A prospective cohort study exploring the impact of tonsillectomy on feeding difficulties in children.

OBJECTIVES: Paediatric feeding difficulties are common, affecting up to 25% of otherwise healthy children, symptoms include food refusal, gagging, choking, and excessive mealtime duration. These symptoms are commonly described in pre-operative discussions about tonsillectomy. This prospective study explores the impact of tonsillectomy on paediatric feeding difficulties. DESIGN: This prospective cohort study invited caregivers of children undergoing tonsillectomy to complete a PediEAT questionnaire about their children's feeding behaviours, pre and post-operatively. The study was completed in two phases with 9 questions administered in phase 1 and three additional questions added for phase 2. A free text comments box was also provided. Responses were graded from 0 to 5, where 0 is 'never a problem' and 5 is 'always a problem' with eating behaviours. SETTING: The study was conducted at our institution, a tertiary paediatric ENT unit. PARTICIPANTS: Children aged between 6 months - 7 years undergoing tonsillectomy for any indication were invited to participate. MAIN OUTCOME MEASURES: Changes to the Pedi-EAT scores pre and post operatively were the main outcome measure. RESULTS: 102 participants were recruited between January 2020 and January 2022. The mean age of participants was 4.1 years, 87% had a concurrent adenoidectomy. The mean time to completion of post-operative questionnaire was 23 weeks after surgery. 9 of the 12 questions showed a statistically significant improvement in post-operative scores using a paired student t-test (p < 0.05). The most significant improvements related to 'gets tired from eating and is not able to finish' (1.49 pre-op, 0.91 post op, p < 0.01) and 'eats food that needs to be chewed' (1.4 pre-op, 0.72 post-op, p < 0.01). 13% of participants only underwent tonsillectomy and this group also showed a statistically significant improvement in fatigue during eating (p < 0.05). CONCLUSION: Symptoms of fatigue during eating and avoidance of food requiring mastication are most likely to improve following tonsillectomy in children.

Paediatric tracheostomy tubes: recent developments and our current practice.

OBJECTIVE: A variety of paediatric tracheostomy tubes are available. This article reviews the tubes in current use at Great Ormond Street Hospital for Children and Evelina London Children's Hospital. METHODS: This paper outlines our current preferences, and the particular indications for different tracheostomy tubes, speaking valves and other attachments. RESULTS: Our preferred types of tubes have undergone significant design changes. This paper also reports further experience with certain tubes that may be useful in particular circumstances. An updated sizing chart is included for reference purposes. CONCLUSION: The choice of a paediatric tracheostomy tube remains largely determined by individual clinical requirements. Although we still favour a small range of tubes for use in the majority of our patients, there are circumstances in which other varieties are indicated.

Coblation® intracapsular tonsillectomy (tonsillotomy) in children: A prospective study of 500 consecutive cases with long-term follow-up.

OBJECTIVES: Intracapsular tonsillectomy (tonsillotomy) has been used internationally, mainly in the management of obstructive sleep apnoea, rather than recurrent tonsillitis, with few published data evaluating its use for this latter indication. We present long-term prospective data from 500 paediatric cases undergoing Coblation® intracapsular tonsillectomy, for both obstructive and infective indications. DESIGN: Prospective case series, March 2013-January 2016, all with completed follow-up. SETTING: Tertiary paediatric otolaryngological practice. PARTICIPANTS: A total of 500 consecutive patients (6 months to 18 years, mean 5.1 years) undergoing Coblation® intracapsular tonsillectomy (with or without adenoidectomy), for obstructive and/ or infective indications, almost exclusively under the care of the senior author (DJT). MAIN OUTCOME MEASURES: Validated parent-reported T-14 tonsil symptom questionnaires were used in all cases pre- and postoperatively, including in the long term. Parents also recorded duration of analgesia, time to return to school, any complications and whether they would recommend the procedure. RESULTS: With a mean follow-up 7.4 months, symptom control has been excellent (mean total T-14 score (/70) 31.01 preoperatively, 2.68 postoperatively, P<.0000001), with similar trends for obstructive and infective domains. Two small secondary haemorrhages required readmission and observation only (0.4%); otherwise, no complications, delayed discharges or readmissions occurred; 12/500 (2.4%) have since undergone revision tonsil surgery, 10 for obstructive and 2 for infective symptoms, the majority in very young children, with revision adenoidectomy at the same time. More than 99% of parents would recommend the surgery. CONCLUSIONS: Our experience of this technique has been very positive, with excellent control of both obstructive and infective symptoms, and exceptionally low rates of complications. Further work will be required to allow conclusive demonstration of its advantages over extracapsular tonsillectomy.

