Comparative pathogenesis of three Mayaro virus genotypes in the cynomolgus macaque.

Mayaro virus (MAYV), a mosquito-borne alphavirus, is considered an emerging threat to public health with epidemic potential. Phylogenetic studies show the existence of three MAYV genotypes. In this study, we provide a preliminary analysis of the pathogenesis of all three MAYV genotypes in cynomolgus macaques (Macaca facicularis, Mauritian origin). Significant MAYV-specific RNAemia and viremia were detected during acute infection in animals challenged intravenously with the three MAYV genotypes, and strong neutralizing antibody responses were observed. MAYV RNA was detected at high levels in lymphoid tissues, joint muscle and synovia over 1 month after infection, suggesting that this model could serve as a promising tool in studying MAYV-induced chronic arthralgia, which can persist for years. Significant leucopenia was observed across all MAYV genotypes, peaking with RNAemia. Notable differences in the severity of acute RNAemia and composition of cytokine responses were observed among the three MAYV genotypes. Our model showed no outward signs of clinical disease, but several major endpoints for future MAYV pathology and intervention studies are described. Disruptions to normal blood cell counts and cytokine responses were markedly distinct from those observed in macaque models of CHIKV infection, underlining the importance of developing non-human primate models specific to MAYV infection.

Insulin reduces the transmission potential of chikungunya virus and activates the toll pathway in Aedes aegypti mosquitoes.

Chikungunya virus (CHIKV) is an alphavirus that has re-emerged globally over the last two decades and has the potential to become endemic in the United States due to the presence of competent mosquito vectors, Aedes aegypti and Aedes albopictus. CHIK disease is characterised by fever, rash, and joint pain, and causes chronic debilitating joint pain and swelling in >50% of infected individuals. Given the disease severity caused by CHIKV and the global presence of vectors to facilitate its spread, strategies to reduce viral transmission are desperately needed; however, the human biological factors driving CHIKV transmission are poorly understood. Towards that end, we have previously shown that mosquitoes fed on alphavirus-infected obese mice have reduced infection and transmission rates compared to those fed on infected lean mice despite similar viremia in lean and obese mice. One of the many host factors that increase in obese hosts is insulin, which was previously shown to impact the infection of mosquitoes by several flaviviruses. However, insulin's impact on alphavirus infection of live mosquitoes is unknown and whether insulin influences mosquito-borne virus transmission has not been tested. To test this, we exposed A. aegypti mosquitoes to bloodmeals with CHIKV in the presence or absence of physiologically relevant levels of insulin and found that insulin significantly lowered both infection and transmission rates. RNA sequencing analysis on mosquito midguts isolated at 1-day-post-infectious-bloodmeal (dpbm) showed enrichment in genes in the Toll immune pathway in the presence of insulin, which was validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We then sought to determine if the Toll pathway plays a role in CHIKV infection of Ae. aegypti mosquitoes; therefore, we knocked down Myd88, a critical immune adaptor molecule for the Toll pathway, in live mosquitoes, and found increased CHIKV infection compared to the mock knockdown control group. Overall, these data demonstrate that insulin reduces CHIKV transmission by Ae. aegypti and activates the Toll pathway in mosquitoes, suggesting that conditions resulting in higher serum insulin concentrations may reduce alphavirus transmission. Finally, these studies suggest that strategies to activate insulin or Toll signalling in mosquitoes may be an effective control strategy against medically relevant alphaviruses.

Tests, Quizzes, and Self-Assessments: How to Construct a High-Quality Examination.

OBJECTIVE: The purposes of this article are to highlight aspects of tests that increase or decrease their effectiveness and to provide guidelines for constructing high-quality tests in radiology. CONCLUSION: Many radiologists help construct tests for a variety of purposes. Only well-constructed tests can provide reliable and valuable information about the test taker.

Assessing the learning potential of an interactive digital game versus an interactive-style didactic lecture: the continued importance of didactic teaching in medical student education.

