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Despite preclinical success, monotherapies targeting EGFR or cyclin D1-CDK4/6 in Head and Neck squamous cell carcinoma (HNSCC) have shown a limited clinical outcome. Here, we aimed to determine the combined effect of palbociclib (CDK4/6) and afatinib (panEGFR) inhibitors as an effective strategy to target HNSCC. Using TCGA-HNSCC co-expression analysis, we found that patients with high EGFR and cyclin D1 expression showed enrichment of gene clusters associated with cell-growth, glycolysis, and epithelial to mesenchymal transition processes. Phosphorylated S6 (p-S6), a downstream effector of EGFR and cyclin D1-CDK4/6 signalling, showed a progressive increase from normal oral tissues to leukoplakia and frank malignancy, and associated with poor outcome of the patients. This increased p-S6 expression was drastically reduced after combination treatment with afatinib and palbociclib in the cell lines and mouse models, suggesting its utiliy as a prognostic marker in HNSCC. Combination treatment also reduced the cell growth and induced cell senescence via increasing reactive oxygen species with concurrent ablation of glycolytic and tricarboxylic acid cycle intermediates. Finally, our findings in sub-cutaneous and genetically engineered mouse model (K14-CreERtam;LSL-KrasG12D/+;Trp53R172H/+) studies showed a significant reduction in the tumor growth and delayed tumor progression after combination treatment. This study collectively demonstrates that dual targeting may be a critical therapeutic strategy in blocking tumor progression via inducing metabolic alteration and warrants clinical evaluation.

to Examine the practice characteristics of same-day clinic appointments and the use of same-day appointment scheduling to provide access to care in an otolaryngology-head and neck surgery clinic.Retrospective chart review of same-day clinic appointments from January 1, 2016, to December 31, 2018, in patients aged19 years at a single academic center. Demographic data, diagnoses, procedures completed, and operations completed were analyzed.There were 2696 visits by 2324 patients during the 3-year study period. More men than women (57% vs 43%) made same-day appointments. The mean age was 50.7 years (range, 19-99 years). Sinonasal and otologic diagnoses were the most frequently coded. A total of 1452 procedures were completed on the day of the visit, and 239 operations were completed as a result of the visit. Overall, a broad spectrum of otolaryngology care was delivered within the organizational new patient access goals.Access to otolaryngology-head and neck surgery care can be challenging. Many patients will seek care when they feel they need it, and patient conditions can change unexpectedly. Offering same-day scheduling can allow patients timely health care and appropriate care.Same-day appointment scheduling can provide access to care and urgent care for patients. The department of otolaryngology-head and neck surgery has been able to maintain a high rate of providing new patient appointments within 10 days with this method. Further considerations for the impact of same-day scheduling on no-show rates and patient satisfaction can be evaluated.

African Americans (AA) with Head and Neck Squamous Cell Carcinoma (HNSCC) have a worse disease prognosis than White patients despite adjusting for socio-economic factors, suggesting the potential biological contribution. Therefore, we investigated the genomic and immunological components that drive the differential tumor biology among race. We utilized the cancer genome atlas and cancer digital archive of HNSCC patients (1992–2013) for our study. We found that AA patients with HNSCC had a higher frequency of mutation compared to Whites in the key driver genes—P53, FAT1, CASP8 and HRAS. AA tumors also exhibited lower intratumoral infiltration of effector immune cells (CD8(+), γδT, resting memory CD4(+) and activated memory CD4(+) T cells) with shorter survival than Whites. Unsupervised hierarchical clustering of differentially expressed genes demonstrated distinct gene clusters between AA and White patients with unique signaling pathway enrichments. Connectivity map analysis identified drugs (Neratinib and Selumetinib) that target aberrant PI3K/RAS/MEK signaling and may reduce racial disparity in therapy response.

Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.

// Muzafar A. Macha 1, 2 , Satyanarayana Rachagani 2 , Asif Khurshid Qazi 2 , Rahat Jahan 2 , Suprit Gupta 2 , Anery Patel 3 , Parthasarathy Seshacharyulu 2 , Chi Lin 4 , Sicong Li 4 , Shuo Wang 4 , Vivek Verma 4 , Shosei Kishida 5 , Michiko Kishida 5 , Norifumi Nakamura 6 , Toshiro Kibe 6 , William M. Lydiatt 1 , Russell B. Smith 1 , Apar K. Ganti 3, 7 , Dwight T. Jones 1 , Surinder K. Batra 2, 8, 9 , Maneesh Jain 2, 8 1 Department of Otolaryngology/Head and Neck Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA 2 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA 3 Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA 4 Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE 68198, USA 5 Department of Biochemistry and Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan 6 Department of Oral and Maxillofacial Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan 7 VA Nebraska Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, NE 68198, USA 8 Buffett Cancer Center, Omaha, NE 68198, USA 9 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA Correspondence to: Muzafar A. Macha, email: muzafar.macha@unmc.edu Keywords: head and neck squamous cell carcinoma (HNSCC), afatinib, radiosensitization Received: November 02, 2016 Accepted: February 06, 2017 Published: February 18, 2017 ABSTRACT The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo . Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication.

Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance. Funding Agencies|Cancer Prevention and Research Institute of Texas (CPRIT) [RP101202, RP57154]; Department of Defense [CDMRP W81XWH-12-1-0508]; Voelcker Fund; National Institutes of Health (NIH)s National Center for Research Resources; National Center for Advancing Translational Sciences [8UL1TR000149]; INSERM; French National Cancer Institute (INCA); Direction Generale de lOffre de Soins (DGOS); INCA [INCA-DGOS_8663]; European Union [633983]; Brazilian National Council for Scientific and Technological Development (CNPq); Cancer Research for PErsonalized Medicine (CARPEM); ERC Advanced Researcher Award

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with high morbidity and mortality. Racial disparity in HNSCC is observed between African Americans (AAs) and whites, effecting both overall and 5-year survival, with worse prognosis for AAs. In addition to socio-economic status and demographic factors, many epidemiological studies have also identified factors including coexisting human papillomavirus (HPV) infection, primary tumor location, and a variety of somatic mutations that contribute to the prognostic incongruities in HNSCC patients among AAs and whites. Recent research also suggests HPV-induced dysregulation of tumor metabolism and immune microenvironment as the major regulators of HNSCC patient prognosis. Outcomes of several preclinical and clinical studies on targeted therapeutics warrant the need to elucidate the inherent mechanistic and population-based disparities underlying patient responses. This review systematically reports the underlying reasons for inconsistency in disease prognosis and therapy responses among HNSCC patients from different racial populations. The focus of this review is twofold: aside from discussing the causes of racial disparity, we also seek to identify the consequences of such disparity in terms of HPV infection and its associated mutational, metabolic, and immune landscapes. Considering the clinical impact of differential patient outcomes among AA and white populations, understanding the underlying cause of this disparity may pave the way for novel precision therapy for HNSCC.

