Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells.

Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less-efficient homeostatic proliferation than CD8(+) T cells do. Here we show that systemic IL-7 concentrations increased during lymphopenia because of diminished use of IL-7 but that IL-7 signaling on IL-7 receptor-alpha-positive (IL-7Ralpha(+)) dendritic cells (DCs) in lymphopenic settings paradoxically diminished the homeostatic proliferation of CD4(+) T cells. This effect was mediated at least in part by IL-7-mediated downregulation of the expression of major histocompatibility complex class II on IL-7Ralpha(+) DCs. Our results indicate that IL-7Ralpha(+) DCs are regulators of the peripheral CD4(+) T cell niche and that IL-7 signals in DCs prevent uncontrolled CD4(+) T cell population expansion in vivo.

A pain in the neck: lateral thyrohyoid ligament syndrome.

A lateralized pain in the neck is a common symptom encountered by the otolaryngologist. This complaint, frequently caused by lateral thyrohyoid ligament syndrome, is often misdiagnosed. The pathophysiology of this syndrome may relate to overuse and inflammation. [change made here after initial online publication]. Typically, patients present with chronic unilateral neck pain often associated with odynophagia. The point of maximum tenderness localizes over the axis of the lateral thyrohyoid ligament. We present a series of 15 patients, in whom treatment with depot steroid and local anesthetic injection (n = 14) improved symptoms in 12 (86%), with complete resolution in nine (64%) patients.

Etiology and Time to Presentation of Unilateral Vocal Fold Paralysis.

OBJECTIVE: To determine the etiology, laterality, and time to presentation of unilateral vocal fold paralysis (UVFP) at a tertiary care institution over 10 years. STUDY DESIGN: Case series with chart review. SETTING: Academic medical center. SUBJECTS AND METHODS: All patients seen between 2002 and 2012 by the Department of Otolaryngology at the Washington University School of Medicine (WUSM), with a diagnosis of unilateral vocal fold paralysis, were included. Medical records were reviewed for symptom onset date, presentation date(s), and etiology of UVFP. RESULTS: Of the patients, 938 met inclusion criteria and were included. In total, 522 patients (55.6%) had UVFP due to surgery; 158 (16.8%) were associated with thyroid/parathyroid surgery, while 364 (38.8%) were due to nonthyroid surgery. Of the patients, 416 (44.4%) had nonsurgical etiologies, 124 (13.2%) had idiopathic UVFP, and 621 (66.2%) had left-sided UVFP. The diagnosis was more common on the left side in cases of intrathoracic surgeries and malignancies, as expected, but also in idiopathic, carotid endarterectomy, intubation, and skull base tumors. In total, 9.8% of patients presented first to an outside otolaryngologist at a median time of 2.1 months after onset, but these patients presented to WUSM at a median time of 9.5 months. Overall, 70.6% of patients presented to a WUSM otolaryngologist within 3 months of onset. CONCLUSION: Iatrogenic injury remains the most common cause of UVFP. Thyroidectomy remains the leading cause of surgery-related UVFP. Patients are typically seen within 3-4 months of onset; however, a significant delay exists for those referred to WUSM.

Systemic effects of subcutaneous heparin use in otolaryngology patients.

