Preservation or removal of the lateral nasal wall in endoscopic management of maxillary sinus neoplasia: A comparison of approach related morbidity.

BACKGROUND: The endoscopic modified medial maxillectomy (MMM) and prelacrimal approach (PLA) are two routinely performed endoscopic approaches to the maxillary sinus when access via a middle meatal antrostomy is insufficient. However, there is no data in the literature that has compared outcomes and complication profile between the two procedures to determine which approach is superior. OBJECTIVE: To compare the approach related morbidity of PLA and MMM. METHODS: A retrospective cohort study of all consecutive adult patients undergoing either MMM or PLA from 2009 to 2023 were identified. The primary outcome was development of epistaxis, paraesthesia, lacrimal injury, iatrogenic sinus dysfunction within a minimum of 3 months post-operative follow up. RESULTS: 39 patients (44 sides) underwent PLA and 96 (96 sides) underwent MMM. There were no statistically significant differences between the rates of paraesthesia (9.1 % vs 14.6 %, p = 0.367) or prolonged paraesthesia (2.3 % vs 5.2 %, p = 0.426), iatrogenic maxillary sinus dysfunction (2.3 % vs 5.2 %, p = 0.426) or adhesions requiring removal (4.5 % vs 4.2 %, p = 0.918). No cases of epiphora or nasal cavity stenosis occurred in either arm in our study. CONCLUSIONS: According to our data, the endoscopic modified medial maxillectomy and prelacrimal approach are both equally safe approaches with their own benefits to access.

Myomodulation Using Botulinum Toxin in Septorhinoplasty for Crooked Noses: Introducing the Concept and Application of Nasal Muscle Imbalance Theory.

The role of septorhinoplasty for adequate correction of deviated nose is well documented, but the rationales and patterns for recurrences after proper rhinoplasty remain unclear. There has also been little attention given to the influence of nasal musculatures on the stability of nasal structures after septorhinoplasty. The aim of this article is to propose our nasal muscle imbalance theory, which may explain the potential reason for redeviation of the noses in the initial period after septorhinoplasty. We postulate that in a chronically deviated nose, the nasal muscles on the convex side will be stretched and develop hypertrophy after prolonged period of increased contractile activity. On the contrary, the nasal muscles on the concave side will undergo atrophy due to reduced load requirement. In the initial period of recovery after a septorhinoplasty to bring the nose back to midline, this muscle imbalance is still uncorrected with unequal pulling forces on the nasal structure because the stronger nasal muscles on the previously convex side is still hypertrophied and exert stronger forces compared with the previously concave side, therefore increasing the risk of redeviation of the nose back to the preoperative side until muscle atrophy occurs in the convex side and a balanced nasal muscle pull is achieved. We believe that postseptorhinoplasty botulinum toxin injections can be used as an adjunct in rhinoplasty surgery to effectively block the pulling actions of the stronger or overacting nasal muscles by speeding up the atrophy process while allowing patient's nose to heal and stabilize in the desired position. However, further studies to objectively confirm this hypothesis is required, which include comparing topographic measurements, imaging and electromyography signals before and after injections in postseptorhinoplasty patients. The authors have already planned a multicenter study to further evaluate this theory.

Monogenic and Polygenic Contributions to QTc Prolongation in the Population.