BACKGROUND: Games with educational intent offer a possible advantage of being more interactive and increasing learner satisfaction. OBJECTIVE: We conducted a two-armed experiment to evaluate student satisfaction and content mastery for an introductory pediatric radiology topic, taught by either an interactive digital game or with a traditional didactic lecture. MATERIALS AND METHODS: Medical students participating in a fourth-year radiology elective were invited to participate. Student cohorts were alternatively given a faculty-supervised 1h session playing a simple interactive digital Tic-tac-toe quiz module on pediatric gastrointestinal radiology or a 1h didactic introductory lecture on the same topic. Survey questions assessed the learners' perceived ability to recall the material as well as their satisfaction with the educational experience. Results of an end-of-rotation exam were reviewed to evaluate a quantitative measure of learning between groups. Survey responses were analyzed with a chi-squared test. Exam results for both groups were analyzed with a paired Student's t-test. RESULTS: Students in the lecture group had higher test scores compared to students in the game group (4.0/5 versus 3.6/5, P = 0.045). Students in the lecture group reported greater understanding and recall of the material than students in the game group (P < 0.001 and P = 0.004, respectively). Students in the lecture group perceived the lecture to be more enjoyable and a better use of their time compared to those in the game group (P = 0.04 and P < 0.001, respectively). There was no statistically significant difference between the lecture and game group in ability to maintain interest (P = 0.187). In comparison to pre-survey results, there was a statistically significant decrease in interest for further digital interactive materials reported by students in the game group (P = 0.146). CONCLUSION: Our experience supported the use of a traditional lecture over a digital game module. While these results might be affected by the specific lecture and digital content in any given comparison, a digital module is not always the superior option.

Can CT features differentiate between inferior vena cava leiomyosarcomas and primary retroperitoneal masses?

OBJECTIVE: The objective of our study was to evaluate and describe CT features that may differentiate inferior vena cava (IVC) leiomyosarcomas from primary retroperitoneal masses. MATERIALS AND METHODS: A records search revealed 18 CT examinations with a soft-tissue mass contacting the IVC. Three readers evaluated the scans for four signs: an imperceptible IVC at the interface with the mass; a "positive embedded organ" sign (IVC embedded in the periphery of the mass); a "negative embedded organ" sign (IVC compressed at the perimeter of the mass); and tumor in the IVC lumen. CT findings were compared with pathology and operative reports. Performance and significance of CT features and interobserver agreement were calculated. RESULTS: Four of 18 (22%) retroperitoneal masses were IVC leiomyosarcomas. The IVC was imperceptible at the interface with the mass in three of the four (75%) IVC leiomyosarcomas (κ = 0.88) and in no alternate diagnosis (p < 0.02). No IVC leiomyosarcoma showed a positive embedded organ sign versus one of 14 masses of alternate origin (p = 1.0, κ = 0.56). The negative embedded organ sign was seen in most primary retroperitoneal masses (11/14 or 79%, κ = 0.85) but in no case of IVC leiomyosarcoma (p = 0.01). Intraluminal tumor was seen in one of four (25%) IVC leiomyosarcomas and in two of 14 other retroperitoneal masses (p = 1.0, κ = 1.0). CONCLUSION: An imperceptible IVC at the point of maximal contact with a retroperitoneal mass was the most useful CT feature for predicting the origin of IVC leiomyosarcoma. A negative embedded organ sign was useful for excluding IVC origin. Knowledge of these CT features may assist with preoperative planning.

Determinants of second-order bile duct visualization at CT cholangiography in potential living liver donors.

OBJECTIVE: The purpose of this article is to investigate the determinants of second-order bile duct visualization at CT cholangiography in living potential liver donors. MATERIALS AND METHODS: We retrospectively identified 143 potential living liver donors (83 men and 60 women; mean age, 37 years) evaluated with CT cholangiography, which included a slow infusion of iodipamide meglumine with CT acquisition 15 minutes after biliary contrast agent administration. Two readers independently scored the visualization of the second-order bile duct branches on a previously established 4-point scale (0 = not seen, 1 = faintly seen, 2 = well seen, and 3 = excellent visualization). Multivariate analysis was used to investigate the correlation between visualization scores and potential determinants of second-order bile duct opacification, specifically age, body mass index, creatinine level, total and direct bilirubin levels, alkaline phosphatase level, aspartate aminotransferase level, alanine aminotransferase level, patient maximum linear width, CT noise, and hepatosplenic attenuation difference at unenhanced CT. RESULTS: The mean (± SD) second-order bile duct visualization scores were 2.35 ± 0.66 and 2.55 ± 0.60 for readers 1 and 2, respectively. In the multivariate analysis, the only independent predictors of reduced second-order bile duct visualization were higher alkaline phosphatase level (p = 0.01) and higher CT noise (p = 0.02). CONCLUSION: Higher serum alkaline phosphatase level and higher CT noise in potential living liver donors indicate a higher risk of poor second-order bile duct visualization at CT cholangiography.

Correctly using sensitivity, specificity, and predictive values in clinical practice: how to avoid three common pitfalls.

