Expert Consensus Statement: Management of Dysphagia in Head and Neck Cancer Patients.

OBJECTIVE: To develop an expert consensus statement (ECS) on the management of dysphagia in head and neck cancer (HNC) patients to address controversies and offer opportunities for quality improvement. Dysphagia in HNC was defined as swallowing impairment in patients with cancers of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, or hypopharynx. METHODS: Development group members with expertise in dysphagia followed established guidelines for developing ECS. A professional search strategist systematically reviewed the literature, and the best available evidence was used to compose consensus statements targeted at providers managing dysphagia in adult HNC populations. The development group prioritized topics where there was significant practice variation and topics that would improve the quality of HNC patient care if consensus were possible. RESULTS: The development group identified 60 candidate consensus statements, based on 75 initial proposed topics and questions, that focused on addressing the following high yield topics: (1) risk factors, (2) screening, (3) evaluation, (4) prevention, (5) interventions, and (6) surveillance. After 2 iterations of the Delphi survey and the removal of duplicative statements, 48 statements met the standardized definition for consensus; 12 statements were designated as no consensus. CONCLUSION: Expert consensus was achieved for 48 statements pertaining to risk factors, screening, evaluation, prevention, intervention, and surveillance for dysphagia in HNC patients. Clinicians can use these statements to improve quality of care, inform policy and protocols, and appreciate areas where there is no consensus. Future research, ideally randomized controlled trials, is warranted to address additional controversies related to dysphagia in HNC patients.

Transcript and blood-microbiome analysis towards a blood diagnostic tool for goats affected by Haemonchus contortus.

The Alpine goat (Capra aegagrus hircus) is parasitized by the barber pole worm (Haemonchus contortus). Hematological parameters from transcript and metagenome analysis in the host are reflective of infestation. We explored comparisons between blood samples of control, infected, infected zoledronic acid-treated, and infected antibody (anti-γδ T cells) treated wethers under controlled conditions. Seven days post-inoculation (dpi), we identified 7,627 transcripts associated with the different treatment types. Microbiome measurements at 7 dpi revealed fewer raw read counts across all treatments and a less diverse microbial flora than at 21 dpi. This study identifies treatment specific transcripts and an increase in microflora abundance and diversity as wethers age. Further, F/B ratio reflect health, based on depression or elevation above thresholds defined by the baseline of non-infected controls. Forty Alpine wethers were studied where blood samples were collected from five goats in four treatment groups on 7 dpi and 21 dpi. Transcript and microbiome profiles were obtained using the Partek Flow (St. Louis, Missouri, USA) software suites pipelines. Inflammation comparisons were based on the Firmicutes/Bacteriodetes ratios that are calculated as well as the reduction of microbial diversity.

Mortality Following Hospital Admission for US Active Duty Service Members Diagnosed With Penetrating Traumatic Brain Injury, 2004-2014.

OBJECTIVE: To examine mortality among active duty US military service members (SMs) with the diagnosis of penetrating traumatic brain injury (PTBI) and a hospital admission between 2004 and 2014. DESIGN: Data on SMs with PTBI and an admission to a military or civilian hospital were obtained from the 2004 to 2014 Military Health System data repository. After applying exclusion criteria, data on 1226 SMs were analyzed. MAIN MEASURES: The number of observed deaths per 100 identified patients with PTBI and time to death from admission were used as main measures. RESULTS: Approximately 25% of the 1226 patients with PTBI included in this study died following admission, with 44.6% of the all deaths occurring within a day following hospital admission and 75% occurring within the first week. Severe comorbid conditions and intentionally self-inflicted injuries are associated with higher mortality rate. SMs' gender, age, year of hospital admission, and service were significantly associated with likelihood of death following PTBI hospitalization. Males had a higher likelihood of dying following hospital admission compared with females (odds ratio = 2.7, confidence interval = 1.03-7.9). SMs in the 35- to 44-year-old and 45- to 64-year-old groups had up to a 2.6 times higher odds of death following their admission compared with the 25- to 34-year-old group. Age, admission year, service, and rank were significantly associated with SMs' time to death from hospitalization. Patients between the ages of 45 and 64 years were significantly more likely to die earlier than other age groups. Furthermore, cases in the Navy Afloat group had a higher fatality rate and were more likely to die earlier than patients in other services. PTBI comorbid conditions and injury type did not significantly affect time to death. CONCLUSION: This study quantifies case fatality rate among hospitalized US SMs with the diagnosis of PTBI. We report a 23.1% crude case fatality rate among the current cohort. Early intensive care for these patients may be the key to improving survival rates.