BACKGROUND: Rare sequence variation in genes underlying cardiac repolarization and common polygenic variation influence QT interval duration. However, current clinical genetic testing of individuals with unexplained QT prolongation is restricted to examination of monogenic rare variants. The recent emergence of large-scale biorepositories with sequence data enables examination of the joint contribution of rare and common variations to the QT interval in the population. METHODS: We performed a genome-wide association study of the QTc in 84 630 UK Biobank participants and created a polygenic risk score (PRS). Among 26 976 participants with whole-genome sequencing and ECG data in the TOPMed (Trans-Omics for Precision Medicine) program, we identified 160 carriers of putative pathogenic rare variants in 10 genes known to be associated with the QT interval. We examined QTc associations with the PRS and with rare variants in TOPMed. RESULTS: Fifty-four independent loci were identified by genome-wide association study in the UK Biobank. Twenty-one loci were novel, of which 12 were replicated in TOPMed. The PRS composed of 1 110 494 common variants was significantly associated with the QTc in TOPMed (ΔQTc/decile of PRS=1.4 ms [95% CI, 1.3 to 1.5]; P=1.1×10-196). Carriers of putative pathogenic rare variants had longer QTc than noncarriers (ΔQTc=10.9 ms [95% CI, 7.4 to 14.4]). Of individuals with QTc>480 ms, 23.7% carried either a monogenic rare variant or had a PRS in the top decile (3.4% monogenic, 21% top decile of PRS). CONCLUSIONS: QTc duration in the population is influenced by both rare variants in genes underlying cardiac repolarization and polygenic risk, with a sizeable contribution from polygenic risk. Comprehensive assessment of the genetic determinants of QTc prolongation includes incorporation of both polygenic and monogenic risk.

Associations between birth defects with neural crest cell origins and pediatric embryonal tumors.

BACKGROUND: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins. METHODS: With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education. RESULTS: The risk of embryonal tumors among those with BDNCOs was 0.09% (co-occurring n = 105) compared to 0.03% (95% CI, 0.03%-0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5-5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3-22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3-4.2) and nephroblastoma (2.9; 95% CI, 1.9-4.4) were elevated. There was no notable HRM by the aforementioned factors. CONCLUSIONS: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions.

Reproductive decision-making and the utilization of preimplantation genetic testing among individuals with inherited aortic or vascular disease.

Preimplantation genetic testing for monogenic disorders (PGT-M) is a reproductive technology used in conjunction with in-vitro fertilization (IVF) to reduce the risk of passing on a known genetic condition from parent to child. There is limited research describing the experience and emotional impact of PGT-M among individuals with inherited aortic or vascular disease (IAVD). Our qualitative study aims to explore the factors that influence reproductive decision-making and the uptake of PGT-M within this population. Individuals diagnosed with IAVD who have considered PGT-M, and/or their reproductive partner, were recruited using internal clinical databases and advocacy organizations. Virtual semi-structured interviews were conducted using an interview guide that included questions related to participants' lived experience of their condition, risk perception, reproductive history, familiarity with PGT-M/IVF, and financial/psychosocial considerations. A total of 17 interviews were completed (13 affected individuals, 4 unaffected partners) and analyzed using thematic analysis. Emergent themes included: (1) the lived experience and perceived severity of disease; (2) need for comprehensive, balanced, and timely information; (3) and impact of personal values and circumstances. When discussing the impact of lived experience on reproductive decision-making, participants identified the physical and emotional impact of disease and variability of disease as factors influencing the uptake of PGT-M. Many described PGT-M as the only reproductive option presented to them by providers. Even so, participants expressed gaps in their understanding of PGT-M, particularly regarding cost/insurance coverage and the experience of IVF. Finally, participants recognized that the decision to pursue PGT-M primarily requires introspection and evaluation of one's values, but that cost remains a significant consideration. The findings from our study highlight the complexity of reproductive decision-making for individuals with IAVD and provide insight into their psychological and informational needs when engaging in this process. Providers can use these findings to tailor their discussions about reproductive decision-making with this patient cohort.

Smell-related quality of life changes after total laryngectomy: a multi-centre study.