Objective To assess the efficacy and safety of endoscopic management of subglottic stenosis both as a primary and as an adjunctive treatment in the pediatric population. Methods Retrospective review of pediatric patients with subglottic stenosis undergoing endoscopic airway procedures at a tertiary care pediatric medical center. Outcomes were assessed by systematic review to determine the success and failure of the endoscopic approach. Results Forty patients (22 male, 18 female) underwent endoscopic interventions for a diagnosis of subglottic airway stenosis between 2003 and 2006. Age ranged from 22 days old to 20 years old. Recorded degree of subglottic stenosis ranged from 10% to 99%. Fifty-three percent (21/40) had a history of prematurity, and 40% (16/40) had secondary airway diagnoses. Twenty-four patients underwent an endoscopic intervention initially (including laser or dilation, with or without topical mitomycin treatment), including four patients who underwent tracheostomy prior to the first endoscopic intervention. Sixteen underwent laryngotracheoplasty initially, including ten patients who underwent tracheostomy prior to the laryngotracheoplasty. Endoscopic treatment resulted in resolution of symptoms, and/or decannulation, and no further need for an open procedure in 58% of patients. Of the 24 patients undergoing endoscopic interventions initially, 14 patients underwent two or more endoscopic interventions, and 10 patients subsequently required tracheostomy or laryngotracheoplasty. When endoscopic procedures were used as an adjunct to laryngotracheoplasty, 60% (12/20) had resolution of symptoms, underwent decannulation, and did not require tracheostomy or revision laryngotracheoplasty. Conclusions The endoscopic approach can be successful in the management of properly selected patients with subglottic stenosis, either as the initial treatment modality or as an adjunctive treatment in cases of re-stenosis after open airway surgery. The likelihood of success with a minimally invasive procedure as the primary treatment decreases with worsening initial grade of subglottic stenosis.

Objective. To compare postoperative pain scores between monopolar electrocautery and coblation subcapsular tonsillectomy.Study Design. Prospective double-blind randomized study.Setting. Tertiary care children’s hospital.Subjects and Methods. Between December 2004 and April 2008, 61 children, ages 4 to 20 years (mean age, 10 years; SD, 4 years), were randomized to have one tonsil removed by electrocautery and the other tonsil removed by coblation. Subjects used the FACES scale to rate pain on each side immediately postoperatively, 2 days postoperatively, and 2 weeks postoperatively. Postoperative hemorrhage was also tracked.Results. Coblation tonsillectomy resulted in statistically less pain than electrocautery immediately after surgery, but this difference was not clinically significant.Conclusions. Pediatric pain is similar following monopolar electrocautery or coblation subcapsular tonsillectomy.

BACKGROUND: The true rate of neurologic sequelae and infection from penetrating palatal trauma in children is unknown, which leads to significant variation in testing and treatment. OBJECTIVES: To (1) determine the incidence of stroke and infection in well-appearing children with penetrating palatal trauma and (2) describe patterns of testing and treatment for uncomplicated palatal trauma. METHODS: We assembled a retrospective cohort of children aged 9 months to 18 years with palatal trauma seen in the emergency department (ED) at a tertiary care pediatric hospital. Patients met the following definition: well-appearing with normal neurologic examination and a palate laceration but no findings requiring immediate operative care. Stroke was defined as any abnormal neurologic examination secondary to palatal trauma. Infection was defined as cellulitis or abscess secondary to palatal injury. All abnormal computed tomographic angiography (CTA) findings, except for free air, were considered positive and potentially significant. RESULTS: We identified 1656 potential subjects. A total of 995 of 1656 subjects were screened, and 205 of 995 met the case definition. A total of 122 of 205 had follow-up through at least 1 week after injury. The incidence of stroke in our study population was 0% (95% confidence interval [CI]: 0–2.5). One of 116 patients developed infection, for an incidence of 0.9% (95% CI: 0–5.3). A total of 90 of 205 (44%) subjects had CTA scans; the results of 9 (10%) were positive. No patients with positive CTA findings required operative care. No patients received anticoagulant medications. CONCLUSIONS: The incidence of morbidity from penetrating palatal trauma in the well-appearing child is extremely low. Diagnostic evaluation in the ED did not prompt clinical interventions other than antibiotics.

An in vitro cadaveric study of interbody fusion devices (IFDs) with differing interface geometries.To quantify the trabecular damage and mechanical property degradation resulting from mechanical testing of bone-implant constructs and evaluate the dependence on the interface geometry.The success of an orthopedic implant depends, in part, on the interaction between the implant and the bone at its interface. IFDs must safely and effectively transfer load between the device and the neighboring vertebral cancellous bone on which the device is supported.Twenty-four vertebral pairs implanted with bilateral cylindrical or hexahedral IFDs were subjected to either 1% or 2.5% compressive strain. The change in structural stiffness and the presence of residual deformation caused by damage processes were measured. Histologic evidence of trabecular damage was quantified using polychromatic labeling and an image processing scheme. Statistical comparisons between groups within a strain level were made using the Mann-Whitney U test. RESULTS.: Permanent deformation and/or decreased structural stiffness was found in all specimens. The overall changes in mechanical stiffness properties were inconsistent with regard to the device interface geometry. Histologic damage was found in all specimens located in a region immediately adjacent to the implant. The distribution of the damage relative to the center of the device cross-section was significantly different for the 2 interface geometries. At the higher strain, damage and the mechanical effect of damage were greater for the cylindrical devices.Histologic damage was found in close proximity to the bone-implant interface and in all specimens, including those which did not demonstrate mechanical damage. Patterns of histologic damage corresponded directly to the bone-implant interface geometry. Gross structural measurements do not reliably detect changes caused by damage at the bone-implant interface.

To identify clinical, audiological, and vestibular characteristics of posterior semicircular canal dehiscence.Retrospective case review.Tertiary referral center.Twelve patients aged 2 to 67 years identified with posterior semicircular canal dehiscence.Patients identified by suspicious clinical history and examination, confirmed by high-resolution computed tomography. Audiological evaluation included air and bone audiometry, tympanometry, acoustic reflexes, and vestibular evoked myogenic potential testing.Hearing loss was mixed in 9 patients, conductive in 2 patients, and sensorineural in 1 patient, with downward-sloping configuration being the most common. Imaging revealed that 7 of 12 patients had dehiscence into a high-riding jugular bulb and 1 patient had an enlarged vestibular aqueduct with a Mondini malformation. One patient had Apert syndrome and another patient had microtia/atresia. Vestibular symptoms were more common in the adult patients than in the pediatric patients, with chronic disequilibrium the most common complaint. Vestibular evoked myogenic potential testing confirmed dehiscence with the characteristic response of reduced threshold and higher amplitude compared with healthy patients.This is the first reported series of adult and pediatric patients with symptomatic posterior semicircular canal dehiscence. Posterior semicircular canal dehiscence represents a third-window lesion manifesting as hearing loss with vestibular dysfunction. Computed tomography findings of a dehiscent posterior canal can be verified with increased vestibular evoked myogenic potential responses as in other third-window lesions. Patients found to have a high-riding jugular bulb and hearing loss should have specific inspection of the posterior canal to ensure it is not dehiscent.