Donor cell leukemia in umbilical cord blood transplant patients: a case study and literature review highlighting the importance of molecular engraftment analysis.

Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pediatric patient with a history of acute myeloid leukemia that manifested as recurrent AML FAB type M5 fourteen months after umbilical cord blood transplantation. Although there was some immunophenotypic drift from the patient's original AML and their posttransplant presentation, the initial pathological impression was of recurrent disease. Bone marrow engraftment analysis by multiplex PCR of short tandem repeat markers performed on the patient's diagnostic specimen showed complete engraftment by donor cells, with a loss of heterozygosity in the donor alleles on chromosome 7. This led to the reinterpretation of this patient's disease as donor-derived leukemia. This interpretation was supported by a routine karyotype and fluorescence in situ hybridization analysis showing loss of chromosome 7 and a male (donor) chromosome complement in this female patient. Also noted was a loss of the patient's presenting chromosomal abnormality, t(11;19)(q23;p13). This case highlights the need for close coordination between all aspects of clinical testing for the transplant patient, including molecular engraftment studies, when distinguishing the very common complication of recurrent disease from the exceedingly rare complication of donor cell leukemia.

Botulinum toxin injections for new onset bilateral vocal fold motion impairment in adults.

OBJECTIVES/HYPOTHESIS: Review of clinical experience and results using botulinum toxin type A (BTX) for the management of adult patients with respiratory compromise due to new onset bilateral vocal fold motion impairment (BVFMI). STUDY DESIGN: Retrospective case series. METHODS: The records of 11 patients from two institutions with respiratory compromise due to bilateral vocal fold motion impairment were reviewed. Age, sex, etiology of motion impairment, subjective response to BTX injections, changes in pulmonary function studies pre- and postinjection when available, the dosage of botulinum toxin required to achieve response, the number of injections per patient, and complications were reported. RESULTS: All patients were over 18 years old. There were three male and eight female subjects. The etiology of BVFMI was due to previous anterior cervical surgery in nine patients and prolonged intubation in two. Ten patients reported symptomatic improvement and returned for an average of nine injections over the 10-year period of study. The most common interval between injections was 3 months. In all patients the dose required to achieve symptomatic improvement was at least 2.5 mouse units injected into each vocal fold. One patient without relief of symptoms had bilateral cricoarytenoid joint fixation. Complications were limited to moderate dysphagia in one patient and breathy dysphonia in all patients. CONCLUSIONS: BTX injection into the vocal folds provides temporary relief of symptoms in airway obstruction in adult patients with BVFMI. Patients require an average of 2.5 units of botulinum injection into each vocal fold and have an average length of response of 3 months. BTX injection may be used as a form of temporary relief of airway obstruction in patients wishing to avoid ablative surgery or tracheotomy.

Vocal fold augmentation with calcium hydroxylapatite: twelve-month report.

OBJECTIVES: To evaluate the long-term effectiveness of calcium hydroxylapatite (CaHA) vocal fold injection for patients with glottal insufficiency. STUDY DESIGN: Multicenter, open-label, prospective clinical study of CaHA vocal fold injection. METHODS: Each patient served as his/her own control. Voice-related outcome measures were collected for pre-injection, 1, 3, 6, and 12 months. RESULTS: Sixty-three patients were available for evaluation. Fifty-three percent of the injection procedures were done in the office. Fifty-seven percent of patients were diagnosed with unilateral paralysis and 43% with glottal incompetence with mobile vocal folds. Patient satisfaction 12 months after injection showed 67% reporting a significant improvement in voice and 81% reporting at least a moderate improvement in voice. Utilizing the Voice Handicap Index-10, visual analog scale (vocal effort), Consensus Assessment Perceptual Evaluation V (judgments of voice severity), and objective voice measures of glottal closure (maximum phonation time and S:Z ratio), paired t tests showed significant improvements after treatment. A 22% further treatment rate was found at the 12-month time point. CONCLUSIONS: One-year results in this large cohort of patients with glottal incompetence treated with CaHA vocal fold injection demonstrate that excellent clinical results were achieved.

