Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy.

OBJECTIVE: GM2 gangliosidosis is usually fatal by 5 years of age in its 2 major subtypes, Tay-Sachs and Sandhoff disease. First reported in 1881, GM2 gangliosidosis has no effective treatment today, and children succumb to the disease after a protracted neurodegenerative course and semi-vegetative state. This study seeks to further develop adeno-associated virus (AAV) gene therapy for human translation. METHODS: Cats with Sandhoff disease were treated by intracranial injection of vectors expressing feline ß-N-acetylhexosaminidase, the enzyme deficient in GM2 gangliosidosis. RESULTS: Hexosaminidase activity throughout the brain and spinal cord was above normal after treatment, with highest activities at the injection sites (thalamus and deep cerebellar nuclei). Ganglioside storage was reduced throughout the brain and spinal cord, with near complete clearance in many regions. While untreated cats with Sandhoff disease lived for 4.4 ± 0.6 months, AAV-treated cats lived to 19.1 ± 8.6 months, and 3 of 9 cats lived >21 months. Correction of the central nervous system was so effective that significant increases in lifespan led to the emergence of otherwise subclinical peripheral disease, including megacolon, enlarged stomach and urinary bladder, soft tissue spinal cord compression, and patellar luxation. Throughout the gastrointestinal tract, neurons of the myenteric and submucosal plexuses developed profound pathology, demonstrating that the enteric nervous system was inadequately treated. INTERPRETATION: The vector formulation in the current study effectively treats neuropathology in feline Sandhoff disease, but whole-body targeting will be an important consideration in next-generation approaches. ANN NEUROL 2023;94:969-986.

Intravenous delivery of adeno-associated viral gene therapy in feline GM1 gangliosidosis.

GM1 gangliosidosis is a fatal neurodegenerative disease caused by a deficiency of lysosomal ß-galactosidase. In its most severe form, GM1 gangliosidosis causes death by 4 years of age, and no effective treatments exist. Previous work has shown that injection of the brain parenchyma with an adeno-associated viral (AAV) vector provides pronounced therapeutic benefit in a feline GM1 model. To develop a less invasive treatment for the brain and increase systemic biodistribution, intravenous injection of AAV9 was evaluated. AAV9 expressing feline ß-galactosidase was intravenously administered at 1.5×1013 vector genomes/kg body weight to six GM1 cats at ∼1 month of age. The animals were divided into two cohorts: (i) a long-term group, which was followed to humane end point; and (ii) a short-term group, which was analysed 16 weeks post-treatment. Clinical assessments included neurological exams, CSF and urine biomarkers, and 7 T MRI and magentic resonance spectroscopy (MRS). Post-mortem analysis included ß-galactosidase and virus distribution, histological analysis and ganglioside content. Untreated GM1 animals survived 8.0 ± 0.6 months while intravenous treatment increased survival to an average of 3.5 years (n = 2) with substantial improvements in quality of life and neurological function. Neurological abnormalities, which in untreated animals progress to the inability to stand and debilitating neurological disease by 8 months of age, were mild in all treated animals. CSF biomarkers were normalized, indicating decreased CNS cell damage in the treated animals. Urinary glycosaminoglycans decreased to normal levels in the long-term cohort. MRI and MRS showed partial preservation of the brain in treated animals, which was supported by post-mortem histological evaluation. ß-Galactosidase activity was increased throughout the CNS, reaching carrier levels in much of the cerebrum and normal levels in the cerebellum, spinal cord and CSF. Ganglioside accumulation was significantly reduced by treatment. Peripheral tissues such as heart, skeletal muscle, and sciatic nerve also had normal ß-galactosidase activity in treated GM1 cats. GM1 histopathology was largely corrected with treatment. There was no evidence of tumorigenesis or toxicity. Restoration of ß-galactosidase activity in the CNS and peripheral organs by intravenous gene therapy led to profound increases in lifespan and quality of life in GM1 cats. These data support the promise of intravenous gene therapy as a safe, effective treatment for GM1 gangliosidosis.

