Changes in the number and outcome of takeaway food outlet planning applications in response to adoption of management zones around schools in England: A time series analysis.

Physical exposure to takeaway food outlets ("takeaways") is associated with poor diet and excess weight, which are leading causes of excess morbidity and mortality. At the end of 2017, 35 local authorities (LAs) in England had adopted takeaway management zones (or "exclusion zones"), which is an urban planning intervention designed to reduce physical exposure to takeaways around schools. In this nationwide, natural experimental study, we used interrupted time series analyses to estimate the impact of this intervention on changes in the total number of takeaway planning applications received by LAs and the percentage rejected, at both first decision and after any appeal, within management zones, per quarter of calendar year. Changes in these proximal process measures would precede downstream retail and health impacts. We observed an overall decrease in the number of applications received by intervention LAs at 12 months post-intervention (6.3 fewer, 95% CI -0.1, -12.5), and an increase in the percentage of applications that were rejected at first (additional 18.8%, 95% CI 3.7, 33.9) and final (additional 19.6%, 95% CI 4.7, 34.6) decision, the latter taking into account any appeal outcomes. This effect size for the number of planning applications was maintained at 24 months, although it was not statistically significant. We also identified three distinct sub-types of management zone regulations (full, town centre exempt, and time management zones). The changes observed in rejections were most prominent for full management zones (where the regulations are applied irrespective of overlap with town centres), where the percentage of applications rejected was increased by an additional 46.1% at 24 months. Our findings suggest that takeaway management zone policies may have the potential to curb the proliferation of new takeaways near schools and subsequently impact on population health.

Laminectomy Adjacent to Instrumented Fusion Increases Adjacent Segment Disease.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To determine if performing a simultaneous laminectomy at an unfused level adjacent to an instrumented fusion increases the risk of adjacent segment disease(ASD). SUMMARY OF BACKGROUND DATA: Laminectomy adjacent to instrumented fusion has uncertain outcomes. The increased mechanical forces at the unfused laminectomy may lead to more ASD. Few studies have examined the development of ASD with regards to laminectomy performed adjacent to instrumented fusions. METHODS: 789 patients underwent instrumented lumbar fusion and laminectomy at the same level(s) (n=676) or with an additional adjacent level laminectomy (n=113) with a minimum of 2-year follow-up. Diagnoses were degenerative spondylosis (n=241), degenerative spondylolisthesis (n=485) and isthmic spondylolisthesis (n=63) in addition to central stenosis. Primary outcome measures included development of ASD, time to development of ASD, revision surgery, and time to revision surgery. RESULTS: The adjacent laminectomy group developed ASD at a significantly greater rate of 57.5% (n=65), compared with 35.2% (n=238) of the non-adjacent laminectomy group (P<0.001). Revision surgery rate was also greater in the adjacent laminectomy group (22.1% v 13.5%, P<0.001). There was no difference in time to revision surgery (31.1 v 32.6 mo, P=0.71) or time to ASD development (31.2 v 32.3 mo, P=0.72). ODI and VAS scores did not differ, nor did patient baseline demographics including sex, BMI, Charleston Comorbidity Index, and tobacco use. The exception was the adjacent laminectomy group average age was 67.6 while the non-adjacent laminectomy group average age was 62.3 (P<0.001). However, age was not found to be an independent predictor of ASD development (P=0.44). CONCLUSION: Surgeons should be cautious when performing a laminectomy adjacent to an instrumented fusion, as this increases the rate of ASD as well as revision surgery.

'Acceleration' of the food delivery marketplace: Perspectives of local authority professionals in the North-East of England on temporary COVID regulations.

