Vocal cord movement: can it be accurately graded?

INTRODUCTION: Flexible nasendoscopy (FNE) is the principal assessment method for vocal cord movement. Because the procedure is inherently subjective it may not be possible for clinicians to grade the degree of vocal cord movement reliably. The aim of this study was to assess the accuracy and consistency of grading vocal cord movement as viewed via FNE. METHODS: Thirty FNE videos, without sound or clinical information, were assessed by six consultant head and neck surgeons. The surgeons were asked to assess and grade right and left vocal cord movement independently, based on a five-category scale. This process was repeated three times on separate occasions. Agreement and reliability were assessed. RESULTS: Mean overall observed inter-rater agreement was 67.7% (sd 1.9) with the five-category scale, increasing to 91.4% (sd 1.9) when a three-category scale was derived. Mean overall observed intra-rater agreement was 78.3% (sd 9.7) for five categories, increasing to 93.1% (sd 3.3) for three categories. Discriminating vocal cord motion was less reliable using the five-category scale (k = 0.52) than with the three-category scale (k = 0.68). CONCLUSIONS: This study demonstrates quantitatively that it is challenging to accurately and consistently grade subtle differences in vocal cord movement, as proven by the reduced agreement and reliability when using a five-point scale instead of a three-point scale. The study highlights the need for an objective measure to help in the assessment of vocal cord movement.

Immune cell profiling in the joint following human and murine articular fracture.

OBJECTIVE: Human and in vivo animal research implicates inflammation following articular fracture as contributing to post-traumatic arthritis. However, relevant immune cell subsets present following injury are currently undefined. Immunophenotyping human and murine synovial fluid may help to identify immune cell populations that play key roles in the response to articular fracture. METHODS: Immunophenotyping by polychromatic flow cytometry was performed on human and mouse synovial fluid following articular fracture. Specimens were collected in patients with closed ankle fracture at the time of surgical fixation and from C57BL/6 mice with closed articular knee fracture. Immune cells were collected from injured and uninjured joints in mice via a novel cell isolation method. Whole blood samples were also collected. Immunohistochemistry (IHC) was performed on mouse synovial tissue to assess for macrophages and T cells. RESULTS: Following intra-articular fracture, the prominent human synovial fluid immune cell subset was CD3+ T cells, containing both CD4+ and CD8+ T cells. In mice, infiltration of CD45+ immune cells in synovial fluid of the fractured limb was dominated by CD19+ B cells and CD3+ T cells at 7 days after intra-articular fracture. We also detected adaptive immune cells, including macrophages, NK cells, dendritic cells and monocytes. Macrophage and T cell findings were supported by IHC of murine synovial tissue. CONCLUSIONS: Determining specific cell populations that mediate the immune response is essential to elucidating the chain of events initiated after injury and may be an important step in identifying potential immune signatures predictive of PTA susceptibility or potential therapeutic targets.

Leukocytes as a reservoir of circulating oncogenic DNA and regulatory targets of tumor-derived extracellular vesicles.

Essentials Tumor-bearing mice were employed to follow oncogenic HRAS sequences in plasma, and blood cells. Cancer DNA accumulated in leukocytes above levels detected in exosomes, platelets and plasma. Extracellular vesicles and nucleosomes are required for uptake of tumor DNA by leukocytes. Uptake of tumor-derived extracellular vesicles by leukocytes triggers coagulant phenotype. SUMMARY: Background Tumor-derived extracellular vesicles (EVs) and free nucleosomes (NSs) carry into the circulation a wealth of cancer-specific, bioactive and poorly understood molecular cargoes, including genomic DNA (gDNA). Objective Here we investigated the distribution of extracellular oncogenic gDNA sequences (HRAS and HER2) in the circulation of tumor-bearing mice. Methods and Results Surprisingly, circulating leukocytes (WBCs), especially neutrophils, contained the highest levels of mutant gDNA, which exceeded the amount of this material recovered from soluble fractions of plasma, circulating EVs, platelets, red blood cells (RBCs) and peripheral organs, as quantified by digital droplet PCR (ddPCR). Tumor excision resulted in disappearance of the WBC-associated gDNA signal within 2-9 days, which is in line with the expected half-life of these cells. EVs and nucleosomes were essential for the uptake of tumor-derived extracellular DNA by neutrophil-like cells and impacted their phenotype. Indeed, the exposure of granulocytic HL-60 cells to EVs from HRAS-driven cancer cells resulted in a selective increase in tissue factor (TF) procoagulant activity and interleukin 8 (IL-8) production. The levels of circulating thrombin-antithrombin complexes (TAT) were markedly elevated in mice harboring HRAS-driven xenografts. Conclusions Myeloid cells may represent a hitherto unrecognized reservoir of cancer-derived, EV/NS-associated oncogenic gDNA in the circulation, and a possible novel platform for liquid biopsy in cancer. In addition, uptake of this material alters the phenotype of myeloid cells, induces procoagulant and proinflammatory activity and may contribute to systemic effects associated with cancer.

