Recent Publications by CFE Educators

OBJECTIVE

There are no validated tools for measuring disease activity in pediatric vasculitis. The Birmingham Vasculitis Activity Score (BVAS) is a valid disease activity tool in adult vasculitis. Version 3 (BVAS v.3) correlates well with physician's global assessment (PGA), treatment decision, and C-reactive protein in adults. The utility of BVAS v.3 in pediatric vasculitis is not known. We assessed the association of BVAS v.3 scores with PGA, treatment decision, and erythrocyte sedimentation rate (ESR) at diagnosis in pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

METHODS

Children with AAV diagnosed between 2004 and 2010 at all ARChiVe centers were eligible. BVAS v.3 scores were calculated with a standardized online tool (www.vasculitis.org). Spearman's rank correlation coefficient (r(s)) was used to test the strength of association between BVAS v.3 and PGA, treatment decision, and ESR.

RESULTS

A total of 152 patients were included. The physician diagnosis of these patients was predominantly granulomatosis with polyangiitis (n = 99). The median BVAS v.3 score was 18.0 (range 0-40). The BVAS v.3 correlations were r(s) = 0.379 (95% CI 0.233 to 0.509) with PGA, r(s) = 0.521 (95% CI 0.393 to 0.629) with treatment decision, and r(s) = 0.403 (95% CI 0.253 to 0.533) with ESR.

CONCLUSION

Applied to children with AAV, BVAS v.3 had a weak correlation with PGA and moderate correlation with both ESR and treatment decision. Prospective evaluation of BVAS v.3 and/or pediatric-specific modifications to BVAS v.3 may be required before it can be formalized as a disease activity assessment tool in pediatric AAV.

AIMS

  The BRAF V600E mutation resulting in the production of an abnormal BRAF protein has emerged as the most frequent genetic alteration in papillary thyroid carcinomas (PTCs). This study was aimed at identifying distinctive features in tumours with and without the mutation.

METHODS AND RESULTS

  Thirty-four mutation-positive and 22 mutation-negative tumours were identified by single-strand conformation polymorphism of the amplified BRAF V600E region in the tumour DNA. Mutation-positive tumours were more common in patients older than 45 years (24/33, P = 0.05), in classic (23/30, P = 0.01), tall cell (4/5) and oncocytic/Warthin-like (2/2) variants of PTC, and in subcapsular sclerosing microcarcinomas (4/4). In contrast, all 12 follicular variants (P  0.0001) and two diffuse sclerosing variants were negative for the mutation. Mutation-positive tumours displayed infiltrative growth (32/34, P = 0.02), stromal fibrosis (33/34, P  0.001), psammoma bodies (17/34, P = 0.05), plump eosinophilic tumour cells (22/34, P = 0.01), and classic fully developed nuclear features of PTC (33/34, P = 0.0001). Encapsulation was significantly associated with mutation-negative tumours (15/22, P = 0.02).

CONCLUSIONS

  BRAF V600E mutation-positive and negative PTCs are morphologically different. Recognition of their morphology may help in the selection of appropriate tumours for genetic testing.

OBJECT

Spinal dural arteriovenous fistulas (SDAVFs) cause myelopathy through arterialization of the perimedullary venous plexus and venous congestion of the spinal cord. The authors hypothesized that the craniocaudal extent of engorgement of intrathecal draining veins between the fistula site and the point of drainage out of the thecal sac correlates with the degree of myelopathy.

METHODS

A retrospective review of the authors' institution's radiology databases identified 31 patients with SDAVFs who had undergone digital subtraction angiography (DSA) and MRI examinations of the spine. The authors counted the number of vertebral body levels of spinal cord enhancement and intrathecal vessel enhancement on T1-weighted postcontrast MRI studies. They also counted the number of levels of cord hyperintensity and intrathecal flow voids on T2-weighted MRI studies. On DSA, the authors identified the number of vertebral body levels of dilated intrathecal draining veins and outflow points from intrathecal veins to epidural veins. Functional status of the patients at the time of diagnosis was assessed using the Aminoff-Logue scale (ALS).