OBJECTIVE: Radiology is the specialty of imaging-based diagnostic tests. Understanding the science behind evaluating diagnostic test performance is essential for radiologists because we provide care to patients and interact with our colleagues. CONCLUSION: Here, we review the key terminology used and common pitfalls encountered in the literature and in day-to-day discussions of diagnostic test performance.

The prevalence and patterns of intraluminal air in acute appendicitis at CT.

The purpose of this study is to investigate if the presence and distribution of intraluminal air in the appendix contributes to the computed tomography (CT) diagnosis of appendicitis. We identified 100 consecutive patients (57 men and 43 women; mean age, 38) with CT prior to appendectomy for acute appendicitis over a 5-year period and a control group of 100 consecutive patients (29 men and 71 women; mean age, 39) who underwent CT for acute abdominal pain without appendicitis. Patients were scanned using multidetector row CT scanners at 1.25 or 5-mm slice thickness, peak tube voltage of 120 kVp, and milliamperse automatically adjusted to attain a noise index of 12. Ninety-two of 100 study patients and 95 of 100 controls received 150 mL intravenous contrast. Two independent readers noted the presence and distribution pattern of intraluminal air in the appendix, appendiceal diameter, wall hyperemia, wall thickening (>3 mm), and wall stratification and presence of any secondary signs of appendicitis including fat stranding and free fluid. Data were compared between groups using Fisher's exact test and Student's t test. Intraluminal air in the appendix was more common in control patients versus patients with appendicitis (66 of 100 versus 27 of 100, p < 0.001). No significant differences in the patterns of intraluminal air were found between cases and controls. Among appendicitis cases, there was no significant difference in mean appendiceal diameter (12.8 versus 12.0, p = 0.20) or number of CT signs of appendicitis (1.93 versus 1.86, p = 0.78) in cases with intraluminal air versus without. No case of appendicitis demonstrated intraluminal air without secondary signs of appendicitis. Although intraluminal air is sometimes assumed to exclude a diagnosis of appendicitis, it is actually a common finding seen in up to 27 % of cases at CT. The pattern of intraluminal air was not helpful in differentiating a normal appendix from appendicitis.

Expression of anti-chikungunya single-domain antibodies in transgenic Aedes aegypti reduces vector competence for chikungunya virus and Mayaro virus.

Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are closely related alphaviruses that cause acute febrile illness accompanied by an incapacitating polyarthralgia that can persist for years following initial infection. In conjunction with sporadic outbreaks throughout the sub-tropical regions of the Americas, increased global travel to CHIKV- and MAYV-endemic areas has resulted in imported cases of MAYV, as well as imported cases and autochthonous transmission of CHIKV, within the United States and Europe. With increasing prevalence of CHIKV worldwide and MAYV throughout the Americas within the last decade, a heavy focus has been placed on control and prevention programs. To date, the most effective means of controlling the spread of these viruses is through mosquito control programs. However, current programs have limitations in their effectiveness; therefore, novel approaches are necessary to control the spread of these crippling pathogens and lessen their disease burden. We have previously identified and characterized an anti-CHIKV single-domain antibody (sdAb) that potently neutralizes several alphaviruses including Ross River virus and Mayaro virus. Given the close antigenic relationship between MAYV and CHIKV, we formulated a single defense strategy to combat both emerging arboviruses: we generated transgenic Aedes aegypti mosquitoes that express two camelid-derived anti-CHIKV sdAbs. Following an infectious bloodmeal, we observed significant reduction in CHIKV and MAYV replication and transmission potential in sdAb-expressing transgenic compared to wild-type mosquitoes; thus, this strategy provides a novel approach to controlling and preventing outbreaks of these pathogens that reduce quality of life throughout the tropical regions of the world.

A Longitudinal Characterization of the Seminal Microbiota and Antibiotic Resistance in Yearling Beef Bulls Subjected to Different Rates of Gain.