In January 2021, we assessed the implications of temporary regulations in the United Kingdom allowing pubs and restaurants to operate on a takeaway basis without instigating a change of use. Local authorities (LAs) across the North-East of England were unaware of any data regarding the take-up of these regulations, partially due to ongoing capacity issues; participants also raised health concerns around takeaway use increasing significantly. One year on, we repeated the study aiming to understand the impact of these regulations on the policy and practice of key professional groups. Specifically, we wanted to understand if LAs were still struggling with staff capacity to address the regulations, whether professionals still had public health trepidations, and if any unexpected changes had occurred across the local food environment because of the pandemic. We conversed with 16 public health professionals, planners and environmental health officers across seven LAs throughout the North-East of England via focus groups and interviews. Data collated were analysed via an inductive and semantic, reflexive-thematic approach. Through analysis of the data, three themes were generated and are discussed throughout: popular online delivery services as a mediator to increased takeaway usage; potential long-term health implications and challenges; continued uncertainty regarding the temporary regulations. This paper highlights important changes to local food environments, which public health professionals should be aware of, so they are better equipped to tackle health inequalities across urban and sub-urban areas.

Changes in the number of new takeaway food outlets associated with adoption of management zones around schools: A natural experimental evaluation in England.

By the end of 2017, 35 local authorities (LAs) across England had adopted takeaway management zones (or "exclusion zones") around schools as a means to curb proliferation of new takeaways. In this nationwide, natural experimental study, we evaluated the impact of management zones on takeaway retail, including unintended displacement of takeaways to areas immediately beyond management zones, and impacts on chain fast-food outlets. We used uncontrolled interrupted time series analyses to estimate changes from up to six years pre- and post-adoption of takeaway management zones around schools. We evaluated three outcomes: mean number of new takeaways within management zones (and by three identified sub-types: full management, town centre exempt and time management zones); mean number on the periphery of management zones (i.e. within an additional 100 m of the edge of zones); and presence of new chain fast-food outlets within management zones. For 26 LAs, we observed an overall decrease in the number of new takeaways opening within management zones. Six years post-intervention, we observed 0.83 (95% CI -0.30, -1.03) fewer new outlets opening per LA than would have been expected in absence of the intervention, equivalent to an 81.0% (95% CI -29.1, -100) reduction in the number of new outlets. Cumulatively, 12 (54%) fewer new takeaways opened than would have been expected over the six-year post-intervention period. When stratified by policy type, effects were most prominent for full management zones and town centre exempt zones. Estimates of intervention effects on numbers of new takeaways on the periphery of management zones, and on the presence of new chain fast-food outlets within management zones, did not meet statistical significance. Our findings suggest that management zone policies were able to demonstrably curb the proliferation of new takeaways. Modelling studies are required to measure the possible population health impacts associated with this change.

The impact of macro- and micro-steatosis on the outcomes of patients who undergo liver transplant: Analysis of the UNOS-STAR database.

BACKGROUND AND AIMS: The presence of steatosis in a donor liver and its relation to post-transplantation outcomes are not well defined. This study evaluates the effect of the presence and severity of micro- and macro-steatosis of a donor graft on post-transplantation outcomes. METHODS: The UNOS-STAR registry (2005-2019) was used to select patients who received a liver transplant graft with hepatic steatosis. The study cohort was stratified by the presence of macro- or micro-vesicular steatosis, and further stratified by histologic grade of steatosis. The primary endpoints of all-cause mortality and graft failure were compared using sequential Cox regression analysis. Analysis of specific causes of mortality was further performed. RESULTS: There were 9184 with no macro-steatosis (control), 150 with grade 3 macro-steatosis, 822 with grade 2 macro-steatosis and 12 585 with grade 1 macro-steatosis. There were 10 320 without micro-steatosis (control), 478 with grade 3 micro-steatosis, 1539 with grade 2 micro-steatosis and 10 404 with grade 1 micro-steatosis. There was no significant difference in all-cause mortality or graft failure among recipients who received a donor organ with any evidence of macro- or micro-steatosis, compared to those receiving non-steatotic grafts. There was increased mortality due to cardiac arrest among recipients of a grade 2 macro-steatosis donor organ. CONCLUSION: This study shows no significant difference in all-cause mortality or graft failure among recipients who received a donor liver with any degree of micro- or macro-steatosis. Further analysis identified increased mortality due to specific aetiologies among recipients receiving donor organs with varying grades of macro- and micro-steatosis.

Informal Family Care Partner Well-Being Is Diminished in End-Stage Liver Disease.