Post-trauma administration of the pifithrin-α oxygen analog improves histological and functional outcomes after experimental traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Programmed death of neuronal cells plays a crucial role in acute and chronic neurodegeneration following TBI. The tumor suppressor protein p53, a transcription factor, has been recognized as an important regulator of apoptotic neuronal death. The p53 inactivator pifithrin-α (PFT-α) has been shown to be neuroprotective against stroke. A previous cellular study indicated that PFT-α oxygen analog (PFT-α (O)) is more stable and active than PFT-α. We aimed to investigate whether inhibition of p53 using PFT-α or PFT-α (O) would be a potential neuroprotective strategy for TBI. To evaluate whether these drugs protect against excitotoxicity in vitro, primary rat cortical cultures were challenged with glutamate (50mM) in the presence or absence of various concentrations of the p53 inhibitors PFT-α or PFT-α (O). Cell viability was estimated by LDH assay. In vivo, adult Sprague Dawley rats were subjected to controlled cortical impact (CCI, with 4m/s velocity, 2mm deformation). Five hours after injury, PFT-α or PFT-α (O) (2mg/kg, i.v.) was administered to animals. Sensory and motor functions were evaluated by behavioral tests at 24h after TBI. The p53-positive neurons were identified by double staining with cell-specific markers. Levels of mRNA encoding for p53-regulated genes (BAX, PUMA, Bcl-2 and p21) were measured by reverse transcription followed by real time-PCR from TBI animals without or with PFT-α/PFT-α (O) treatment. We found that PFT-α(O) (10 µM) enhanced neuronal survival against glutamate-induced cytotoxicity in vitro more effectively than PFT-α (10 µM). In vivo PFT-α (O) treatment enhanced functional recovery and decreased contusion volume at 24h post-injury. Neuroprotection by PFT-α (O) treatment also reduced p53-positive neurons in the cortical contusion region. In addition, p53-regulated PUMA mRNA levels at 8h were significantly reduced by PFT-α (O) administration after TBI. PFT-α (O) treatment also decreased phospho-p53 positive neurons in the cortical contusion region. Our data suggest that PFT-α (O) provided a significant reduction of cortical cell death and protected neurons from glutamate-induced excitotoxicity in vitro, as well as improved neurological functional outcome and reduced brain injury in vivo via anti-apoptotic mechanisms. The inhibition of p53-induced apoptosis by PFT-α (O) provides a useful tool to evaluate reversible apoptotic mechanisms and may develop into a novel therapeutic strategy for TBI.

Transporter studies in drug development: experience to date and follow-up on decision trees from the International Transporter Consortium.

The International Transporter Consortium (ITC) organized a second workshop in March 2012 to expand on the themes developed during the inaugural ITC workshop held in 2008. The final session of the workshop provided perspectives from regulatory and industry-based scientists, with input from academic scientists, and focused primarily on the decision trees published from the first workshop. These decision trees have become a central part of subsequent regulatory drug-drug interaction (DDI) guidances issued over the past few years.

Highlights from the International Transporter Consortium second workshop.