In this study, we evaluated the seminal and fecal microbiota in yearling beef bulls fed a common diet to achieve moderate (1.13 kg/day) or high (1.80 kg/day) rates of weight gain. Semen samples were collected on days 0 and 112 of dietary intervention (n = 19/group) as well as postbreeding (n = 6/group) using electroejaculation, and the microbiota was assessed using 16S rRNA gene sequencing, quantitative PCR (qPCR), and culturing. The fecal microbiota was also evaluated, and its similarity with seminal microbiota was assessed. A subset of seminal bacterial isolates (n = 33) was screened for resistance against 28 antibiotics. A complex and dynamic microbiota was detected in bovine semen, and the community structure was affected by sampling time (R2 = 0.16, P < 0.001). Microbial richness increased significantly from day 0 to day 112, and diversity increased after breeding (P > 0.05). Seminal microbiota remained unaffected by the differential rates of gain, and its overall composition was distinct from fecal microbiota, with only 6% of the taxa shared between them. A total of 364 isolates from 49 different genera were recovered under aerobic and anaerobic culturing. Among these seminal isolates were pathogenic species and those resistant to several antibiotics. Overall, our results suggest that bovine semen harbors a rich and complex microbiota which changes over time and during the breeding season but appears to be resilient to differential gains achieved via a common diet. Seminal microbiota is distinct from the fecal microbiota and harbors potentially pathogenic and antibiotic-resistant bacterial species. IMPORTANCE Increasing evidence from human and other animal species supports the existence of a commensal microbiota in semen and that this seminal microbiota may influence not only sperm quality and fertility but also female reproduction. Seminal microbiota in bulls and its evolution and factors shaping this community, however, remain largely underexplored. In this study, we characterized the seminal microbiota of yearling beef bulls and its response to the bull age, different weight gains, and mating activity. We compared bacterial composition between seminal and fecal microbiota and evaluated the diversity of culturable seminal bacteria and their antimicrobial resistance. Our results obtained from sequencing, culturing, and antibiotic susceptibility testing provide novel information on the taxonomic composition, evolution, and factors shaping the seminal microbiota of yearling beef bulls. This information will serve as an important basis for further understanding of the seminal microbiome and its involvement in reproductive health and fertility in cattle.

Sequencing and culture-based characterization of the vaginal and uterine microbiota in beef cattle that became pregnant or remained open following artificial insemination.

IMPORTANCE: Emerging evidence suggests that microbiome-targeted approaches may provide a novel opportunity to reduce the incidence of reproductive failures in cattle. To develop such microbiome-based strategies, one of the first logical steps is to identify reproductive microbiome features related to fertility and to isolate the fertility-associated microbial species for developing a future bacterial consortium that could be administered before breeding to enhance pregnancy outcomes. Here, we characterized the vaginal and uterine microbiota in beef cattle that became pregnant or remained open via artificial insemination and identified microbiota features associated with fertility. We compared similarities between vaginal and uterine microbiota and between heifers and cows. Using culturing, we provided new insights into the culturable fraction of the vaginal and uterine microbiota and their antimicrobial resistance. Overall, our findings will serve as an important basis for future research aimed at harnessing the vaginal and uterine microbiome for improved cattle fertility.

Data Driven Computational Design and Experimental Validation of Drugs for Accelerated Mitigation of Pandemic-like Scenarios.

Emerging pathogens are a historic threat to public health and economic stability. Current trial-and-error approaches to identify new therapeutics are often ineffective due to their inefficient exploration of the enormous small molecule design space. Here, we present a data-driven computational framework composed of hybrid evolutionary algorithms for evolving functional groups on existing drugs to improve their binding affinity toward the main protease (Mpro) of SARS-CoV-2. We show that combinations of functional groups and sites are critical to design drugs with improved binding affinity, which can be easily achieved using our framework by exploring a fraction of the available search space. Atomistic simulations and experimental validation elucidate that enhanced and prolonged interactions between functionalized drugs and Mpro residues result in their improved therapeutic value over that of the parental compound. Overall, this novel framework is extremely flexible and has the potential to rapidly design inhibitors for any protein with available crystal structures.

Seminal and vagino-uterine microbiome and their individual and interactive effects on cattle fertility.

Reproductive failure is a major economical drain on cow-calf operations across the globe. It can occur in both males and females and stem from prenatal and postnatal influences. Therefore, the cattle industry has been making efforts to improve fertility and the pregnancy rate in cattle herds as an attempt to maintain sustainability and profitability of cattle production. Despite the advancements made in genetic selection, nutrition, and the implementation of various reproductive technologies, fertility rates have not significantly improved in the past 50 years. This signifies a missing factor or factors in current reproductive management practices that influence successful fertilization and pregnancy. Emerging lines of evidence derived from human and other animals including cattle suggest that the microbial continuum along the male and female reproductive tracts are associated with male and female fertility-that is, fertilization, implantation, and pregnancy success-highlighting the potential for harnessing the male and female reproductive microbiome to improve fertility in cattle. The objective of this narrative review is to provide an overview of the recent studies on the bovine seminal and vagino-uterine microbiome and discuss individual and interactive roles of these microbial communities in defining cattle fertility.

