Extracellular Pax6 Regulates Tangential Cajal-Retzius Cell Migration in the Developing Mouse Neocortex.

The embryonic mouse cortex displays a striking low caudo-medial and high rostro-lateral graded expression of the homeoprotein transcription factor Pax6, which presents both cell autonomous and direct noncell autonomous activities. Through the genetic induction of anti-Pax6 single-chain antibody secretion, we have analyzed Pax6 noncell autonomous activity on the migration of cortical hem- and septum-derived Cajal-Retzius (CR) neurons by live imaging of flat mount developing cerebral cortices. Blocking extracellular Pax6 disrupts tangential CR cell migration patterns by decreasing the distance traveled and changing both directionality and depth at which CR cells migrate. Tracking of single CR cells in mutant cortices revealed that extracellular Pax6 neutralization enhances contact repulsion in medial regions yet reduces it in lateral regions. This study demonstrates that secreted Pax6 controls neuronal migration and distribution and suggests that it acts as a bona fide morphogen at an early stage of cerebral cortex development.

Vocal palsy increases the risk of lower respiratory tract infection in low-risk, low-morbidity patients undergoing thyroidectomy for benign disease: A big data analysis.

OBJECTIVES: Thyroidectomy is the commonest operation that places normally functioning laryngeal nerves at risk of injury. Vocal palsy is a major risk factor for dysphonia, dysphagia, and less commonly, airway obstruction. We investigated the association between post-thyroidectomy vocal palsy and long-term risks of pneumonia and laryngeal failure. DESIGN: An N=near-all analysis of the English administrative dataset using a previously validated informatics algorithm to identify young and otherwise low-risk patients undergoing first-time elective thyroidectomy for benign disease. Information about age, sex, morbidities, social deprivation and post-operative and late complications were derived. MAIN OUTCOME MEASURES: Between 2004 and 2012, 43 515 patients between the ages of 20 and 69 who had no history of cancer, neurological, or respiratory disease underwent elective total or hemithyroidectomy without concomitant or late neck dissection, parathyroidectomy or laryngotracheal surgery for benign thyroid disease for the first and only time. Information about age, sex, morbidities and in-hospital and late complications was recorded. RESULTS: Mean age at surgery was 46±12. There was a strong female preponderance (85%), and most patients (89%) had no recorded Charlson comorbidities Most patients (65%) underwent hemithyroidectomy. Late vocal palsy was recorded in 449 (1.03%) patients, and its occurrence was an independent risk factor for emergency hospital readmission (n=7113; Hazard Ratio 1.52; 95% confidence interval 1.21-1.91), hospitalisation for lower respiratory tract infection (n=944; HR 2.04; 95% CI 1.07-3.75), dysphagia (n=564; HR 3.47; 95% CI 1.57-7.65) and gastrostomy/tracheostomy placement (n=80; HR 20.8; 95% CI 2.5-171.2). Independent risk factors for late vocal palsy were age, burden of morbidities, total thyroidectomy, post operative bleeding, male sex, and annual surgeon volume <30. CONCLUSIONS: There is a significant association between post-thyroidectomy vocal palsy and long-term risks of hospital readmission, dysphagia, hospitalisation for lower respiratory tract infection, and gastrostomy/tracheostomy tube placement. This adds weight to the need, from a thyroid surgical perspective, to undertake universal post-thyroidectomy laryngeal surveillance as a minimum standard of care, with a focus on post-operative dysphagia and aspiration, and from a medical/respiratory perspective, to initiate investigations to identify occult vocal palsy in patients who present with pneumonia, who have a history of thyroid surgery.

A national analysis of trends, outcomes and volume-outcome relationships in thyroid surgery.

OBJECTIVES: Thyroid conditions are common, and their incidence is increasing. Surgery is the mainstay treatment for many thyroid conditions, and understanding its utilisation trends and morbidity is central to improving patient care. DESIGN: An N = near-all analysis of the English administrative dataset to identify trends in thyroid surgery specialisation, volume-outcome relationships, and the incidence and risk factors for short- and long-term morbidity. MAIN OUTCOME MEASURES: Between 2004 and 2012, 72 594 patients underwent elective thyroidectomy in England. Information about age, sex, morbidities, nature of thyroid disease and surgery, adjuvant treatments and complications including hypocalcaemia and vocal palsy was recorded. RESULTS: Mean age at surgery was 49 ± 30, and a female predominance (82%) was observed. Most patients underwent hemithyroidectomy (51%) or total thyroidectomy (32%). Patients underwent surgery for benign (52.5%), benign inflammatory (21%) and malignant (17%) thyroid diseases. Thyroid surgery grew by 2.9% a year and increased in specialisation. Increased surgeon volume significantly reduced lengths of stay: the proportion of length of stay outliers fell from 11.8% for patients of occasional thyroidectomists (<5 per year) to 2.8% for patients of high-volume surgeons (>50 thyroidectomies a year). Post-discharge vocal palsy and hypocalcaemia occurred in 1.87% and 1.58% of cases, respectively. High-volume surgeons had a reduced incidence of vocal palsy, and volumes >30 were consistently protective. CONCLUSIONS: Thyroid surgery is increasingly specialised. High-volume surgeons, that is patients who perform 50 or more thyroidectomies per year, achieve lower complications and shorter lengths of stay.