The Second International Transporter Consortium (ITC) Workshop was held with the purpose of expanding on previous white-paper recommendations, discussing recent regulatory draft guidance documents on transporter-drug interactions, and highlighting transporter-related challenges in drug development. Specific goals were to discuss additional clinically relevant transporters (MATEs, MRP2, BSEP) and best-practice methodologies and to re-evaluate ITC decision trees based on actual case studies. The outcome of the workshop will be a series of white papers targeted for publication in 2013.

Peri-operative complications after adenotonsillectomy in a UK pediatric tertiary referral centre.

OBJECTIVES: Adenoidectomy and/or tonsillectomy are commonly performed in tertiary pediatric hospitals for the management of obstructive sleep apnea, often in children with significant comorbidities. This study examines the peri-operative course of a large series of complex patients undergoing such surgery at a major pediatric centre, reporting particularly cases of respiratory compromise requiring intensive care admission, both electively and unplanned. METHODS: This study was conducted by the pediatric ENT department at Great Ormond Street Hospital. All children undergoing adenoidectomy and/or tonsillectomy from July 2003 to December 2010 were included in this study. This involved a retrospective review of the case notes and hospital databases, with particular emphasis on those children requiring admission to the pediatric intensive care unit. RESULTS: A total of 1735 consecutive admissions for adenoidectomy and/or tonsillectomy (1627 individual patients aged 4-197 months, median 46 months) were included between 2003 and 2010 (998 adenotonsillectomies, 182 tonsillectomies and 555 adenoidectomies). In this group, 999/1627 patients (61.4%) had a diagnosis of sleep disordered breathing or sleep apnea, including 258 who had polysomnography. 407/1627 (25.0%) had no specific comorbidities which were felt likely to influence their surgical outcome. Established high risk factors included age less than 24 months (292), Down syndrome (99), neuromuscular problems (314), craniofacial abnormalities (94), storage diseases (23), morbid obesity (20), cardiovascular disease (133), respiratory disease (261), hemoglobinopathy (76) and coagulophathy (34). 300/1735 admissions were day cases and 1082/1735 were observed for one night. 353/1735 required more than one night in hospital (294 for two to three nights). 7/1735 had primary hemorrhage necessitating return to the operating room, all after tonsillectomy. 41/1735 (38 with major comorbidities) required peri-operative intensive care admission, mostly for respiratory support. Of these, 7 were admitted pre-operatively to intensive care, and 17 were planned post-operative transfers. Only 17/1735 required unanticipated post-operative admission to intensive care. Odds ratio analysis suggested a significantly higher chance of PICU admission in children with particular comorbidities (Down Syndrome, cardiac disease, obesity, cerebral palsy, craniofacial anomalies, mucopolysaccharidoses and hemoglobinopathy) when compared to children without comorbidities. Adenotonsillectomy was associated with a higher risk of PICU admission than adenoidectomy alone, but patient age less than 24 months was not associated with significantly higher rates of PICU admission. There were no peri-operative mortalities in this cohort. CONCLUSIONS: The peri-operative course was largely uneventful for the majority of children undergoing surgery during this period, particularly given the high prevalence of sleep apnea and other risk factors in this cohort. Major complications were uncommon, with 2.4% of these selected, typically high risk cases requiring peri-operative intensive care admission. Importantly, only 1% of all admissions required unanticipated transfer to intensive care. This has informed changes in peri-operative management in this unit, with implications for other pediatric tertiary referral centres.

The effects of age and lipopolysaccharide (LPS)-mediated peripheral inflammation on numbers of central catecholaminergic neurons.

