Elucidating survival and functional outcomes in patients with primary head and neck malignancies treated in academic versus community settings.

BACKGROUND: Differences in treatment outcomes between community or academic centers are incompletely understood. METHODS: Retrospective review of head and neck cancer patients between 2010 and 2020 in a rural health region. Kaplan-Meier curves and log-rank tests were used to evaluate survival outcomes, along with bivariate and multivariable Cox proportional hazards models. Linear regression was used for functional outcomes of tracheotomy and gastrostomy tube dependence. RESULTS: Two hundred and forty-eight patients treated at an academic center were compared with 94 patients treated in community centers. In multivariable analysis, the risk of death (HR = 0.60, p = 0.019), and risk of recurrence were lower (HR = 0.29, p < 0.001) for patients treated in academic centers. Patients treated in community centers had longer gastrostomy tube dependence (p = 0.002). CONCLUSION: Our findings suggest that treatment at an academic center was associated with a lower risk of recurrence and shorter gastrostomy tube dependence compared to treatment in the community.

Surgical closure of enlarged tracheoesophageal fistula after laryngectomy: A systematic review of techniques.

OBJECTIVES: The objectives of the study were (1) systematically review the data on surgical closure of enlarged tracheoesophageal fistula after laryngectomy and (2) to perform a comparison of reconstruction of surgical techniques. METHODS: Systematic review was performed using PRISMA methodology. Cumulative patient data were compared between patients reconstructed with vascularized tissue (sternocleidomastoid fascia and muscle, pectoralis major, deltopectoral, radial forearm) and those closed primarily (two-layer, three-layer, and tracheal transposition). RESULTS: Fourteen studies reported outcomes for the reconstruction of tracheoesophageal fistula. Primary closure was used in 98 patients, vascularized flap in 74, and occlusive device in 8. Vascularized flap resulted in successful closure of the fistula in 89 % of cases compared to primary closure in 62 % (p = 0.0003). CONCLUSION: Systematic review of the literature supports an improved surgical closure rate with vascularized flap interposed between the esophageal and tracheal lumens compared to primary closure.

Scalp and Calvarium Reconstruction.

Defects of the scalp and calvarium pose unique reconstructive challenges due to the importance of this area in protecting the brain and its distance from larger donor vessels for free flap transfer. The wide range and complexity of reconstructive options make this a broad topic because the simplest defects are often closed or managed in the outpatient setting and the most complex require multilayer closure in the operating room with a multidisciplinary team and intensive postoperative care. In hair-bearing individuals, the scalp is an esthetically important area due to the importance of hair to self-esteem and sexual attraction.

Psychological Survivorship in Head and Neck Cancer.

Survivorship for head and neck cancer patients presents unique challenges related to the anatomic location of their disease. After treatment, patients often have functional impairments requiring additional care and support. In addition, patients may have psychological challenges managing the effect of the disease and treatment. Routine screening is recommended for the identification of psychological conditions. This article reviews the latest research on key psychological conditions associated with head and neck cancer. It discusses risk factors for the development of each condition and provides recommendations for the management of patients who may present with psychological concerns.

Geospatial analysis of hypospadias and cryptorchidism prevalence rates based on postal code in a Canadian province with stable population.