Gene-based therapeutics for rare genetic neurodevelopmental psychiatric disorders.

We are in an emerging era of gene-based therapeutics with significant promise for rare genetic disorders. The potential is particularly significant for genetic central nervous system disorders that have begun to achieve Food and Drug Administration approval for select patient populations. This review summarizes the discussions and presentations of the National Institute of Mental Health-sponsored workshop "Gene-Based Therapeutics for Rare Genetic Neurodevelopmental Psychiatric Disorders," which was held in January 2021. Here, we distill the points raised regarding various precision medicine approaches related to neurodevelopmental and psychiatric disorders that may be amenable to gene-based therapies.

PEA15 loss of function and defective cerebral development in the domestic cat.

Cerebral cortical size and organization are critical features of neurodevelopment and human evolution, for which genetic investigation in model organisms can provide insight into developmental mechanisms and the causes of cerebral malformations. However, some abnormalities in cerebral cortical proliferation and folding are challenging to study in laboratory mice due to the absence of gyri and sulci in rodents. We report an autosomal recessive allele in domestic cats associated with impaired cerebral cortical expansion and folding, giving rise to a smooth, lissencephalic brain, and that appears to be caused by homozygosity for a frameshift in PEA15 (phosphoprotein expressed in astrocytes-15). Notably, previous studies of a Pea15 targeted mutation in mice did not reveal structural brain abnormalities. Affected cats, however, present with a non-progressive hypermetric gait and tremors, develop dissociative behavioral defects and aggression with age, and exhibit profound malformation of the cerebrum, with a 45% average decrease in overall brain weight, and reduction or absence of the ectosylvian, sylvian and anterior cingulate gyrus. Histologically, the cerebral cortical layers are disorganized, there is substantial loss of white matter in tracts such as the corona radiata and internal capsule, but the cerebellum is relatively spared. RNA-seq and immunohistochemical analysis reveal astrocytosis. Fibroblasts cultured from affected cats exhibit increased TNFα-mediated apoptosis, and increased FGFb-induced proliferation, consistent with previous studies implicating PEA15 as an intracellular adapter protein, and suggesting an underlying pathophysiology in which increased death of neurons accompanied by increased proliferation of astrocytes gives rise to abnormal organization of neuronal layers and loss of white matter. Taken together, our work points to a new role for PEA15 in development of a complex cerebral cortex that is only apparent in gyrencephalic species.

Use of tongue base palpation among oral healthcare providers: Cross-sectional survey.

OBJECTIVES: To assess the use of tongue base palpation during cancer screening exams by Oral Healthcare Providers (OHPs) and explore attitudes about (1) the usefulness of oral cancer screening (OCS) in detecting early, asymptomatic lesions and (2) routine OCS of the general population. STUDY DESIGN: Survey study. SETTING: Private and hospital-based clinical practices of OHPs located in Massachusetts and Connecticut, United States. METHODS: An anonymous, online 9-item survey assessing beliefs and practice patterns about cancer screening exams was distributed to OHPs with practices in Massachusetts and Connecticut from August 2020 to June 2021. Data were analyzed using chi-square tests and Pearson correlations. Statistically significant levels were established at P < .050. RESULTS: One hundred seventy-one responses were analyzed (response rate 17 %). Tongue base palpation was performed as part of a routine cancer screening exam by 55 % of otolaryngologists, 34 % of dentists and 29 % of OMFS (P = .030). Providers who palpated the tongue base were also more likely to use palpation as an exam technique in the tonsils (r = 0.52 [95 % CI 0.40-0.62]; P < .001) among other intra-and extra-oral anatomical subsites. Almost all dentists (92 %) and OMFS (98 %) but only 58 % of otolaryngologists considered OCS useful for detection of early, asymptomatic malignant lesions in the oral cavity (P < .001). CONCLUSIONS: While tongue base palpation can detect oropharyngeal cancers in a pre-symptomatic stage, it is underutilized during routine cancer screening exams. Considering the rising incidence of oropharyngeal cancer, tongue base palpation should be established as a routine part of cancer screening by OHPs.

