Tracheal size variability is associated with sex: implications for endotracheal tube selection.

PURPOSE: Whereas selection of endotracheal tube (ETT) size in pediatric patients benefits from predictive nomograms, adult ETT sizing is relatively arbitrary. We sought to determine associations between cervical tracheal cross-sectional area (CTCSA) and clinical variables. METHODS: One hundred thirty-two consecutive patients undergoing noncontrasted chest computed tomography (CT) at a single tertiary care institution from January 2010 to June 2011 were reviewed. Patients with improper CT technique, endotracheal intubation, and pulmonary/tracheal pathology were excluded. Tracheal luminal diameters in anteroposterior (D1) and transverse (D2) were measured 2 cm inferior to the cricoid and used to determine CTCSA = π*D1*D2*». The demographic variables of age, height, weight, and body mass index (BMI) were tested for association with CTCSA by Spearman correlation. Wilcoxon rank-sum test was used to compare CTCSA by race and sex. Multivariate linear regression was performed including all clinical variables. RESULTS: There were 91 patients who met inclusion criteria. There was no correlation between age, weight, or BMI and CTCSA. There was a significant positive correlation between patient height and CTCSA (P = .001, R = 0.35); however, this was confounded by sex. Female patients had significantly smaller CTCSA (mean = 241 mm(2)) compared to male patients (mean = 349 mm(2), P < .001). Multivariate linear regression stratified by sex revealed that height is correlated with CTCSA only in males (P = .028). Males also had more variability in CTCSA (SD 118.6) compared to females (SD 65.5). CONCLUSION: Our data suggest that selection of ETT size in male patients should include height as a predictive factor. For female patients, it may be appropriate to select a uniformly smaller diameter ETT size.

Microdebrider complications in laryngologic and airway surgery.

OBJECTIVES/HYPOTHESIS: There is a paucity of experience in the published literature documenting complications of powered surgical instruments in laryngologic surgery. Our objective was to ascertain the nature of these complications from expert opinion and review of the literature, and to recommend strategies to decrease major complications. STUDY DESIGN: Review of the literature and an e-mail survey. METHODS: A literature review of microdebrider complications in laryngologic surgery was conducted using PubMed and Ovid (1985 to 2013), along with an analysis of a confidential e-mail survey of various surgeons in selected high-volume laryngologic centers. RESULTS: Powered instrumentation is frequently used in the operating room for larynx and airway surgery. The microdebrider can improve efficiency, lower costs, and shorten operative times. However, use of the microdebrider has the potential for serious complications in the larynx and airway. Great care must be taken when utilizing the microdebrider in laryngologic surgery. Significant complications including major vocal fold scar, airway compromise, severe hemorrhage, and unintentional tissue loss have occurred. CONCLUSIONS: The microdebrider is a popular and valuable tool for the otolaryngologist. A thorough knowledge of the instrument and its potential complications will improve surgical outcomes and may prevent complications. Awareness of the risks and surgeon experience with use of the microdebrider will allow the surgeon to successfully utilize this device in a safe and effective manner. LEVEL OF EVIDENCE: 5.

Patient and physician views on providing cancer patient-specific survival information.

OBJECTIVES/HYPOTHESIS: To gather input regarding the presentation, content, and understanding of survival and support information for Prognostigram, a computer-based program that uses standard cancer registry data elements to present individualized survival estimates. STUDY DESIGN: Cross-sectional survey research. METHODS: Two groups of patients (total n=40) and one group of physicians (n=5) were interviewed. The patient groups were interviewed to assess baseline patient numeracy and health literacy, and patient desire for prognostic information. The first group (n=20) was introduced to generalized survival curves in a paper booklet. The second group (n=20) was introduced to individualized survival curves from Prognostigram on the computer. Both patient groups were queried about the survival curves. The physicians were asked their opinions on sharing prognostic information with patients. RESULTS: Numeracy assessments indicated that the patients are able to understand concepts and statistics presented by Prognostigram. According to the patient interviews, the Internet is the most frequent source for survival statistics. Of the 40 patient participants, 39 reported survival statistics as being somewhat or very useful to cancer patients. All five physicians believed survival statistics were useful to patients and physicians, and noted accurate and understandable survival statistics are fundamental to facilitate discussions with patients regarding prognosis and expectations. CONCLUSIONS: Formative research indicates that cancer patients and their families actively seek survival statistics on their own. All patients indicated strong interest in Prognostigram, which is a software tool designed to produce individualized survival statistics to oncologists and cancer patients in a user-friendly manner. LEVEL OF EVIDENCE: 4.

