant abdominal pain or suspected acute cecal pathology. Strengths of MDCT include rapid acquisition of images, high spatial resolution, and ability to create multi-planar reconstructed images. In this pictorial review, we illustrate and describe key MDCT findings for various acute cecal conditions with which the emergency radiologist should be familiar.

Utility of additional CT examinations driven by completion of a standard trauma imaging protocol in patients transferred for minor trauma.

Many clinicians order focused computed tomography (CT) examinations for trauma patients based on history and physical examinations. Trauma patients transferred to our level I trauma center undergo an extensive, nonfocused standard trauma CT protocol. We hypothesize that the use of the standard trauma CT protocol does not contribute significant clinical information for patient care when compared with CT examinations based on history and physical examination. We aim to quantify the utility of the additional CT examinations required by our institution's trauma protocol compared with emergent CT examinations dictated by the patient's history and physical examination findings. In this IRB-approved study, we retrospectively evaluated 132 trauma patients transferred to our center who underwent additional CT examinations as determined by fulfillment of our institution's standard trauma CT protocol. The emergency radiologist evaluated the CT examinations acquired after the patient's transfer to determine if there were any additional acute findings that were identified on these additional examinations compared with the initial assessment undertaken at the outside institution. A total of 101 patients transferred to our trauma center met inclusion criteria. The majority of these patients sustained minor trauma. The standard trauma protocol generated 474 negative CT examinations in 101 patients. In seven patients, there were unexpected acute findings. However, these unexpected acute findings did not change clinical management in any of the patients. After initial evaluation, the acquisition of additional nonfocused CT examinations based on the standard trauma CT protocol provides little useful clinical information in patients who are transferred for minor trauma. Rather, CT utilization should be based on clinical findings. Replacement of standard trauma CT protocol with focused CT examinations in trauma patients is a way to curtail overutilization, thereby decreasing health care cost and the amount of patient radiation exposure.

Evaluation of a Patient Decision Aid for Refractive Eye Surgery.

BACKGROUND: We developed a prototype patient decision aid, EyeChoose, to assist college-aged students in selecting a refractive surgery. EyeChoose can educate patients on refractive errors and surgeries, generate evidence-based recommendations based on a user's medical history and personal preferences, and refer patients to local refractive surgeons. OBJECTIVES: We conducted an evaluative study on EyeChoose to assess the alignment of surgical modality recommendations with a user's medical history and personal preferences, and to examine the tool's usefulness and usability. METHODS: We designed a mixed methods study on EyeChoose through simulations of test cases to provide a quantitative measure of the customized recommendations, an online survey to evaluate the usefulness and usability, and a focus group interview to obtain an in-depth understanding of user experience and feedback. RESULTS: We used stratified random sampling to generate 245 test cases. Simulated execution indicated EyeChoose's recommendations aligned with the reference standard in 243 (99%). A survey of 55 participants with 16 questions on usefulness, usability, and general impression showed that 14 questions recorded more than 80% positive responses. A follow-up focus group with 10 participants confirmed EyeChoose's useful features of patient education, decision assistance, surgeon referral, as well as good usability with multimedia resources, visual comparison among the surgical modalities, and the overall aesthetically pleasing design. Potential areas for improvement included offering nuances in soliciting user preferences, providing additional details on pricing, effectiveness, and reversibility of surgeries, expanding the function of surgeon referral, and fixing specific usability issues. CONCLUSION: The initial evaluation of EyeChoose suggests that it could provide effective patient education, generate appropriate recommendations, connect to local refractive surgeons, and demonstrate good system usability in a test environment. Future research is required to enhance the system functions, fully implement and evaluate the tool in naturalistic settings, and examine the findings' generalizability to other populations.

Correlation of ultrasound findings with the Bethesda cytopathology classification for thyroid nodule fine-needle aspiration: a primer for radiologists.

OBJECTIVE: Ultrasound and ultrasound-guided fine-needle aspiration play a critical role in the evaluation of thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was developed to facilitate communication among cytopathologists, radiologists, and referring physicians. The reporting scheme has rapidly become one of the most important contributions to thyroid nodule management. In this article, we review the significance of the TBSRTC categories and their implications in stratifying risk in the management of thyroid nodules. CONCLUSION: Knowledge of TBSRTC will allow the radiologist to better understand the criteria for thyroid nodule specimen adequacy, the components of risk stratification, and the standard terminology used for effective communication between patients and clinicians.

