SNOT-22 subdomain outcomes following treatment for sinonasal malignancy: A prospective, multicenter study.

BACKGROUND: Patients with sinonasal malignancy (SNM) present with significant sinonasal quality of life (QOL) impairment. Global sinonasal QOL as measured by the 22-item Sinonasal Outcomes Test (SNOT-22) has been shown to improve with treatment. This study aims to characterize SNOT-22 subdomain outcomes in SNM. METHODS: Patients diagnosed with SNM were prospectively enrolled in a multi-center patient registry. SNOT-22 scores were collected at the time of diagnosis and through the post-treatment period for up to 5 years. Multivariable regression analysis was used to identify drivers of variation in SNOT-22 subdomains. RESULTS: Note that 234 patients were reviewed, with a mean follow-up of 22 months (3 months-64 months). Rhinologic, psychological, and sleep subdomains significantly improved versus baseline (all p < 0.05). Subanalysis of 40 patients with follow-up at all timepoints showed statistically significant improvement in rhinologic, extra-nasal, psychological, and sleep subdomains, with minimal clinically important difference met between 2 and 5 years in sleep and psychological subdomains. Adjuvant chemoradiation was associated with worse outcomes in rhinologic (adjusted odds ratio (5.22 [1.69-8.66])), extra-nasal (2.21 [0.22-4.17]) and ear/facial (5.53 [2.10-8.91]) subdomains. Pterygopalatine fossa involvement was associated with worse outcomes in rhinologic (3.22 [0.54-5.93]) and ear/facial (2.97 [0.32-5.65]) subdomains. Positive margins (5.74 [2.17-9.29]) and surgical approach-combined versus endoscopic (3.41 [0.78-6.05])-were associated with worse psychological outcomes. Adjuvant radiation (2.28 [0.18-4.40]) was associated with worse sleep outcomes. CONCLUSIONS: Sinonasal QOL improvements associated with treatment of SNM are driven by rhinologic, extra-nasal, psychological, and sleep subdomains.

Predictive factors for decreased baseline quality of life in patients with sinonasal malignancies.

BACKGROUND: The impact of sinonasal malignancies (SNMs) on quality of life (QOL) at presentation is poorly understood. The Sinonasal Outcome Test (SNOT-22) and University of Washington Quality of Life (UWQOL) are validated QOL instruments with distinctive subdomains. This study aims to identify factors impacting pretreatment QOL in SNM patients to personalize multidisciplinary management and counseling. METHODS: Patients with previously untreated SNMs were prospectively enrolled (2015-2022) in a multicenter observational study. Baseline pretreatment QOL instruments (SNOT-22, UWQOL) were obtained along with demographics, comorbidities, histopathology/staging, tumor involvement, and symptoms. Multivariable regression models identified factors associated with reduced baseline QOL. RESULTS: Among 204 patients, presenting baseline QOL was significantly reduced. Multivariable regression showed worse total SNOT-22 QOL in patients with skull base erosion (p = 0.02). SNOT-rhinologic QOL was worse in women (p = 0.009), patients with epistaxis (p = 0.036), and industrial exposure (p = 0.005). SNOT extranasal QOL was worse in patients with industrial exposure (p = 0.016); worse SNOT ear/facial QOL if perineural invasion (PNI) (p = 0.027). Squamous cell carcinoma pathology (p = 0.037), palate involvement (p = 0.012), and pain (p = 0.017) were associated with worse SNOT sleep QOL scores. SNOT psychological subdomain scores were significantly worse in patients with palate lesions (p = 0.022), skull base erosion (p = 0.025), and T1 staging (p = 0.023). Low QOL was more likely in the presence of PNI on UW health (p = 0.019) and orbital erosion on UW overall (p = 0.03). UW social QOL was worse if palatal involvement (p = 0.023) or PNI (p = 0.005). CONCLUSIONS: Our findings demonstrate a negative impact on baseline QOL in patients with SNMs and suggest sex-specific and symptom-related lower QOL scores, with minimal histopathology association. Anatomical tumor involvement may be more reflective of QOL than T-staging, as orbital and skull base erosion, PNI, and palate lesions are significantly associated with reduced baseline QOL.

Diagnostic yield of workups ordered by pediatric ophthalmologists for bilateral pediatric cataracts at a tertiary pediatric hospital in the United States.