Functional connectivity during modulation of tinnitus with orofacial maneuvers.

OBJECTIVE: To determine changes in cortical neural networks as defined by resting-state functional connectivity magnetic resonance imaging during voluntary modulation of tinnitus with orofacial maneuvers. STUDY DESIGN: Cross-sectional study. SETTING: Academic medical center. SUBJECTS AND METHODS: Participants were scanned during the maneuver and also at baseline to serve as their own control. The authors chose, a priori, 58 seed regions to evaluate previously described cortical neural networks by computing temporal correlations between all seed region pairs. Seed regions whose correlations significantly differed between rest and maneuver (P < .05, uncorrected) entered into a second-stage analysis of computing the correlation coefficient between the seed region and time courses in each of the remaining brain voxels. A threshold-free cluster enhancement permutation analysis evaluated the distribution of these correlation coefficients after transformation to Fisher z scores and registration to a surface-based reconstruction using Freesurfer. RESULTS: The median age for the 16 subjects was 54 years (range, 27-72 years), and all had subjective, unilateral or bilateral, nonpulsatile tinnitus for 6 months or longer. In 9 subjects who could voluntarily increase the loudness of their tinnitus, there were no significant differences in functional connectivity in any cortical networks. A separate analysis evaluated results from 3 patients who decreased the loudness of their tinnitus. Four subjects were excluded because of excessive motion in the scanner. CONCLUSION: The absence of significant differences in functional connectivity due to voluntary orofacial maneuvers that increased tinnitus loudness failed to confirm prior reports of altered cerebral blood flows during somatomotor behaviors.

The role of T helper cell differentiation in promoting nerve allograft survival with costimulation blockade.

OBJECT: Peripheral nerve allografts provide a temporary scaffold for host nerve regeneration and allow for the repair of significant segmental nerve injuries. Despite this potential, nerve allograft transplantation requires temporary systemic immunosuppression. Characterization of the immunological mechanisms involved in the induction of immune hyporesponsiveness to prevent nerve allograft rejection will help provide a basis for optimizing immunomodulation regimens or manipulating donor nerve allografts to minimize or eliminate the need for global immunosuppression. METHODS: The authors used C57Bl/6 mice and STAT4 and STAT6 gene BALB/c knockout mice. A nonvascularized nerve allograft was used to reconstruct a 1-cm sciatic nerve gap in the murine model. A triple costimulatory blockade of the CD40, CD28/B7, and inducible costimulatory (ICOS) pathways was used. Quantitative assessment was performed at 3 weeks with nerve histomorphometry, walking track analysis, and the enzyme-linked immunospot assay. RESULTS: The STAT6 -/- mice received 3 doses of costimulation-blocking antibodies and had axonal regeneration equivalent to nerve isografts, while treated STAT4 -/- mice demonstrated moderate axonal regeneration but inferior to the T helper cell Type 2-deficient animals. Enzyme-linked immunospot assay analysis demonstrated a minimal immune response in both STAT4 -/- and STAT6 -/- mice treated with a costimulatory blockade. CONCLUSIONS: The authors' findings suggest that Type 1 T helper cells may play a more significant role in costimulatory blockade-induced immune hyporesponsiveness in the nerve allograft model, and that Type 2 T helper differentation may represent a potential target for directed immunosuppression.

Transgenic models of nerve repair and nerve regeneration.

OBJECTIVE: The mainstays of peripheral nerve research have historically involved quantifying nerve regeneration by the staining of fixed specimens at multiple time points and by assessing the function of innervated targets. We review advances in transgenic techniques that significantly improve upon standard nerve imaging. METHODS: The emergence of transgenic mice whose axons or Schwann cells constitutively express chromophores and techniques enabling direct visualization of nerve regeneration over time after a nerve injury are evaluated. RESULTS: These techniques have enabled investigators to monitor the behaviors of single axons after injury over time. DISCUSSION: Transgenic tools that overexpress proteins or desired factors at certain targets are available, thus circumventing methodological difficulties in drug delivery, maintenance of constant neurotrophic factor concentrations and the comorbidities associated with achieving these aims. In this chapter, we will outline the advancements made in peripheral nerve research using transgenic mouse models. We focus on transgenic tools that have fluorescing nervous system components, overexpress factors at desired targets, or knockout mice with hereditable or modifiable deficits.