BACKGROUND: Chronic liver disease is a significant global neglected public health problem. End-stage liver disease is associated with substantial symptom complexity, disability, and care needs that require assistance from informal family care partners. Research on these care partners' caregiver burden or strain, symptoms, and quality of life is sparse and has not focused on these variables as co-occurring or in the context of the quality of the relationship care partners have with the patients. OBJECTIVES: The purpose of this study was to provide a collective presentation of patterns and determinants of well-being as measured by caregiver strain, depression, sleep, and quality of life in a cohort of informal family care partners for adult outpatients with end-stage liver disease. METHODS: Care partners (age > 18 years) were recruited from two liver clinics within two tertiary health care systems and invited to complete a cross-sectional survey. They completed the Multidimensional Caregiver Strain Index, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Short Form Health Survey, and Mutuality Scale. Descriptive statistics and latent class mixture modeling were used to analyze these data. RESULTS: The sample was predominantly female and White. The well-being of care partners was diminished. Three distinct classes of well-being were identified: mildly diminished (53.2%), moderately diminished (39.0%), and severely diminished (7.8%). Those at greater risk of worse well-being were younger, spouses, and had poorer relationship quality with the patients. DISCUSSION: To improve the well-being of care partners in moderately and severely diminished classes, assessing and addressing caregiver strain and co-occurring symptoms is essential. Addressing this strain and symptoms has the potential to maintain or optimize care partners' ability to provide care to patients. Future researchers should include longitudinal and dyadic studies to examine how patients' disease progression and symptoms may affect family care partners well-being and vice versa.

Can the implementation of net gain requirements in England's planning system be applied to health?

This Personal View considers the relationship between spatial planning and health and the potential benefits of requiring health net gain from land use decisions and new developments. We explore how a health net gain objective could be applied in spatial planning policy and practice to improve people's health and wellbeing, using England's implementation of a biodiversity net gain objective as a model. This Personal View emphasises the need for a systems approach to the definition and strategic coordination of health gains, recognising the breadth of health determinants and inter-related economic, environmental, and social policy objectives. By considering the potential application of a net gain principle to health in spatial planning, we offer valuable insights into how the spatial planning system could be used to build the conditions of health creation. A road map is provided for exploration of health net gain in other national contexts in support of the operationalisation of global urban health initiatives.

Response rate and molecular correlates to encorafenib and binimetinib in BRAF-V600E mutant high-grade glioma.

PURPOSE: While fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600 mutated HGG. PATIENTS AND METHODS: In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles. Eligible patients were required to have high-grade glioma or glioblastoma with a BRAF-V600E alteration that was recurrent following at least one line of therapy including radiation. RESULTS: Five patients enrolled between January 2020 and administrative termination in November 2021 (due to closure of the ABTC). Enrolled patients received treatment for 2-40 months; currently one patient remains on treatment. Centrally determined radiographic response rate was 60%, with one complete response and two partial responses. Methylation profiling revealed all tumors cluster most closely with anaplastic PXA. Transcriptional profile for MAPK-response signature was similar across all tumors at baseline and did not correlate with response in this small population. Circulating tumor DNA measured in plasma samples prior to treatment, during response, and upon progression showed feasibility of detection for the BRAF-V600E alteration. No new safety signal was detected. CONCLUSIONS: Encorafenib and binimetinib exhibit positive tumor responses in patients with recurrent BRAF-V600E mutant HGG in this small series, warranting therapeutic consideration. Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients.

Multicenter prospective blinded melanoma detection study with a handheld elastic scattering spectroscopy device.