A comprehensive study of a 29-capsid AAV library in a non-human primate central nervous system.

Non-human primates (NHPs) are a preferred animal model for optimizing adeno-associated virus (AAV)-mediated CNS gene delivery protocols before clinical trials. In spite of its inherent appeal, it is challenging to compare different serotypes, delivery routes, and disease indications in a well-powered, comprehensive, multigroup NHP experiment. Here, a multiplex barcode recombinant AAV (rAAV) vector-tracing strategy has been applied to a systemic analysis of 29 distinct, wild-type (WT), AAV natural isolates and engineered capsids in the CNS of eight macaques. The report describes distribution of each capsid in 15 areas of the macaques' CNS after intraparenchymal (putamen) injection, or cerebrospinal fluid (CSF)-mediated administration routes (intracisternal, intrathecal, or intracerebroventricular). To trace the vector biodistribution (viral DNA) and targeted tissues transduction (viral mRNA) of each capsid in each of the analyzed CNS areas, quantitative next-generation sequencing analysis, assisted by the digital-droplet PCR technology, was used. The report describes the most efficient AAV capsid variants targeting specific CNS areas after each route of administration using the direct side-by-side comparison of WT AAV isolates and a new generation of rationally designed capsids. The newly developed bioinformatics and visualization algorithms, applicable to the comparative analysis of several mammalian brain models, have been developed and made available in the public domain.

Limited English proficiency and head and neck cancer outcomes.

PURPOSE: Limited English proficiency (LEP) is common among hospitalized patients and may impact clinical care and outcomes. This study aimed to examine the relationship between LEP and clinical oncological outcomes for patients with head and neck cancer (HNC). MATERIALS AND METHODS: A single center retrospective review was conducted including adult patients with squamous cell carcinoma of the head and neck who received treatment with curative intent between January 1, 2014 and July 1, 2019. Clinical data collected included patient demographics and clinical variables. Univariate and multivariate analysis was performed to determine whether there was an association between LEP and demographic and clinical factors. RESULTS: There were 477 patients included in the study; 426 (81%) were English proficient (EP) while 51 (10.7%) were LEP. The LEP patients were diagnosed with cancer at a later overall stage (p = 0.03) and less frequently treated with surgery alone compared to English speaking patients (p < 0.001). After adjusting for overall stage and primary site, LEP patients were significantly more likely to receive primary surgical management compared to primary non-surgical management [OR = 2.29 95% CI (0.93, 5.58), p = 0.008]. There was also a significant association between LEP and primary site of tumor (p < 0.01). Kaplan-Meyer curves for overall survival and disease specific survival showed no significant differences between the two cohorts (p = 0.8063 and p = 0.4986, respectively). CONCLUSIONS: LEP may impact access to care resulting in more advanced overall tumor stage at presentation and treatment with primary surgery compared to non-surgical management after adjusting for tumor stage and primary site. Interventions to provide better access to care, awareness of HNC in the LEP populations, and earlier detection may improve outcomes for LEP patients.

Unusual presentation of HPV-positive squamous cell carcinoma of the nasolacrimal duct as carcinoma of unknown primary.