Impact of unilateral vocal fold mobility impairment on laryngopulmonary physiology.

OBJECTIVE: To examine the impact of unilateral vocal fold mobility impairment (UVFMI) on airway physiology. STUDY DESIGN: Cross-sectional observational study. PARTICIPANTS: There were 21 patients with UVFMI and 53 controls. MAIN OUTCOME MEASURES: All patients and patient controls underwent a maximum-effort flow-volume loop examination. Forced expiratory flow in one second (FEV1 ), forced expiratory volume (FVC), peak inspiratory flow rate and peak expiratory flow rate (PIFR and PEFR, respectively) and area under the inspiratory and expiratory flow-volume loops (AUCI nspiratory and AUCE xpiratory, respectively) were measured. The ratio of PEFR to PIFR and AUCE xpiratory to AUCI nspiratory was derived. RESULTS: There were 48 males and 26 females. Mean age at measurement was 39 ± 11 years. Patients and controls were matched for age, sex, height and weight. None of the expiratory variables were significantly different between the groups. PIFR was significantly lower in UVFMI patients compared with controls (3.4 ± 1.2 versus 5.3 ± 1.8; P < 0.0001), as was AUCI nspiratory (11.5 ± 6.3 versus 17.5 ± 8.5; P = 0.0002). PEFR/PIFR provided the best differentiation between patients with UVFMI and controls with an area under the Receiver Operating Characteristic (ROC) curve of 0.96 and at a threshold of 1.9, and PEFR/PIFR had sensitivity and specificity of 95.2% and 90.6%, respectively. CONCLUSIONS: Flow-volume loops are a non-invasive method of studying vocal abduction and could compliment voice assessment and laryngoscopy in UVFMI. With further research, they could provide an outcome measure for laryngeal rehabilitative procedures, and a shared physiological language for screening and surgical quality assurance.

A national analysis of the outcome of major head and neck cancer surgery: implications for surgeon-level data publication.

OBJECTIVES: To undertake a national outcomes analysis following major head and neck cancer surgery in order to identify risk factors for complications and in-hospital mortality, as well as areas whose closer examination and formal benchmarking in the context of local and national quality assurance audits may lead to improved results for this condition. DESIGN: An analysis using Hospital Episode Statistics data. SETTINGS: All units undertaking major head and neck cancer surgery in England. MAIN OUTCOME MEASURES: Cancer sites, co-morbidities, social deprivation, surgical and non-surgical treatments, complications, and in-hospital mortality were recorded. Regression analysis was used for casemix adjustment and for identifying independent predictors of complications and mortality. Funnel plots were used for data visualisation. RESULTS: We identified 10,589 major head and neck cancer operations performed in England between 2006 and 2011. There were 7312 males, and mean age at surgery was 63 ± 13 years. Oral cavity (42%) and the larynx (28%) were the commonest cancer sites. At least one complication occurred in 33.1% of patients, and there were 322 (3.05%) in-hospital deaths. Variables associated with in-hospital mortality were trust volume, age, co-morbidities, performing emergency major surgery and performing a tracheostomy or reconstructive surgery. Occurrence of major medical complications including pulmonary infections (7%), major acute cardiovascular events (4.7%) and acute renal failure (0.6%) also increased mortality risk. The analysis identified units that were outside of crude and risk-adjusted 99.8% limits of confidence for complications and mortality. CONCLUSION: Mortality following head and neck cancer surgery shows significant national variation and is associated with fixed risk factors like age and co-morbidities, but also with modifiable risk factors like performing major surgery during an emergency admission, tracheostomy, reconstructive surgery and medical complications. We propose that the quality of tracheostomy care, reconstructive surgery, emergency major surgery rate, and occurrence and treatment of major medical complications should be closely examined and formally benchmarked as part of loco-regional and national quality improvement audits.

Vocal fold paralysis following first dose of Oxford-AstraZeneca coronavirus disease 2019 vaccine.

