Objective To determine whether clinical scoring systems or physician gestalt can obviate the need for CT in patients with possible appendicitis. Methods Prospective, observational study of patients with abdominal pain at an academic emergency department from 2/2012–2/2014. Patients over 11 years old who had a CT ordered for possible appendicitis were eligible. All parameters needed to calculate the scores were recorded on standardized forms prior to CT. Physicians also estimated the likelihood of appendicitis. Test characteristics were calculated using clinical follow up as the reference standard. ROC curves were drawn. Results Of the 287 patients (mean age [range], 31 [12–88] years; 60% women), the prevalence of appendicitis was 33%. The Alvarado score had a positive likelihood ratio [LR(+)] (95% confidence interval) of 2.2 (1.7–3) and a negative likelihood ratio [LR(−)] of 0.6 (0.4–0.7). The modified Alvarado score (MAS) had LR(+) 2.4 (1.6–3.4) and LR(−) 0.7 (0.6–0.8). The RIPASA score had LR(+) 1.3 (1.1–1.5) and LR(−) 0.5 (0.4–0.8). Physician-determined likelihood of appendicitis had LR(+) 1.3 (1.2–1.5) and LR(−) 0.3 (0.2–0.6). When combined with physician likelihoods, LR(+) and LR(−) was 3.67 and 0.48 (Alvarado), 2.33 and 0.45 (RIPASA), and 3.87 and 0.47 (MAS). The AUC was highest for physician-determined likelihood (0.72), but was not statistically significantly different from the clinical scores (RIPASA – 0.67, Alvarado 0.72, MAS 0.7). Conclusions Clinical scoring systems performed equally well as physician gestalt in predicting appendicitis. These scores do not obviate the need for imaging for possible appendicitis when a physician deems it necessary.

f Two transcription factors, ZEBRA and Rta, switch Epstein-Barr virus (EBV) from the latent to the lytic state. While ZEBRA also plays an obligatory role as an activator of replication, it is not known whether Rta is directly required for replication. Rta is dispensable for amplification of an oriLyt-containing plasmid in a transient-replication assay. Here, we assessed the requirement for Rta in activation of viral DNA synthesis from the endogenous viral genome, a function that has not been established. Initially, we searched for a ZEBRA mutant that supports viral replication but not transcription. We found that Z(S186A), a mutant of ZEBRA unable to activate transcription of Rta or viral genes encoding replication proteins, is competent to bind to oriLyt and to function as an origin recognition protein. Ectopic expression of the six components of the EBV lytic replication machinery failed to rescue replication by Z(S186A). However, addition of Rta to Z(S186A) and the mixture of replication factors activated viral replication and late gene expression. Deletion mutagenesis of Rta indicated that the C-terminal 10 amino acids (aa) were essential for the function of Rta in replication. In vivo DNA binding studies revealed that Rta interacted with the enhancer region of oriLyt. In addition, expression of Rta and Z(S186A) together, but not individually, activated synthesis of the BHLF1 transcript, a lytic transcript required for the process of viral DNA replication. Our findings demonstrate that Rta plays an indispensable role in the process of lytic DNA replication. L ytic infection is intrinsic to Epstein-Barr virus (EBV) pathogenesis. Viral particles are synthesized and assembled exclusively during the lytic state. Activation of the lytic cycle gene expression program is the only route for virus propagation. Activation of the lytic program is mediated by two transcription factors, ZEBRA and Rta, encoded by the viral BZLF1 and BRLF1 genes (1-4). Both proteins are required to trigger sequential events that include expression of replication proteins (RPs), viral genome amplification, and synthesis of late structural proteins (1,2,(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).A complete linear viral genome contains two copies of the origin of lytic DNA replication (oriLyt), which regulate the process of genome amplification. These oriLyt sequences are ϳ105 kbp apart and are located in the left and right duplicated sequences of the genome (DS L and DS R ) (15). Naturally occurring EBV strains with deletions of one copy of either origin, such as the B95-8 and P3HR1 virus strains, still maintain the capacity to replicate the entire viral genome (16,17). Each origin of replication contains the DNA regulatory elements sufficient to replicate a surrogate oriLyt plasmid in cis (15). Previous studies with oriLyt plasmids characterized three important cis elements present in the DS L origin, also known as BamHI-H oriLyt (18). These cis elements are the upstream and downstream elements, which are essential for genome amplification, and a ...