Most human papillomavirus (HPV)-positive carcinomas of unknown primary (CUP) in the cervical lymph nodes are ultimately found to arise from the oropharynx, which has by far the highest prevalence of HPV-positivity among head and neck tumors. However, HPV is also detected in a subset of tumors from other sites. In this case report, we describe the first reported instance of a lacrimal sac carcinoma presenting as an HPV-positive CUP. A 64-year-old male presented with isolated right-sided neck swelling, found on core biopsy to be HPV-positive squamous cell carcinoma (SCC). Initial diagnostic workup did not reveal a primary site, and he was treated for T0N1M0 oropharyngeal SCC with chemoradiation. Shortly afterwards he developed epiphora and was found to have an FDG-avid lesion along his inferior right orbit. Biopsy revealed HPV-positive SCC, presumed to be the true primary site of his previously diagnosed CUP. He was treated with surgical resection, proton-beam radiation, and carboplatin-paclitaxel. He had an excellent outcome with no evidence of disease 18 months following treatment completion. This case underscores the importance of continued vigilance and thorough investigation for a primary tumor site even when cervical nodal metastases are HPV-positive. While the vast majority of HPV-positive head and neck tumors arise in the oropharynx, other anatomical sites may also harbor HPV-positive malignancies.

The effect of a statewide prescription drug monitoring program on opioid prescribing patterns.

PURPOSE: Determine whether opioid prescribing patterns have changed as a result of implementation of a prescription drug monitoring program (PDMP) in the state of Massachusetts. MATERIALS AND METHODS: A multicentered retrospective study was performed including patients who received tonsillectomy, parotidectomy, thyroidectomy or direct laryngoscopy and biopsy with or without rigid esophagoscopy and/or rigid bronchoscopy at Lahey Hospital and Medical Center (Burlington, MA) or Boston Medical Center (Boston, MA). Opioid prescribing patterns were compared for the 12 months prior to implementation of the Massachusetts Prescription Awareness Tool (MassPAT) to 36 months of prescribing patterns post implementation. Quantity of opioids prescribed was based on morphine milligram equivalents (MME). Continuous variables were compared using analysis of variance (ANOVA) while categorical variables were compared using chi-squared test or Fisher's exact test. Multivariate analysis was performed using linear regression. RESULTS: A total of 2281 patients were included in the study. There was a significant association in mean overall MME prescribed comparing pre-MassPAT and post-MassPAT data [tonsillectomy: 635.9 ± 175.6 vs 463.3 ± 177.7 (p < 0.0001), parotidectomy: 250.4 ± 71.33 vs 169.8 ± 79.26 (p < 0.0001), thyroidectomy: 186.2 ± 81.14 vs 118.3 ± 88.79 (p < 0.0001), direct laryngoscopy with biopsy: 308.3 ± 246.9 vs 308.3 ± 246.9 (p = 0.0201)]. There was also a significant association between length of opioid prescription (days) and implementation of MassPAT, but there was no significant difference in the percent of patients requiring refills pre- MassPAT and post-MassPAT. CONCLUSION: This study demonstrates that prescribers have been able to significantly decrease the amount of opioids prescribed for tonsillectomy, parotidectomy, thyroidectomy, and direct laryngoscopy and biopsy and patients have not required additional opioid refills.

Therapeutic benefit after intracranial gene therapy delivered during the symptomatic stage in a feline model of Sandhoff disease.

Sandhoff disease (SD) is an autosomal recessive lysosomal storage disease caused by defects in the ß-subunit of ß-N-acetylhexosaminidase (Hex), the enzyme that catabolizes GM2 ganglioside. Hex deficiency causes neuronal storage of GM2 and related glycoconjugates, resulting in progressive neurodegeneration and death, typically in infancy. No effective treatment exists for human patients. Adeno-associated virus (AAV) gene therapy led to improved clinical outcome and survival of SD cats treated before the onset of disease symptoms. Most human patients are diagnosed after clinical disease onset, so it is imperative to test AAV-gene therapy in symptomatic SD cats to provide a realistic indication of therapeutic benefits that can be expected in humans. In this study, AAVrh8 vectors injected into the thalamus and deep cerebellar nuclei of symptomatic SD cats resulted in widespread central nervous system enzyme distribution, although a substantial burden of storage material remained. Cats treated in the early symptomatic phase showed delayed disease progression and a significant survival increase versus untreated cats. Treatment was less effective when administered later in the disease course, although therapeutic benefit was still possible. Results are encouraging for the treatment of human patients and provide support for the development AAV-gene therapy for human SD.