OBJECTIVES: To describe a population of otolaryngology patients who developed systemic anticoagulation from pharmacologic deep vein thrombosis prophylaxis using subcutaneous low-dose unfractionated heparin and describe associated adverse events and identify risk factors for this occurrence. STUDY DESIGN: Retrospective case series with chart review. SETTING: Single-institution, academic tertiary care center. SUBJECTS AND METHODS: Patients who developed prolonged partial thromboplastin times from routine administration of subcutaneous low-dose unfractionated heparin postoperatively were retrospectively identified during a 16-month period. Data regarding demographics, disease characteristics, laboratory values, associated complications, and risk factors were collected and analyzed. RESULTS: Five patients, all with head and neck cancer, postoperatively developed prolonged partial thromboplastin time levels with prophylactic subcutaneous low-dose unfractionated heparin. All had body mass index ≤ 20 kg/m(2) and received 5000 units of subcutaneous low-dose unfractionated heparin 3 times daily. Four had impaired renal function. Adverse events included 5 postoperative wound hematomas, an emergent reintubation, and a case of persistent mucosal bleeding. These bleeding complications accounted for 25% of all bleeding complications in otolaryngology patients during the same period. CONCLUSION: Unanticipated systemic effects of subcutaneous low-dose unfractionated heparin can cause significant morbidity in surgically treated patients with head and neck cancer. From this case series, risk factors appear to include subcutaneous low-dose unfractionated heparin 3 times daily dose frequency, low body mass index, and renal dysfunction. For this at-risk patient population, a protocol is needed to minimize both deep vein thromboses and complications of prophylactic therapy.

Impact of Otitis Media Severity on Children's Quality of Life.

OBJECTIVE: Children with otitis media (OM) suffer sleep disturbances, loss of appetite, earache, and behavioral problems. Our objective was to quantitate the average burden of OM and to compare the associated impact of tympanostomy tubes on infant health related quality of life (HR-QoL). STUDY DESIGN: Multi-institutional prospective cross-sectional study. SETTING: Otolaryngology, family practice, and pediatric clinics. SUBJECTS AND METHODS: Children ages 6 to 24 months of age with or without recurrent OM. Patient history, the PedsQL Infant QoL survey, and the 6-item child with OM survey (Otitis Media 6 [OM-6]) were collected from providers and parents. RESULTS: Data from 1208 patients were analyzed. Mean age was 14.7 months, and 54% were male. The mean OM-6 score of children with recurrent OM was 3.3, whereas similarly aged well-children had a mean OM-6 score of 2.5. The mean PedsQL Infant scores of recurrent OM patients were significantly worse than those of children from well-child visits. Worse OM-6 scores were correlated with poorer PedsQL Infant scores, Pearson r = -0.581 (1-12 months) and -0.558 (13-24 months), P < .001. Otolaryngology patients who were recommended to undergo ear tube placement had significantly poorer OM-6 scores and worse PedsQL Infant scores, whereas patients with prior tube placement had significantly better OM-6 and PedsQL Infant scores. CONCLUSION: Children with recurrent OM had significantly worse HR-QoL than similarly aged healthy children. Increased burden of OM strongly affected HR-QoL, and recommendation for tube placement was associated with increased disease burden and poorer HR-QoL. The presence of tympanostomy tubes was associated with better OM-6 and PedsQL Infant scores.

Caregiver Quality of Life Is Related to Severity of Otitis Media in Children.

OBJECTIVE: Otitis media (OM) in children is the most frequent reason for physician visits in developed countries and burdens caregivers, society, and the child. Our objective was to describe the impact of OM severity on parent/caregiver quality of life (QoL). STUDY DESIGN: Multi-institutional prospective cross-sectional study. SETTING: Otolaryngology, family, and pediatric practices. SUBJECTS AND METHODS: Children 6 to 24 months old with and without a primary diagnosis of recurrent OM and their caregivers. Physicians provided patient history, and parents/caregivers completed a Family Information Form, the PedsQL Family Impact survey, the Patient Reported Outcomes Measurement Information System (PROMIS) survey, and the OM 6-item severity survey (OM-6). RESULTS: A total of 2413 subjects were enrolled and data from 1208 patients and physician were analyzed. The average child age was 16 months, and 54% were male. The mean OM-6 score was 3.2. The mean PedsQL Family Impact score for parents was 66.9 from otolaryngology sites and 78.8 from pediatrics/family practice sites (P < .001). Higher (worse) OM-6 scores correlated significantly with worse PedsQL Family Impact scores (Pearson r = -0.512, P < .01). Similarly, increasing OM-6 scores strongly correlated with increased parental anxiety, depression, and fatigue, as well as decreased satisfaction (all P < .01). CONCLUSIONS: Worse PedsQL Family Impact and PROMIS scores were highly correlated with elevated OM-6 scores, suggesting that severity of childhood OM significantly affects parent/caregiver QoL. Understanding the impact of a child's illness on parent/caregiver QoL can help physicians counsel patients and families and provide better family-centered, compassionate care.