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are heritable neoplasms that can be classified into gene-expression subtypes corresponding to their underlying specific genetic drivers. OBJECTIVE: This study aimed to develop a diagnostic and research tool (Pheo-type) capable of classifying PPGL tumors into gene-expression subtypes that could be used to guide and interpret genetic testing, determine surveillance programs, and aid in elucidation of PPGL biology. DESIGN: A compendium of published microarray data representing 205 PPGL tumors was used for the selection of subtype-specific genes that were then translated to the Nanostring gene-expression platform. A support vector machine was trained on the microarray dataset and then tested on an independent Nanostring dataset representing 38 familial and sporadic cases of PPGL of known genotype (RET, NF1, TMEM127, MAX, HRAS, VHL, and SDHx). Different classifier models involving between three and six subtypes were compared for their discrimination potential. RESULTS: A gene set of 46 genes and six endogenous controls was selected representing six known PPGL subtypes; RTK1-3 (RET, NF1, TMEM127, and HRAS), MAX-like, VHL, and SDHx. Of 38 test cases, 34 (90%) were correctly predicted to six subtypes based on the known genotype to gene-expression subtype association. Removal of the RTK2 subtype from training, characterized by an admixture of tumor and normal adrenal cortex, improved the classification accuracy (35/38). Consolidation of RTK and pseudohypoxic PPGL subtypes to four- and then three-class architectures improved the classification accuracy for clinical application. CONCLUSIONS: The Pheo-type gene-expression assay is a reliable method for predicting PPGL genotype using routine diagnostic tumor samples.

Implant success is dependent in part on the interaction of the implant with the surrounding tissues. Porous tantalum implants (Trabecular Metal™, TM) have been shown to have excellent osseointegration. Machining this material to complex shapes with close tolerances is difficult because of its open structure and the ductile nature of metallic tantalum. Conventional machining results in occlusion of most of the surface porosity by the smearing of soft metal. This study compared TM samples finished by three processing techniques: conventional machining, electrical discharge machining, and nonmachined, “as-prepared.” The TM samples were studied in a rabbit distal femoral intramedullary osseointegration model and in cell culture. We assessed the effects of these machining methods at 4, 8, and 12 weeks after implant placement. The finishing technique had a profound effect on the physical presentation of the implant interface: conventional machining reduced surface porosity to 30% compared to bulk porosities in the 70% range. Bone ongrowth was similar in all groups, while bone ingrowth was significantly greater in the nonmachined samples. The resulting mechanical properties of the bone implant-interface were similar in all three groups, with only interface stiffness and interface shear modulus being significantly higher in the machined samples. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007

Stiffness degradation and strength degradation are often measured to monitor and characterize the effects of damage accumulation in bone. Based on evidence that these properties could be affected by not only damage magnitude but also test conditions, the present study investigated the effect of hold condition and recovery time on measures of tensile damage. Machined human femoral cortical bone specimens were subjected to tensile tests consisting of a pre-damage diagnostic loading cycle, a damage loading cycle and post-damage cycle. Controlled variables were recovery time (1, 10, and 100 min) and hold condition (zero load or zero strain) after the damage cycle. Damage measures were calculated as the ratio of each post-damage cycle to the pre-damage value for loading modulus, secant modulus, unloading modulus, stress relaxation and strain (stress) recovery at 1 min post-diagnostic time. The damage cycle caused reductions in all measures, and some measures varied with recovery time and hold condition. Apparent modulus degradation for both hold conditions decreased with recovery time. Stress relaxation was unaffected by recovery time for both hold conditions. Zero-strain hold conditions resulted in lower values for degradation of modulus and change of relaxation. Stress or strain recovery after the damage cycle was evident through 100 min, but 90% of the recovery occurred within 10 min. The results demonstrate that choice of test conditions can influence the apparent magnitude of damage effects. They also indicate that 10 min recovery time was sufficient to stabilize most measures of the damage state.

Objective Determine if passive smoke exposure (PSE) increases airway complications during outpatient mask anesthesia procedures in children. Methods A prospective cohort of children who underwent surgical procedures under mask anesthesia was studied with the American Thoracic Society children’s questionnaire on environmental and respiratory factors. Double-blinded outcomes with respect to adverse airway events were recorded both intraoperatively and in the recovery room for patients with and without passive smoke exposure. Multivariate comparisons assessing the likelihood of these airway complications were conducted between the PSE and nonexposed groups. Results Of 405 children, 168 (41.5%) had PSE. The incidence of airway complications during anesthesia or postanesthetic recovery was higher for all outcome measures for PSE children (all P ≤ 0.005), except for recovery room breath holding ( P = 0.086). Intraoperative laryngospasm and airway obstruction were 4.9 and 2.8 times more likely with PSE, respectively. Conclusions PSE significantly increases the risk of anesthesia-related airway complications during outpatient pediatric procedures. EBM rating: A-1b

The present study examines the viscoelastic behavior of cancellous bone at low strains and the effects of damage on this viscoelastic behavior. It provides experimental evidence of interaction between stress relaxation behavior and the effect of accumulated damage. The results suggest that damage is at least orthotropic in trabecular bone specimens under uniaxial loading. Simple linear models of viscoelasticity described the time-dependent stress-strain behavior at low strains before and after specimen damage, although better fits of these models were obtained prior to damage. Modeling the observed changes in relaxation times with damage accumulation appears necessary to successfully predict the post-damage viscoelastic response.

Objective: To identify the most common otolaryngologic causes of mortality in the 0 to 19 age group in the state of Massachusetts and to estimate the pediatric otolaryngologic mortality rate based on population data. Study Design: Population-based retrospective cohort study. Methods: The Massachusetts State Registry of Vital Records and Statistics electronic database was searched for all otolaryngology related causes of death from 1990 to 2002 for children aged 0 to 19. The individual death certificates were then reviewed, and a database of otolaryngology related pediatric deaths was created. Results: A total of 59 otolaryngology related deaths were identified in the pediatric population from 1990 to 2002. Eighty-one percent of deaths occurred because of airway compromise caused by infection, anatomic obstruction, or congenital anomaly. The remaining 19% of deaths occurred because of aspiration, nonairway infections, and malignant neoplasms. Ninety-five percent of deaths in the children under age 10 were caused by airway compromise. Six of seven deaths (86%) in the age 15 to 19 group occurred because of malignant neoplasms. The overall mortality rate caused by otolaryngologic causes was estimated to be 0.28 per 100,000 population. Conclusions: The overall mortality rate for otolaryngology related deaths is low in the pediatric population. The vast majority of deaths are caused by airway compromise, primarily because of laryngotracheobronchitis or other upper airway obstruction. In older children (ages 15–19), malignant head and neck neoplasms are the leading cause of otolaryngology related deaths.