Background: The elastic scattering spectroscopy (ESS) device (DermaSensor Inc., Miami, FL) is a noninvasive, painless, adjunctive tool for skin cancer detection. Objectives: To investigate the performance of the ESS device in the detection of melanoma. Methods: A prospective, investigator-blinded, multicenter study was conducted at 8 United States (US) and 2 Australian sites. All eligible skin lesions were clinically concerning for melanoma, examined with the ESS device, subsequently biopsied according to dermatologists' standard of care, and evaluated with histopathology. A total of 311 participants with 440 lesions were enrolled, including 44 melanomas (63.6% in situ and 36.4% invasive) and 44 severely dysplastic nevi. Results: The observed sensitivity of the ESS device for melanoma detection was 95.5% (95% CI, 84.5% to 98.8%, 42 of 44 melanomas), and the observed specificity was 32.5% (95% CI, 27.2% to 38.3%). The positive and negative predictive values were 16.0% and 98.1%, respectively. Limitations: The device was tested in a high-risk population with lesions selected for biopsy based on clinical and dermoscopic assessments of board-certified dermatologists. Most enrolled lesions were pigmented. Conclusion: The ESS device's high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.

Case series: Stenotrophomonas maltophilia in pediatric oncology patients.

BACKGROUND: Stenotrophomonas maltophilia is a bacterial pathogen that can be fatal in hospitalized and immunocompromised patients with mortality as high as 69%. Pediatric cancer patients often have risk factors that are common for this infection, making them particularly susceptible. Managing S. maltophilia is especially challenging as it has inherent resistance to several antibiotics. Furthermore, soft tissue infections in neutropenic patients may deviate from the typical clinical presentation of S. maltophilia. CASE DETAILS: This case series describes an in-depth examination of three cases involving immunocompromised pediatric patients with S. maltophilia infections. Each case exhibited a distinct clinical presentation, encompassing infection of the blood, lung, and skin, which highlights the variability in which S. maltophilia manifests in immunocompromised pediatric patients. These patients were treated at MD Anderson Cancer Center (MDACC) from 2020 to 2023, unfortunately resulting in fatality. CONCLUSIONS: The study aims to provide valuable insights and guidance for the management of patients with S. maltophilia infections. Emphasizing a heightened clinical suspicion will potentially lead to early initiation of directed therapy against S. maltophilia. Timely intervention may play a pivotal role in improving patient outcomes and reduce further burden to the healthcare system.

Esophageal anatomy and physiology vary across spastic and non-spastic phenotypes of disorders of esophagogastric junction outflow.

BACKGROUND: Pathophysiologic mechanisms of disorders of esophagogastric junction (EGJ) outflow are poorly understood. We aimed to compare anatomic and physiologic characteristics among patients with disorders of EGJ outflow and normal motility. METHODS: We retrospectively evaluated adult patients with achalasia types 1, 2, 3, EGJ outflow obstruction (EGJOO) or normal motility on high-resolution manometry who underwent endoscopic ultrasound (EUS) from January 2019 to August 2022. Thickened circular muscle was defined as ≥1.6 mm. Characteristics from barium esophagram (BE) and functional lumen imaging probe (FLIP) were additionally assessed. KEY RESULTS: Of 71 patients (mean age 56.2 years; 49% male), there were 8 (11%) normal motility, 58 (82%) had achalasia (5 (7%) type 1, 32 (45%) classic type 2, 21 (30%) type 3 [including 12 type 2 with FEPs]), and 7 (7%) had EGJOO. A significantly greater proportion of type 3 achalasia had thickened distal circular muscle (76.2%) versus normal motility (0%; p < 0.001) or type 2 achalasia (25%; p < 0.001). Type 1 achalasia had significantly wider mean maximum esophageal diameter on BE (57.8 mm) compared to type 2 achalasia (32.8 mm), type 3 achalasia (23.4 mm), EGJOO (15.9 mm), and normal motility (13.5 mm). 100% type 3 achalasia versus 0% type 1 achalasia/normal motility had tertiary contractions on BE. Mean EGJ distensibility index on FLIP was lower for type 3 achalasia (1.2 mmHg/mm2 ) and EGJOO (1.2 mmHg/mm2 ) versus type 2 (2.3 mmHg/mm2 ) and type 1 achalasia (2.9 mmHg/mm2 ). CONCLUSIONS: Our findings suggest distinct pathologic pathways may exist: type 3 achalasia and EGJOO may represent a spastic outflow phenotype consisting of a thickened, spastic circular muscle, which is distinct from type 1 and 2 achalasia consisting of a thin caliber circular muscle layer with more prominent esophageal dilation.