Fellowship training in otolaryngology-head and neck surgery.

Fellowship training in otolaryngology-head and neck surgery is a relatively new phenomenon that reflects the increasing complexity of clinical medicine. Despite an expansion of fellowship opportunities over the last three decades, there is still incomplete regulation and standardization of fellowship training. Approximately one third of residency graduates obtain some form of fellowship training. This article describes the fellowship opportunities that are currently available within the field of otolaryngology. Fellowship training serves as an avenue to gain further credentials and certification, although only the fields of neurotology, pediatric otolaryngology, and sleep medicine are accredited by the ACGME.

Injection versus medialization laryngoplasty for the treatment of unilateral vocal fold paralysis.

OBJECTIVE/HYPOTHESIS: To determine whether injection laryngoplasty or medialization laryngoplasty is more effective in the treatment of unilateral vocal fold paralysis. STUDY DESIGN: A retrospective study of patients with unilateral vocal fold paralysis who underwent either injection or medialization laryngoplasty at the University of Arkansas for Medical Sciences between July 29, 2003 and March 8, 2005. METHODS: The data analyzed included patient characteristics and type of intervention, along with the pretreatment and posttreatment voice parameters of videostrobolaryngoscopy, perceptual analysis, and patients' subjective voice assessment. RESULTS: Nineteen patients were evaluated. The average time from intervention to posttreatment evaluation was 3 (range, 1-9) months. Improvements were demonstrated in all three voice parameters in both the injection and the medialization groups. No significant differences were found in the degree of improvement between the two groups. Videostrobolaryngoscopy and the perceptual analysis, both rated by the authors, correlated well with each other, but they both correlated poorly with the patients' subjective voice analysis. CONCLUSIONS: Injection and medialization laryngoplasty were comparable in their improvement of subjective and objective voice outcomes. Both treatment modalities should be included in the otolaryngologist's armamentarium for managing unilateral vocal fold paralysis.

Vocal fold augmentation with calcium hydroxylapatite (CaHA).

OBJECTIVES: Evaluate the effectiveness of CaHA injection for patients with glottal incompetence. METHODS: Multi-center, open-label, prospective clinical study with each patient serving as his/her own control. Voice-related outcome measures were collected for pre-injection and 1, 3, and 6 months. RESULTS: Sixty-eight patients were available for evaluation. Fifty percent of the injection procedures were done in office. Fifty-seven percent were diagnosed with unilateral paralysis and 42% with glottal incompetence with mobile vocal folds. Patient satisfaction 6 months post showed 56% had significantly improved voice and 38% reported moderately improved voice. Paired t tests from baseline to 6 months showed significant improvements on the VHI and VAS (vocal effort), CAPE-V judgments of voice severity and videoendostroboscopy ratings of glottal closure, and objective voice measures of glottal closure (MPT and S:Z ratio). CONCLUSIONS: Preliminary results in this large cohort of patients demonstrate excellent clinical results.

Patient versus partner perception of voice handicap.

The primary purpose of this study was to compare patient's and communication partner's perceptions of handicap secondary to dysphonia. A secondary purpose was to compare patient health-related quality of life (HRQOL) to that of speakers with normal voice. Participants were 20 adults (mean age=69.15 years) with dysphonia and their communication partners. Patients completed the Voice Handicap Index (VHI), a questionnaire of self-perceived voice handicap, and the Short-Form 36 (SF-36), a general health questionnaire. Partners completed the Voice Handicap Index-Partner (VHI-P), a questionnaire derived from the VHI for this pilot study, to gauge partner perception of voice handicap. Patients in this study viewed themselves as only moderately handicapped by their dysphonia and their partners were in close agreement. Patients and their partners were also in close agreement on each of three VHI subscales (physical, functional, and emotional), and in all cases the physical domain was perceived by both patients and their partners to be most handicapped. Patients had lower SF-36 mean scores than those of persons with normal voice from the general U.S. population on scales assessing physical functioning, physical role, general health, vitality, social functioning, emotional role, and mental health. The results of this study are consistent with previous studies examining patient-partner agreement, which consider proxy ratings to be a useful alternative or collaborative source of patient's self-perception. Further research regarding the reliability of patient and partner agreement is necessary to most effectively assess and manage patients with dysphonia.