Objectives. To endeavor to explain why some graduates of extracorporeal membrane oxygenation (ECMO) therapy develop sensorineural hearing loss (SNHL) whereas others do not, to study the variability seen in the degree of SNHL, to attempt to explain why some graduates with SNHL experience progressive worsening whereas others do not, and to describe the time course of the onset of SNHL on the basis of identified risk factors.Design. A retrospective chart review with proportional-hazards regression analysis to identify specific risk factors for SNHL from a list of patient and treatment variables.Setting. Children’s Hospital Boston, a pediatric tertiary-care facility and ECMO center.Patients. Neonatal ECMO graduates born in 1986–1994 who survived to discharge and underwent audiologic evaluations (n = 111) and a random sample of ECMO graduates who survived to discharge and did not undergo audiologic evaluations (n = 30).Outcome Measures. Audiologic data, including the presence or absence of SNHL, the severity of SNHL at the most recent evaluation, the stability or progressive worsening of hearing (with the first evaluation compared with the most recent evaluation), and the occurrence of delayed-onset SNHL.Results. Twenty-nine (26%) of 111 ECMO graduates who underwent audiologic testing had SNHL at the last evaluation. Of these 29 subjects with SNHL, 21 (72%) had progressive SNHL, of whom 14 (48%) had delayed-onset SNHL. The age of identification of SNHL ranged from 4 months to 8 years 11 months. Factors identified with proportional-hazards regression analyses as being associated significantly with the time to onset of SNHL were a primary diagnosis of congenital diaphragmatic hernia (hazard ratio: 2.60), length of ECMO therapy (hazard ratio: 7.18), and number of days children received aminoglycoside antibiotics (hazard ratio: 5.56). Kaplan-Meier “time-to-event” curves were constructed to illustrate the time course of onset of SNHL, as affected by each of the variables identified as significant risk factors.Conclusions. These findings illustrate the need for early, routine, audiologic evaluations throughout childhood for all ECMO graduates. Children at even greater risk for developing SNHL because of a history of congenital diaphragmatic hernia, prolonged ECMO therapy, and/or a lengthy course of aminoglycoside antibiotic therapy should be monitored even more closely throughout childhood, depending on the child’s individual risk indicators, as suggested here. On the basis of these risk indicators, efforts can be made to minimize the risk of hearing loss while a child is being treated with ECMO. In addition, these risk indicators can assist with counseling families of ECMO graduates regarding the child’s specific risk of developing SNHL and how it can be managed should it occur.

Objective To describe the epidemiology, natural history, and treatment of epiglottitis in the Hemophilus influenzae type B (Hib) vaccine era. Design Ten-year retrospective study. Setting Tertiary-care children's hospital. Patients Nineteen patients with a discharge diagnosis of epiglottitis. Intervention As indicated by the presentation of the patient, including direct laryngoscopy, intubation, intravenous antibiotics, and steroids. Main outcome measures Presentation, management, and microbiology. Results Presenting symptoms included fever, drooling, and hot potato voice. Patients' ages ranged from 15.8 months to 17.5 (mean 8.9) years. From 1992 to 1997, the mean age was 5.8 years; from 1998 to 2002, the mean age was 11.6 years. Sixty-eight percent of patients were transferred from an outside hospital. A lateral neck radiograph was recorded in 84% of patients. Mean leukocyte count was 16,600. Direct laryngoscopy with intubation was performed in 79%; intubation was for an average of 3.5 days. H. influenzae was cultured in six patients, five of which had up-to-date immunizations. The most commonly administered antibiotics were ampicillin/sulbactam and ceftriaxone. Steroids were administered to 63% of patients. Complications included deep neck space infection (2), seizure (1), recurrent illness (1), and vocal granuloma (1). There were no deaths. Conclusion The demographics, causative organisms, and natural history of epiglottitis have changed substantially in the Hib vaccination era. The clinician evaluating and treating patients with epiglottitis should be aware of current trends.

The accumulation of damage and the associated degradation of the mechanical properties of cortical bone are postulated to contribute to age-, disease-, overuse-, and disuse-related skeletal fragilities. Therefore, gaining insight into the relationship between damage and degradation processes is essential in understanding the etiology of skeletal fractures. In investigating this relationship, the damage measure ideally needs to account for the size, the distribution density, and the orientation of microcracks. Existing measures of damage address the size and distribution density of microcracks; however, the orientation of cracks has not been well-investigated. Because the overall orientation of microcracks determines the material axis along which the greatest degradation will be experienced, we hypothesized that the incorporation of the relative orientation between microcracks and loading direction will improve the significance of the relationship between damage accumulation and material property degradation. A three-cycle damage protocol was used to induce tensile damage and to quantify the degradation of the elastic modulus of specimens from human donor femoral cortical bone (a 24-year-old and a 72-year-old man). Microcracks were evaluated by en bloc basic fuchsin staining of specimens after testing. The length (L(i)) and the orientation with respect to the loading direction (beta(i)) of each crack were quantified by a video microscopy system. Three damage measures were quantified for each specimen: the number of linear microcracks (Cr #), the sum of the crack lengths (SigmaL(i)) accounting for the microcrack size alone, and the sum of the projected crack length [SigmaL(Pi) = SigmaL(i)cos(beta(i))] accounting for both crack size and orientation. Inclusion of the orientation parameter improved the coefficient of determination between damage accumulation and the degradation of the elastic modulus: the coefficient of determination of the sum of the projected crack length (R(2) = 0.239) was 60% greater than that of the sum the projected crack length (R(2) = 0.149) and 33% greater than that of the number of linear microcracks (R(2) = 0.180). We conclude that microcrack orientation is an essential physical variable in the relationship between damage accumulation and degradation of mechanical properties of cortical bone tissue.

Adenotonsillectomy (AT) is commonly performed for childhood OSA syndrome (OSAS), but little is known about prognosis without treatment.The Childhood Adenotonsillectomy Trial (CHAT) randomized 50% of eligible children with OSAS to a control arm (watchful waiting), with 7-month follow-up symptom inventories, physical examinations, and polysomnography. Polysomnographic and symptomatic resolution were defined respectively by an apnea/hypopnea index (AHI)2 and obstructive apnea index (OAI)1 and by an OSAS symptom score (Pediatric Sleep Questionnaire [PSQ])0.33 with ≥ 25% improvement from baseline.After 194 children aged 5 to 9 years underwent 7 months of watchful waiting, 82 (42%) no longer met polysomnographic criteria for OSAS. Baseline predictors of resolution included lower AHI, better oxygen saturation, smaller waist circumference or percentile, higher-positioned soft palate, smaller neck circumference, and non-black race (each P.05). Among these, the independent predictors were lower AHI and waist circumference percentile90%. Among 167 children with baseline PSQ scores ≥ 0.33, only 25 (15%) experienced symptomatic resolution. Baseline predictors were low PSQ and PSQ snoring subscale scores; absence of habitual snoring, loud snoring, observed apneas, or a household smoker; higher quality of life; fewer attention-deficit/hyperactivity disorder symptoms; and female sex. Only lower PSQ and snoring scores were independent predictors.Many candidates for AT no longer have OSAS on polysomnography after 7 months of watchful waiting, whereas meaningful improvement in symptoms is not common. In practice, a baseline low AHI and normal waist circumference, or low PSQ and snoring score, may help identify an opportunity to avoid AT.ClinicalTrials.gov; No.: NCT00560859; URL: www.clinicaltrials.gov.