Parkinson's disease (PD), an age-related movement disorder, is characterized by severe catecholaminergic neuron loss in the substantia nigra pars compacta (SN(PC))-ventral tegmental area (VTA) and locus coeruleus (LC). To assess the stability of these central catecholaminergic neurons following an acute episode of severe inflammation, 6 to 22 month old C57/Bl6 mice received a maximally tolerated dose of lipopolysaccharide (LPS) followed by euthanasia 2 hours later to assay peak levels of peripheral and central cytokines; and, 14 weeks later for computerized stereology of tyrosine hydroxylase-immunopositive (tyrosine hydroxylase-positive [TH+]) neurons in the SN(PC)-VTA and LC. Two hours after LPS, cytokine levels varied in an age-related manner, with the greatest peripheral and central elevations in old and young mice, respectively. Severe inflammation failed to cause loss of TH+ neurons in SN(PC)-VTA or LC; however, there was an age-related decline in these TH+ neurons in LPS-treated and control groups. Thus, unknown mechanisms in the B6 mouse brain appear to protect against catecholaminergic neuron loss following an acute episode of severe inflammation, while catecholaminergic neuron loss occurs during normal aging.

Branchial anomalies in children.

BACKGROUND: Branchial cleft anomalies are the second most common head and neck congenital lesions seen in children. Amongst the branchial cleft malformations, second cleft lesions account for 95% of the branchial anomalies. This article analyzes all the cases of branchial cleft anomalies operated on at Great Ormond Street Hospital over the past 10 years. METHODS: All children who underwent surgery for branchial cleft sinus or fistula from January 2000 to December 2010 were included in this study. RESULTS: In this series, we had 80 patients (38 female and 42 male). The age at the time of operation varied from 1 year to 14 years. Amongst this group, 15 patients had first branchial cleft anomaly, 62 had second branchial cleft anomaly and 3 had fourth branchial pouch anomaly. All the first cleft cases were operated on by a superficial parotidectomy approach with facial nerve identification. Complete excision was achieved in all these first cleft cases. In this series of first cleft anomalies, we had one complication (temporary marginal mandibular nerve weakness. In the 62 children with second branchial cleft anomalies, 50 were unilateral and 12 were bilateral. In the vast majority, the tract extended through the carotid bifurcation and extended up to pharyngeal constrictor muscles. Majority of these cases were operated on through an elliptical incision around the external opening. Complete excision was achieved in all second cleft cases except one who required a repeat excision. In this subgroup, we had two complications one patient developed a seroma and one had incomplete excision. The three patients with fourth pouch anomaly were treated with endoscopic assisted monopolar diathermy to the sinus opening with good outcome. CONCLUSION: Branchial anomalies are relatively common in children. There are three distinct types, first cleft, second cleft and fourth pouch anomaly. Correct diagnosis is essential to avoid inadequate surgery and multiple procedures. The surgical approach needs to be tailored to the type of anomaly of origin of the anomaly. Complete excision is essential for good outcomes.

Single stage laryngotracheal reconstruction using endoscopic posterior grafting in isolated posterior glottic stenosis in children - how we do it.

OBJECTIVE: Posterior glottic stenosis is a well recognised though rare condition. A wide range of treatment options have been proposed including endoscopic laser techniques and open techniques with grafting. The objective of this study was to present our experience of single stage laryngotracheal reconstruction with endoscopic technique of placement of posterior graft in isolated posterior glottic stenosis. METHODS: This study was conducted at the Department of Paediatric Otolaryngology at Great Ormond Street Hospital, London. The senior authors (ALT, DMA) were involved in the management of two children with isolated posterior glottic stenosis operated on as single stage reconstruction. RESULTS: The two children in this small series had isolated posterior glottic stenosis. The aetiology in both the cases was previous prolonged intubation. Both patients underwent a successful placement of the posterior graft endoscopically, though it was a challenging task because of space constraints. None of these children required an intra-operative or post-operative tracheostomy. There were no complications in these patients. At follow up endoscopic examinations, both these patients have had their airway widened successfully. CONCLUSION: Single stage laryngotracheal reconstruction with endoscopic placement of posterior graft in cases with isolated posterior glottic stenosis is a good alternative to open surgical techniques, although is technically a challenging procedure.

The perils of paint-balling.