Endoscopic vocal fold injection using a 25-gauge butterfly needle.

OBJECTIVE: To describe a useful technique for infiltrating a bulking agent using a butterfly needle, as part of a transoral endoscopic vocal fold medialisation procedure. METHODS: This paper describes the procedure of grasping the needle with phonosurgery forceps and administering the injectate to the vocal fold through careful application of the syringe plunger via a length of rubber tubing from outside the mouth. RESULTS: This procedure is performed routinely in our institution without complication. The advantages of this technique are discussed. CONCLUSION: This is a safe and easy method of injecting into a vocal fold.

Is there a change in the epidemiology of nasal fractures in females in the UK?

OBJECTIVE: To determine whether there is a change in the epidemiology of nasal fractures in females in the UK, and the potential contribution of the 'ladette' culture. METHODS: This paper reports a multi-centre retrospective study. Operating theatre data for all females who underwent manipulation of nasal fractures under anaesthesia between 2002 and 2009 were analysed. In addition, the case notes of all females presenting with nasal fractures over a five-year period (2004-2009) were retrospectively reviewed and the cited cause of the fracture was noted. RESULTS: From 2002 to 2009, there was an 825 per cent increase in nasal fractures in women aged 13-20 years. Almost one-quarter of all nasal fractures in one centre was attributed to non-domestic violence. The highest incidence of nasal fractures (67 per cent) was amongst white British females. CONCLUSION: There is an increasing trend in the number of women sustaining nasal fractures in the UK. The cause may be multi-factorial, but could be partially attributed to a rise in ladette culture. Further research on the role of alcohol consumption in this phenomenon is needed.

Pain and health-related quality of life in people with chronic leg ulcers.

INTRODUCTION: Venous leg ulceration is associated with pain and poor health-related quality of life (HRQL). The purpose of this study was to identify demographic and clinical characteristics associated with pain and decreased HRQL in patients with active venous ulcers. METHODS: Baseline data were combined from two trials that took place between 2001 and 2007 (n = 564). Pain was measured using the Numeric Pain Scale (NPS), and HRQL was measured using the Medical Outcomes Survey 12-item Short Form (SF-12), which generates a Physical (PCS) and Mental Component Summary (MCS). Analyses included logistic and linear regression (for pain and HRQL, respectively). RESULTS: Mean age was 66.5 years; 47% were male. Median NPS score was 2.2 (out of 10) and mean PCS and MCS scores were 38.0 and 50.5, respectively (scores are standardized to a mean of 50 representing average HRQL). Younger age, living with others, and arthritis were associated with pain. Poorer PCS was associated with being female, venous/mixed ulcer etiology, larger ulcers, longer ulcer duration, cardiovascular disease, arthritis and higher pain intensity. Poorer MCS was associated with younger age, longer ulcer duration, comorbidity and higher pain intensity. CONCLUSION: Research is needed to test strategies to reduce pain and possibly improve HRQL in high risk groups.