The management of a mastoid subperiosteal abscess has traditionally required mastoidectomy. With the improvement of antibiotic therapy current literature supports the treatment of uncomplicated acute mastoiditis with myringotomy and intravenous antibiotics. Treatment of a mastoid subperiosteal abscess with tympanostomy tube insertion, intravenous antibiotics, and postauricular incision and drainage of the abscess avoids the morbidity and potential complications of mastoid surgery in young children. Three patients diagnosed with a mastoid subperiosteal abscess were managed in this way. The outcome of their treatment has been documented with lengthy otologic follow-up. Complete resolution of the acute infectious process was achieved in all cases with no evidence of recurrent disease.

Objective: To examine the effects of endoscopic sinus surgery on the pulmonary status of cystic fibrosis (CF) patients through the objective parameters of steroid use, pulmonary function tests (PFTs), and inpatient hospital days (IHDs). Methods: Retrospective chart review of all patients with CF who underwent endoscopic sinus surgery from 1993 to 1999 at a tertiary care children's hospital. Preoperative pulmonary function, inhaler and steroid use, and IHDs were compared to postoperative parameters within a 1-year period. Results: Sixty-six patients, including eight lung transplant patients, underwent a total of 112 endoscopic sinus surgery procedures; 25 patients underwent more than one procedure. Patients were taking oral steroids preoperatively in 28% of procedures and inhaled steroids in 40%. Postoperatively, there was no statistically significant change in oral or inhaled steroid use, or in postoperative pulmonary function. If the index hospitalization, which was often for reasons not related to sinus disease, was considered part of the preoperative time period, endoscopic sinus surgery (ESS) was noted to result in a marked reduction (9.5 days (adjusted), P =0.001) in hospital days during the subsequent 6 months. If the date of the procedure alone was used to define pre- and postoperative time periods, the reduction in postoperative days was more modest and not statistically significant (3.5 days (adjusted), P =0.21). Conclusions: Although we found no statistically significant difference in PFTs, or steroid requirements following ESS, ESS may have resulted in a reduced need for hospitalization in the 6 months following the procedure. Future prospective studies in a larger number of patients and using more detailed outcome measures are needed to better evaluate the effects of endoscopic sinus surgery in pediatric patients with CF.

In this report an integrated approach to the three-dimensional material optimization of femoral components of hip prostheses is described. The effectiveness of using reinforced fiber composites for the material optimization of hip implants has been demonstrated and general guidelines on some material design aspects of total hip replacement (THR), in terms of fiber volume fraction and fiber orientation angles, are provided. A modular program was developed to interface the optimization routine with the finite element code. In this study two cases of cemented and non-cemented THR were investigated. In both cases perfectly bonded interfaces were assumed. Two objective functions were defined based on interface failure criteria and bone adaptive remodeling to avoid interface disruption and to reduce the risk of bone loss. The overall results demonstrated the effectiveness of the technique, which can provide meaningful insights into the fiber-reinforced composite material design of orthopaedic implants.

Two studies have reported that young women with breast cancer face increased risk of early mortality if their first child was male rather than female. An immunological mechanism has been suggested. We sought to confirm these results in a larger, historical cohort study of 223 parous women who were aged45 years at breast cancer diagnosis during 1983-1987. Subjects were identified through the Maine Cancer Registry. Follow-up data were obtained from hospitals, physicians, and death certificates. Reproductive history data were obtained from the next of kin of the deceased women, birth certificates, physicians, hospitals, and lastly, subjects. With a 7-year follow-up, multivariate modeling found a lower mortality risk in women with a male first child (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32-0.81, log-rank comparison). The survival advantage remained for at least 13 years in women with a male firstborn. Thus, previous studies were not confirmed. Mortality risk in young women with breast cancer is not increased by having borne a male first child rather than a female first child.

To describe the time-dependent nonlinear tensile behavior observed in experimental studies of cortical bone, a damage model was developed using two internal state variables (ISV’s). One ISV is a damage parameter that represents the loss of stiffness. A rule for the evolution of this ISV was defined based on previously observed creep behavior. The second ISV represents the inelastic strain due to viscosity and internal friction. The model was tested by simulating experiments in tensile and bending loading. Using average values from previous creep studies for parameters in the damage evolution rule, the model tended to underestimate the maximum nonlinear strains and to overestimate the nonlinear strain accumulated after load reversal in the tensile test simulations. Varying the parameters for the individual tests produced excellent fits to the experimental data. Similarly, the model simulations of the bending tests could produce excellent fits to the experimental data. The results demonstrate that the 2-ISV model combining damage (stiffness loss) with slip and viscous behavior could capture the nonlinear tensile behavior of cortical bone in axial and bending loading.

Because the biomechanical competence of the graft is a central issue, many research studies of bone grafts include a biomechanical component. The biomechanical evaluation serves as a bottom-line measure of the experimental outcome in which some measure of mechanical performance is compared among treatment groups. This article considers the biomechanics of grafts in the context of this experimental work and focuses on three issues: (1) the interplay between biology and biomechanics of grafts, (2) the effects of treatment choices on biomechanical properties, and (3) model factors that may influence biomechanical performance.

From 1982 to 1984, the authors conducted a population-based case-control study of lung cancer in men and women nonsmokers in New York State. In-person interviews were completed for 437 lung cancer cases (197 never smokers, 240 former smokers) and 437 matched population controls. Cases and controls were asked to report any history of physician-diagnosed nonmalignant lung disease; cases were more likely than controls to report such a history. Statistically significant associations were found for emphysema (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.10-3.43), chronic bronchitis (OR = 1.73, 95% CI 1.10-2.72), and the combined endpoint of emphysema, chronic bronchitis, or asthma (OR = 1.82, 95% CI 1.26-2.63). After adjustment for active and passive tobacco smoke exposure, emphysema, chronic bronchitis, and asthma (each condition and the combined endpoint) were significantly associated with lung cancer risk. The risk was more marked for squamous cell carcinomas and for subjects who were diagnosed at older ages, and it remained significant when surrogate interviews were excluded. These results are consistent with the hypothesis that certain prior lung conditions increase the risk of lung cancer in men and women nonsmokers.

To study the complication rates of skin overgrowth, infection, and the need for revision surgery in longer length Baha™ abutments.Prospective observational cohort study compared with a retrospective historical control.After the University of Nebraska Medical Center (UNMC) Institutional Review Board approval was obtained, data was collected from a prospective 8.5-mm abutment study group of 21 subjects with informed consent from October 2011 through October 2012, and was compared to a retrospective 5.5-mm abutment historical cohort of 23 patients who had undergone Baha™ by the same surgeon from May 2010 to October 2011. Patient demographics, body mass index (BMI), smoking status, and wound complications (skin overgrowth, infection, the need for revision surgery) were statistically investigated and compared between the groups.Forty-four patients were studied. The groups were similar in smoking status, diabetes, and a female preponderance. The 8.5-mm abutment group was older (P = 0.012). The average BMI for both groups was classified as overweight and nearly obese (BMI 28.8). Rates of infection, skin overgrowth, and the need for revision surgery related to wound complications were significantly decreased in the longer 8.5-mm abutment group (P = 0.020, P = 0.012, P = 0.007, respectively). BMI did not correlate with decreased infection, skin overgrowth, and the need for revision surgery based on abutment length as hypothesized (P = 0.214, P = 0.206, P = 0.408).The 8.5-mm abutment lends to decreased complications postoperatively, including infection, skin overgrowth, and the need for revision surgery.3b.