BACKGROUND: In a bid to end the ongoing coronavirus disease 2019 pandemic, many countries, including the UK, have rolled out mass immunisation programmes. While considered generally safe and effective, vaccines against coronavirus disease 2019 have been reported to be associated with rare and potentially adverse reactions and side effects. CASE REPORT: This paper reports an unusual case of a patient who developed a unilateral vocal fold paralysis shortly after receiving the first dose of the Oxford-AstraZeneca ChAdOx1 nCov-19 vaccine. CONCLUSION: To our knowledge, this is the first reported case of vocal fold paralysis following administration of the Oxford-AstraZeneca vaccine. The authors support the position that currently approved coronavirus disease 2019 vaccines remain safe and effective; however, further surveillance and vigilance using real-world data are highly encouraged.

Patterns, timing and consequences of post-thyroidectomy haemorrhage.

INTRODUCTION Post-thyroidectomy bleeding is a low frequency but potentially life threatening event that is very difficult to predict. Given the increasing drive towards thyroidectomy with same day discharge, this study was conducted with the aim of identifying patterns, timing and consequences of post-thyroidectomy bleeding to assess the feasibility of day-case thyroidectomy. METHODS All patients who underwent a thyroidectomy between 2008 and 2015 at our institution were identified. Patterns, timing and consequences in all those who developed post-thyroidectomy bleeding were studied. RESULTS Of the 805 patients included in the study, 14 required re-exploration for bleeding; 7 (50%) of these within 8 hours of surgery, 6 (43%) between 18 and 30 hours, and 1 (7%) at 49 hours. Just under half (43%) of those with post-thyroidectomy bleeding had thyrotoxicosis. CONCLUSIONS A significant number of postoperative haemorrhages occurred beyond the immediate postoperative period. Same day discharge after thyroidectomy cannot therefore be recommended as a routine practice.

[Efficacy of a combined Sabal-urtica preparation in the symptomatic treatment of benign prostatic hyperplasia. Results of a placebo-controlled double-blind study]. / Symptomatische Wirksamkeit eines Sabal-urtica-Kombinationspräparats in der Therapie des benignen Prostatasyndroms. Ergebnisse einer plazebokontrollierten Doppelblindstudie.

UNLABELLED: This re-evaluation of a double-blind placebo-controlled therapeutic study of the combined sabal-urtica preparation PRO 160/120 investigates the changes in the irritative symptoms of benign prostatic hyperplasia (BPH) under the test substance in comparison with placebo. It was found that, over the study period of 24 weeks, the micturition symptoms frequency and urgency were statistically significantly improved under the well-tolerated PRO 160/120 in comparison with placebo. The patient's quality of life was also significantly better under PRO 160/120 in comparison with placebo. CONCLUSION: The often distressing symptoms of BPH can be effectively ameliorated already after only a few weeks of treatment with the sabal-urtica preparation PRO 160/120. In particular those patients with the stigmatizing symptoms urinary urgency and frequency benefit from such treatment.

Endotracheal tube positioning during neck extension in thyroidectomy.

OBJECTIVE: To evaluate the effect of body mass index and neck length on endotracheal tube movement during neck extension in thyroidectomy. METHODS: A prospective study was conducted of 30 patients undergoing thyroidectomy during an 8-month period. Patient characteristics were recorded and endotracheal tube displacement was determined. RESULTS: Mean body mass index was 27.8 kg/m2 (range, 17.5-34.7 kg/m2) and mean neck circumference was 43.2 cm (range, 28-56 cm). The mean (± standard deviation) upward displacement of the endotracheal tube during neck extension was 7.17 ± 5.87 mm. Patients with a larger body mass index had a significantly greater amount of tube displacement (R2 = 0.67, p < 0.0001), as did patients with a smaller neck length (R2 = 0.48, p < 0.0001). CONCLUSION: Neck extension results in upward displacement of the endotracheal tube. The amount of displacement is significantly higher in patients with a larger body mass index or shorter neck length. This has particular relevance for nerve monitoring in thyroidectomy.

Endoscopic-guided injection of botulinum toxin into the cricopharyngeus muscle: our experience.

OBJECTIVE: To assess the efficacy of endoscopic-guided botulinum toxin injection into the cricopharyngeus muscle and evaluate the duration of its effects. METHODS: A 3-year prospective study of 12 patients undergoing injection of botulinum toxin was conducted, with a telephone survey to assess dysphagia pre-operatively, and at 1, 3 and 6 months post-treatment, using the MD Anderson Dysphagia Inventory. RESULTS: Median age was 66.2 years. Causes of cricopharyngeal dysphagia included idiopathic cricopharyngeal hypertrophy (67 per cent), previous cerebrovascular accident (17 per cent), cranial nerve palsy (8 per cent) and previous chemoradiotherapy to the neck (8 per cent). There were no complications. Two patients had repeat injections after six months. There was significant improvement in MD Anderson Dysphagia Inventory scores at one and three months versus pre-operative scores (73.1 ± 14.9 vs 46.9 ± 7.6, p = 0.0001, and 65.1 ± 11.5 vs 46.9 ± 7.6, p = 0.0001), but not at six months (51.0 ± 11.0 vs 46.9 ± 7.6, p = 0.14). CONCLUSION: Endoscopic-guided injection of botulinum toxin into the cricopharyngeus muscle is a safe and effective method for treating cricopharyngeal muscle dysfunction, lasting up to six months.