INTRODUCTION: Hypospadias and cryptorchidism are hormone-mediated malformations that occur during male development. Prevalence rates of hypospadias and cryptorchidism are thought to be increasing worldwide. In-utero exposure to endocrine-disrupting chemicals (EDCs) may have a role in the occurrence of these malformations. Our group has reported significant clustering of hypospadias and cryptorchidism at the county level in areas of intense agricultural activity in the Canadian province of Nova Scotia (NS). Finer scale spatial analysis has shown clustering near urban centres. OBJECTIVES: The objectives of the study were: 1) to perform a granular geospatial analysis of hypospadias and cryptorchidism prevalence, at the postal code level, of all babies born in NS over a 26-year period; and 2) to determine whether there is spatial correlation between these conditions and industries linked to toxic output. STUDY DESIGN: Cases of hypospadias and cryptorchidism were identified based on ICD-10 codes from the Nova Scotia Atlee Perinatal Database with records of all live births in NS between 1988 and 2013. Data were geocoded and mapped based on the three first digits of the maternal postal code (Forward Sortation Area [FSA]). Regional prevalence of congenital anomalies was calculated for each of the 77 FSAs. To identify statistically significant high and low prevalence clusters for each anomaly, Local Morans I was used on the spatial data. Geospatial point data was created for industries linked to toxic output and correlation between clusters of malformations and proximity to these industries was assessed. RESULTS: During the study period, there were 1045 cases of hypospadias and 993 cases of cryptorchidism. Both hypospadias and cryptorchidism demonstrated statistically significant areas of high prevalence clusters. There was no significant spatial correlation between the local clustering of the congenital malformations and proximity to toxic industries. DISCUSSION AND CONCLUSION: Our study shows heterogeneity in the distribution of hypospadias and cryptorchidism, which is consistent with previously published works. In this follow-up, granular geospatial analysis of hypospadias and cryptorchidism prevalence in an area with stable population, we did not confirm the previous findings of high clustering in areas of intense agricultural activity. Furthermore, our analysis did not find high clustering of the congenital malformations in areas near toxic industries to support a clear environmental role in their development. Some of the limitations include underdiagnosis of hypospadias and cryptorchidism (as they both present with a clinical spectrum and are non-life threatening), and limited data currently available on the route of exposure to EDC industries in Nova Scotia.

Longitudinal functional outcomes and late effects of radiation following treatment of nasopharyngeal carcinoma: secondary analysis of a prospective cohort study.

BACKGROUND: The study objectives were: provide longitudinal data on upper aerodigestive tract function and late complications following IMRT for nasopharyngeal carcinoma, and elucidate factors that might predict a worse outcome. The hypotheses were: (1) Despite advances such as IMRT, radiation will cause significant functional decline and late complications that often progress or arise years after treatment. (2) Larger radiation volume will be associated with poorer outcomes. METHODS: Longitudinal, observational cohort study of nasopharyngeal carcinoma patients with retrospective analysis of prospectively collected, population-based data. Late sequelae and validated measures of overall performance, speech, and swallowing were documented pre-treatment and 3,6,12, 24, 36 and ≥ 60-months post-treatment. RESULTS: Forty-two patients treated curatively with radiation (N = 9) or chemoradiation (N = 33) were followed for a median 74 months. Functional outcomes showed an initial nadir at 3 months associated with acute effects of treatment, followed by initial recovery. There was subsequent functional decline years post-treatment with advancing dysphagia/aspiration, trismus, muscle spasm, and hypoglossal nerve palsy. Univariable regression analysis revealed that increasing high-dose radiation volumes (PTV 70 Gy) were associated with increased likelihood of less than solid diet (Performance Status Scale (PSS)-Normalcy of Diet score < 50; p = 0.04), and reduced PSS-Understandability of Speech (p = 0.005). The probability of poor outcome increased with time. Eleven percent of patients were tube feed dependent at ≥ 5 years. CONCLUSIONS: Despite improvements in radiation delivery, late effects of radiation remain common. Higher radiation volumes are associated with poorer outcomes that worsen over time.

Selected functional outcomes in advanced oral cancer: Comparison of surgery alone versus surgery with postoperative radiotherapy.

BACKGROUND: Study objectives were to determine whether the addition of postoperative radiation (PORT) resulted in a decline in oral function relative to surgery alone and to describe the longitudinal course of oral function following treatment of advanced oral cancer. METHODS: This was a 36-month retrospectively analyzed observational cohort study of patients with stage III-IV oral cancer. Prospectively collected, oral functional outcomes were acquired pretreatment and 3, 6, 12, 24, and 36 months post-treatment. RESULTS: One hundred and eighteen patients were included. Forty-three patients treated with surgery alone were compared to 75 who received surgery with PORT. Mixed model analysis demonstrated the acute effect of PORT was associated with patient-rated xerostomia (p < 0.001) and the late or persistent effect was associated with decreased clinician-rated eating in public (p = 0.008), understandability of speech (p = 0.02), and normalcy of diet (p = 0.005) compared with surgery alone. There were no differences between surgery alone and PORT groups in clinician-rated feeding tube dependence or patient-rated speech handicap. CONCLUSIONS: The use of PORT was associated with a demonstrable decline in oral function in four of six outcomes measures relative to surgery alone.

