Recent Publications by CFE Educators

OBJECTIVE AND BACKGROUND

Spinal arteriovenous fistula (SAVF) is a rare but treatable cause of myelopathy. The diagnostic accuracy of MRI for detecting SAVF is unknown. Our objective was to determine the sensitivity and specificity of MRI in the diagnosis SAVF and characterize its radiographic features.

METHODS

We conducted a retrospective case-control study of all SAVF treated at our institution from 1995 to 2010, including patients who presented with myelopathy, had MRIs available for review, and underwent either spinal angiogram or had another diagnosis confirming test. Two blinded board-certified radiologists reviewed a series of MRIs and listed the most likely diagnoses, radiologic findings, and recommended follow-up. Sensitivities and specificities of MRI compared to spinal angiogram were calculated. We additionally conducted a literature review of cases describing MRI findings in spinal dural and perimedullary arteriovenous fistula.

RESULTS

We identified 36 cases of SAVF (median age 56, 67% male) and 32 controls (median age 54, 44% male). MRI was sensitive in identifying SAVF as the primary diagnosis in 94% (radiologist A, 95% confidence interval [CI] 0.87-1.02) and 89% (radiologist B, 95% CI 0.79-0.99) of cases. The sensitivity of spinal cord T2 hyperintensity or flow voids was 100% and the specificity of T2 hyperintensity and flow voids was 97%.

CONCLUSIONS

Among patients with myelopathy, spinal angiography is mandatory in the presence of both T2 hyperintensity and flow voids but may be unnecessary if both of these findings are absent.

BACKGROUND & AIMS

Almost all colorectal polyps ≤ 5 mm are benign, yet current practice requires costly pathologic analysis. We aimed to develop and evaluate the validity of a simple narrow-band imaging (NBI)-based classification system for differentiating hyperplastic from adenomatous polyps.

METHODS

The study was conducted in 4 phases: (1) evaluation of accuracy and reliability of histologic prediction by NBI-experienced colonoscopists; (2) development of a classification based on color, vessels, and surface pattern criteria, using a modified Delphi method; (3) validation of the component criteria by people not experienced in endoscopy or NBI analysis (25 medical students, 19 gastroenterology fellows) using 118 high-definition colorectal polyp images of known histology; and (4) validation of the classification system by NBI-trained gastroenterology fellows, using still images. We performed a pilot evaluation during real-time colonoscopy.

RESULTS

We developed a classification system for the endoscopic diagnosis of colorectal polyp histology and established its predictive validity. When all 3 criteria were used, the specificity ranged from 94.9% to 100% and the combined sensitivity ranged from 8.5% to 61.0%. The specificities of the individual criteria were lower although the sensitivities were higher. During real-time colonoscopy, endoscopists made diagnoses with high confidence for 75% of consecutive small colorectal polyps, with 89% accuracy, 98% sensitivity, and 95% negative predictive values.

CONCLUSIONS

We developed and established the validity of an NBI classification system that can be used to diagnose colorectal polyps. In preliminary real-time evaluation, the system allowed endoscopic diagnoses of colorectal polyp histology.

OBJECTIVE

Granulomatosis with polyangiitis (Wegener's; GPA) and other antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare in childhood and are sometimes difficult to discriminate. We compared use of adult-derived classification schemes for GPA against validated pediatric criteria in the ARChiVe (A Registry for Childhood Vasculitis e-entry) cohort, a Childhood Arthritis and Rheumatology Research Alliance initiative.

METHODS

Time-of-diagnosis data for children with physician (MD) diagnosis of AAV and unclassified vasculitis (UCV) from 33 US/Canadian centers were analyzed. The European Medicines Agency (EMA) classification algorithm and European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) and American College of Rheumatology (ACR) criteria for GPA were applied to all patients. Sensitivity and specificity were calculated (MD-diagnosis as reference).

RESULTS

MD-diagnoses for 155 children were 100 GPA, 25 microscopic polyangiitis (MPA), 6 ANCA-positive pauciimmune glomerulonephritis, 3 Churg-Strauss syndrome, and 21 UCV. Of these, 114 had GPA as defined by EMA, 98 by EULAR/PRINTO/PRES, and 87 by ACR. Fourteen patients were identified as GPA by EULAR/PRINTO/PRES but not by ACR; 3 were identified as GPA by ACR but not EULAR/PRINTO/PRES. Using the EMA algorithm, 135 (87%) children were classifiable. The sensitivity of the EMA algorithm, the EULAR/PRINTO/PRES, and ACR criteria for classifying GPA was 90%, 77%, and 69%, respectively, with specificities of 56%, 62%, and 67%. The relatively poor sensitivity of the 2 criteria related to their inability to discriminate patients with MPA.