PURPOSE: A total laryngectomy creates an alternate airway for gas exchange that bypasses the upper aerodigestive tract. The subsequent reduction in nasal airflow, and therefore, reduction in deposition of particles to the olfactory neuroepithelium leads to hyposmia or anosmia. The aim of this study was to assess the quality of life impairment conferred by anosmia following laryngectomy and identify any specific patient-related risk factors that are associated with poorer outcomes. METHODS: Consecutive patients with a total laryngectomy presenting for review at three tertiary head and neck services (in Australia, the United Kingdom and India) over a 12-month period were recruited. Patient demographic and clinical data were collected, and each subject completed the validated assessment of self-reported olfactory functioning and olfaction-related quality of life questionnaire (ASOF). Dichotomous comparisons were performed using the student's unpaired t-test for continuous variables (SRP), a chi-squared test for categorical variables, and a Kendall's tau-b for ordinal variables (SOC) to assess for a correlation with poorer questionnaire scores. RESULTS: A total of 66 laryngectomees (13.4% female; age 65.7 ± 8.6 years) were included in the study. The mean SRP score of the cohort was found to be 15.6 ± 7.4, while the mean ORQ score was noted to be 16.4 ± 8.1. No other specific risk factors associated with poorer quality of life were identified. CONCLUSION: A significant quality of life detriment from hyposmia is conferred following laryngectomy. Further research to assess treatment options and the patient population that would best benefit from these interventions is required.

An artificial intelligence algorithm for the classification of sphenoid sinus pneumatisation on sinus computed tomography scans.

BACKGROUND: Classifying sphenoid pneumatisation is an important but often overlooked task in reporting sinus CT scans. Artificial intelligence (AI) and one of its key methods, convolutional neural networks (CNNs), can create algorithms that can learn from data without being programmed with explicit rules and have shown utility in radiological image classification. OBJECTIVE: To determine if a trained CNN can accurately classify sphenoid sinus pneumatisation on CT sinus imaging. METHODS: Sagittal slices through the natural ostium of the sphenoid sinus were extracted from retrospectively collected bone-window CT scans of the paranasal sinuses for consecutive patients over 6 years. Two blinded Otolaryngology residents reviewed each image and classified the sphenoid sinus pneumatisation as either conchal, presellar or sellar. An AI algorithm was developed using the Microsoft Azure Custom Vision deep learning platform to classify the pattern of pneumatisation. RESULTS: Seven hundred eighty images from 400 patients were used to train the algorithm, which was then tested on a further 118 images from 62 patients. The algorithm achieved an accuracy of 93.2% (95% confidence interval [CI] 87.1-97.0), 87.3% (95% CI 79.9-92.7) and 85.6% (95% CI 78.0-91.4) in correctly identifying conchal, presellar and sellar sphenoid pneumatisation, respectively. The overall weighted accuracy of the CNN was 85.9%. CONCLUSION: The CNN described demonstrated a moderately accurate classification of sphenoid pneumatisation subtypes on CT scans. The use of CNN-based assistive tools may enable surgeons to achieve safer operative planning through routine automated reporting allowing greater resources to be directed towards the identification of pathology.

Perceived usefulness of, engagement with, and effectiveness of virtual reality environments in learning industrial operations: the moderating role of openness to experience.

The development of virtual reality (VR) in enhancing the effectiveness of the learning process, with its interactive, immersive, and intuitive pedagogical environment, has become a necessity for corporations with increasingly complex operations. However, VR users' perceptions, openness and learning effectiveness are seldom comprehensively evaluated, particularly in learning complex industrial operations. In this study, grounded in the technology acceptance model, a moderated mediation model of perceived usefulness, ease of use, openness to experience, and engagement in VR-based learning was developed. The model was empirically validated using responses collected from 321 users who were trained on aircraft and cargo terminal operations powered by a novel VR-based learning platform. A survey to measure openness to experience and a pre-training performance test were carried out, followed by a post-training survey of learners' intrinsic factors, including the influence of perceived usefulness, openness to experience, and attitude towards learning. The study revealed that learners with an open attitude towards experiencing new technology tend to perceive VR technology as a useful platform for training. In addition, the learners with more positive views of VR technology-supported training were more engaged in learning.