Systematic review and meta-analysis of transoral laser microsurgery in hypopharyngeal carcinoma.

BACKGROUND: Transoral laser microsurgery has been suggested as an alternative treatment modality for hypopharyngeal carcinoma. The purpose of this study is to systematically review the oncologic and functional outcomes of patients with hypopharyngeal carcinoma when treated with primary transoral laser microsurgery. METHODS: A comprehensive literature search was performed using PRISMA methodology on OVID MEDLINE and EMBASE. Meta-analysis was completed for oncological outcomes. RESULTS: Six studies reported quality of life outcomes five reported oncologic outcomes. A median of 95% (range 0.83-0.98) patients achieving gastrostomy independence, a median of 3% (range 0%-6%) were tracheostomy dependent, and a median of 97% (Range 0.89-1.0) were able to preserve their larynx. Pooled five-year overall survival was 54% (CI, 0.50-0.58, I2 = 29%), pooled disease-specific survival was 72% (CI, 0.68-0.77, I2 = 46%), and pooled local control rate was 78% (CI, 0.72-0.85, I2 = 69%). CONCLUSION: Systematic review supports improvements in functional outcomes and oncologic outcomes with transoral laser microsurgery.

Cochlear implant failures and reimplantation: A 30-year analysis and literature review.

OBJECTIVES/HYPOTHESIS: The objectives of the study were to present an institutional experience with device failures and cochlear reimplantation rates over a 30-year period and to perform a detailed literature review. STUDY DESIGN: Retrospective institutional experience and literature review. METHODS: A review of cochlear implant failures over a period of 30 years, between January 1988 and March 2017, at a single institution was conducted. Cochlear implant failures were calculated based on manufacturer, type of failure, and overall failure rate. Survival analysis was performed using Kaplan-Meier curves. An electronic search of the PubMed, Web of Science, and EMBASE databases revealed 24 articles on the topic of cochlear device failure. Data on reimplantation and device failure rates were extracted from this literature review and analyzed. RESULTS: A total of 804 cochlear implantations were reviewed from three manufacturers. The institutional reimplantation rate was 2.9% compared to the pooled rate of 6.0% calculated from the literature review. Medical failures accounted for 0.5% of the overall failures, device failures accounted for 1.6%, and inconclusive failures account for 0.7%. Survival analysis revealed a significant difference among manufacturers. An improved device failure rate was noted in the adult population (0.8%) as compared to the pediatric population (2.8%). CONCLUSIONS: This 30-year review represents one of the longest series in the literature examining reimplantation, device failure, and medical failure rates. Cochlear implant survival varied by manufacturer and was significantly better in adult compared to pediatric patients. LEVEL OF EVIDENCE: NA Laryngoscope, 130:782-789, 2020.

Anxiety and Depression in Adult First Seizure Presentations.

OBJECTIVE: To define the prevalence of psychiatric symptoms of anxiety and depression in patients at the time of their first seizure presentation to a neurologist. METHODS: Our pilot study uses a cohort approach with multimodal data (clinical, social, structural [3T magnetic resonance imaging], and functional [electroencephalogram]). We screened 105 patients referred to the Halifax First Seizure Clinic between 2014 and 2016 and 51 controls. All participants completed two screening questionnaires: Neurological Disorders Depression Inventory for Epilepsy and Generalized Anxiety Disorder 7-Item. After applying the exclusion criteria, the study population consisted of 57 patients with unprovoked first seizure and 31 controls. The prevalence of anxiety and depression was based on cutoff scores of >15 and >14 respectively. RESULTS: Unprovoked first seizure patients showed higher prevalence of depression (33%) compared with control (6%) with an odds ratio (OR) of 2.75 (95% confidence interval [CI], 0.72-10.5). There was no significant difference in the prevalence of anxiety between control subjects (9.7%) and unprovoked first seizure patients (23%). Subcategory analysis conducted after diagnosis confirmation revealed significantly increased OR of depression in patients diagnosed with new-onset epilepsy (OR, 11.6; 95% CI, 2.1-64.0) and newly diagnosed epilepsy (OR, 20.0; 95% CI,2.2-181), but not first seizure only patients (OR, 2.2; 95% CI,0.28-17.6) compared with control. CONCLUSIONS: Our study supports a bidirectional relationship between the first seizure and depression. Prevalence rate of depression increased with duration of undiagnosed epilepsy at the time of first clinical assessment.