TITLE: Douleur et qualité de vie liée à la santé chez les personnes souffrant d'ulcères chroniques aux jambes. INTRODUCTION: L'ulcération veineuse de la jambe est associée à de la douleur et à une mauvaise qualité de vie liée à la santé (QVLS). Cette étude visait à définir les caractéristiques démographiques et cliniques associées à la douleur et à une diminution de la QVLS chez les patients présentant des ulcères veineux actifs. MÉTHODOLOGIE: Les données de base obtenues dans le cadre de deux essais menés entre 2001 et 2007 (n = 564) ont été combinées. La douleur a été mesurée à l'aide de l'échelle numérique de la douleur (END), et la QVLS a été mesurée à l'aide du formulaire abrégé comportant 12 questions de l'Enquête sur la santé (SF-12), qui produit un sommaire de la composante physique (SCP) et un sommaire de la composante mentale (SCM). Les analyses ont notamment été effectuées par régression logistique (pour la douleur) et par régression linéaire (pour la QVLS). RÉSULTATS: L'âge moyen était de 66,5 ans; 47 % étaient des hommes. Le score médian sur l'END était de 2,2 (sur 10) et les scores moyens du SCP et du SCM étaient respectivement de 38,0 et de 50,5 (les scores sont normalisés à une moyenne de 50, qui représente la QVLS moyenne). Le jeune âge, le fait de vivre avec d'autres personnes et l'arthrite ont été associés à la douleur. Un score plus faible pour le SCP a été associé au fait d'être une femme, aux ulcères d'origine veineuse/mixte, aux gros ulcères, aux ulcères de longue durée, aux maladies cardiovasculaires, à l'arthrite et la douleur intense. Un score plus faible pour le SCM a été associé au jeune âge, aux ulcères de longue durée, aux affections concomitantes et à la douleur intense. CONCLUSION: Il convient de mener des recherches pour mettre à l'essai des stratégies d'atténuation de la douleur et d'amélioration potentielle de la QVLS chez les groupes à risque élevé.

Internal nasal valve incompetence is effectively treated using batten graft functional rhinoplasty.

Introduction. Internal nasal valve incompetence (INVI) has been treated with various surgical methods. Large, single surgeon case series are lacking, meaning that the evidence supporting a particular technique has been deficient. We present a case series using alar batten grafts to reconstruct the internal nasal valve, all performed by the senior author. Methods. Over a 7-year period, 107 patients with nasal obstruction caused by INVI underwent alar batten grafting. Preoperative assessment included the use of nasal strips to evaluate symptom improvement. Visual analogue scale (VAS) assessment of nasal blockage (NB) and quality of life (QOL) both pre- and postoperatively were performed and analysed with the Wilcoxon signed rank test. Results. Sixty-seven patients responded to both pre- and postoperative questionnaires. Ninety-one percent reported an improvement in NB and 88% an improvement in QOL. The greatest improvement was seen at 6 months (median VAS 15 mm and 88 mm resp., with a P value of <0.05 for both). Nasal strips were used preoperatively and are a useful tool in predicting patient operative success in both NB and QOL (odds ratio 2.15 and 2.58, resp.). Conclusions. Alar batten graft insertion as a single technique is a valid technique in treating INVI and produces good outcomes.

ADAR1 is essential for intestinal homeostasis and stem cell maintenance.

Adenosine deaminase acting on RNA 1 (ADAR1) is a double-stranded RNA-editing enzyme that converts adenosine (A) to inosine (I), and essential for normal development. In this study, we reported an essential role of ADAR1 in the survival and maintenance of intestinal stem cells and intestinal homoeostasis by suppressing endoplasmic reticulum (ER) stress and interferon (IFN) signaling. ADAR1 was highly expressed in the Lgr5+ cells, and its deletion in adult mice led to a rapid apoptosis and loss of these actively cycling stem cells in the small intestine and colon. ADAR1 deletion resulted in a drastic expansion of progenitors and Paneth cells but a reduction of three other major epithelial lineages. Moreover, loss of ADAR1 induced ER stress and activation of IFN signaling, and altered expression in WNT targets, followed by intestinal inflammation. An ER stress inhibitor partially suppressed crypt apoptosis. Finally, data from cultured intestinal crypts demonstrated that loss of ADAR1 in the epithelial cells is the primary cause of these effects. These results support an essential role of ADAR1 and RNA editing in tissue homeostasis and stem cells.