Practical guide to understanding clinical research compliance.

Noncompliance with federal regulations, as monitored through institutional review boards for the ethical conduct of clinical research, can occur, even to seasoned investigators. The cause of this noncompliance can be that an investigator is overloaded, does not know the regulations, or does not take the time to pay attention to the details. Sometimes it happens just because of inevitable human error that can befall us all at any time. The authors begin by citing the inherent differences between clinical practice and clinical research. This is followed by an illustration of common noncompliance errors, with examples, followed by general and specific concepts and methods to minimize noncompliance events. The objective of this article is to condense the myriad details involved in conducting clinical research into a set of manageable recommendations that can be recalled easily before and during the research. The material supporting these recommendations comes from years of institutional review board work at several institutions and consultation with experienced principal investigators and their research coordinators.

Practical guide to understanding the need for clinical practice guidelines.

With recent changes in the landscape of health care, clinical practice guidelines (CPGs) have proliferated. Attitudes about guidelines differ considerably, forming 2 competing viewpoints with considerable tension between them. Some feel CPGs are unneeded or are efforts to create automated "cookie cutter" medical practice; at best, they are perceived as suggestions that may be altered by experience. Others feel they are mandates that must be followed to the letter. This article attempts to explain how and why we have arrived at this point and to explain the origins of the differing viewpoints. We begin by describing the 2 viewpoints and proceed to define the origin of medicine as a profession and to chronicle the evolution of health insurance, medical education, and scientific methods for evaluating evidence.

Practical guide to understanding Comparative Effectiveness Research (CER).

"Comparative effectiveness research" (CER) is not a new concept; however, recently it has been popularized as a method to develop scientifically sound actionable data by which patients, physicians, payers, and policymakers may make informed health care decisions. Fundamental to CER is that the comparative data are derived from large diverse populations of patients assembled from point-of-care general primary care practices and that measured outcomes include patient value judgments. The challenge is to obtain scientifically valid data to be acted upon by decision-making stakeholders with potentially quite diversely different agenda. The process requires very thoughtful research designs modulated by complex statistical and analytic methods. This article is composed of a guiding narrative with an extensive set of tables outlining many of the details required in performing and understanding CER. It ends with short discussions of three example papers, limitations of the method, and how a practicing physician may view such reports.

Practical guide to understanding multivariable analyses: Part A.

Multivariable analyses are complex statistical methods to evaluate the impact of multiple variables on outcomes of interest. Books have been written on each of these methods detailing the mathematical and statistical objectives and processes. However, we have found very little in the way of brief reports that help the nonstatistically trained physician obtain a basic understanding of multivariable analyses in order to have some understanding of the increasing literature using these methods. This work is organized in 2 parts. This article, Part A, addresses the "big 4" algebraic methods of multivariable analysis. The primary focus of Part A is to present a brief "primer" to help the reader understand the methods and uses; it expressly avoids the many details of statistical assumptions, calculations, and myriad branching alternatives. Part B will concentrate on conjunctive consolidation and will focus on enough information to allow the interested reader to actually perform the analysis. For the statistical scholar, we have included references to several voluminous serious works.

Practical guide to understanding multivariable analyses, Part B: conjunctive consolidation.

Conjunctive consolidation, one method of multivariable analysis by arranging data into clusters, is intuitive and transparent. An unexpected consequence in writing this article was the discovery of just how useful it is in critically analyzing articles and in designing new projects. It has stimulated a fresh understanding as to the value of multivariable thinking in all clinical research. This article is organized into the sequential steps for performing conjunctive consolidation for critically analyzing an article of interest and for completing the process, pending all required data are available. Investigators, particularly those who perform clinical research, should consider conjunctive consolidation as a valuable method of multivariable analysis with which to report data.