Comparative evaluation of no dye assistance, indocyanine green and triamcinolone acetonide for internal limiting membrane peeling during macular hole surgery.

PURPOSE: To evaluate the anatomical closure rate and visual outcome in patients undergoing pars plana vitrectomy with internal limiting membrane peeling without dye enhancement and with indocyanine green or triamcinolone acetonide assistance. METHODS: This is a retrospective, comparative interventional case series. The electronic charts of 435 eyes of 415 patients with idiopathic macular holes who underwent macula hole surgery were reviewed from January 2003 to April 2010. The patients were assigned to 3 groups: no dye assistance (Group 1), indocyanine green-assisted (Group 2), and triamcinolone acetonide-assisted internal limiting membrane peel (Group 3). The data were recorded for 3-, 6-, and 12-month follow-up visits. Main outcome measures were postoperative visual acuity and macular hole closure. RESULTS: The overall macular hole closure rate with a single surgery was 94.7% (108 of 114). In Group 1: 91.4% (191 of 209), in Group 2: 94.1% (112 of 119), and in Group 3: 95.9% (93 of 97) achieved closure. Closure rate for holes that were ≤400 µm in diameter was 98.8% compared with >400 µm, which was 90.4% (P = 0.001). There was a statistically significant (P < 0.001) improvement from preoperative visual acuity to postoperative visual acuity in all groups across all time points. There was no statistically significant visual acuity difference among three groups. At 12-month follow-up, 77.7% in Group 1, 66.1% in Group 2, and 81.3% in Group 3 achieved 20/50 visual acuity or better. CONCLUSION: The study shows that good anatomical and functional results can be achieved with no dye and with indocyanine green or triamcinolone acetonide dye assistance for internal limiting membrane peeling during macular hole surgery. Overall, visual acuity levels did not differ among groups, although subanalysis of the results suggests subtle indocyanine green toxicity.

Hepatic transplantation: postoperative complications.

Advances in surgical techniques and immunosuppression have made orthotopic liver transplantation a first-line treatment for many patients with end-stage liver disease. The early detection and treatment of postoperative complications has contributed significantly to improved graft and patient survival with imaging playing a critical role in detection. Complications that can lead to graft failure or patient mortality include vascular abnormalities, biliary abnormalities, allograft rejection, and recurrent or post-transplant malignancy. Vascular abnormalities include stenosis and thrombosis of the hepatic artery, portal vein, and inferior vena cava, as well as hepatic artery pseudoaneurysm, arteriovenous fistula, and celiac stenosis. Biliary abnormalities include strictures, bile leak, obstruction, recurrent disease, and infection. While imaging is not used to diagnose allograft rejection, it plays an important role in identifying complications that can mimic rejection. Ultrasound is routinely performed as the initial imaging modality for the detection and follow-up of both early and delayed complications. Cholangiography and magnetic resonance cholangiopancreatography are used to characterize biliary complications and computed tomography is used to confirm abnormal findings on ultrasound or for the evaluation of postoperative collections. The purpose of this article is to describe and illustrate the imaging appearances and management of complications associated with liver transplantation.

Pneumopericardium due to gastropericardial fistula: a delayed, rare complication of gastric bypass surgery.

Pneumopericardium is a rare clinical finding with various etiologies. Pneumopericardium ranges from an asymptomatic to life-threatening condition, e.g., in cases of cardiac tamponade. The underlying etiology should be sought so that treatment can be expedited. Pneumopericardium may result from traumatic and nontraumatic etiologies. Although the mortality associated with pneumopericardium is high, its rarity precludes determination of its true incidence. We present an unusual case of pneumopericardium due to gastropericardial fistula which developed as a delayed complication of a Roux-en-Y gastric bypass performed 11 years prior.

Cocaine use disorder patients develop distinct patterns of regulation of acth secretion by a vasopressin agonist and oxytocin: Report on a laboratory study.