RESULTS

Enlargement of the intrathecal draining veins averaged 10 ± 7.7 spinal levels on DSA. Patients with enlarged draining veins extending 10 or more spinal levels on DSA had worse ALS scores (mean gait 3.4, mean micturition 1.5) than patients with draining veins extending fewer than 10 levels (mean gait 1.8, mean micturition 0.6; p = 0.009 and 0.02, respectively). The number of vertebral body levels of enlarged draining veins correlated with the ALS score (gait r = 0.42, p = 0.009; and micturition r = 0.55, p = 0.0006). More extensive enlarged draining veins were associated with more spinal cord T2 hyperintensity, T2 intrathecal flow voids, and T1 vessel enhancement but not cord enhancement.

CONCLUSIONS

The craniocaudal extent of enlarged intrathecal veins draining SDAVF correlates with patient functional status, providing further insight into the pathophysiology of venous hypertensive myelopathy.

OBJECTIVES

Blood transfusion has been shown to have deleterious effect on lung cancer survival, but little data are available that assess whether leukocyte-depleted (LD) blood has a similar adverse effect. Our institution has been using LD red cells since 2001. We sought to determine whether LD blood has an effect on survival after resection of early-stage lung cancer.

METHODS

From a prospective database, we evaluated all patients with pathologic stage I non-small cell lung cancer. Patients receiving LD blood were compared with those receiving no transfusion. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis by Cox regression was used to identify independent risk factors affecting survival.

RESULTS

From 2001 to 2009, 361 patients were evaluated; 63 received LD red cell cell transfusion and 298 received no transfusion. Median follow-up was 48 months. Disease-free survival (P .001) and overall survival (P .001) were worse in patients receiving LD blood. Stratifying for stage, disease-free survival continued to be worse with transfusion for stage IA (P = .002) and IB (P = .002). Similarly, overall survival continued to be worse with transfusion for stage IA (P .001) and IB (P .001). For disease-free and overall survival, univariate analysis revealed increased age, male gender, anemia, transfusion, and higher stage to be adverse factors, with transfusion and higher stage continuing to be significant adverse factors after multivariate analysis.

CONCLUSIONS

Our data suggest that transfusion of LD blood is associated with a worse disease-free and overall survival in patients with resected stage I non-small cell lung cancer.

BACKGROUND

The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury).

METHODS AND RESULTS

We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury.

CONCLUSION

Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.

CONTEXT

The amount of enteral nutrition patients with acute lung injury need is unknown.

OBJECTIVE

To determine if initial lower-volume trophic enteral feeding would increase ventilator-free days and decrease gastrointestinal intolerances compared with initial full enteral feeding.

DESIGN, SETTING, AND PARTICIPANTS

The EDEN study, a randomized, open-label, multicenter trial conducted from January 2, 2008, through April 12, 2011. Participants were 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation whose physicians intended to start enteral nutrition at 44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network.

INTERVENTIONS

Participants were randomized to receive either trophic or full enteral feeding for the first 6 days. After day 6, the care of all patients who were still receiving mechanical ventilation was managed according to the full feeding protocol.

MAIN OUTCOME MEASURES

Ventilator-free days to study day 28.

RESULTS

Baseline characteristics were similar between the trophic-feeding (n = 508) and full-feeding (n = 492) groups. The full-feeding group received more enteral calories for the first 6 days, about 1300 kcal/d compared with 400 kcal/d (P .001). Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, -0.1 [95% CI, -1.4 to 1.2]; P = .89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, -4.1% to 6.3%]; P = .77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting (2.2% vs 1.7% of patient feeding days; P = .05), elevated gastric residual volumes (4.9% vs 2.2% of feeding days; P .001), and constipation (3.1% vs 2.1% of feeding days; P = .003). Mean plasma glucose values and average hourly insulin administration were both higher in the full-feeding group over the first 6 days.

CONCLUSION

In patients with acute lung injury, compared with full enteral feeding, a strategy of initial trophic enteral feeding for up to 6 days did not improve ventilator-free days, 60-day mortality, or infectious complications but was associated with less gastrointestinal intolerance.

TRIAL REGISTRATION

clinicaltrials.gov Identifiers: NCT00609180 and NCT00883948.