To ban or not to ban tanning bed use for minors: A cost-effectiveness analysis from multiple US perspectives for invasive melanoma.

BACKGROUND: Tanning bed use is common among US adolescents, but is associated with increased melanoma risk. The decision to ban tanning bed use by adolescents should be made in consideration of the potential health benefits and costs. METHODS: The US population aged 14 to 17 years was modeled by microsimulation, which compared ban versus no ban strategies. Lifetime quality-adjusted life years (QALYs) and costs were estimated from a health care sector perspective and two societal perspectives: with and without the costs of policy enforcement and the economic losses of the indoor-tanning bed industry. RESULTS: Full adherence to the ban prevented 15,102 melanoma cases and 3299 recurrences among 17.1 million minors, saving $61in formal and informal health care costs per minor and providing an increase of 0.0002 QALYs. Despite the intervention costs of the ban and the economic losses to the indoor-tanning industry, banning was still the dominant strategy, with a savings of $12 per minor and $205.4 million among 17.1 million minors. Findings were robust against varying inspection costs and ban compliance, but were sensitive to lower excess risk of melanoma with early exposure to tanning beds. CONCLUSIONS: A ban on tanning beds for minors potentially lowers costs and increases cost effectiveness. Even after accounting for the costs of implementing a ban, it may be considered cost effective. Even after accounting for the costs of implementing a ban and economic losses in the indoor-tanning industry, a tanning bed ban for US minors may be considered cost effective. A ban has the potential to reduce the number of melanoma cases while decreasing health care costs. LAY SUMMARY: Previous meta-analyses have linked tanning bed use with an increased risk of melanoma, particularly with initial use at a young age. Yet, it remains unclear whether a ban of adolescents would be cost effective. Overall, a ban has the potential to reduce the number of melanoma cases while promoting a decrease in health care costs. Even after accounting for the costs of implementing a ban and the economic losses incurred by the indoor-tanning industry, a ban would be cost effective.

Natural history of Tay-Sachs disease in sheep.

Tay-Sachs disease (TSD) is a fatal neurodegenerative disease caused by a deficiency of the enzyme ß-N-acetylhexosaminidase A (HexA). TSD naturally occurs in Jacob sheep is the only experimental model of TSD. TSD in sheep recapitulates neurologic features similar to juvenile onset and late onset TSD patients. Due to the paucity of human literature on pathology of TSD, a better natural history in the sheep TSD brain, which is on the same order of magnitude as a child's, is necessary for evaluating therapy and characterizing the pathological events that occur. To provide clinicians and researchers with a clearer understanding of longitudinal pathology in patients, we compare spectrum of clinical signs and brain pathology in mildly symptomatic (3-months), moderately symptomatic (6-months), or severely affected TSD sheep (humane endpoint at ~9-months of age). Increased GM2 ganglioside in the CSF of TSD sheep and a TSD specific biomarker on MRS (taurine) correlate with disease severity. Microglial activation and reactive astrocytes were observed globally on histopathology in TSD sheep with a widespread reduction in oligodendrocyte density. Myelination is reduced primarily in the forebrain illustrated by loss of white matter on MRI. GM2 and GM3 ganglioside were increased and distributed differently in various tissues. The study of TSD in the sheep model provides a natural history to shed light on the pathophysiology of TSD, which is of utmost importance due to novel therapeutics being assessed in human patients.

Multispecialty surgical management of carotid body tumors in the modern era.