Oncological safety of the Hayes-Martin manoeuvre in neck dissections for node-positive oropharyngeal squamous cell carcinoma.

INTRODUCTION: The Hayes-Martin manoeuvre involves ligation of the posterior facial vein and superior reflection of the investing fascia below the mandible to preserve the marginal mandibular nerve. The peri-facial nodes thus remain undissected. We perform this manoeuvre routinely during modified radical neck dissection for metastatic oropharyngeal squamous cell cancer. Here, we review the oncological safety and marginal mandibular nerve preservation rates of this manoeuvre from 2004 to 2009. METHOD: Retrospective review of the head and neck oncology database (2004-2009) at Addenbrooke's Hospital, Cambridge, UK, a tertiary referral centre for head and neck oncology. RESULTS: Thirty-four patients underwent modified radical neck dissection for metastatic oropharyngeal squamous cell carcinoma. The primary tumour included the tonsil in 19 cases, base of tongue in 10 and posterior pharyngeal wall in 5. The neck nodal status was N1 in 4 cases, N(2a) in 11, N(2b) in 10, N(2c) in 4 and N(3) in 5. All patients had adjuvant radiotherapy. Median follow up was four years (range, two to five). No peri-facial nodal region recurrences were seen. Four patients had temporary marginal mandibular nerve weakness; beyond two months, no weakness was seen. CONCLUSION: In neck dissections for oropharyngeal squamous cell carcinoma, the marginal mandibular nerve and accompanying facial nodes can be safely preserved without oncological risk using the Hayes-Martin manoeuvre.

Ultrasound-guided core-needle biopsy and magnetic resonance imaging in the accurate diagnosis of intramuscular haemangiomas of the head and neck.

INTRODUCTION: Intramuscular haemangiomas of the digastric muscle are often misdiagnosed due to their low incidence and non-specific manifestation. Only two out of six previously reported cases were diagnosed correctly before excision. Ultrasound may not reveal their vascularity, and fine-needle aspiration biopsy is unhelpful as it reveals only blood. METHODS: A case of intramuscular haemangioma of the posterior belly of the digastric muscle is described. Previously reported cases are reviewed. Investigations used to diagnose the lesions and reasons for their common failure are discussed. RESULTS: Core-needle biopsy led to the correct histological diagnosis, and magnetic resonance imaging precisely located the lesion within the digastric muscle. CONCLUSION: Core-needle biopsy was safely used in the diagnosis of an intramuscular haemangioma. The combination of core-needle biopsy and meticulous review of magnetic resonance imaging enables accurate diagnosis pre-operatively.

Safety of extracapsular dissection in benign superficial parotid lesions.

INTRODUCTION: The current practice for removal of clinically benign superficial parotid lesions is an appropriate superficial parotidectomy with a cuff of normal parotid tissue for complete pathological clearance. This technique requires the identification of the facial nerve at the main trunk and dissection of the segment of the facial nerve deep to the lesion. The reported major complications of this procedure include temporary or permanent facial nerve weakness, Frey's syndrome and salivary leaks. In order to avoid these complications, a local extracapsular dissection technique can be utilised in the management of small inferiorly located benign lesions of the parotid gland. METHODS: A retrospective case note review was performed for all parotidectomies between 2004 and 2009 in Addenbrooke's Hospital, Cambridge by the senior authors. RESULTS: A total of 172 cases were identified out which 46 underwent an extracapsular dissection. The average size of these lesions was 1.9 cm (0.9-2.4 cm) with all universally located inferior or posterior to the angle of the mandible. The pathologies were 14 pleomorphic adenomas, 24 Warthin's tumours, 6 lymphangiomas and 2 simple cysts. There were no post-operative facial nerve weaknesses, Frey's syndrome or salivary leaks within the extracapsular dissection group. The median follow-up of these patients were 4.6 years (2-6 years) with 6 patients lost to follow-up. No recurrences have been noted in the cohort at follow-up.

Teaching veterinary obstetrics using three-dimensional animation technology.