Bivalent single domain antibody constructs for effective neutralization of Venezuelan equine encephalitis.

Venezuelan equine encephalitis virus (VEEV) is a mosquito borne alphavirus which leads to high viremia in equines followed by lethal encephalitis and lateral spread to humans. In addition to naturally occurring outbreaks, VEEV is a potential biothreat agent with no approved human vaccine or therapeutic currently available. Single domain antibodies (sdAb), also known as nanobodies, have the potential to be effective therapeutic agents. Using an immune phage display library derived from a llama immunized with an equine vaccine that included inactivated VEEV, five sdAb sequence families were identified that showed varying ability to neutralize VEEV. One of the sequence families had been identified previously in selections against chikungunya virus, a related alphavirus of public health concern. A key advantage of sdAb is the ability to optimize properties such as neutralization capacity through protein engineering. Neutralization of VEEV was improved by two orders of magnitude by genetically linking sdAb. One of the bivalent constructs showed effective neutralization of both VEEV and chikungunya virus. Several of the bivalent constructs neutralized VEEV in cell-based assays with reductions in the number of plaques by 50% at protein concentrations of 1 ng/mL or lower, making future evaluation of their therapeutic potential compelling.

The negative appendectomy rate: who benefits from preoperative CT?

OBJECTIVE: The purpose of this article is to determine the negative appendectomy rates of patients who did and did not undergo preoperative CT and to determine, more specifically, whether men benefit from preoperative CT. MATERIALS AND METHODS: We identified 512 patients who had a nonincidental appendectomy between July 1, 2002, and June 30, 2007. Pathology records were compared with a radiology records search to determine which patients underwent preoperative CT. Proportions of patients were compared between groups using the Fisher exact test. RESULTS: Of 512 patients who had a nonincidental appendectomy, 465 (91%) underwent preoperative CT, and 47 (9%) underwent appendectomy only on the basis of clinical findings. Overall, 22 of 465 patients (4.7%) who underwent preoperative CT had a negative appendectomy compared with six of 47 patients who did not undergo preoperative imaging (negative appendectomy rate, 12.7%; p = 0.03). Among men, six of 237 (2.5%) with preoperative CT had a negative appendectomy, versus five of 42 without imaging (negative appendectomy rate, 11.9%; p = 0.01). CONCLUSION: The negative appendectomy rate was decreased for adult patients who underwent preoperative CT compared with patients who did not undergo preoperative imaging. Although most prior studies have suggested that CT is efficacious only in decreasing the negative appendectomy rate among women, we found that men benefit from CT as well.

T1 pseudohyperintensity on fat-suppressed magnetic resonance imaging: a potential diagnostic pitfall.

Magnetic resonance imaging findings in 2 patients with misleading T1 hyperintensity seen only on fat-suppressed images are presented; one with a renal cell carcinoma that was misinterpreted as a hemorrhagic cyst and the other with an ovarian serous cystadenocarcinoma that was misinterpreted as a complicated endometrioma. The apparent T1 hyperintensity on fat-suppressed images in these cases was likely due to varying perception of image signal dependent on local contrast, an optical effect known as the checker-shadow illusion. T1 pseudohyperintensity should be considered when apparently high T1 signal intensity is seen only on fat-suppressed images; review of non-fat-suppressed images may help prevent an erroneous diagnoses of blood-containing lesions.

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2.

SARS-CoV-2 emerged in 2019 as a devastating viral pathogen with no available preventative or treatment to control what led to the current global pandemic. The continued spread of the virus and increasing death toll necessitate the development of effective antiviral treatments to combat this virus. To this end, we evaluated a new class of organometallic complexes as potential antivirals. Our findings demonstrate that two pentamethylcyclopentadienyl (Cp*) rhodium piano stool complexes, Cp*Rh(1,3-dicyclohexylimidazol-2-ylidene)Cl2 (complex 2) and Cp*Rh(dipivaloylmethanato)Cl (complex 4), have direct virucidal activity against SARS-CoV-2. Subsequent in vitro testing suggests that complex 4 is the more stable and effective complex and demonstrates that both 2 and 4 have low toxicity in Vero E6 and Calu-3 cells. The results presented here highlight the potential application of organometallic complexes as antivirals and support further investigation into their activity.

Stabilization of a Broadly Neutralizing Anti-Chikungunya Virus Single Domain Antibody.