OBJECTIVES. Each case of a continuous series of invasive cervical cancer cases was studied with a structured review procedure conducted by an expert panel to assess the reason that it was not detected before it became invasive. METHODS. All cases of invasive cervical cancer diagnosed in a 5-year period among Connecticut residents were identified; a screening history and screening outcome were obtained for 72% (481 of 664). RESULTS. Two hundred fifty women (51.9%) had suboptimal screening. One hundred thirty-seven women (28.5%) had never had a screening test, and their mean age was greater than that of the rest of the study population (64.5 years vs 46.5 years). Of the 344 women who had ever had a Pap test, 113 (32.8%) had their last Pap test 5 or more years before their diagnosis of invasive cancer; 52 (15.1%) were not followed up properly; 33 (9.6%) had their last smear misread as normal; and 118 (34.3%) developed cervical cancer within 3 years of their last Pap test. CONCLUSIONS. Physicians, nurses, and other care providers need to ensure that woman have timely and accurate screening with proper follow-up, make increased efforts to reach older women, and improve quality control of Pap smear readings.

Retropatellar pain often accompanies malalignment syndromes and frequently is attributed to excessive patellofemoral contact stresses. Elevation (anterior displacement) of the tibial tubercle has been recommended to relieve these conditions. The degree to which patellar contact forces are decreased and the extent to which elevation alters medial-lateral forces have not been studied directly. We performed anterior translation of the tibial tubercle in knees from cadavers and measured the effect on the magnitude of the three-dimensional patellofemoral contact force with use of a specially designed 6-degrees-of-freedom force transducer, with the natural patellar articular surface in place. Measurements were made in nine knees (average age 67 years, range 46-92 years). The resultant contact force decreased linearly with increasing tubercle elevations of as much as 2.5 cm. The average reduction per centimeter of elevation was 17% of the force measured with no elevation. Elevation of the tubercle had an inconsistent effect on the medial-lateral component of the contact force. As the elevation was increased, six knees exhibited an increase in the medial-lateral component of the contact force acting medially on the knee and three knees exhibited a decrease in this force component. The results of this study show that, while elevation of the tubercle without medialization reduced the total contact force on the patella, the medial-lateral component of this force was altered in an unpredictable way.

Results of the direct in vitro measurement of the full three-dimensional representation of the patellofemoral contact force and the point of application on the patella of the resultant contact force for eleven normal knees are presented. The applied knee moment versus flexion angle pattern was similar to that experienced when rising from a chair. There was a wide variability of the details of the patellofemoral force interaction among the specimens tested. The magnitude of the resultant contact force increased approximately linearly with flexion angle for some knees while in others the force leveled off or decreased at higher flexion angles. The change in direction of the resultant contact force with respect to the patella was relatively small compared to the angular rotation of the patella. The medial-lateral component of the contact force exhibited substantial variability among knees. The direction of this force (medially or laterally directed) varied among knees and, in some knees, changed direction as a function of flexion angle. The point of application on the patella of the resultant contact force migrated superiorly from 20 to 90 deg flexion. Above 90 deg flexion this point tended to migrate inferiorly. The only significant and consistent effect of varying the direction of the quadriceps extension force was a change in the medial-lateral component of the contact force. In all cases, the tendency to sublux laterally increased when the extensor force was rotated 10 deg laterally and decreased when the extensor force was rotated 10 deg medially.

Objectives/Hypothesis Penetrating palatal trauma in children presents a diagnostic dilemma regarding the small but severe risk of injury to carotid vessels. Decisions regarding which children require computed tomography with angiography must be balanced against the risk of radiation-induced malignancy. Our objectives were to compare outcomes between children with and without computed tomography with angiography in the evaluation of palatal trauma and to identify thresholds where the ideal strategy changes in the management of children with palatal trauma through sensitivity analyses. Study Design Decision analytic techniques were used to compare management strategies for penetrating palatal trauma. Methods We assigned utilities to the following outcomes: 1) perfect health, 2) future malignancy, 3) carotid injury diagnosed by computed tomography with angiography, and 4) delayed diagnosis of stroke. We calculated outcomes when the risk of stroke ranged from 0.01% to 5.0% for a hypothetical cohort of 10,000 injured children. Results Not obtaining computed tomography with angiography is the optimal strategy when the stroke risk is less than 4.5%. In two-way sensitivity analyses that consider a range of probabilities of radiation-induced malignancy and stroke, not obtaining computed tomography with angiography on all patients dominates as a strategy until the risk of stroke exceeds 2.3%, and the risk of malignancy is under 0.24%. Routine imaging would introduce 20 additional malignancies for each additional stroke diagnosed. Conclusions Routine use of computed tomography with angiography for well-appearing children with palatal trauma should be reconsidered, as the risk of radiation-induced malignancy may outweigh the benefit of identifying the rare carotid injury. Level of Evidence 2b.

The relationship between patella alta and patellar subluxation may, in part, reflect the relationship between the height of the patella above the tibiofemoral joint line and the patellofemoral contact force. This study reports on the direct in vitro measurement of the patellofemoral contact force, and its point of application on the patella, as a function of patellar height. The contact force was measured by a specially designed six-degree-of-freedom force transducer under loading simulating rising from a chair. The magnitude of the resultant contact force increased significantly with superior displacement of the patella. The magnitude of the resultant contact force changed as much as 3% per millimeter of change in patellar height. The details of this response varied among the knees tested and depended on the original anatomical patellar height. For a high-riding patella, the onset of tendofemoral contact is delayed and the magnitude of the patellofemoral contact continues to increase with increasing flexion angle. Early onset of tendofemoral contact associated with a low-riding patella results in a concomitant reduction in the magnitude of the contact force. The medially directed component of the contact force acting on the patella resists lateral subluxation of the patella. This force component increased with superior displacement of the patella. This may explain in part the tendency for a high-riding patella to sublux. For all seven specimens tested the point of application of the resultant contact force migrated superiorly with inferior displacement of the patella.

Many investigations report hip-contact-force estimates based either on mathematical models or on the output of instrumented implants. Data from instrumented implants have been consistently lower than mathematical predictions. The authors compared mathematical estimates derived from gait laboratory observations made in a patient with an instrumented hip implant. Appropriate modifications to past models resulted in force predictions that were reasonably similar to the output of the instrumented implant. Peak resultant forces were in the range of 2.5-3.5 body weight during level walking at a freely selected speed, while peak out-of-plane forces ranged from 0.6 to 0.9 body weight. Previous parametric hip-force predictions resulting from mathematically modeled surgical alterations may be high insofar as absolute peak values, but trends are likely correct.

