Ara A. Chalian

Clinical practice guideline: benign paroxysmal positional vertigo.

Objectives: This guideline provides evidence-based recommendations on managing benign paroxysmal positional vertigo (BPPV), which is the most common vestibular disorder in adults, with a lifetime prevalence of 2.4 percent. The guideline targets patients aged 18 years or older with a potential diagnosis of BPPV, evaluated in any setting in which an adult with BPPV would be identified, monitored, or managed. This guideline is intended for all clinicians who are likely to diagnose and manage adults with BPPV. Purpose: The primary purposes of this guideline are to improve quality of care and outcomes for BPPV by improving the accurate and efficient diagnosis of BPPV, reducing the inappropriate use of vestibular suppressant medications, decreasing the inappropriate use of ancillary tests such as radiographic imaging and vestibular testing, and to promote the use of effective repositioning maneuvers for treatment. In creating this guideline, the American Academy of Otolaryngology—Head and Neck Surgery Foundation selected a panel representing the fields of audiology, chiropractic medicine, emergency medicine, family medicine, geriatric medicine, internal medicine, neurology, nursing, otolaryngology–head and neck surgery, physical therapy, and physical medicine and rehabilitation. Results The panel made strong recommendations that 1) clinicians should diagnose posterior semicircular canal BPPV when vertigo associated with nystagmus is provoked by the Dix-Hallpike maneuver. The panel made recommendations against 1) radiographic imaging, vestibular testing, or both in patients diagnosed with BPPV, unless the diagnosis is uncertain or there are additional symptoms or signs unrelated to BPPV that warrant testing; and 2) routinely treating BPPV with vestibular suppressant medications such as antihistamines or benzodiazepines. The panel made recommendations that 1) if the patient has a history compatible with BPPV and the Dix-Hallpike test is negative, clinicians should perform a supine roll test to assess for lateral semicircular canal BPPV; 2) clinicians should differentiate BPPV from other causes of imbalance, dizziness, and vertigo; 3) clinicians should question patients with BPPV for factors that modify management including impaired mobility or balance, CNS disorders, lack of home support, and increased risk for falling; 4) clinicians should treat patients with posterior canal BPPV with a particle repositioning maneuver (PRM); 5) clinicians should reassess patients within 1 month after an initial period of observation or treatment to confirm symptom resolution; 6) clinicians should evaluate patients with BPPV who are initial treatment failures for persistent BPPV or underlying peripheral vestibular or CNS disorders; and 7) clinicians should counsel patients regarding the impact of BPPV on their safety, the potential for disease recurrence, and the importance of follow-up. The panel offered as options that 1) clinicians may offer vestibular rehabilitation, either self-administered or with a clinician, for the initial treatment of BPPV and 2) clinicians may offer observation as initial management for patients with BPPV and with assurance of follow-up. The panel made no recommendation concerning audiometric testing in patients diagnosed with BPPV. Disclaimer: This clinical practice guideline is not intended as a sole source of guidance in managing benign paroxysmal positional vertigo. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. The guideline is not intended to replace clinical judgement or establish a protocol for all individuals with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem. ® 2008 American Academy of Otolaryngology–Head and Neck Surgery Foundation. All rights reserved.

Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens

Immunization with nucleic acids has been shown to induce both antigen‐specific cellular and humoral immune responses in vivo. We hypothesize that immunization with DNA could be enhanced by directing specific immune responses induced by the vaccine based on the differential correlates of protection known for a particular pathogen. Recently we and others reported that specific immune responses generated by DNA vaccine could be modulated by co‐delivery of gene expression cassettes encoding for IL‐12, granulocyte‐macrophage colony‐stimulating factor and the co‐stimulatory molecule CD86. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses following the co‐delivery of pro‐inflammatory cytokine (IL‐1α, TNF‐α, and TNF‐β), Th1 cytokine (IL‐2, IL‐12, IL‐15, and IL‐18), and Th2 cytokine (IL‐4, IL‐5 and IL‐10) genes. We observed enhancement of antigen‐specific humoral response with the co‐delivery of Th2 cytokine genes IL‐4, IL‐5, and IL‐10 as well as those of IL‐2 and IL‐18. A dramatic increase in antigen‐specific T helper cell proliferation was seen with IL‐2 and TNF‐α gene co‐injections. In addition, we observed a significant enhancement of the cytotoxic response with the co‐administration of TNF‐α and IL‐15 genes with HIV‐1 DNA immunogens. These increases in CTL response were both MHC class I restricted and CD8+ T cell dependent. Together with earlier reports on the utility of co‐immunizing using immunologically important molecules together with DNA immunogens, we demonstrate the potential of this strategy as an important tool for the development of more rationally designed vaccines.

CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines.

The potential roles of CD8(+) T-cell-induced chemokines in the expansion of immune responses were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the alpha-chemokines IL-8 and SDF-1alpha and the beta-chemokines MIP-1alpha, RANTES, and MCP-1 along with DNA immunogens and analyzed the resulting antigen-specific immune responses. In a manner more similar to the traditional immune modulatory role of CD4(+) T cells via the expression of Th1 or Th2 cytokines, CD8(+) T cells appeared to play an important role in immune expansion and effector function by producing chemokines. For instance, IL-8 was a strong inducer of CD4(+) T cells, indicated by strong T helper proliferative responses as well as an enhancement of antibody responses. MIP-1alpha had a dramatic effect on antibody responses and modulated the shift of immune responses to a Th2-type response. RANTES coimmunization enhanced the levels of antigen-specific Th1 and cytotoxic T lymphocyte (CTL) responses. Among the chemokines examined, MCP-1 was the most potent activator of CD8(+) CTL activity. The enhanced CTL results are supported by the increased expression of Th1 cytokines IFN-gamma and TNF-alpha and the reduction of IgG1/IgG2a ratio. Our results support that CD8(+) T cells may expand both humoral and cellular responses in vivo through the elaboration of specific chemokines at the peripheral site of infection during the effector stage of the immune response.

Organ Preservation Therapy Using Induction Plus Concurrent Chemoradiation for Advanced Resectable Oropharyngeal Carcinoma: A University of Pennsylvania Phase II Trial

PURPOSE To determine the efficacy, feasibility, and toxicity of a new regimen for locally advanced oropharyngeal carcinoma. PATIENTS AND METHODS Patients had technically resectable stage III/IV squamous cell carcinoma of the oropharynx, exclusive of T1-2N1. Induction chemotherapy consisted of carboplatin (area under the curve formula equal to 6) and paclitaxel 200 mg/m(2) for two cycles, followed by re-evaluation. Patients with major response continued to definitive radiotherapy (70 Gy over 7 weeks) plus concurrent once-weekly paclitaxel (30 mg/m(2)/wk). Patients with advanced neck disease also underwent post-radiation therapy neck dissection and two more chemotherapy cycles. RESULTS Fifty-three patients were enrolled. Median follow-up was 31 months (minimum follow-up for survivors was 18 months). The major response rate to induction chemotherapy was 89%; 90% of patients had a complete response after concurrent chemoradiation. Actuarial survival at 3 years was 70%, and 3-year event-free survival was 59%. The 3-year actuarial locoregional control was 82% and the 3-year actuarial rate of distant metastases was 19%. Organ preservation was achieved in 77% of all patients. One patient (2%) died during therapy. Late grade 3 toxicity occurred in 24% of patients, consisting mainly of chronic dysphagia/aspiration and/or radiation soft tissue ulceration. The treatment-related mortality rate was 4% (two patients died from respiratory failure). CONCLUSION Response to induction chemotherapy as studied in this trial was not useful as a predictive marker for ultimate outcome or organ conservation. Overall, however, this regimen offers good disease control and survival for patients with locally advanced oropharyngeal carcinoma, comparable with other concurrent chemoradiation programs. Further study of similar protocols is indicated.

Multivariate Predictors of Occult Neck Metastasis in Early Oral Tongue Cancer

OBJECTIVES: The elective dissection of cervical lymph nodes from patients with early oral tongue cancer and a clinically negative neck (T1/T2N0), remains an unsettled issue that continues to be investigated. This study examines clinical and histopathologic factors through univariate and multi-variate analysis to correlate the risk of neck micrometastasis in patients with T1/T2N0 squamous cell carcinoma of the oral tongue. STUDY DESIGN AND METHODS: The clinical files and histologic sections of tumor from 45 clinically determined N0 patients were retrospectively analyzed. The factors examined include degree of tumor cell differentiation, T1/T2 staging, presence of perineural invasion, presence of angiolymphatic invasion, type of invasion front, depth of muscle invasion, and tumor thickness. RESULTS: Independent correlates of positive occult neck metastasis included greater tumor thickness (P = 0.01), greater depth of muscle invasion (P = 0.01), T2 stage (P = 0.01), poorly differentiated tumors (P = 0.007), infiltrating-type invasion front (P = 0.03), presence of perineural invasion (P = 0.001), and presence of angiolymphatic invasion (P = 0.005). The final multivariate model for estimation of an increased probability of occult neck disease included greater tumor thickness, presence of perineural invasion, infiltrating-type invasion front, poorly differentiated tumors, and T2 stage. CONCLUSIONS: The clinical and histopathologic factors studied herein permit greater selectivity and more informed decision-making than does presurgical evaluation, when addressing elective neck treatment for early N0 oral tongue cancer. The multivariate model derived from this study appears to be a more reliable method for determining the patients most likely to benefit from elective neck dissection.