OBJECTIVE: The objective of this study was to assess the perioperative and long-term outcomes of carotid body tumor (CBT) resection with a multispecialty (head and neck surgery/vascular surgery) approach. METHODS: Our institutional data registry was queried for Current Procedural Terminology codes (60600, 60605) pertaining to CBT excision. These patient records and operative reports were individually reviewed to determine laterality, preoperative tumor embolization, operative time, estimated blood loss, need for intraoperative transfusion, intraoperative electroencephalogram changes, intraoperative division of the external carotid artery, carotid artery repair, resection of the carotid bifurcation, tumor volume, final pathology, cranial nerve injury, stroke, death, and clinical or radiographic evidence of recurrence. RESULTS: From 1996 to 2018, 74 CBT resections were identified in 68 patients (41 [60%] females; mean age, 50.83 years). The mean tumor volume was 9.92 ± 14.26 cm3 (range, 0.0250-71.0627 cm3). Embolization was performed by a neurointerventional specialist in 27 CBT resections (36%) based on size (embolization 14.27 ± 16.84 cm3 vs 7.17 ± 11.86 cm3; P = .063) and superior extension. This practice resulted in one asymptomatic vertebral dissection, which postponed the surgery. There was a trend toward greater blood loss in the embolization group (embolization 437 ± 545 mL vs 262 ± 222 mL; P = .17); however, no transfusions were required in any patient. The mean operative time was also significantly longer in the embolization group (198.33 ± 61.13 minutes vs 161.5 ± 55.56 minutes; P = .03). Three resections had reversible intraoperative electroencephalogram changes, one of which occurred during carotid clamping. These changes resolved with shunting. Eight external carotid resections (11%) and 6 carotid reconstructions (8.1%; two primary, two patch, and two primary anastomosis) were required. Malignancy was identified in four tumors (5.4%), accounting for four of the six carotid reconstructions. There were no postoperative cranial nerve injuries, no strokes, no reexplorations, and no deaths. One patient developed transient dysphagia from pharyngeal tumor infiltration. Long-term follow-up (mean, 43 ± 54 months), available in 61 of the 68 patients (89.7%), revealed three (4.4%) recurrences. CONCLUSIONS: This large, single-institution series demonstrates that a multispecialty team combining two surgical skill sets for the treatment of this rare, challenging condition yields unparalleled low complication rates with short operative times. This approach, including long-term surveillance for recurrent disease, should be considered to optimize outcomes of CBT resection.

Pronounced Therapeutic Benefit of a Single Bidirectional AAV Vector Administered Systemically in Sandhoff Mice.

The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are fatal lysosomal storage disorders caused by mutations in the HEXA and HEXB genes, respectively. These mutations cause dysfunction of the lysosomal enzyme ß-N-acetylhexosaminidase A (HexA) and accumulation of GM2 ganglioside (GM2) with ensuing neurodegeneration, and death by 5 years of age. Until recently, the most successful therapy was achieved by intracranial co-delivery of monocistronic adeno-associated viral (AAV) vectors encoding Hex alpha and beta-subunits in animal models of SD. The blood-brain barrier crossing properties of AAV9 enables systemic gene therapy; however, the requirement of co-delivery of two monocistronic AAV vectors to overexpress the heterodimeric HexA protein has prevented the use of this approach. To address this need, we developed multiple AAV constructs encoding simultaneously HEXA and HEXB using AAV9 and AAV-PHP.B and tested their therapeutic efficacy in 4- to 6-week-old SD mice after systemic administration. Survival and biochemical outcomes revealed superiority of the AAV vector design using a bidirectional CBA promoter with equivalent dose-dependent outcomes for both capsids. AAV-treated mice performed normally in tests of motor function, CNS GM2 ganglioside levels were significantly reduced, and survival increased by >4-fold with some animals surviving past 2 years of age.

A Safe and Reliable Technique for CNS Delivery of AAV Vectors in the Cisterna Magna.