Cascade testing for inherited arrhythmia conditions: Experiences and attitudes of family communication approaches for a Canadian cohort.

Inherited arrhythmia conditions (IAC) can lead to sudden cardiac death at any age, and relatives of an affected person have up to a 50% chance of inheriting the condition and are at risk for developing features. Cascade testing is a stepwise approach for identifying relatives at risk for IACs through clinical screening and genetic testing. Early detection can reduce morbidity and mortality for affected individuals and determine potential risk mitigation strategies for relatives. However, cardiovascular genetic studies have reported an incomplete uptake of cascade testing in at-risk relatives. We explored patient perspectives on cascade testing for IACs and alternative approaches to family communication. Twelve semi-structured phone interviews were conducted with probands of the British Columbia Inherited Arrhythmia Program confirmed to carry a pathogenic or likely pathogenic variant in a gene associated with an IAC. Thematic analysis of transcripts through an iterative coding process revealed five main themes: (a) a stepwise approach is followed in disclosing risk to relatives, (b) relatives' autonomy in cascade testing is supported, (c) lived experience with the condition influences disclosure and uptake of cascade testing, (d) collaborative approach to informing relatives reduces negative impact of disclosure, and (e) direct contact from a healthcare provider is viewed as acceptable. The findings highlight this patient cohort's experiences and opinions with approaches to disclosure and demonstrate their understanding and acceptance of their relatives' approaches to cascade testing. In addition, while the notion of direct contact was generally accepted, a collaborative approach to contacting relatives between the proband and provider may be most effective.

Artificial intelligence to classify ear disease from otoscopy: A systematic review and meta-analysis.

OBJECTIVES: To summarise the accuracy of artificial intelligence (AI) computer vision algorithms to classify ear disease from otoscopy. DESIGN: Systematic review and meta-analysis. METHODS: Using the PRISMA guidelines, nine online databases were searched for articles that used AI computer vision algorithms developed from various methods (convolutional neural networks, artificial neural networks, support vector machines, decision trees and k-nearest neighbours) to classify otoscopic images. Diagnostic classes of interest: normal tympanic membrane, acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with or without perforation, cholesteatoma and canal obstruction. MAIN OUTCOME MEASURES: Accuracy to correctly classify otoscopic images compared to otolaryngologists (ground truth). The Quality Assessment of Diagnostic Accuracy Studies Version 2 tool was used to assess the quality of methodology and risk of bias. RESULTS: Thirty-nine articles were included. Algorithms achieved 90.7% (95%CI: 90.1-91.3%) accuracy to difference between normal or abnormal otoscopy images in 14 studies. The most common multiclassification algorithm (3 or more diagnostic classes) achieved 97.6% (95%CI: 97.3-97.9%) accuracy to differentiate between normal, AOM and OME in three studies. AI algorithms outperformed human assessors to classify otoscopy images achieving 93.4% (95%CI: 90.5-96.4%) versus 73.2% (95%CI: 67.9-78.5%) accuracy in three studies. Convolutional neural networks achieved the highest accuracy compared to other classification methods. CONCLUSION: AI can classify ear disease from otoscopy. A concerted effort is required to establish a comprehensive and reliable otoscopy database for algorithm training. An AI-supported otoscopy system may assist health care workers, trainees and primary care practitioners with less otology experience identify ear disease.