BACKGROUND: Children with unexplained bilateral cataracts routinely undergo testing for genetic, infectious, and metabolic etiologies. We evaluated the diagnostic yield of various tests ordered by pediatric ophthalmologists to evaluate bilateral cataracts in children at a single institution. METHODS: We retrospectively identified all children with bilateral unexplained cataracts who underwent cataract surgery by a pediatric ophthalmologist at Children's Hospital Colorado from 2006 to 2022. We reviewed the results of genetic, infectious, and metabolic testing ordered by pediatric ophthalmologists to evaluate the cataracts in these children. RESULTS: A total of 43 children met inclusion criteria. Of these, 34 (79%) had genetic testing, 34 (79%) had infectious disease testing, 33 (77%) had galactosemia testing, and 17 (40%) had urine-reducing substances testing performed during their cataract evaluation. Of the genetic tests ordered, 17 (50%) revealed a pathogenic mutation associated with cataracts. Twenty-three (68%) patients were IgG-positive for a TORCH infection, but no child was found to be positive on confirmatory testing. Of the galactosemia and URS tests ordered, 3 tests (9%) and 1 (6%) test were initially found to be abnormal, respectively, but confirmatory testing and clinical judgment ruled out metabolic disease in each case. CONCLUSIONS: Genetic testing should be strongly considered in all cases of unexplained bilateral pediatric cataracts. Metabolic and infectious testing is best considered only after consultation with the child's pediatrician, guided by the patient's clinical context and the availability of genetic testing.

Cataract Surgery Outcomes in Patients with Non-ocular Autoimmune Disease.

INTRODUCTION: While phacoemulsification cataract extraction is generally highly effective and safe, patients with a history of uveitis are at higher risk for postoperative complications and often require a modified perioperative medication regimen. No data exists on risks of postoperative complications and persistent anterior uveitis (PAU) in patients with non-ocular autoimmune disease. METHODS: Medical records were reviewed of patients who underwent phacoemulsification cataract surgery with intraocular lens implantation between January 1, 2014 and December 31, 2019 at the University of Colorado Hospital (UCH) as part of a retrospective cohort study. Exclusion criteria included patient history of ocular inflammation and cataract surgery combined with another intraocular surgery. Patients were only included as having autoimmune disease if the diagnosis was confirmed by a relevant specialist at UCH. Patients with autoimmune disease were then stratified into systemic versus organ-specific autoimmune disease, and patients with systemic autoimmune disease were further stratified into immunosuppressed and not immunosuppressed at the time of cataract surgery. Patients with PAU were identified according to the Standardization of Uveitis Nomenclature Working Group. Data including sex, race/ethnicity, intraoperative cumulative dissipated energy (CDE), and postoperative best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were obtained. RESULTS: A total of 422 eyes from 248 patients had confirmed autoimmune disease, compared to a control group of 10,201 eyes. The autoimmune and systemic autoimmune disease groups were not more likely to have postoperative complications or PAU compared to the control group. Immunosuppression status among the systemic autoimmune disease group was also not associated with postoperative complications or PAU. CONCLUSION: Patients with non-ocular autoimmune disease do not appear to be at higher risk for postoperative complications, including worse BCVA or increased rates of IOP elevation and PAU, following phacoemulsification cataract surgery. These patients do not appear to require modification of the typical perioperative medication regimen.

Recurrence patterns among patients with sinonasal mucosal melanoma: A multi-institutional study.

OBJECTIVE: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM). METHODS: This was a multi-institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan-Meier tests were used to evaluate disease-free survival (DFS), overall survival (OS), and post-recurrence survival (PRS) reported with standard errors (SE) and log-rank testing used for comparison. Cox-regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported. RESULTS: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60-month DFS (SE) was 15.5% (2.9%), 60-month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60-month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60-month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12-month PRS (HR = 0.32, 95% CI = 0.11-0.92, p = 0.034), and no treatment group was associated with improved 24- or 60-month PRS (p > 0.05). CONCLUSION: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12-month PRS.

Long-term quality of life after treatment in sinonasal malignancy: A prospective, multicenter study.

BACKGROUND: Quality of life (QOL) for individuals with sinonasal malignancy (SNM) is significantly under-studied, yet it is critical for counseling and may impact treatment. In this study we evaluated how patient, treatment, and disease factors impact sinonasal-specific and generalized QOL using validated metrics in a large cohort over a 5-year posttreatment time frame. METHODS: Patients with SNM who underwent definitive treatment with curative intent were enrolled in a prospective, multisite, longitudinal observational study. QOL was assessed using the 22-item Sino-Nasal Outcome Test (SNOT-22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pretreatment baseline and multiple follow-ups through 5 years posttreatment. Multivariable modeling was used to determine demographic, disease, and treatment factors associated with disease-specific and generalized physical and social/emotional function QOL. RESULTS: One hundred ninety-four patients with SNM were analyzed. All QOL indices were impaired at pretreatment baseline and improved after treatment. SNOT-22 scores improved 3 months and UWQOL scores improved 6 to 9 months posttreatment. Patients who underwent open compared with endoscopic tumor resection had worse generalized QOL (p < 0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT-22, p < 0.001; UWQOL Physical dimension, p = 0.02). Adjuvant radiation was associated with worse disease-specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01). CONCLUSION: Disease-specific and generalized QOL is impaired at baseline in patients with SNM and improves after treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL posttreatment.