While paint-balling a 15-year-old boy was shot on the front of his face guard causing him to hyperextend his neck. Over the next few days he developed neck stiffness and a large painful swelling over his upper left sternocleidomastoid muscle. CT confirmed this to be a haematoma abscess and at operation it was found to originate from the parapharyngeal vessels, extending from the skull base and tracking inferiorly along the carotid sheath, compressing (and partially thrombosing) the internal jugular vein (IJV). After surgical decompression, double-dose low molecular weight heparin and antibiotics, the patient made an uneventful recovery, including recanalisation of his IJV. Delayed cervical haematoma can result in neck space infection and potential airway compromise. Early CT scanning optimises timely intervention, consisting of airway protection, broad-spectrum antibiotics and surgical drainage.

Choosing a paediatric tracheostomy tube: an update on current practice.

OBJECTIVES: A variety of paediatric tracheostomy tubes are available. This article reviews those in current use at Great Ormond Street Hospital. METHODS: We outline our preferences and the particular indications for the different tubes, speaking valves and other attachments. RESULTS: Practice has changed significantly in recent years. One product has been re-sized by its manufacturer; others are no longer commonly used. An updated sizing chart is included for reference purposes, together with manufacturers' contact details. CONCLUSIONS: The choice of paediatric tracheostomy tube is driven by clinical requirements. A small range of tubes are suitable for the majority of children, but some will require other varieties in specific circumstances.

Suction diathermy for adenoidectomy: complications and risk of recurrence.

OBJECTIVES: When introduced, suction coagulation was initially utilised for haemorrhage control following curettage of the adenoid pad. More recently the whole procedure has been performed using the technique. This study aims to report post-operative haemorrhage rates and risk of recurrence in adenoidectomy performed solely by suction diathermy in children. METHODS: A retrospective study of 1411 consecutive paediatric patients. Surgery was performed using suction diathermy. No patients were excluded. All patients were followed up. RESULTS: There were no cases of post-operative haemorrhage. 1.7% of patients remained symptomatic and underwent revision adenoidectomy. None required a third procedure. CONCLUSIONS: Re-growth of adenoid tissue may occur despite visualisation of the nasopharynx at the time of surgery. The incidence of re-growth is similar to that reported in patients undergoing conventional adenoidectomy by curettage. Post-operative haemorrhage was not encountered in children having adenoidectomy by suction diathermy. The authors suggest suction diathermy as the most appropriate method for adenoidectomy in children.

The nasopharyngeal prong airway: an effective post-operative adjunct after adenotonsillectomy for obstructive sleep apnoea in children.

OBJECTIVES: Obstructive sleep apnoea is a common childhood disorder. Adenotonsillar enlargement is most commonly implicated, with adenotonsillectomy representing an effective treatment in the majority of cases. Such children may develop respiratory compromise post-operatively, sometimes necessitating admission to the intensive care unit. We describe insertion of a nasopharyngeal "prong" airway and evaluate its benefits after adenotonsillectomy for obstructive sleep apnoea and milder forms of sleep-disordered breathing. METHODS: The prong is easily fashioned from a paediatric endotracheal tube. It is inserted once surgery is complete, remaining in situ overnight. We retrospectively examine its elective use over an 18-month period in selected children considered to be at high risk of post-operative respiratory compromise. Existing practice over the preceding 18-month period is also examined, by way of comparison. RESULTS: Forty-three children underwent adenotonsillectomy for sleep-disordered breathing/OSAS in the 18 months prior to introduction of the prong. Ten were considered "high risk" cases: post-operative intensive care beds were pre-booked for these, but none were eventually required. During the subsequent 18 months, 60 children underwent adenotonsillectomy for the same indication. Seventeen "high risk" cases received the prong post-operatively. No intensive care beds were pre-booked and all children were managed safely on the ENT ward, with minimal intervention. CONCLUSIONS: Use of a nasopharyngeal prong significantly improves the post-operative course of selected children who are at high risk of respiratory compromise after adenotonsillectomy. This largely avoids the need for medical intervention and intensive care admission.