CYTOKINE MOLECULAR ADJUVANTS MODULATE IMMUNE RESPONSES INDUCED BY DNA VACCINE CONSTRUCTS FOR HIV-1 AND SIV

DNA or nucleic acid immunization has been shown to induce both antigen-specific cellular and humoral immune responses in vivo. Moreover, immune responses induced by DNA immunization can be enhanced and modulated by the use of molecular adjuvants. To further engineer the immune response in vivo, we investigated the induction and regulation of immune responses from the codelivery of Thl cytokines (interleukin-2 [IL-2] and IL-12), Th2 cytokines (IL-4 and IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes along with a DNA vaccine construct encoding for simian immunodeficiency virus (SIV) gag/pol proteins. We observed that coinjection with IL-2, IL-4, IL-10, and GM-CSF resulted in increased levels of antigen-specific antibodies. In addition, we found that coinjection with cytokine genes drove the immune responses toward a more Thl or Th2 phenotype. We also observed that coadministration of IL-2, IL-12, and GM-CSF genes resulted in a dramatic enhancement of Th proliferation responses. Moreover, coimmunization with IL-12 genes resulted in a dramatic enhancement of antigen-specific cytotoxic T lymphocyte (CTL) responses. These results support the potential utility of molecular adjuvants in DNA vaccine regimens.

Importance of the treatment package time in surgery and postoperative radiation therapy for squamous carcinoma of the head and neck

To determine the effect of treatment time‐related factors on outcome in patients treated with surgery and postoperative radiation therapy (RT) for locally advanced squamous cell carcinoma of head and neck (SCCHN)

Laryngeal preservation with supracricoid partial laryngectomy results in improved Quality of Life when compared with total laryngectomy

Objectives/Hypotheses Study 1: To assess the oncologic outcome following supracricoid partial laryngectomy (SCPL). Study 2: To compare the quality of life (QOL) following SCPL to total laryngectomy (TL) with tracheoesophageal puncture (TEP). Study 3: To analyze whole organ TL sections to determine the percentage of lesions amenable to SCPL.

Prediction of response to chemoradiation therapy in squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging.

BACKGROUND AND PURPOSE: Tumor microenvironment, including blood flow and permeability, may provide crucial information regarding response to chemoradiation therapy. Thus, the objective of this study was to investigate the efficacy of pretreatment DCE-MR imaging for prediction of response to chemoradiation therapy in HNSCC. MATERIALS AND METHODS: DCE-MR imaging studies were performed on 33 patients with newly diagnosed HNSCC before neoadjuvant chemoradiation therapy by using a 1.5T (n = 24) or a 3T (n = 9) magnet. The data were analyzed by using SSM for estimation of Ktrans, ve, and τi. Response to treatment was determined on completion of chemoradiation as CR, with no evidence of disease (clinically or pathologically), or PR, with pathologically proved residual tumor. RESULTS: The average pretreatment Ktrans value of the CR group (0.64 ± 0.11 minutes−1, n = 24) was significantly higher (P = .001) than that of the PR (0.21 ± 0.05 minutes−1, n = 9) group. No significant difference was found in other pharmacokinetic model parameters: ve and τi, between the 2 groups. Although the PR group had larger metastatic nodal volume than the CR group, it was not significantly different (P = .276). CONCLUSIONS: These results indicate that pretreatment DCE-MR imaging can be potentially used for prediction of response to chemoradiation therapy of HNSCC.

Postoperative Delirium in Older Adults: Best Practice Statement from the American Geriatrics Society

Disclosure Information: Disclosures for the members of t Geriatrics Society Postoperative Delirium Panel are listed in Support: Supported by a grant from the John A Hartford Fou to the Geriatrics-for-Specialists Initiative of the American Geri (grant 2009-0079). This article is a supplement to the American Geriatrics Soci Practice Guidelines for Postoperative Delirium in Older Adu at the American College of Surgeons 100 Annual Clinic San Francisco, CA, October 2014.