Impact of the COVID-19 pandemic on pediatric faculty: a report from nine academic institutions.

BACKGROUND: The COVID-19 pandemic affected home and work routines, which may exacerbate existing academic professional disparities. Objectives were to describe the impact of the pandemic on pediatric faculty's work productivity, identify groups at risk for widening inequities, and explore mitigation strategies. METHODS: A cross-sectional study of faculty members was conducted at nine U.S. pediatric departments. Responses were analyzed by demographics, academic rank, and change in home caregiving responsibility. RESULTS: Of 5791 pediatric faculty members eligible, 1504 (26%) completed the survey. The majority were female (64%), over 40 years old (60%), and assistant professors (47%). Only 7% faculty identified as underrepresented in medicine. Overall 41% reported an increase in caregiving during the pandemic. When comparing clinical, administrative, research, and teaching activities, faculty reported worse 1-year outlook for research activities. Faculty with increased caregiving responsibilities were more likely to report concerns over delayed promotion and less likely to have a favorable outlook regarding clinical and research efforts. Participants identified preferred strategies to mitigate challenges. CONCLUSIONS: The COVID-19 pandemic negatively impacted pediatric faculty productivity with the greatest effects on those with increased caregiving responsibilities. COVID-19 was particularly disruptive to research outlook. Mitigation strategies are needed to minimize the long-term impacts on academic pediatric careers. IMPACT: The COVID-19 pandemic most negatively impacted work productivity of academic pediatric faculty with caregiving responsibilities. COVID-19 was particularly disruptive to short-term (1-year) research outlook among pediatric faculty. Faculty identified mitigation strategies to minimize the long-term impacts of the pandemic on academic pediatric career pathways.

Environmental Risk Factors for Pediatric Epistaxis vary by Climate Zone.

INTRODUCTION AND OBJECTIVE: Prior studies have provided variable results regarding environmental risk factors for epistaxis. These studies were conducted in varying climate zones, which may explain discrepancies in results. The objective of this study is to investigate correlations between season, temperature, and humidity on frequency of pediatric epistaxis across climate zones. METHODS: Children seen in the outpatient setting for epistaxis were identified from the 2007-2010 IBM MarketScan database. Climate zones were assigned according to International Energy Conservation Code (IECC) classification, where temperature zones in the United States and territories were assigned on an ordinal scale from 1 (tropical) to 8 (subarctic), and humidity zones were categorized as moist, dry, or marine. The control population was a sample of all well-child visits matched by age and county. RESULTS: We identified 184,846 unique children seen for epistaxis and 1,897,012 matched controls. Moderate temperature zones were associated with lower odds of epistaxis compared with the hottest and coldest zones. Humidity was associated inversely with epistaxis rates in moderate temperature zones but was not a significant predictor of epistaxis in climates with extreme heat. Additionally, summer was associated with lower odds of epistaxis compared to winter. Interestingly, however, there were significantly higher rates of cautery procedures during summer months, driven largely by increased procedures performed in clinic, as opposed to the operating room or emergency room. CONCLUSIONS: Environmental risk factors for epistaxis vary by climate zone. The model presented reconciles prior reports and may allow for more personalized clinical management based on regional climate. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1450-1456, 2024.

Surgical Correction of Nasal Obstruction and Its Effect on Eustachian Tube Dysfunction Symptoms.