A population-based study of prevalence trends and geospatial analysis of hypospadias and cryptorchidism compared with non-endocrine mediated congenital anomalies.

INTRODUCTION: Several reports have suggested an increase in the prevalence of hypospadias and cryptorchidism over the last few decades. Endocrine disruption caused by exposure to environmental chemicals has been postulated as a possible cause. OBJECTIVES: The objectives of our study were: 1) to determine whether the prevalence of hypospadias and cryptorchidism is increasing compared with other congenital anomalies not known to be mediated by endocrine factors; and 2) to perform a geospatial analysis of these congenital malformations looking for clustering that could offer insight into environmental risk factors. MATERIAL AND METHODS: Data were obtained from the Nova Scotia ATLEE Perinatal Database containing the perinatal records of all live births in Nova Scotia, Canada since 1988. Records from 1988 to 2013 defined the study cohort. Overall prevalence rates and prevalence trends by year were calculated for hypospadias, cryptorchidism, gastroschisis, and clubfoot. County of residence was collected and spatial autocorrelation testing for clustering was performed for each of the congenital anomalies. RESULTS: There were 258,147 live births during the study period. Overall prevalence rates for the four malformations over the study period were: hypospadias 78 per 10,000 male births, cryptorchidism 75 per 10,000 male births, clubfoot 24 per 10,000 total births, and gastroschisis 4 per 10,000 total births. Incidence rate ratios per year for hypospadias, cryptorchidism, clubfoot, and gastroschisis were 1.00 (0.99-1.01), 0.99 (0.98-1.00), 0.98 (0.97-0.99), and 1.04 (1.04-1.07), respectively. During the study period, the prevalence rates in the region were unchanged for hypospadias, slightly reduced for cryptorchidism and clubfoot, and rising for gastroschisis (Figure). Spatial autocorrelation testing revealed statistically significant clustering for hypospadias (p = 0.03) and cryptorchidism (p = 0.03), while no spatial autocorrelation was observed for the other malformations. DISCUSSION: Contrary to previous studies we show that hypospadias and cryptorchidism prevalence rates are not increasing over time in our region. Nonetheless, rates for these conditions in our area are high compared with other regions of the world. Local clustering of these congenital anomalies without clustering of the control, non-endocrine mediated congenital malformations supports a possible unique spatial distribution associated with environmental exposure. The hotspots identified for hypospadias and cryptorchidism are associated with intense agricultural activity. CONCLUSIONS: Our study found no increase in hypospadias and cryptorchidism prevalence over a 26-year period compared with other congenital anomalies not known to be associated with endocrine factors. Geospatial analysis supports high clustering for hypospadias and cryptorchidism in areas of intense agricultural activity.

Twelve tips for medical students to facilitate a Photovoice project.

Participatory action projects, such as Photovoice, can provide medical trainees with a unique opportunity for community engagement. Through Photovoice, participants with lived experience engage in dialog and capture photographs of community issues. Participants subsequently develop narratives that accompany photos to raise awareness about community needs. In this paper, we describe twelve tips to develop a Photovoice project and discuss how medical students can engage communities through a participatory action lens. Such an approach not only serves as a method for medical students to learn about social determinants of health through the perspective of lived experience, but also has the capacity of building advocacy and community collaboration skills. Through providing a voice to marginalized individuals using Photovoice, medical students can partner with communities to work toward social change. Photovoice participants also benefit from the project as it provides them with a platform to highlight strengths and weaknesses in their community.

NCK is critical for the development of deleted in colorectal cancer (DCC) sensitive spinal circuits.