In this three-year study, test scores for students taught veterinary obstetrics in a classroom setting with either traditional media (photographs, text, and two-dimensional graphical presentations) were compared with those for students taught by incorporating three-dimensional (3D) media (linear animations and interactive QuickTime Virtual Reality models) into the classroom lectures. Incorporation of the 3D animations and interactive models significantly increased students' scores on essay questions designed to assess their comprehension of the subject matter. This approach to education may help to better prepare students for dealing with obstetrical cases during their final clinical year and after graduation.

Initial UK experience of patient satisfaction with the Meniett® device for Ménière's disease treatment.

OBJECTIVES: To evaluate patient satisfaction and symptom improvement following treatment of Ménière's disease with the Meniett® device. METHODS: Retrospective, questionnaire-based audit and analysis of unilateral Ménière's disease patients' records, following on from a previous study from our departments on intra-tympanic gentamicin for Ménière's disease, using the Vertigo Symptom Scale and Glasgow Benefit Inventory as outcome measures. RESULTS: Of 33 consecutive patients treated with the Meniett® device for four to six weeks, 30 responded to the questionnaires (90.9 per cent). Respondents' mean Vertigo Symptom Scale score was 0.7 (range 0-2.1), and their mean Glasgow Benefit Inventory general subscale score was 24.1. Nineteen (63.3 per cent) patients felt that the device had alleviated their vertigo and tinnitus. CONCLUSIONS: This is the first UK study of the effectiveness of the Meniett® device in treating Ménière's disease. It shows that the Meniett® device is a well tolerated, useful and minimally invasive means of treating Ménière's disease after medical treatment has failed, and before more potentially cochleo- and vestibulo-toxic therapies and invasive procedures are utilised.

Internal jugular vein thrombosis secondary to a permanent cardiac pacemaker: an unusual case of lateral neck swelling.

OBJECTIVE: To describe an unusual case of lateral neck swelling in a patient with a permanent cardiac pacemaker. CASE REPORT: We describe a patient who presented with a painful, lateral neck swelling due to an internal jugular vein thrombus. This thrombus originated from around pacemaker wires in the subclavian vein. This case is unusual, as the vast majority of thromboses in patients with cardiac pacemakers are found in the subclavian vein alone. We also review the literature on the relationship between cardiac pacemakers and internal jugular vein thrombosis, and on the management of the latter. CONCLUSION: Our patient illustrates a rare cause of a painful, lateral neck swelling: an internal jugular vein thrombus secondary to a cardiac pacemaker. Clinicians should be wary of such pathology in similar patients, in order to ensure early treatment and avoidance of complications.

Normal incidence detection of ultraviolet, visible, and mid-infrared radiation in a single GaAs/AlGaAs device.

A GaAs/AlGaAs detector is demonstrated showing multiple detection capabilities. This detector exhibits a broad spectral response in the 200-870 nm (ultraviolet-visible) range for forward bias and in the 590-870 nm (visible) range for reverse bias. In the mid-IR region, two peaks at 5 and 8.9 microm can be observed for low and high forward bias voltages, respectively. In addition, the peak at 8.9 microm is sensitive to the polarization of the incoming radiation.

Associations between chronic disease, age and physical and mental health status.

This paper examines the associations between chronic disease, age, and physical and mental health-related quality of life (HRQOL), using data collected in 10 studies representing five chronic conditions. HRQOL was measured using the SF-36 or the shorter subset, SF-12. Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were graphed by condition in age increments of 10 years, and compared to age- and sex-adjusted normative data. Linear regression models for the PCS and MCS were controlled for available confounders. The sample size of 2418 participants included 129 with renal failure, 366 with osteoarthritis (OA), 487 with heart failure, 1160 with chronic wound (leg ulcer) and 276 with multiple sclerosis (MS). For the PCS, there were large differences between the normative data and the mean scores of those with chronic diseases, but small differences for the MCS. Female gender and comorbid conditions were associated with poorer HRQOL; increased age was associated with poorer PCS and better MCS. This study provided additional evidence that, while physical function could be severely and negatively affected by both chronic disease and advanced age, mental health remained relatively high and stable.