Background: : Oxytocin and Vasopressin systems in the brain sustain adaptation to stressors. Cocaine being a stressor, it may alter brain homeostatic function. This dysregulation may entrench cocaine use disorder. Method: : This is a human laboratory study of the effects of intranasal desmopressin (a Vasopressin 1b receptor agonist) and oxytocin on ACTH secretion in cocaine use disorder patients versus a control group. It consisted of two endocrine challenges performed on consecutive days. On day 1, the effect of intranasal desmopressin (80 IU) on ACTH secretion was measured. On day 2, a pre-treatment with intranasal oxytocin (24 IU) preceded intranasal desmopressin to monitor its effect on desmopressin-induced ACTH secretion. We hypothesized that the effect of intranasal oxytocin in controls would differ from the effect in cocaine use disorder patients. Results: : Forty-three patients were included in this study: 14 controls and 29 cocaine use disorder patients. Significant differences were noted in the direction of change of ACTH secretion between the two groups. In cocaine use disorder patients, overall ACTH secretion was on average 2.7 pg/ml/min higher after intranasal desmopressin than after intranasal oxytocin/desmopressin (t292 = 2.91, p = 0.004). The opposite was observed in controls: overall ACTH secretion averaged 3.3 pg/ml/min less after intranasal desmopressin than after intranasal oxytocin/desmopressin (t292 = -2.35, p = 0.02). Conclusion: : Intranasal oxytocin and desmopressin revealed a pattern of ACTH secretion in cocaine use disorder patients that is distinct from a non-addicted control group. (ClinicalTrial.gov00255357, 10/2014).

Refinement of saliva microRNA biomarkers for sports-related concussion.

BACKGROUND: Recognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise. METHODS: This case-control study harmonized data from concussed and non-concussed athletes recruited across 10 sites. Levels of salivary miRNAs within 455 samples from 314 individuals were measured with RNA sequencing. Within-subjects testing was used to identify and exclude miRNAs that changed with either (a) a single episode of exercise (166 samples from 83 individuals) or (b) season-long participation in contact sports (212 samples from 106 individuals). The miRNAs that were not impacted by exercise were interrogated for SRC diagnostic utility using logistic regression (172 samples from 75 concussed and 97 non-concussed individuals). RESULTS: Two miRNAs (miR-532-5p and miR-182-5p) decreased (adjusted p < 0.05) after a single episode of exercise, and 1 miRNA (miR-4510) increased only after contact sports participation. Twenty-three miRNAs changed at the end of a contact sports season. Two of these miRNAs (miR-26b-3p and miR-29c-3p) were associated (R > 0.50; adjusted p < 0.05) with the number of head impacts sustained in a single football practice. Among the 15 miRNAs not confounded by exercise or season-long contact sports participation, 11 demonstrated a significant difference (adjusted p < 0.05) between concussed and non-concussed participants, and 6 displayed moderate ability (area under curve > 0.70) to identify concussion. A single ratio (miR-27a-5p/miR-30a-3p) displayed the highest accuracy (AUC = 0.810, sensitivity = 82.4%, specificity = 73.3%) for differentiating concussed and non-concussed participants. Accuracy did not differ between participants with SRC and non-SRC (z = 0.5, p = 0.60). CONCLUSION: Salivary miRNA levels may accurately identify SRC when not confounded by exercise. Refinement of this approach in a large cohort of athletes could eventually lead to a non-invasive, sideline adjunct for SRC assessment.

A mouse model of ß-thalassemia shows a liver-specific down-regulation of Abcc6 expression.

ß-Thalassemia and pseudoxanthoma elasticum (PXE) are distinct genetic disorders. Yet, a dystrophic mineralization phenotype similar to PXE has frequently been associated with ß-thalassemia or sickle cell anemia patients of Mediterranean descent. These calcifications are clinically and structurally identical to inherited PXE. As we previously excluded the presence of PXE-causing mutations in the ABCC6 gene of ß-thalassemia patients with PXE manifestations, we hypothesized that a molecular mechanism independent of gene mutations either altered the ABCC6 gene expression or disrupted the biologic properties of its product in the liver or kidneys, which are the tissues with the highest levels of expression. To test this possibility, we investigated Abcc6 synthesis in the liver and kidneys of a ß-thalassemia mouse model (Hbb(th3/+)). We found a progressive liver-specific down-regulation of the Abcc6 gene expression and protein levels by quantitative PCR, Western blotting, and immunofluorescence. The levels of Abcc6 protein decreased significantly at 6 months of age and stabilized at 10 months and older ages at ∼25% of the wild-type protein levels. We studied the transcriptional regulation of the Abcc6 gene in wild-type and Hbb(th3/+) mice, and we identified the erythroid transcription factor NF-E2 as the main cause of the transcriptional down-regulation using transcription factor arrays and chromatin immunoprecipitation. The Hbb(th3/+) mice did not develop spontaneous calcification as seen in the Abcc6(-/-) mice probably because the Abcc6 protein decrease occurred late in life and was probably insufficient to promote mineralization in the Hbb(th3/+) mouse C57BL/6J genetic background. Nevertheless, our result suggested that a similar decrease of ABCC6 expression occurs in the liver of ß-thalassemia patients and may be responsible for their frequent PXE-like manifestations.