CONCLUSION

EULAR/PRINTO/PRES was more sensitive than ACR criteria in classifying pediatric GPA. Neither classification system has criteria for MPA; therefore usefulness in discriminating patients in ARChiVe was limited. Even when using the most sensitive EMA algorithm, many children remained unclassified.

Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. To explore how these changes interact with lentiviral infections in vivo, animals from two nonhuman primate species (African green monkeys and pigtailed macaques) were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g. lymph node, colon, cerebrospinal fluid, and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an interorgan, interindividual, and interspecies basis. In both species, morphine was associated with decreased levels of Ki-67(+) T-cell activation but with only minimal changes in overall T-cell counts, neutrophil counts, and NK cell counts. Although changes in T-cell maturation were observed, these varied across the various tissue/fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in lymph nodes, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have direct relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the potential interplay between opioid abuse and the immunological response to an infective agent.

Research on the prevalence of pediatric-specific tuberculosis (TB) diagnostics in sub-Saharan Africa is scarce. We assessed the availability of pediatric TB diagnostic tests at 651 pediatric human immunodeficiency virus care and treatment sites across nine African countries: 54% of the sites had access to sputum culture capacity and 51% to chest X-ray services. While 87% of sites had access to smear microscopy, only 6% had the capacity to perform sputum induction and 5% to perform gastric aspirate. These findings confirm that diagnostic resources for the accurate diagnosis of pediatric TB are limited. Capacity-building initiatives to improve sputum collection in children are urgently required.

Since the first biologic agent was tested in the treatment of ankylosing spondylitis (AS), the ability of these therapies to dramatically improve the clinical symptoms and signs of the disease was very evident. Over the past decade, 4 tumor necrosis factor-alpha inhibitors have been approved by the Food and Drug Administration for the treatment of AS. Published data include randomized controlled trials, registries and observational studies. Guidelines have also been developed for the use of biologics in AS. Although a lot is known about the use of biologics in the AS, several "unknowns" remain. Whether these agents can alter the natural history of AS if started very early in the course or whether they can prevent extra-articular manifestations are among the important unanswered questions. Most of the data summarized in this review relate to tumor necrosis factor-alpha inhibitors, and other biologic agents that have been studied are included, as well. This review also summarizes what questions remain about the use of biologics in AS and what type of studies will be required to answer them.

OBJECTIVE

Several genetic risk variants for ankylosing spondylitis (AS) have been identified in genome-wide association studies. Our objective was to examine whether familial AS cases have a higher genetic load of these susceptibility variants.

METHODS

Overall, 502 AS patients were examined, consisting of 312 patients who had first-degree relatives (FDRs) with AS (familial) and 190 patients who had no FDRs with AS or spondylarthritis (sporadic). All patients and affected FDRs fulfilled the modified New York criteria for AS. The patients were recruited from 2 US cohorts (the North American Spondylitis Consortium and the Prospective Study of Outcomes in Ankylosing Spondylitis) and from the UK-Oxford cohort. The frequencies of AS susceptibility loci in IL-23R, IL1R2, ANTXR2, ERAP-1, 2 intergenic regions on chromosomes 2p15 and 21q22, and HLA-B27 status as determined by the tag single-nucleotide polymorphism (SNP) rs4349859 were compared between familial and sporadic cases of AS. Association between SNPs and multiplex status was assessed by logistic regression controlling for sibship size.

RESULTS

HLA-B27 was significantly more prevalent in familial than sporadic cases of AS (odds ratio 4.44 [95% confidence interval 2.06, 9.55], P = 0.0001). Furthermore, the AS risk allele at chromosome 21q22 intergenic region showed a trend toward higher frequency in the multiplex cases (P = 0.08). The frequency of the other AS risk variants did not differ significantly between familial and sporadic cases, either individually or combined.

CONCLUSION

HLA-B27 is more prevalent in familial than sporadic cases of AS, demonstrating higher familial aggregation of AS in patients with HLA-B27 positivity. The frequency of the recently described non-major histocompatibility complex susceptibility loci is not markedly different between the sporadic and familial cases of AS.