The Benefits and Limitations of Targeted Training in Flexible Transnasal Laryngoscopy Diagnosis.

Importance: Targeted laryngoscopy training can be used successfully in de novo learners. Objective: To determine the value of targeted laryngoscopy education in interns. Design, Setting, and Participants: This prospective study of fiberoptic laryngoscopy interpretations enrolled 13 participants in an academic hospital setting from August 1 to December 31, 2015. Participants included 10 postgraduate year 1 emergency and otolaryngology interns and 3 board-certified otolaryngology attending physicians. Interventions: Participants viewed 25 selected and digitally recorded fiberoptic laryngoscopies and were asked to rate 13 items relating to abnormalities in the pharynx, hypopharynx, larynx, and subglottis; the level of concern; and confidence with the diagnosis. A laryngoscopy teaching video was then administered to the interns before rating a second set of 25 videos. Improvement in diagnosis and intraclass correlation coefficients (ICC) were calculated for each question and compared between the first and second administration. Main Outcomes and Measures: Improvement in correct diagnosis of abnormalities in recorded laryngoscopies. Results: All 13 participants completed the interventions. The ICCs for all questions were generally low for the intern groups and higher for the attending group. For vocal cord mobility, a preintervention ICC of 0.25 (95% CI, 0.16-0.37) improved to 0.47 (95% CI, 0.36-0.59) among interns after the intervention. The ICCs for vocal cord mobility were higher among attendings for the preintervention (0.89; 95% CI, 0.84-0.93) and postintervention (0.89; 95% CI, 0.83-0.93) assessments. Minimal improvement was observed in intern scores for base of tongue abnormalities, subglottic stenosis, vocal cord abnormalities, level of comfort, level of concern, pharyngeal abnormalities, or laryngeal, pharyngeal, and hypopharyngeal masses. Conclusions and Relevance: Learning of flexible laryngoscopy can be improved with the use of a teaching video; however, additional interventions are needed to attain competence in accurately diagnosing upper airway lesions. Clinicians who seek to perform flexible laryngoscopy require robust training.

Influence of adolescence and obesity on the rate of stillbirth.

BACKGROUND: We hypothesise that the rate of stillbirth is increased in mothers younger than 18 years of age compared to adult mothers, and that obesity further increases the risk of stillbirth in this population. METHODS: We conducted a population-based cohort study comparing rates of stillbirth between adolescent, defined as young women under the age of 18 and adult women. We then compared the rate of stillbirth in normal weight vs. obese adolescents. These effects were stratified according to gestational age. Log-binomial regression models were used to estimate the effect of adolescence and obesity on stillbirth risk while adjusting for important confounders. Risk ratios (RR) with 95% confidence intervals [CI]were calculated. RESULTS: We reviewed data from 650 760 births in Missouri between 1998 and 2005. Stillbirth rates were 6.7 and 4.1 per 1000 in adolescents and adult women, respectively (RR 1.2, 95% CI 1.03-1.5). A higher proportion of stillbirths occurred prior to 28 weeks in adolescents vs. adults (53% vs. 37% respectively, P = 0.002). The risk of stillbirth in obese adolescents was further increased over normal weight adolescents (adjusted RR [aRR] 1.7, 95% CI 1.02-2.9). CONCLUSION: Adolescent pregnancies, particularly obese adolescents, are at an increased risk of stillbirth.

Antineutrophil cytoplasmic antibodies reacting with human neutrophil elastase as a diagnostic marker for cocaine-induced midline destructive lesions but not autoimmune vasculitis.