Imaging of the female perineum in adults.

The female perineum is a diamond-shaped structure inferior to the pelvic diaphragm and between the symphysis pubis and coccyx. The perineum is divided into the anterior urogenital triangle and the posterior anal triangle; the vulva represents the external genitalia. A wide array of diseases affect the female perineum in adults. Vulvar trauma, infection (including Fournier gangrene), developmental lesions, and thrombophlebitis can be investigated with various imaging modalities; vulvar malignancies are best imaged with magnetic resonance (MR) imaging to identify local-regional extent of disease. MR imaging is also the modality of choice for imaging of the distal urethra, although imaging of a urethral diverticulum also includes voiding cystourethrography and ultrasonography. The distal vagina at the level of the introitus is best imaged with MR imaging for assessment of Bartholin gland cysts and malignancies. Diseases encountered in the anus include anal carcinoma, fistula-in-ano, and anovaginal fistula, which can all be imaged with various modalities offering different sensitivities and fields of view. Lastly, musculoskeletal neoplasms affecting the perineum and vulva include mesenchymal, lipomatous, nerve sheath, and osseous neoplasms. These neoplasms can be imaged with both computed tomography and MR imaging, although the latter provides higher soft-tissue contrast and greater anatomic detail for diagnosis and determination of the extent of necessary surgery. Familiarity with the anatomy of the female perineum and appropriate selection of imaging modalities facilitate prompt and accurate diagnosis and treatment.

Seminal vesicle cysts causing pelvic pain: importance of computed tomography.

A seminal vesicle cyst is a rare etiology of pelvic pain. However, its rarity may result in oversight or misinterpretation if the radiologist or emergency physician is unfamiliar with this entity. Seminal vesicle cysts may cause pelvic pain because of mass effect, infection, internal hemorrhage, or urinary and bladder obstruction. Because seminal vesicle cysts rarely result in physical examination findings or laboratory abnormalities, pelvic computed tomography plays a pivotal role in their diagnosis and in evaluating patients with pelvic pain. Recognition of the imaging findings of seminal vesicle cysts is necessary to allow prompt, accurate diagnosis. Therefore, emergency physicians and radiologists interpreting examinations from the emergency department should be familiar with these imaging findings because seminal vesicle cysts may be the etiology of pelvic pain and the patient may benefit from urologic consultation and cyst aspiration or resection. The purposes of this article are to provide examples of pelvic pain caused by seminal vesicle cysts, illustrate the key imaging findings on computed tomography, and briefly review the literature.

Imaging of acute conditions affecting the hepatic vasculature.

Liver imaging primarily consists of evaluating the parenchyma and biliary system. However, the liver has a rich, complex vascularity which can also be affected by numerous disease processes. By considering disease processes that primarily affect the hepatic veins, portal veins, and hepatic arteries, an anatomy-based approach of hepatic vascular diseases can be applied to image interpretation to allow rapid diagnosis and prompt initiation of treatment. Computed tomography, magnetic resonance imaging, and ultrasound are all effectively used to evaluate the liver and can play complimentary roles. In this article, the key imaging findings of acute conditions affecting the hepatic veins (passive congestion, acute thrombosis/Budd-Chiari, stenosis), portal veins (thrombosis, phlebitis, stenosis), hepatic arteries (laceration, pseudoaneurysm, thrombosis), and arteriovenous structures (hereditary hemorrhagic telangiectasis, arteriovenous fistula) will be reviewed.