As our understanding of motor circuit function increases, our need to understand how circuits form to ensure proper function becomes increasingly important. Recently, deleted in colorectal cancer (DCC) has been shown to be important in the development of spinal circuits necessary for gait. Importantly, humans with mutation in DCC show mirror movement disorders pointing to the significance of DCC in the development of spinal circuits for coordinated movement. Although DCC binds a number of ligands, the intracellular signaling cascade leading to the aberrant spinal circuits remains unknown. Here, we show that the non-catalytic region of tyrosine kinase adaptor (NCK) proteins 1 and 2 are distributed in the developing spinal cord. Using dissociated dorsal spinal neuron cultures we show that NCK proteins are necessary for the outgrowth and growth cone architecture of DCC(+ve) dorsal spinal neurons. Consistent with a role for NCK in DCC signaling, we show that loss of NCK proteins leads to a reduction in the thickness of TAG1(+ve) commissural bundles in the floor plate and loss of DCC mRNA in vivo. We suggest that DCC signaling functions through NCK1 and NCK2 and that both proteins are necessary for the establishment of normal spinal circuits necessary for gait. Reduction in NCK proteins in the developing CNS leads to a reduction in TAG1(+ve) commissural tract thickness, a reduction in growth cone complexity of DCC(+ve) spinal interneurons, and a reduction in DCC mRNA. These are consistent with an in vivo role for NCK in the development of critical DCC spinal circuits, and may be important for the normal development of spinal circuits critical for walking.

A novel method for synthesizing PEGylated chitosan nanoparticles: strategy, preparation, and in vitro analysis.

Preparation of poly (ethylene glycol) (PEG)-grafted chitosan is essential for improving the biocompatibility and water solubility of chitosan. Presently available methods for this have limitations. This article describes a new method for preparing PEGylated chitosan nanoparticles. For this chitosan was chemoselectively modified using a novel scheme at the C6 position of its repeating units by PEG. The amine groups at the C2 position of the chitosan were protected using phthalic anhydride. Sodium hydride was used to catalyze the etherification reaction between chlorinated chitosan and methyl-PEG, and PEG-grafted chitosan was successfully synthesized. Each step was characterized using 13C nuclear magnetic resonance and Fourier transform infrared. After PEGylation the phthaloylated chitosan was successfully deprotected using hydrazine monohydrate. The synthetic scheme proposed demonstrates a new method for grafting PEG onto chitosan with a moderate degree of substitution. The potential of this polymer in nanoparticle preparation using an ionic gelation method and its gene delivery potentials were investigated by complexing a fluorescently labeled control siRNA. The result showed that suitable nanoparticles can be synthesized using this polymer and that they have capacity to carry genes and provide adequate transfection efficacy with no toxicity when tested in neuronal cells.

Oxysterol binding protein-dependent activation of sphingomyelin synthesis in the golgi apparatus requires phosphatidylinositol 4-kinase IIα.

Cholesterol and sphingomyelin (SM) associate in raft domains and are metabolically coregulated. One aspect of coordinate regulation occurs in the Golgi apparatus where oxysterol binding protein (OSBP) mediates sterol-dependent activation of ceramide transport protein (CERT) activity and SM synthesis. Because CERT transfer activity is dependent on its phosphatidylinositol 4 phosphate [PtdIns(4)P]-specific pleckstrin homology domain, we investigated whether OSBP activation of CERT involved a Golgi-associated PtdIns 4-kinase (PI4K). Cell fractionation experiments revealed that Golgi/endosome-enriched membranes from 25-hydroxycholesterol-treated Chinese hamster ovary cells had increased activity of a sterol-sensitive PI4K that was blocked by small interfering RNA silencing of OSBP. Consistent with this sterol-requirement, OSBP silencing also reduced the cholesterol content of endosome/trans-Golgi network (TGN) fractions containing PI4KIIα. PI4KIIα, but not PI4KIIIß, was required for oxysterol-activation of SM synthesis and recruitment of CERT to the Golgi apparatus. However, neither PI4KIIα nor PI4KIIIß expression was required for 25-hydroxycholesterol-dependent translocation of OSBP to the Golgi apparatus. The presence of OSBP, CERT, and PI4KIIα in the TGN of oxysterol-stimulated cells suggests that OSBP couples sterol binding or transfer activity with regulation of PI4KIIα activity, leading to CERT recruitment to the TGN and increased SM synthesis.