The First Report on Incidence of Nasopharyngeal Carcinoma in Sabah, Borneo.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the fourth common cancer in Malaysia. A few studies have looked into the incidence of NPC in Malaysia in general, but there has been no published data on its incidence in Sabah specifically, where NPC is very common among the population. The aim of this study is to present the first report on the incidence of NPC in the state of Sabah, Borneo. METHODS: Data of all patients diagnosed with NPC over a 5-year period from January 2015 to December 2019 inclusive were collected from the NPC registry of 3 main hospitals in Sabah. Age-standardized rates (ASRs) for different genders, ethnicities, and districts of origin were calculated. RESULTS: 215 NPC patients were identified with a mean age at diagnosis of 49 (range 9-82). The ASR of NPC was 7.9/100,000 where the average age-adjusted male-to-female ratio was 2.4. The highest ASR was found in Dusun ethnicity in both male (3.19/100,000) and female (1.69/100,000) individuals, followed by Chinese (both genders), and Kadazan (for male individuals) and Bajau (for female individuals). The highest ASR was found in patients originating from Sandakan, Kota Kinabalu, Keningau, and Tawau. CONCLUSION: This is the first report on the incidence of NPC in Sabah, Borneo. The data suggest high ASRs among the population, especially in male Dusun and Chinese ethnic groups. Further research looking into NPC in this state, especially on risk factors and ways to improve diagnosis and prevention among the population, is recommended.

Objective and subjective changes in voice after endoscopic sinus surgeries in patients with and without nasal polyps.

BACKGROUND: Many studies have looked at the effect of functional endoscopic sinus surgeries (FESS) on nasalance, nasal consonant and nasalized vowels. Only two studies investigated the effect of FESS on vocal sound quality and have not found statistically significant changes before and after operations. The aim of this study was to examine the short-term and long-term objective and subjective changes in the vocal quality of patients after FESS, comparing patients with and without nasal polyps. METHODS: Sixteen patients were recruited for voice analysis during pre-operative, within two weeks and at least three months post-operatively. Subjective questionnaire was used to assess perception of voice changes. RESULTS: There were no statistically significant changes in the acoustic parameters of patients with nasal polyposis. In patients with CRS without polyps, there was a statistically significant increase in fundamental frequency (F0) in nasal sound during early follow up. The changes in soft phonation index (SPI) values between the two groups were statistically significant during early follow-ups. Only patients with nasal polyposis perceived a subjective change in their voice post-operatively. CONCLUSIONS: Clinicians should inform all patients, especially voice professionals about the possible effects of endoscopic sinus surgeries on their voice quality.

Risk factors associated with microbial colonisation and infection of tracheostomy tubes.

BACKGROUND: A long-term tracheostomy tube has the potential to cause significant morbidity and mortality in both hospitalised patients and those in the community. This study aims to assess the rates of microbial colonisation and infection of tracheostomy tubes. MATERIALS AND METHODS: Consecutive patients were enrolled from both inpatient and outpatient settings during their routine tracheostomy changes. During changes, culture swabs were taken from the cuff/outer-cannula and inner-cannula. Analysis were performed to compare culture results with risk factors. RESULTS: 65 patients were enrolled in the study. Inpatients (65.9% vs 38.1%, χ2 4.48, p = 0.03), increasing acuity of care (from outpatient; ward; HDU; and ICU in increasing acuity) (τb = 0.289, p = 0.012), cuffed tracheostomy tubes, (66.7% vs 39.1%; χ2 4.59, p = 0.032); diabetics (64.6% vs 35.3%; χ2 4.39, p = 0.036); and males were associated with increased colonisation (72.4% vs 44.4%; χ2 5.12, p = 0.024). CONCLUSION: Factors associated with an increase in colonisation and infection of tracheostomy tubes were location, and in males, diabetics and in cuffed tubes.

Comparison of arytenoid vertical height discrepancy in normal versus patients with vocal cord palsy.