A single domain antibody (clone CC3) previously found to neutralize a vaccine strain of the chikungunya virus (PRNT50 = 2. 5 ng/mL) was found to be broadly neutralizing. Clone CC3 is not only able to neutralize a wild-type (WT) strain of chikungunya virus (CHIKV), but also neutralizes WT strains of Mayaro virus (MAYV) and Ross River virus (RRV); both arthralgic, Old World alphaviruses. Interestingly, CC3 also demonstrated a degree of neutralizing activity against the New World alphavirus, Venezuelan equine encephalitis virus (VEEV); albeit both the vaccine strain, TC-83, and the parental, WT Trinidad donkey strain had PRNT50 values ~1,000-fold higher than that of CHIKV. However, no neutralization activity was observed with Western equine encephalitis virus (WEEV). Ten CC3 variants designed to possess a range of isoelectric points, both higher and lower, were constructed. This approach successfully identified several lower pI mutants which possessed improved thermal stabilities by as much as 10°C over the original CC3 (Tm = 62°C), and excellent refolding abilities while maintaining their capacity to bind and neutralize CHIKV.

Visualization of renal medullary hyperattenuation at unenhanced CT: what is the effect of furosemide administration?

PURPOSE: To retrospectively investigate the effects of furosemide on the visualization of renal medullary hyperattenuation at unenhanced computed tomography (CT). MATERIALS AND METHODS: This retrospective single-institution study was HIPAA compliant and approved by the institutional review board; requirement for informed consent was waived. This study identified 289 consecutive patients (152 men, 137 women; mean age, 59 years) without ureteral obstruction who underwent unenhanced scanning as part of CT urography; of these, 178 patients did not receive intravenous furosemide prior to imaging and 111 did. The presence of renal medullary hyperattenuation, renal stones, and bladder urine attenuation levels were recorded and compared between patients who did not receive furosemide prior to imaging and those who did by using the chi(2) and unpaired Student t tests. A multiple logistic regression model was used to evaluate independent predictors of visualization of renal medullary hyperattenuation. RESULTS: Renal medullary hyperattenuation was seen less commonly in patients who received furosemide (27 of 111, 24%) than in those who did not receive furosemide prior to imaging (79 of 178, 44%, P = .001). Bladder urine attenuation was lower in patients who received furosemide (-0.1 HU) compared with those who did not (6.4 HU, P < .001). A multiple logistic regression model revealed independent associations between the visualization of renal medullary hyperattenuation and the absence of furosemide administration (P = .002), younger age (P < .001), and presence of renal stones (P = .047). CONCLUSION: Furosemide administration prior to unenhanced CT is associated with decreased visualization of renal medullary hyperattenuation.

Acute appendicitis: clinical outcome in patients with an initial false-positive CT diagnosis.

PURPOSE: To investigate the clinical outcome in patients with a diagnosis of appendicitis at computed tomography (CT) in whom treatment is deemed unnecessary after clinical evaluation. MATERIALS AND METHODS: After institutional review board approval, 2283 patients (856 men, 1427 women; mean age, 46 years; age range, 18-99 years) who underwent CT because they were suspected of having appendicitis between 2002 and 2007 were retrospectively identified. CT reports were reviewed, and the likelihood of appendicitis was assigned a score on a five-point scale: score 1, definitely absent; score 2, nonvisualized appendix with no secondary signs of inflammation; score 3, equivocal; score 4, probable; and score 5, definitely present. Diagnosis of appendicitis at CT was considered a false-positive result if the CT report was classified as probable or definite appendicitis but the patient was not treated within 4 days. Cases with false-positive results were reviewed by two readers blinded to patient outcome, supporting clinical data, and prospective scan interpretation, and a grade was assigned by using the same scale. Medical records were reviewed to determine outcomes. Descriptional statistics were used. RESULTS: Overall, 516 (23%) of 2283 patients had CT findings of probable or definite appendicitis. Thirteen (3%) of 516 patients did not receive immediate treatment for appendicitis. Of these, five (38%; 95% confidence interval: 18%, 65%) underwent later appendectomy with proved appendicitis after a mean interval of 118 days (range, 5-443 days). Seven (54%) of 13 patients never developed appendicitis across a mean follow-up of 583 days (range, 14-1460 days). One (8%) of 13 had a normal appendix at eventual surgery. CONCLUSION: Five of 13 patients with CT findings of appendicitis and reassuring clinical evaluation results in whom immediate treatment was deferred ultimately returned with appendicitis. In patients with CT results positive for appendicitis and benign or atypical clinical findings, a diagnosis of chronic or recurrent appendicitis may be considered.