Purpose To perform a systematic review and meta-analysis of all published studies since 2005 that evaluate the accuracy of MRI for the diagnosis of acute appendicitis in the general population presenting to emergency departments. Materials and Methods All retrospective and prospective studies evaluating the accuracy of MRI to diagnose appendicitis published in English and listed in PubMed, Web of Science, Cinahl Plus, and the Cochrane Library since 2005 were included. Excluded studies were those without an explicitly stated reference standard, with insufficient data to calculate the study outcomes, or if the population enrolled was limited to pregnant women or children. Data were abstracted by one investigator and confirmed by another. Data included the number of true positives, true negatives, false positives, false negatives, number of equivocal cases, type of MRI scanner, type of MRI sequence, and demographic data including study setting and gender distribution. Summary test characteristics were calculated. Forest plots and a summary receiver operator characteristic plot were generated. Results Ten studies met eligibility criteria, representing patients from seven countries. Nine were prospective and two were multi-center studies. A total of 838 subjects were enrolled; 406 (48%) were women. All studies routinely used unenhanced MR images, though two used intravenous contrast-enhancement and three used diffusion-weighted imaging. Using a bivariate random-effects model the summary sensitivity was 96.6% (95% CI: 92.3%–98.5%) and summary specificity was 95.9% (95% CI: 89.4%–98.4%). Conclusion MRI has a high sensitivity and specificity for the diagnosis of appendicitis, similar to that reported previously for CT.

Purpose To compare the accuracy of magnetic resonance (MR) imaging with that of computed tomography (CT) for the diagnosis of acute appendicitis in emergency department (ED) patients. Materials and Methods This was an institutional review board-approved, prospective, observational study of ED patients at an academic medical center (February 2012 to August 2014). Eligible patients were nonpregnant and 12- year-old or older patients in whom a CT study had been ordered for evaluation for appendicitis. After informed consent was obtained, CT and MR imaging (with non-contrast material-enhanced, diffusion-weighted, and intravenous contrast-enhanced sequences) were performed in tandem, and the images were subsequently retrospectively interpreted in random order by three abdominal radiologists who were blinded to the patients' clinical outcomes. Likelihood of appendicitis was rated on a five-point scale for both CT and MR imaging. A composite reference standard of surgical and histopathologic results and clinical follow-up was used, arbitrated by an expert panel of three investigators. Test characteristics were calculated and reported as point estimates with 95% confidence intervals (CIs). Results Analysis included images of 198 patients (114 women [58%]; mean age, 31.6 years ± 14.2 [range, 12-81 years]; prevalence of appendicitis, 32.3%). The sensitivity and specificity were 96.9% (95% CI: 88.2%, 99.5%) and 81.3% (95% CI: 73.5%, 87.3%) for MR imaging and 98.4% (95% CI: 90.5%, 99.9%) and 89.6% (95% CI: 82.8%, 94.0%) for CT, respectively, when a cutoff point of 3 or higher was used. The positive and negative likelihood ratios were 5.2 (95% CI: 3.7, 7.7) and 0.04 (95% CI: 0, 0.11) for MR imaging and 9.4 (95% CI: 5.9, 16.4) and 0.02 (95% CI: 0.00, 0.06) for CT, respectively. Receiver operating characteristic curve analysis demonstrated that the optimal cutoff point to maximize accuracy was 4 or higher, at which point there was no difference between MR imaging and CT. Conclusion The diagnostic accuracy of MR imaging was similar to that of CT for the diagnosis of acute appendicitis.

Background Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that is classically characterized by fluctuating weakness and fatigability of the ocular, bulbar, limb, or respiratory muscles. Over half of patients with MG will initially experience isolated ocular symptoms in one or both eyes. Most patients report that ocular symptoms are mild or undetectable upon awakening, and worsen throughout the day or with tasks such as driving. We describe an unusual case of MG presenting with an acute onset of persistent unilateral ptosis and ipsilateral facial droop without diurnal variation or other fluctuation in severity. Case Report A 58-year-old male presented to the Emergency Department with a three day history of persistent, unilateral ptosis with facial droop, concerning for stroke. However, head MRI found no evidence of stroke or any other central etiology. Routine laboratory testing was unremarkable. Neurology was consulted and they recommended sending acetylcholine receptor antibody tests. At the patient’s subsequent neurology clinic visit, these tests were found to be abnormal. Electromyography was also done at this visit, confirming the diagnosis of MG. The patient subsequently underwent thymectomy and immunosuppressive therapy, with great improvement in his symptoms. Why should an emergency physician be aware of this? MG may present as unilateral ptosis or facial drooping without the hallmark characteristic of fluctuating muscle weakness. Early diagnosis and subsequent treatment of MG improves long term prognosis and remission rates. Emergency physicians should consider myasthenia gravis in cases of unilateral ocular symptoms after ruling-out emergent central etiologies.