Diagnosis, Prognosticators, and Management of Acute Invasive Fungal Rhinosinusitis: Multidisciplinary Consensus Statement and Evidence-Based Review with Recommendations.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated. RESULTS: A review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms.

Outcomes of chronic macula-off retinal detachment repair.

PURPOSE: There have been disparate outcomes in the few studies that have looked at anatomic success and visual acuity (VA) in chronic retinal rhegmatogenous detachment (RRD) repair. Chronic retinal detachments (RD) without a posterior vitreous detachment (PVD) occur in young myopes often secondary to an atrophic hole. These patients are often asymptomatic, and studies report good surgical anatomic results. However, chronic RD with a PVD is symptomatic but presents late due to patient compliance. This paper aims to evaluate this lesser-studied chronic macula-off RD with PVD. METHODS: After obtaining Institutional Review Board (IRB) approval, patients who had undergone surgical intervention for all diagnosis codes of RD were identified in the Denver Health Medical Center database. Medical records were reviewed, and patients found to have open-globe injuries, tractional RD due to proliferative diabetic retinopathy, macula-on detachments, and RD due to previous ocular surgery were excluded. Similarly, patients without PVD were also excluded. A total of 37 patients with PVD-type chronic macula-off RD were thus identified and preoperative characteristics, surgical intervention, and complications were analyzed. RESULTS: The average patient age was 53.8 years. The length of RRD duration ranged from 30 to 365 days (mean 136.7 days). Twenty-six (70.3% patients had proliferative vitreoretinopathy (PVR) grade C or greater. Initial anatomic success-defined as re-attachment after one surgery-was 54.1%. The final attachment was 94.6%. Fifteen of 37 (40.5%) of the patients had issues with drop adherence, positioning, or missing post-operative appointments. CONCLUSION: Chronic macula-off RD with a PVD should be identified as it is associated with much lower rates of initial re-attachment. Socioeconomic factors likely are the driving factor for patients with PVD-type chronic macula-off RD to present late, struggle with positioning, and have difficulty with follow-up and drop compliance. These extended periods without treatment then lead to high rates of PVR and poor initial anatomic success. However, repair of PVD-type chronic macula-off RD should still be pursued as final anatomic success is high.

Rheumatologic associations of microscopic colitis: A narrative review.

Extraintestinal manifestations (EIMs) are frequent complications of the classical inflammatory bowel diseases, Crohn's disease and ulcerative colitis. However, in addition to the classical diseases, there is a spectrum of conditions, often termed 'microscopic colitis' (MC), in which EIMs are less well described. Our objective was to review the literature regarding the EIMs complicating MC and describe their association with systemic autoimmune rheumatic diseases. A comprehensive search and review of peer-reviewed English-language and international journals and reports was completed based on key terms, including 'microscopic colitis', 'lymphocytic colitis', 'collagenous colitis', 'inflammatory bowel disease', and 'extraintestinal manifestations', and the specific disease associations utilizing the PubMed Central database and MEDLINE. A broad spectrum of rheumatologic manifestations has been reported in patients with MC. The identification of rheumatoid arthritis and limited scleroderma as comorbidities with MC was noteworthy. Inflammatory arthropathy was frequently seen in MC, usually preceding or occurring in conjunction with the onset of gastrointestinal symptoms. A variety of presentations of associated arthritis were reported: migratory, symmetric or asymmetric, peripheral or axial, oligoarticular or polyarticular, and erosive or non-erosive. There was a high incidence of autoantibodies in these patients, supporting a potential autoimmune association. On the basis of these anecdotal reports, we would suggest the development of a clinical registry to help define the incidence of EIMs and systemic autoimmune rheumatic diseases among MC patients to help elucidate shared predispositions, pathogenic mechanisms, and therapeutic opportunities.

Live-cell photo-activated localization microscopy correlates nanoscale ryanodine receptor configuration to calcium sparks in cardiomyocytes.

Ca2+ sparks constitute the fundamental units of Ca2+ release in cardiomyocytes. Here we investigate how ryanodine receptors (RyRs) collectively generate these events by employing a transgenic mouse with a photo-activated label on RyR2. This allowed correlative imaging of RyR localization, by super-resolution Photo-Activated Localization Microscopy, and Ca2+ sparks, by high-speed imaging. Two populations of Ca2+ sparks were observed: stationary events and "travelling" events that spread between neighbouring RyR clusters. Travelling sparks exhibited up to 8 distinct releases, sourced from local or distal junctional sarcoplasmic reticulum. Quantitative analyses showed that sparks may be triggered by any number of RyRs within a cluster, and that acute ß-adrenergic stimulation augments intra-cluster RyR recruitment to generate larger events. In contrast, RyR "dispersion" during heart failure facilitates the generation of travelling sparks. Thus, RyRs cooperatively generate Ca2+ sparks in a complex, malleable fashion, and channel organization regulates the propensity for local propagation of Ca2+ release.