OBJECTIVE: Cadaveric experiments and more recently clinical data have demonstrated that patients with vertical height discrepancy between their arytenoids experience poorer voice outcomes in patients with unilateral vocal cord palsy (UVP) after medialisation laryngoplasty. However, the presence or severity of height discrepancy in normal patients without UVP has not yet been clearly defined. STUDY DESIGN: Case-control study. SETTING: Tertiary Australian hospitals. SUBJECTS AND METHODS: A retrospective review was performed on patients who underwent high computed tomography imaging of the neck. Scans were assessed for discrepancy in arytenoid vertical height discrepancy and compared to a cohort with known UVP. RESULTS: 44 normal patients (50% female, mean age 57.6 ±â€¯14.8 years) were compared to 23 patients with UVP (43.4% female, mean age 52.3 ±â€¯14.9 years.) Normal patients were found to have a smaller height discrepancy compared to UVP patients (student's t-test,2.00 mm ±â€¯0.00 vs 2.39 mm ±â€¯0.72, p < .001.) CONCLUSION: This study suggests that discrepancy is pathologic, and it is plausible that this results in acoustic consequences.

Turbinate loss from non-inflammatory sinonasal surgery does not correlate with poor sinonasal function.

OBJECTIVE: The impact of turbinate resection on nasal function remains a controversial topic. In surgery for inflammatory sinonasal disease, turbinate resection is often avoided. In contrast, turbinate tissue is routinely sacrificed in endoscopic tumor and skull base surgery to achieve negative margins or gain adequate exposure. Anecdotally, these patients experience good self-reported post-operative nasal function despite extensive turbinate tissue loss. This study investigates the impact of turbinate resection on self-reported sinonasal function following endoscopic tumor or skull base surgery. STUDY DESIGN: Retrospective case series. SETTING: Tertiary Australian Hospitals. SUBJECTS AND METHODS: A retrospective review was performed on consecutive post-surgical patients after management for non-inflammatory sinus disease such as tumor resection or endoscopic skull base reconstruction. Outcome variables assessed included a 6-point Likert score for nasal obstruction, a 13-point Likert score for global nasal function and a 5-question sleep score. The degree of turbinate tissue loss (0-4) was determined by the number of inferior or middle turbinate subtotal resections. Regression analysis was performed, accounting for the effect of relevant demographic variables (smoking; asthma; allergic status; gastroesophageal reflux; malignancy; vestibule mucositis) and treatment variables (subtotal septectomy; Draf III; nasal radiotherapy.) RESULTS: 294 patients (age 52.9 ±â€¯17.6 years, 51.0% female) were assessed. Number of turbinates resected was not associated with poorer nasal obstruction score, global nasal function score or sleep score (OR = 1.77[0.93-3.38], OR = 0.60[0.33-1.12], B = 0.56[-1.58-2.69] respectively). Allergy and Draf3 were found to improve postoperative global nasal function score (OR = 2.07[1.04-4.13], P = 0.04, OR = 3.97[1.08-14.49], P = 0.04, respectively). CONCLUSION: In patients where surgery was performed for non-inflammatory sinus disease, turbinate resection is not correlated with poorer postoperative nasal obstruction, sinonasal function nor sleep quality.

Fungal ball of the maxillary sinus and the risk of persistent sinus dysfunction after simple antrostomy.

BACKGROUND: Maxillary sinus fungal ball is a common cause of unilateral maxillary sinusitis. Fungal balls or mycetomas are primarily treated with surgery to remove the fungus. However, this assumes the pre-fungal ball sinus cavity was normal and post-surgery patients may suffer from mucostasis in the sinus cavity with persistent symptoms. It is proposed that fungal balls are potentially a feature of impaired mucus clearance as they are a pathology in their own right. METHODS: A case series of consecutive patients undergoing antrostomy for maxillary sinus fungal ball was performed. Patient factors including age, gender, smoking status, comorbidities (allergy, asthma, and reflux), disease specific factors including duration of symptoms, microbiology (bacterial co-infection, Gram-positive and/or Gram-negative) and preoperative radiologic findings (extent of sinus development, and neo-osteogenesis/bone thickness) were collected. The primary outcome was sinus function defined by evidence of a normal functioning maxillary sinus, with the absence of mucostasis or pooling, on endoscopic exam at three months, six months and last follow-up. Endoscopic evaluation of inflammation was also collected. RESULTS: 28 patients (age 58.5 ± 15.5 years, 64.3% female) were assessed. Mucostasis was present at three months in 39.3%, at six months in 32.1%, and 17.9% at last follow-up. There was no comorbidity or radiologic finding that was associated with failure to normalize. Those patients with mucostasis had a higher modified Lund-Mackay endoscopic score at last follow-up (5.0 ± 0.7 v 0.2 ± 0.6, p < 0.01). CONCLUSIONS: Long term post-operative mucostasis occurred in 17.9% of patients following an adequate maxillary antrostomy for treatment of a fungal ball. Patients with mucostasis had persistent mucosal inflammation and a greater need for further surgery (modified medial maxillectomy).