Malignant peripheral nerve sheath tumor arising in association with the sural nerve.

Malignant peripheral nerve sheath tumor is a rare sarcoma of peripheral nerves found most often in deep soft tissue. This aggressive tumor is difficult to diagnose clinically and must be surgically excised for therapy. An incisional biopsy will allow for testing and in most cases, diagnosis. The authors present a case of a 39-year-old African American woman with malignant peripheral nerve sheath tumor in association with the sural nerve. The tumor was surgically removed and sent for pathologic studies. The patient reported to her first postoperative appointment and was referred to an oncologist for follow-up. Despite multiple attempts at contacting the patient and explaining the prognosis of the diagnosis, the patient refused further follow-up care including referral to an oncologist.

Prediction of T-cell epitopes using biosupport vector machines.

The immune system is concerned with the recognition and disposal of foreign or "non self" molecules or cells that enter the body of an immunologically competent individual. The generation of an immune response depends on the interaction of components, namely, the immunogen (nonself or foreign cell or molecule), antibody producing humoral immune system, and sensitized lymphocyte producing cellular immune system. An immunogen possesses surface structures referred to as epitopes; the precise pattern of each epitope enables an individual's immune system to recognize cells or molecules as self or immunogens. During the recognition process, the specific cells known as macrophages identify the epitope structures on the immunogen and save them in the form of short peptides 10-18 amino-acids-long known as immune dominant peptides (IDPs). IDPs are then bound with surface proteins on macrophages known as MHC protein complexes. The macrophages then present this IDP-MHC complex to a T cell that possesses a specific receptor that is specific for the foreign epitope on the IDP bound to MHC complex. This initiates an immune system cascade that results in the disposal of the immunogen. The study and accurate prediction of T-cell epitopes is, thus, very important for designing vaccines against pathogenic diseases. The present study applied the newly developed biosupport vector machine to the T-cell epitope data. This new algorithm introduces a biobasis function into the conventional support vector machines so that the nonnumerical attributes (amino acids) in protein sequences can be recognized without a feature extraction process, which often fails to properly code the biological content in protein sequences. The prediction accuracy of a 10-fold cross validation is 90.31%, compared with 87.86% using support vector machines reported as the best compared with other algorithms in an earlier study.

Management of advanced premalignant laryngeal lesions.

PURPOSE OF REVIEW: Laryngeal carcinogenesis is a multistep process with premalignant lesions progressing to invasive carcinoma over a period of years. The approach to these advanced premalignant lesions has always been early diagnosis and treatment to prevent further progression. Unfortunately, with the current means of diagnosis and a lack of consensus regarding treatment of these lesions, the incidence of advanced laryngeal malignancies continues to rise. The purpose of this article is to review the most recent contributions to the literature regarding diagnosis and management of advanced laryngeal premalignant lesions. RECENT FINDINGS: The current literature focuses on several new diagnostic procedures to improve early detection of high-risk laryngeal lesions. These procedures include autofluorescence endoscopy, compact endoscopy, and topical 5-aminolevulinic acid. One large long-term study suggests an aggressive surgical approach in the treatment of advanced laryngeal premalignancies to decrease the incidence of malignant transformation. The preliminary results of chemoprevention trials as well as potential new biomarkers are discussed. SUMMARY: There are several new promising procedures that may have an impact on the early diagnosis of laryngeal precursor lesions. In addition, we are gaining knowledge about the molecular events occurring along the continuum of laryngeal carcinogenesis. This will hopefully allow the identification of additional biomarkers and future targets for chemoprevention.