BACKGROUND Approximately 15% of all lung cancer deaths in the United States (about 22,350 deaths annually) may not be directly attributable to active cigarette smoking. Consumption of beta carotene, which is derived almost exclusively from intake of fruits and vegetables, has been associated with a reduced risk of lung cancer in smokers. However, studies examining this association in nonsmokers, particularly nonsmoking men, are limited. PURPOSE The purpose of this study was to examine whether dietary factors including beta carotene and retinol are associated with a reduced risk for lung cancer in nonsmoking men and women. METHODS A population-based, matched case-control study of lung cancer in nonsmokers was conducted in New York State from 1982 to 1985. Dietary interviews were completed for 413 individually matched case-control pairs of subjects. To determine whether the relationship between dietary intake from specific food groups and lung cancer differed by type of interview, smoking history, sex, age, or histologic type, we examined data on the case-control pairs from each subgroup separately. The intake of beta carotene and retinol was calculated as the weighted sum of the monthly frequencies of consumption of food items containing these nutrients, where the weights correspond to the nutrient content of a typical portion of the food items. RESULTS Consumption of greens (P for trend < .01), fresh fruits (P for trend < .01), and cheese (P for trend < .05) was associated with a significant dose-dependent reduction in risk for lung cancer, whereas consumption of whole milk (P for trend < .01) was associated with a significant dose-dependent increase in risk. Use of vitamin E supplements was also protective (odds ratio = 0.55; 95% confidence interval [CI] = 0.35-0.85). Increased consumption of the following food groups was associated with a reduction in risk among females: vegetables (P for trend < .025), raw fruits and vegetables (P for trend < .005), and dairy products (P for trend < .025). In males, increased consumption of raw fruits and vegetables was associated with a reduced risk for lung cancer (P for trend < .005). Dietary beta carotene (OR = 0.70; 95% CI = 0.50-0.99), but not retinol (OR = 0.98; 95% CI = 0.82-1.17), was significantly associated with risk reduction. CONCLUSIONS This is the largest study to date of dietary factors and lung cancer in nonsmokers; results suggest that dietary beta carotene, raw fruits and vegetables, and vitamin E supplements reduce the risk of lung cancer in nonsmoking men and women.

Hemangioma is a well-recognized cause of airway obstruction in the infant with stridor. Corticosteroid and laser therapy are effective in stabilizing the airway in most cases. There are, however, some extensive airway lesions that are not adequately managed by these modalities. This report describes the use of recombinant interferon alfa-2a in 15 patients with life-threatening airway hemangiomas. All patients had failed corticosteroid and/or laser therapy. Multiple upper airway sites were involved, including the base of the tongue, supraglottis, subglottis, trachea, and mediastinum. Eleven patients have completed therapy and are doing well. Four patients have resolving lesions on the drug regimen. Life-threatening airway lesions unresponsive to conventional treatment should be considered for a trial of interferon alfa-2a.

We examined the relationship between the survival of women with breast cancer and the gender of their first children using a genealogy-based survival analysis. The study group consisted of 2,155 parous women diagnosed in Utah (United States) with first primary breast cancers (excludingin situ tumors). We calculated hazard rate ratios (HRR) which were adjusted for stage, median survival times, and proportions surviving for three-, five-, and 10-year intervals stratified by age at diagnosis. Median survival among women diagnosed under the age of 45 was 171 months if the first child was female, but only 66 months if the first child was male (HRR=1.66, 95 percent confidence interval=1.07–2.57, for male children). For women diagnosed at age 45 or older, all survival times were similar, although women whose first child was male had slightly longer median survival time. These findings suggest that the gender of the first child has a strong influence on survival among women diagnosed under 45 years of age, but not among those diagnosed later in life. Gender of the first offspring may be a useful clinical indicator of prognosis and survival and may provide insights into etiologic and promotional factors for breast cancer.Cancer Causes and Control 1994, 5, 26–30.

Objectives To review the characteristic microbiology of the paranasal sinuses in patients with cystic fibrosis who undergo endoscopic sinus surgery. To examine the subtypes of organisms cultured from the maxillary sinuses and determine their sensitivity to antibiotic therapy. Study design Retrospective chart review. Setting Tertiary care children's hospital. Methods Sinus cultures were obtained from 51 patients with cystic fibrosis during endoscopic sinus procedures between 2000 and 2004 at a tertiary care children's hospital. A retrospective chart review was undertaken to obtain culture and sensitivity data of the sinus contents. Results The most common bacteria isolated was Staphylococcus aureus (71%), followed by Pseudomonas aeruginosa (PSA) (27%), Haemophilus influenzae (21%), Staphylococcus non-aureus (16%) and Streptococcus viridans (12%). Streptococcus pneumoniae and Moraxella catarrhalis were rarely isolated (2% and 0% respectively). Twenty-nine percent of the patients with cultures positive for PSA were of the mucoid variant. Only one patient had culture positive Escherichia coli. Antibiotic resistance among the more common organisms cultured from the sinus samples is also listed. Conclusion Staph. aureus is the most common isolate in the sinuses of this pediatric CF population followed by P. aeruginosa and H. influenzae. Although many isolates are pansensitive, some isolates are panresistant.

Background: Although seldom described, varus and valgus osteotomies of the proximal femur can affect femoral version. The magnitude of the effect can be predicted with an understanding of the distinction between femoral version and femoral neck inclination. The purpose of this study was to elucidate this relationship. Methods: Version, inclination, apparent neck-shaft angle, and true neck-shaft angle were defined and measured in 72 preserved femora. Results: Average values were 19.8 ± 11.8 degrees for version versus 14.5 ± 10.1 degrees for inclination (P=0.004), giving a mean difference of 27% between version and inclination, with greater discrepancy with increasing neck-shaft angle. There were high correlations between measured inclination and inclination calculated using version and apparent neck-shaft angle (r=0.96) and true neck-shaft angle (r=0.97), validating our formulaic relationship between these variables. Conclusions: We present and validate the concept of inclination, and its relationship with version and neck-shaft angle. This explains the mechanism for a varus osteotomy decreasing anteversion, and a valgus osteotomy increasing anteversion. Clinical Relevance: With an understanding of these concepts, a surgeon can incline the femoral neck axis to achieve a desired amount of version, for any given neck-shaft angle. Without this understanding, precise control of the version and neck-shaft angle is difficult.

Cerebrospinal fluid leaks can be difficult management problems. Little information has been published about handling these cases in the pediatric population. A review of cases over the past 10 years at Boston Children's Hospital was undertaken to identify any prognostic factors and therapeutic recommendations. Twenty-seven patients were identified. While most patients responded to conservative therapy, those with leaks that persisted longer than 8 days required some type of operative closure. Severity of injury had little correlation with the occurrence of a leak. The findings in this study indicate that most pediatric cases can be managed on a conservative basis.