Global gene delivery to the CNS has therapeutic importance for the treatment of neurological disorders that affect the entire CNS. Due to direct contact with the CNS, cerebrospinal fluid (CSF) is an attractive route for CNS gene delivery. A safe and effective route to achieve global gene distribution in the CNS is needed, and administration of genes through the cisterna magna (CM) via a suboccipital puncture results in broad distribution in the brain and spinal cord. However, translation of this technique to clinical practice is challenging due to the risk of serious and potentially fatal complications in patients. Herein, we report development of a gene therapy delivery method to the CM through adaptation of an intravascular microcatheter, which can be safely navigated intrathecally under fluoroscopic guidance. We examined the safety, reproducibility, and distribution/transduction of this method in sheep using a self-complementary adeno-associated virus 9 (scAAV9)-GFP vector. This technique was used to treat two Tay-Sachs disease patients (30 months old and 7 months old) with AAV gene therapy. No adverse effects were observed during infusion or post-treatment. This delivery technique is a safe and minimally invasive alternative to direct infusion into the CM, achieving broad distribution of AAV gene transfer to the CNS.

Exploring disconnected discourses about Patient and Public Involvement and Volunteer Involvement in English health and social care.

BACKGROUND: Patient and public involvement (PPI) in health and social care policy, service decision-making and research are presented as good practice in England. Yet the explicit rationale for PPI and how it is positioned within the literature, policy and practice remain confused, in particular, in relation to Volunteer Involvement (VI). In health and social care, PPI and VI are managed and valued as conceptually distinct, yet the discourses in their policy and practice documents treat them as closely related in fundamental ways. OBJECTIVE: Compare and critically evaluate discourses framing PPI and VI within English health and social care. DESIGN: A critical discourse approach was used to explore the accounts of PPI and VI in policy. These accounts were then compared and contrasted with personal accounts of volunteering in health and social care settings. RESULTS: Twenty documents from key national health and social care bodies were discursively examined in terms of their framing PPI and VI. A narrative disconnect between the two was repeatedly confirmed. This finding contrasted with an analysis of personal accounts of VI which displayed VI as a form of PPI. CONCLUSION: There is a disconnect between language, narratives and practice in PPI and in VI which may have direct consequences for policy and practice. Recognising and managing it can offer innovative ways of enabling volunteers to be involved across health and social care settings, ensuring the experiential value added by volunteers' service contributions, to be recognised so that their democratic participation may be seen to shape services.

Review of probiotic use in otolaryngology.

OBJECTIVE: Probiotics have garnered considerable attention as an intervention for various conditions common to otolaryngology. The purpose of this review is to evaluate the current literature to offer recommendations about the safety and efficacy of probiotic management in otolaryngologic conditions. STUDY DESIGN: Narrative review. METHODS: PubMed and Google Scholar were queried using pertinent keywords to retrieve relevant studies with particular focus in the recent 5 years. All abstracts were assessed and studies, reviews and meta-analyses achieving evaluation of probiotic therapies or characterization of microbiome changes were included for further review. Studies were categorized by condition or anatomic region across various subspecialties. Key data parameters were extracted and evaluated across studies and treatment types. RESULTS: Strong evidence exists for the use probiotic agents to improve symptoms for allergic rhinitis, chronic rhinosinusitis and certain dental conditions. Despite promising results, further investigation is needed to evaluate and optimize probiotic delivery for mitigating otitis media, oropharyngeal inflammation and upper respiratory tract infections. Preclinical studies suggest that probiotics may potentially offer benefit for voice prosthesis maintenance, wound healing and mitigation of oral dysplasia. CONCLUSION: Probiotic therapies may offer clinical benefit in a variety of contexts within the field of otolaryngology, especially for short-term relief of certain inflammatory conditions of the oral cavity, auditory and nasal cavities. Further investigation is warranted for evaluation of long-term outcomes and pathogenic deterrence.

Anesthesia screen use may impact operating room communication practices in otolaryngology.