OBJECTIVES: To investigate how eustachian tube dysfunction symptoms change following surgical treatment of nonsinusitis-related nasal obstruction. STUDY DESIGN: Retrospective chart review. SETTING: Single academic center. METHODS: We assessed patients who underwent septoplasty, turbinate reduction, or both for nasal obstruction. Chronic sinusitis patients were excluded. Eustachian tube dysfunction (ETD) symptoms were studied using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7), collected preoperatively and postoperatively (1 week, 1 month, 3 months, 6 months postop). Patients with preoperative ETDQ-7 > 14.5 were considered to have clinically significant symptoms. Sinonasal outcomes test scores were also assessed. Pre- and postoperative ETDQ-7 scores were compared using t test. Multivariate linear regression analysis identified factors associated with ETDQ-7 change. RESULTS: We analyzed 259 patients. Preoperatively, 37.5% of patients with nasal obstruction had clinically significant ETD symptoms. These patients exhibited significant improvement in ETDQ-7 at all postoperative timepoints from 23.3 ± 7.6 at baseline to 19.1 ± 9.1 at 1 week, 16.5 ± 8.0 at 1 month, 16.2 ± 7.8 at 3 months, and 16.7 ± 10.4 at 6 months (all P < .01). In patients without baseline ETD symptoms, (baseline ETDQ-7: 9.1 ± 2.3) ETDQ-7 scores did not change significantly at postoperative timepoints, except for an acute worsening at 1 week postoperatively (10.7 ± 5.1, P < .001). Regression analysis showed that higher preoperative ETDQ-7 score (ß = -0.84, 95% confidence interval [CI]: -1.10 to -0.59) and postoperative antihistamine spray usage (ß = -8.70, 95% CI: -14.20 to -3.20) were associated with ETDQ-7 improvement, while comorbid GERD (ß = 7.50, 95% CI: 3.42-11.58) and asthma (ß = 5.62, 95% CI: 0.80-10.45) were negatively associated with improvement. CONCLUSION: Surgical correction of nasal obstruction may improve ETD symptoms.

Inhibition of Neurogenic Inflammatory Pathways Associated with the Reduction in Discogenic Back Pain.

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to determine whether the initiation of anti-calcitonin gene-related peptide (CGRP inhibitor) medication therapy for migraines was also associated with improvements in back/neck pain, mobility, and function in a patient population with comorbid degenerative spinal disease and migraine. OVERVIEW OF LITERATURE: CGRP upregulates pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, brain-derived neurotrophic factor, and nerve growth factor in spinal spondylotic disease, which results in disc degeneration and sensitization of nociceptive neurons. Although CGRP inhibitors can quell neurogenic inflammation in migraines, their off-site efficacy as a therapeutic target for discogenic back/neck pain conditions remains unknown. METHODS: All adult patients diagnosed with spinal spondylosis and migraine treated with CGRP inhibitors at a single academic institution between 2017 and 2020 were retrospectively identified. Patient demographic and medical data, follow-up duration, migraine severity and frequency, spinal pain, functional status, and mobility before and after the administration of CGRP inhibitors were collected. Paired univariate analysis was conducted to determine significant changes in spinal pain, headache severity, and headache frequency before and after the administration of CGRP inhibitors. The correlation between changes in the spinal pain score and functional or mobility improvement was assessed with Spearman's rho. RESULTS: In total, 56 patients were included. The mean follow-up time after the administration of CGRP inhibitors was 123 days for spinal pain visits and 129 days for migraine visits. Back/neck pain decreased significantly (p <0.001) from 6.30 to 4.36 after starting CGRP inhibitor therapy for migraine control. As recorded in the spine follow-up notes, 25% of patients experienced a functional improvement in the activities of daily living, and 17.5% experienced mobility improvement while taking CGRP inhibitors. Change in back/ neck pain moderately correlated (ρ=-0.430) with functional improvement but was not correlated with mobility improvement (ρ=-0.052). CONCLUSIONS: Patients taking CGRP inhibitors for chronic migraines with comorbid degenerative spinal conditions experienced significant off-target reduction of back/neck pain.

Druggable genomic landscapes of high-grade gliomas.