Brachiocephalic artery haemorrhage during percutaneous tracheostomy.

Percutaneous tracheostomy was performed on a 69-year-old woman to facilitate weaning. Insertion of the size 7 tracheostomy tube resulted in profuse bleeding around the tracheostomy site. On inflation of the tracheostomy balloon, the bleeding stopped. Urgent computed tomography demonstrated the brachiocephalic artery was abnormally high and lying in an oblique fashion over the trachea, and the tracheostomy tube was displacing the trachea posteriorly. Surgical repair of the defect in the brachiocephalic artery was undertaken and a surgical tracheostomy was performed in theatre. This case raises important issues about the potential dangers of percutaneous tracheostomy in cases of abnormal anatomy. It also emphasises the importance of direct visualisation of the seeker needle using the endoscope. In cases where there is a suspicion of abnormal anatomy, it is safer to obtain preprocedural imaging or perform a surgical tracheostomy.

Lacrimal gland abscess complicating acute sinusitis.

Infections of the lacrimal gland are uncommon, with suppuration and abscess formation being exceedingly rare. Acute bacterial dacryoadenitis may develop secondary to an adjacent infection, from blood-borne spread or after trauma. We report a paediatric case of lacrimal gland abscess thought to be caused by spread of infection from the paranasal sinuses. The possible mechanisms of spread of infection to the lacrimal gland are discussed as well as the management of this unusual complication of sinusitis.

Recurrent meningitis due to a congenital fistula of the stapedial footplate.

A rare case of a congenital fistula of the stapes footplate, in a 10-year-old girl, resulting in recurrent meningitis, is reported. A full ENT examination and a high index of suspicion, is essential if the diagnosis is to be made. Exploratory tympanotomy should be considered on clinical grounds, even if a high resolution CT scan of the temporal bones does not show any anomalies, in order to ascertain the definite diagnosis of a fistula and to seal it permanently.

Necrotizing fasciitis of the neck.

Necrotizing fasciitis (N.F.) is a rare but serious infection of subcutaneous tissues and deep fascia with resulting skin gangrene and septicaemia. It is due to mixed anaerobic and aerobic organisms. It has been reported under a variety of synonyms. We describe two cases of necrotizing fasciitis of the neck probably secondary to chronic dental infection, one was diagnosed early and the other late with very different outcomes. We highlight the importance of early and aggressive surgical treatment to complement parenteral antibiotics covering both aerobic and anaerobic organisms.

Transitional papilloma of the middle ear.

We present a rare case of a transitional papilloma of the middle ear, occurring several years after excision of a similar lesion from the nose. There was no continuity between the two lesions suggesting that these tumours can be multicentric in origin.

Alar cartilage haematoma.

We present a previously undescribed site of a subperichondrial haematoma--the alar cartilage. Two children presenting acutely, following trauma, with the clinical appearance of a 'blueberry' within the nasal vestibule are described. We recommend early surgical drainage of this lesion, as delay in definitive treatment may give rise to a cosmetic deformity.

Ameloblastoma: a rare nasal polyp.

Ameloblastoma is an odontogenic neoplasm of enamel organ type tissue which does not undergo transformation to the point of enamel formation. We present the second case in the English literature of maxillary ameloblastoma that presented with nasal obstruction and rhinorrhoea, and the first to be excised using a combined maxillotomy and endoscopic ethmoidectomy. The patient had no previous dental history. The unusual presenting symptoms, as well as the highly destructive nature of these lesions when arising in the maxilla, make them worthy of consideration in the differential diagnosis of nasal and maxillary masses. We discuss the clinical features, pathology and management of these lesions and review the literature.

Myringoplasty under local anaesthesia: day case surgery.

Eleven patients underwent fat graft myringoplasty, using EMLA cream local anaesthetic, as day cases. 10 of them were followed up, and 3 months post-operatively, 8/10 (80%) of the perforations were completely closed, with an average improvement of the hearing threshold of 11 dB. All the patients were satisfied with the procedure and it is concluded that fat graft myringoplasty under local anaesthesia as a day case is safe, simple, reliable and cost effective. It should be considered for closure of small perforations (30% or less) of the tympanic membrane.