OBJECTIVES: Failures in communication are a leading contributor to medical error. There is increasing attention on cultivating robust communication practices in the Operating Room (OR) to mitigate against patient injury and optimize efficient patient care. Few studies have evaluated how surgical equipment may introduce barriers to team dynamics. DESIGN: We conducted a pilot observational study to examine the relationship between anesthesia screen drapes (which are used inconsistently) and the frequency of verbal exchanges between surgical and anesthesia members. 25 procedures spanning various procedures in Otolaryngology were covertly observed, 12 of which employed a screen. Verbal exchanges were recorded across three stages of the surgery: pre-procedure (before the draping), procedure (drapes placed throughout) and post-procedure (after the removal of the draping). Speaker and content of the exchange was noted as well as various features about the procedure. RESULTS: Decreases in rates of exchanges were most pronounced during the procedure stage, although they did not reach significance on T-testing (p = 0.0719). After controlling for attending, table orientation and number of professionals, regression analysis did reveal a statistically significant decrease in rates of verbal exchanges during the procedure in the presence of the anesthesia screen (7.17 (± 6.33) versus 2.23 (± 1.00), p = 0.0318). Differences were also significant among surgeon-initiated and patient-care-related exchanges (p = 0.0168 and p = 0.0432, respectively). Decreases in anesthesiologist-initiated and non-clinical exchanges did not reach significance (p = 0.1530 and p = 0.5120, respectively). CONCLUSION: This pilot study suggests that anesthesia screens may negatively impact communication practices in the OR.

Paediatric laryngeal squamous cell carcinoma: Systematic review and pooled analysis.

BACKGROUND: Paediatric squamous cell carcinoma (SCC) of the larynx is rare; however, recent data seem to support the notion that this pathology is increasing in incidence. Although this has been the case for several decades, treatment algorithms for this patient population remain identical to those of adults. METHODS: The study consists of a systematic review and pooled analysis of oncologic outcomes in paediatric laryngeal SCC from a comprehensive literature search on OVID MEDLINE and EMBASE. RESULTS: The average cohort age was 12.1 years. Nine (36%) had supraglottic primaries, and 16 (64%) had glottic primaries. Treatment included unimodal and combination therapy. No significant difference in survival was noted between surgically treated and non-surgically treated patients (5-year overall survival (OS): 68.2% vs 76.2%, P = .905), even when stratified for advanced-stage and supraglottic disease. CONCLUSIONS: Paediatric patients with laryngeal HNSCC may have different presentations and responses to therapy than their adult counterparts.

Choice of imaging modality for pre-treatment staging of head and neck cancer impacts TNM staging.

PURPOSE: The purpose of this retrospective cohort study was to determine whether there is a difference in the sensitivity of chest computed tomography (CT) versus 18F-fluorodeoxyglucose positron emission tomography with low-dose nonenhanced CT (18F-FDG PET/CT or PET/CT) in the detection of distant metastases in head and neck cancer, within a tertiary care setting. MATERIALS AND METHODS: Patients with head and neck cancer, and known distant metastases, who underwent both 18F-FDG PET/CT with integrated low-dose nonenhanced CT and diagnostic chest CT prior to initiation of therapy from 2008 to 2017 were included. Two head and neck radiologists, blinded to all patient information and to each other's readings, reviewed the PET/CT or CT chest images for each patient and identified whether distant metastases were present. No radiologist read both modalities for a single patient. Concordance between imaging modalities was quantitatively analyzed using McNemar's test. RESULTS: 27 patients were included. McNemar's mid p-value analysis showed no significant difference in the detection of distant metastases (p = .6875). However, PET/CT detected distant metastases in three patients that chest CT did not, while chest CT identified distant metastatic disease in two patients that were negative on PET/CT. CONCLUSIONS: While this study did not identify a statistically significant difference in sensitivity, five patients had distant metastases identified on only one of the two modalities. Use of a single modality would have resulted in inaccurate staging in 7-11% of patients in our study. The use of both modalities offers the greatest accuracy when providing stage-adapted oncologic treatment.