Diffuse intrinsic pontine glioma cells are vulnerable to low intensity electric fields delivered by intratumoral modulation therapy.

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a high fatality pediatric brain cancer without effective treatment. The field of electrotherapeutics offers new potential for other forms of glioma but the efficacy of this strategy has not been reported for DIPG. This pilot study evaluated the susceptibility of patient-derived DIPG cells to low intensity electric fields delivered using a developing technology called intratumoral modulation therapy (IMT). METHODS: DIPG cells from autopsy specimens were treated with a custom-designed, in vitro IMT system. Computer-generated electric field simulation was performed to quantify IMT amplitude and distribution using continuous, low intensity, intermediate frequency stimulation parameters. Treatment groups included sham, IMT, temozolomide (TMZ) chemotherapy and radiation therapy (RT). The impact of single and multi-modality therapy was compared using spectrophotometric and flow cytometry viability analyses. RESULTS: DIPG cells exhibited robust, consistent susceptibility to IMT fields that significantly reduced cell viability compared to untreated control levels. The ratio of viable:non-viable DIPG cells transformed from ~ 6:1 in sham-treated to ~ 1.5:1 in IMT-treated conditions. The impact of IMT was similar to that of dual modality TMZ-RT therapy and the addition of IMT to this treatment combination dramatically reduced DIPG cell viability to ~ 20% of control values. CONCLUSIONS: This proof-of-concept study provides a novel demonstration of marked DIPG cell susceptibility to low intensity electric fields delivered using IMT. The potent impact as a monotherapy and when integrated into multi-modality treatment platforms justifies further investigations into the potential of IMT as a critically needed biomedical innovation for DIPG.

Changing biological disease modifying treatment for paediatric uveitis in the real world.

IMPORTANCE: Paediatric uveitis is a severe sight-threatening uveitis due to disease progression and treatment failure. Biological agents are a promising new treatment. This study provides real-world data on their use from Sydney, Australia. BACKGROUND: Traditionally corticosteroids and non-biological immunosuppressive agents were used to treat paediatric uveitis, often with poor outcomes. DESIGN: Retrospective, chart review over an 8-year period at a tertiary referral eye hospital. PARTICIPANTS: A total of 27 paediatric uveitis patients treated with biological agents. METHODS: Chart review of demographic data and treatment outcomes. MAIN OUTCOME MEASURES: Treatment efficacy (corticosteroid-sparing effect, topical steroid cessation/reduction, reduction in systemic-steroid sparing agents, change in intraocular inflammation, visual acuity and central macular thickness); treatment failure; and adverse events. Data were collected at biological initiation, 6 weeks, 6 months and 12 months. RESULTS: Biological therapy over 1 year was effective with prednisolone dose reduced to <5 mg/day in five of six patients (83%), number of systemic steroid-sparing agents was reduced to ≤1 in two of four patients (50%) and cessation of topical steroid achieved in 12/41 of eyes (29%). Improvement of anterior chamber cells by two grades occurred in 20/25 eyes (80%), improvement of logMAR to ≤0.3 occurred in 12/18 eyes (67%) and macular oedema decreased in 4/5 eyes (80%). Treatment failure occurred in six eyes (13.01%) and five patients (18.5%) developed an adverse reaction. CONCLUSIONS AND RELEVANCE: Biological therapy was effective in paediatric patients with uveitis. Intraocular inflammation improved with maintained visual acuity, systemic corticosteroid dose decreased and there was a low frequency of adverse events.