Objective The use of image guidance for sinonasal and skull base surgery has been well-characterized in adults but there is limited information on the use of these systems in the pediatric population, despite their widespread use. The aim of this study is to evaluate the use of image guidance systems to facilitate an endoscopic minimally invasive approach to sinonasal and skull base surgery in a pediatric population. Methods A retrospective cohort study was performed at a tertiary pediatric hospital. Thirty-three children presented with complications of sinusitis, tumors, traumatic, or congenital lesions of the skull base and underwent endoscopic surgery using image guidance from March 2000 to April 2007. Patient variables including diagnosis, extent of disease, and complications were extracted from paper and computer charts. Additional surgical variables including set-up time, accuracy, surgeon satisfaction index and number of uses per case were also reviewed. Results Twenty-eight patients (85%) underwent sinonasal surgery and five (15%) underwent skull base surgery. Indications included infectious complications of acute sinusitis ( N = 15), neoplasms ( N = 12), choanal atresia ( N = 4), and cerebrospinal fluid leak ( N = 2). Thirty-one patients (94%) required only one procedure. No surgical complications were reported. Surgeon satisfaction, mean accuracy and number of uses per procedure increased over time ( p Conclusions Image guidance systems are safe and effective tools that facilitate a minimally invasive approach to sinonasal and skull base surgery in children. Consistent with adult literature, usage and surgeon comfort increased with experience. The additional anatomical information obtained by image guidance systems facilitates a minimally invasive endoscopic approach for sinonasal and skull base pathologies.

To determine the prevalence of sensorineural hearing loss (SNHL) in cystic fibrosis (CF) patients and its relationship to antibiotic use.Case series with chart review.Tertiary care pediatric hospital.We reviewed the medical records of CF patients seen in our children's hospital between March 1994 and December 2007. Data collected included patient demographics, audiograms, tympanograms, genotype, and use of potentially ototoxic antibiotics.Seven of 50 (14%) patients had SNHL. Three percent of patients who receivedor=10 courses of intravenous aminoglycosides had SNHL versus 43 percent of those who received10 courses (P0.01). No patients who received five or fewer courses of nasal irrigation with aminoglycosides had SNHL versus 23 percent of those who received more than five courses (P0.05). Nine percent of patients who received five or fewer courses of macrolides had SNHL versus 60 percent of those who received more than five courses (P=0.079).CF patients receiving aminoglycosides are at high risk for developing SNHL.

Incidence rates and standardized incidence ratios (SIRs) for invasive and in situ cervical cancers diagnosed in 1982-87 were analyzed according to total population size of 148 towns, using data from the population-based Connecticut Tumor Registry. Previous studies have not considered socioeconomic or sociodemographic variables in analyzing cervical cancer rates in urban-rural or population density groups. In multiple regression analyses, increases in SIRs for invasive and in situ cancer from medium-sized to large towns were explained by differences in poverty prevalence or other socio-demographic variables. Nevertheless, cancer screening programs (aimed at preventing invasive cancer through early detection) could be targeted to some extent on the basis of town size category, because larger towns include large numbers of poorer and minority women with higher rates of invasive cervical cancer. SIRs for in situ cancer were significantly elevated in the largest towns (100,000 + total population), and primary prevention programs could target these larger towns with a higher prevalence of poverty.

As knee flexion increases, so do tendofemoral and patellofemoral compression forces. Three cases of long-standing uncorrected flexion contractures of the knees are presented that resulted in marked erosion of the femoral trochlea, patella baja, and remodeled patellar articular surfaces likely reflecting increased angles of flexion. It is probable that the deep femoral grooves are the result of adaptation under high-level persistent contact loads from the quadriceps tendon. These examples expand our knowledge of bone remodeling and offer information of potential use in studying ancient skeletal samples.

OBJECTIVE: To determine the efficacy of a preoperative bleeding questionnaire (POBQ) and coagulation screening in predicting hemorrhage associated with adenotonsillectomy. STUDY DESIGN: Retrospective study. SUBJECTS AND METHODS: Between January 1998 and December 2003, 7730 tonsillectomy and adenotonsillectomy patients were administered the POBQ preoperatively. Further coagulation screening was based on POBQ responses. RESULTS: A total of 232 (3.0%) of 7730 had postoperative bleeding; 184 (3.2%) of 5782 patients who had negative questionnaires bled postoperatively compared with 48 (2.5%) of 1948 patients with positive questionnaires (P = 0.126). Of 1948 patients with positive questionnaires, 141 (7.2%) had abnormal preoperative coagulation screens and 9 (6.4%) of 141 bled; of the 1807 (92.8%) with negative coagulation screens, 39 (2.2%) bled (P = 0.005). CONCLUSION: The POBQ is an effective tool for identifying patients who are at potential risk for post-tonsillectomy bleeding. Patients with both a positive POBQ and coagulation screen had a statistically higher likelihood of postoperative bleeding than other patients. The POBQ allowed the identification of individuals with bleeding disorders to be treated before surgery, likely decreasing the risk of bleeding in these patients.

Objective To assess the benefits of adenotonsillectomy in the treatment of pediatric patients with PFAPA (periodic fever, aphthous ulcers, pharyngitis, and adenitis) syndrome. Design Prospective case series. Setting Tertiary care pediatric hospital. Patients Pediatric patients meeting criteria for PFAPA syndrome. Intervention Tonsillectomy with or without adenoidectomy. Main Outcome Measure Resolution of PFAPA symptoms. Results Twenty-seven (14 female, 13 male) children with PFAPA syndrome underwent tonsillectomy with or without adenoidectomy from 2004 through 2006. The length of follow-up for all patients ranged from 8 to 41 months. A total of 26 patients experienced a complete resolution of their symptoms. The 1 child who continued to have febrile episodes had fever cycles that were not regular in duration or interval and in hindsight was not likely a patient with PFAPA syndrome. Conclusions Our findings showed complete resolution of symptoms in 26 of 27 patients with PFAPA syndrome treated surgically. Patients who meet clinical criteria for PFAPA syndrome should be considered for tonsillectomy and adenoidectomy if they do not respond to medical management.

Data from a large case-control study of breast cancer were examined to test the hypothesis that maternal age at the birth of female offspring is related to the incidence of breast cancer in daughters. Participants were between the ages of 20 and 54 at the time of the study. Based on results for 2,492 parous women who were newly diagnosed with breast cancer and 2,687 parous controls from the general population, a 15-year increase in maternal age was found to be associated with a 29% increase in the risk of breast cancer in daughters. Adjustment for the daughter's age, her own reproductive history, and other potential confounding factors yielded an estimate of 25% for this increase in risk (95% CI, 8% to 46%). The corresponding increase among 499 nulliparous cases and 457 nulliparous controls was 7%, which was not statistically significantly different in magnitude from the increase among parous women. These findings provide evidence for perinatal influences on the subsequent incidence of breast cancer during adulthood. Although specific mechanisms cannot be inferred directly, the results are consistent with the hypothesis that mutations in the genes of the human egg or sperm play a role in the etiology of breast cancer in female offspring.