Ecthyma gangrenosum: a rare cutaneous manifestation of a potentially fatal disease.

Ecthyma gangrenosum is a cutaneous lesion frequently associated with Pseudomonas aeruginosa bacteremia, although it may develop in the absence of bacteremia and may originate from other bacterial and fungal organisms. Ecthyma gangrenosum most often occurs in patients with neutropenia and other immunocompromised hosts. It typically occurs on the extremities and gluteal and perineal regions. We report a rare case of ecthyma gangrenosum presenting as an aggressive necrotic skin lesion on the nasal ala of a patient with myelofibrosis. Tissue and blood cultures were positive for P aeruginosa. This clinical entity should be considered when otolaryngologists are asked to evaluate necrotic cutaneous lesions of the head and neck.

Binding and functional comparisons of two types of tumor necrosis factor antagonists.

Two tumor necrosis factor (TNF) antagonists infliximab (a chimeric monoclonal antibody) and etanercept (a p75 TNF receptor/Fc fusion protein) have been approved for treatment of rheumatoid arthritis. However, these agents have shown different degrees of clinical benefit in controlled clinical trials in other TNF-mediated diseases such as Crohn's disease (CD) and psoriasis. We investigated whether structural differences between these two antagonists translate into different binding and functional characteristics. To study the binding of infliximab and etanercept to both the soluble and cell-surface transmembrane forms of TNF, a variety of in vitro binding and cell-based assays were performed. Binding assays using (125)I-labeled TNF showed that infliximab binds to both monomer and trimer forms of soluble TNF (sTNF), whereas etanercept binding is restricted to the trimer form. Infliximab formed stable complexes with sTNF, whereas etanercept formed relatively unstable complexes, resulting in release of dissociated TNF. KYM-1D4 cell killing assays and human umbilical vein endothelial cell activation assays demonstrated that TNF that had dissociated from etanercept was bioactive. Infliximab also formed more stable complexes with the transmembrane form of TNF expressed on transfected cells relative to analogous complexes formed with etanercept. Additionally, more infliximab molecules bound to the transmembrane TNF with higher avidity than etanercept. Although both infliximab and etanercept inhibited transmembrane TNF-mediated activation of human endothelial cells, infliximab was significantly more effective. The differences between infliximab and etanercept in their TNF binding characteristics may help explain their differential efficacy in CD and psoriasis clinical trials.

Effect of anti-tumor necrosis factor-alpha polyclonal antibody on restenosis after balloon angioplasty in a rabbit atherosclerotic model.

Inflammation has been postulated to contribute to restenosis after balloon angioplasty. Tumor necrosis factor (TNF)-alpha is a pleiotropic proinflammatory cytokine involved in many features of inflammation. We examined the tissue expression pattern of TNF-alpha and the inflammatory response to arterial injury, and the effects of a goat anti-rabbit-TNF-alpha polyclonal antibody on tissue TNF-alpha expression, inflammation and restenosis in a rabbit atherosclerotic model. At different time points following air dessication and subsequent balloon injury, fresh rabbit femoral artery tissues were homogenized and analyzed for TNF-alpha levels by quantitative TNF-alpha bioassay. Rabbits were treated with a goat anti-rabbit-TNF-alpha polyclonal antibody, Serum and tissue TNF-alpha neutralization, macrophage infiltration (as an indicator of inflammation), and neointimal areas were determined. Balloon angioplasty increased tissue TNF-alpha expression 100000-fold over baseline, and this increase persisted over 6 days after arterial injury, serum anti-TNF-alpha antibody levels were sufficient to neutralize tissue TNF-alpha activity by 60-75%, macrophage infiltration was suppressed, but did not decrease the neointimal formation. These data indicate that tissue TNF-alpha levels were markedly increased after balloon angioplasty. Anti-TNF-alpha treatment was sufficient to neutralize tissue TNF-alpha activity, reduce inflammation, but did not inhibit neointimal formation following balloon angioplasty in a rabbit atherosclerotic model.