OBJECTIVE: Human neutrophil elastase (HNE) and proteinase 3 (PR3) are structurally and functionally related. PR3 is the prominent target antigen for antineutrophil cytoplasmic antibodies (ANCAs) in Wegener's granulomatosis (WG). Reported frequencies of HNE ANCAs in WG and other autoimmune diseases range from 0% to 20%. We previously detected HNE ANCAs in patients with cocaine-induced midline destructive lesions (CIMDL). We tested the hypothesis that discrepancies in the reported frequencies of HNE ANCAs in patients with vasculitis may be related to differences in detection methods, and that HNE ANCA may be a marker for CIMDL. METHODS: HNE ANCA reactivity in 25 patients with CIMDL was characterized and compared with that in a control cohort of 604 consecutive patients (64 with WG, 14 with microscopic polyangiitis [MPA], and 526 others) and 45 healthy volunteers. HNE ANCAs were measured by indirect immunofluorescence using a previously undescribed expression system for recombinant HNE and by direct and capture enzyme-linked immunosorbent assays using purified native HNE as target antigen. RESULTS: Among patients with CIMDL, HNE ANCAs were detectable by 1 assay in 84%, by 2 assays in 68%, and by all 3 assays in 36%. Fifty-seven percent of HNE ANCA-positive CIMDL sera were also PR3 ANCA-positive by at least 1 assay. In contrast, only 8 (1.3%) of 604 control sera reacted with HNE in at least 1 assay, 3 (0.5%) reacted in 2 assays, and only 1 serum sample (0.16%) reacted in all 3 assays. Sera obtained from patients with WG or MPA were universally HNE ANCA-negative, as were sera obtained from healthy controls. CONCLUSION: Optimal sensitivity for HNE ANCA requires multimodality testing. HNE ANCAs are frequent in CIMDL but not in other autoimmune diseases, including classic ANCA-associated vasculitis. HNE ANCAs may discriminate between CIMDL and WG, whereas a positive test result for PR3 ANCA may not.

Different gender-associated genotype risks of Wegener's granulomatosis and microscopic polyangiitis.

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are systemic small vessel vasculitides associated with ANCA (AAV). Predominant Th1 and Th2 cytokine patterns have been reported for WG and MPA, respectively. Consequently, genotypes suppressing Th1 responses or augmenting Th2 responses may be more frequent in MPA than in WG. Transforming growth beta1 (TGF-beta1) and interleukin-10 (IL-10) genes may modify the course of vasculitis. Therefore, we investigated associations between genotype frequencies of functional polymorphisms of these cytokine genes and clinical manifestations in AAV. One hundred sixty-one AAV patients and 153 healthy blood donors were genotyped for the biallelic polymorphism in codon 25 of the TGF-beta1 gene and the biallelic polymorphism at position -1082 of the IL-10 gene. No difference was found for TGF-beta1 codon 25 polymorphism between control and patient groups. In contrast, a significant shift toward the homozygous AA genotype of the IL-10 (-1082) polymorphism was found in WG (25%, p<0.005) and MPA patients (39%; p<0.00001) compared to controls (10.5%). Furthermore, in MPA the AA homozygous genotype was significantly more frequent in females (62.5%) compared to males (20%, p<0.05). A contribution of the TGF-beta1 codon 25 polymorphism to the susceptibility-defining genetic backgrounds of AAV appears unlikely. In contrast, our findings suggest a role of the enhanced IL-10 (-1082) PM in WG and MPA with a significant gender difference in MPA.

Detection of anti-neutrophil cytoplasmic antibodies under actual clinical testing conditions.

Anti-neutrophil cytoplasmic antibodies (ANCA) are a useful diagnostic tool for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). To maximize diagnostic utility, current guidelines recommend dual testing by standard indirect immunofluorescence (IIF) and target antigen-specific assays. Most published data come from specialized research laboratories, not reflecting the performance of assays under routine clinical conditions. Therefore, we compared the performance of standard IIF, PR3-, and MPO-ANCA-specific direct ELISA, and a PR3-ANCA-specific capture ELISA used alone and in combination under routine clinical conditions. Consecutive serum samples (615) submitted for routine ANCA testing over a 10-month period were assayed. Diagnoses were WG/MPA (n = 86), other autoimmune disease (n = 118), and various others (n = 411). The combination of PR3-ANCA and MPO-ANCA ELISA had the highest sensitivity (72.1%), and C-ANCA determination using IIF, the highest specificity (99.6%). While maintaining maximal diagnostic accuracy, significant labor savings are achieved by screening for WG/MPA by ELISA followed by confirmatory IIF.