Background: Despite the putatively targetable genomic landscape of high-grade gliomas, the long-term survival benefit of genomically-tailored targeted therapies remains discouraging. Methods: Using glioblastoma (GBM) as a representative example of high-grade gliomas, we evaluated the clonal architecture and distribution of hotspot mutations in 388 GBMs from the Cancer Genome Atlas (TCGA). Mutations were matched with 54 targeted therapies, followed by a comprehensive evaluation of drug biochemical properties in reference to the drug's clinical efficacy in high-grade gliomas. We then assessed clinical outcomes of a cohort of patients with high-grade gliomas with targetable mutations reviewed at the Johns Hopkins Molecular Tumor Board (JH MTB; n = 50). Results: Among 1,156 sequence alterations evaluated, 28.6% represented hotspots. While the frequency of hotspot mutations in GBM was comparable to cancer types with actionable hotspot alterations, GBMs harbored a higher fraction of subclonal mutations that affected hotspots (7.0%), compared to breast cancer (4.9%), lung cancer (4.4%), and melanoma (1.4%). In investigating the biochemical features of targeted therapies paired with recurring alterations, we identified a trend toward higher lipid solubility and lower IC50 in GBM cell lines among drugs with clinical efficacy. The drugs' half-life, molecular weight, surface area and binding to efflux transporters were not associated with clinical efficacy. Among the JH MTB cohort of patients with IDH1 wild-type high-grade gliomas who received targeted therapies, trametinib monotherapy or in combination with dabrafenib conferred radiographic partial response in 75% of patients harboring BRAF or NF1 actionable mutations. Cabozantinib conferred radiographic partial response in two patients harboring a MET and a PDGFRA/KDR amplification. Patients with IDH1 wild-type gliomas that harbored actionable alterations who received genotype-matched targeted therapy had longer progression-free (PFS) and overall survival (OS; 7.37 and 14.72 respectively) than patients whose actionable alterations were not targeted (2.83 and 4.2 months respectively). Conclusion: While multiple host, tumor and drug-related features may limit the delivery and efficacy of targeted therapies for patients with high-grade gliomas, genotype-matched targeted therapies confer favorable clinical outcomes. Further studies are needed to generate more data on the impact of biochemical features of targeted therapies on their clinical efficacy for high-grade gliomas.

An Exploratory Analysis of the Chronic Rhinosinusitis Online Support Community.

Objective: To characterize the users of the largest chronic rhinosinusitis (CRS) online support communities (OSCs), describe the perceived benefits of OSCs for their users, and understand how patient medical decision making is affected by membership in OSCs. Study Design: Cross-sectional online survey. Setting: Online. Methods: A cross-sectional online survey was adapted from the existing literature on patient support groups and modified for CRS patients. The survey was posted on multiple Facebook/Reddit groups aimed at providing support toward patients with CRS. Survey data was collected over 3 months and analyzed thereafter. Results: There were 127 total participants. The majority were female (65.35%), white (76.98%), and the median age was 38 years. Just under half of patients had nasal polyps (48.67%) and 54.54% had undergone surgery. Many participants (69.42%) reported engaging in the OSC at least multiple times per month. The most common reason for joining an OSC was to learn tips on how to manage CRS (89.7%) and the most achieved goal from membership was hearing from others undergoing a similar experience (79.5%). Involvement in an OSC impacted knowledge of CRS in 87.41% of participants. Most users (81.1%) would recommend membership in an OSC and 54.33% reported the OSC influenced their medical decision-making. Conclusion: A majority of patients with CRS who frequently engage in an OSC for CRS have a positive experience. OSCs are a resource that CRS patients utilize to manage their disease.

Rhinolithiasis misdiagnosed as intranasal osteoma: Diagnostic challenges in the telehealth era.

Rhinolithiasis is a rare clinical presentation and may be a diagnostic challenge, often mimicking other intranasal pathologies and difficult to differentiate based on imaging alone. We present the case of a 50-year-old patient with rhinolithiasis who presented with chronic left nasal obstruction and unilateral cyclic pain with foul discharge. After review of her imaging, she was initially misdiagnosed with an intranasal osteoma via telehealth and scheduled for surgical resection. Her true pathology of rhinolithiasis was subsequently identified and treated during an in-person pre-operative clinic visit. In this case report, we review the key characteristic elements of rhinolithiasis presentation, and in doing so, we reveal the limitations inherent to telehealth evaluations, and the considerations needed to be taken into account by providers evaluating intranasal lesions. Specifically, in-person assessment with a detailed endoscopy is critical as part of the complete workup of nasal cavity lesions.