Frontal Sinus Osteoma: From Direct Excision to Endoscopic Removal.

Frontal sinus osteomas are benign bone-forming neoplasms. Ongoing advancements in endoscopic surgery have allowed less invasive surgical approaches to be adopted for removal. The authors systematically reviewed the literature to provide analysis and recommendations for management.One hundred ninety-three publications encompassing 1399 patients met inclusion, with mean age 42.1 ±â€Š13.8 years and a male predominance (59.2%). Symptoms included pain (70.8%); orbital/ocular (20.7%); sinonasal (36.4%); neurologic (6.0%); other (14.5%); and asymptomatic (4.8%). Osteoma was isolated to the frontal sinus (82.9%) or extended into the ethmoid (16.6%), maxillary (0.3%), and sphenoid sinuses (0.2%). There was intracranial extension in 9.5% and intraorbital extension in 18.7%. Of those proceeding to surgery, majority (59.8%) underwent open approaches, followed by endoscopic (25.0%) and combined (11.5%). A significant (P < 0.01) increase in proportion of cases utilizing endoscopic approaches versus open/combined was observed over the period studied. Seventy-one postoperative complications were reported, in 7.5% of endoscopic cases, 27% of open, and 8.8% of combined. Complications were more likely in open/combined surgery, compared with endoscopic (22.3% versus 7.5%, P < 0.001). In 181 patients, completeness of resection was reported (complete resection; 87.8%) and found to be a significant predictor (P < 0.01) for disease recurrence/progression. Mean length of stay for the endoscopic group was 3.1 ±â€Š1.3 days, compared with 7.9 ±â€Š3.1 for open/combined (P < 0.0001).In the management of frontal sinus osteoma, indications for selecting endoscopic versus open approaches have expanded over the past 30 years, as techniques, equipment, and understanding of pathophysiology have evolved. Where endoscopic approaches are possible, they are associated with reduced morbidity and length of stay compared with open approaches.

Comparing the outcomes of severe versus mild/moderate ptosis using closed posterior levator advancement.

Traditionally, posterior eyelid surgical approaches such as Müller's muscle-conjunctival resection (MMCR) have been utilised with great success for mild cases of ptosis, with external levator approaches having been used for more severe cases of ptosis. We present a new technique which we label closed posterior levator advancement (CPLA) for the correction of all grades of ptosis. This article is a retrospective cohort study reviewing patients with mild, moderate, and severe ptosis over a 6-year period, treated by a single surgeon using CPLA. Minimum follow-up was 3 months. Patients with good levator function (levator palpebrae superioris (LPS) function >10 mm) without concomitant procedures were subdivided based on margin-to-reflex-distance-1 (MRD1) into mild-to-moderate ptosis (MRD1 > 1.5 mm) and severe ptosis (MRD1 ≤ 1.5 mm) cohorts. The outcome measures were preoperative and postoperative MRD1, lid contour, intereye symmetry, complications, and revision rates. 393 eyes of 313 patients were identified. 91 eyes in the mild-to-moderate cohort had a preoperative MRD1 of 2.38 mm, and 302 eyes in the severe cohort had a preoperative MRD1 of 0.27 mm. Postoperatively, MRD1 was 3.86 mm and 3.49 mm, respectively. There were no significant complications in both cohorts, and revision rates were 3.3% (3 of 91 eyes) in the mild-to-moderate and 2% (6 of 302 eyes) in the severe cohorts. Upper-eyelid contour was satisfactory in 98.2% of eyes, and 97.5% intereye symmetry within 1 mm was observed. Our results show an effective correction of all ptosis grades with satisfactory cosmetic outcomes and low complication and revision rates.