Creation and cost-evaluation of a student-run podcast in ophthalmology.

Podcasts are an increasingly popular medical education modality, especially in surgical fields. However, the cost of developing a high-quality medical education podcast presents a barrier to many content creators. The authors developed the podcast series 'The Lenspod,' designed to be a cost-efficient but high-quality education resource in ophthalmology. The REC financial framework has been previously used to estimate the financial costs of technology-based medical education. Using this framework, costs were competitive with other medical education podcasts. It is our hope that similar methodology may be used to create and disseminate future podcasts for medical education.

Les balados sont une modalité d'enseignement médical de plus en plus populaire, en particulier dans les domaines chirurgicaux. Cependant, le coût de création d'un balado éducatif de qualité en médecine constitue un obstacle pour de nombreux créateurs de contenu. Les auteurs sont les créateurs de la série de balados The Lenspod, qui se veut une ressource éducative à la fois rentable et de qualité en ophtalmologie. Appliquant le cadre financier REC, déjà utilisé pour estimer les coûts financiers de modes d'enseignement médical basés sur la technologie, nous avons constaté que les coûts de notre balado sont compétitifs par rapport à d'autres en éducation médicale. Nous espérons qu'une méthode similaire sera utilisée pour créer et diffuser davantage de balados éducatifs en médecine.

Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology.

BACKGROUND: Conventional preclinical models often miss drug toxicities, meaning the harm these drugs pose to humans is only realized in clinical trials or when they make it to market. This has caused the pharmaceutical industry to waste considerable time and resources developing drugs destined to fail. Organ-on-a-Chip technology has the potential improve success in drug development pipelines, as it can recapitulate organ-level pathophysiology and clinical responses; however, systematic and quantitative evaluations of Organ-Chips' predictive value have not yet been reported. METHODS: 870 Liver-Chips were analyzed to determine their ability to predict drug-induced liver injury caused by small molecules identified as benchmarks by the Innovation and Quality consortium, who has published guidelines defining criteria for qualifying preclinical models. An economic analysis was also performed to measure the value Liver-Chips could offer if they were broadly adopted in supporting toxicity-related decisions as part of preclinical development workflows. RESULTS: Here, we show that the Liver-Chip met the qualification guidelines across a blinded set of 27 known hepatotoxic and non-toxic drugs with a sensitivity of 87% and a specificity of 100%. We also show that this level of performance could generate over $3 billion annually for the pharmaceutical industry through increased small-molecule R&D productivity. CONCLUSIONS: The results of this study show how incorporating predictive Organ-Chips into drug development workflows could substantially improve drug discovery and development, allowing manufacturers to bring safer, more effective medicines to market in less time and at lower costs.

Drug development is lengthy and costly, as it relies on laboratory models that fail to predict human reactions to potential drugs. Because of this, toxic drugs sometimes go on to harm humans when they reach clinical trials or once they are in the marketplace. Organ-on-a-Chip technology involves growing cells on small devices to mimic organs of the body, such as the liver. Organ-Chips could potentially help identify toxicities earlier, but there is limited research into how well they predict these effects compared to conventional models. In this study, we analyzed 870 Liver-Chips to determine how well they predict drug-induced liver injury, a common cause of drug failure, and found that Liver-Chips outperformed conventional models. These results suggest that widespread acceptance of Organ-Chips could decrease drug attrition, help minimize harm to patients, and generate billions in revenue for the pharmaceutical industry.

Developing the HLS19-YP12 for measuring health literacy in young people: a latent trait analysis using Rasch modelling and confirmatory factor analysis.

BACKGROUND: Accurate and precise measures of health literacy (HL) is supportive for health policy making, tailoring health service design, and ensuring equitable access to health services. According to research, valid and reliable unidimensional HL measurement instruments explicitly targeted at young people (YP) are scarce. Thus, this study aims at assessing the psychometric properties of existing unidimensional instruments and developing an HL instrument suitable for YP aged 16-25 years. METHODS: Applying the HLS19-Q47 in computer-assisted telephone interviews, we collected data in a representative sample comprising 890 YP aged 16-25 years in Norway. Applying the partial credit parameterization of the unidimensional Rasch model for polytomous data (PCM) and confirmatory factor analysis (CFA) with categorical variables, we evaluated the psychometric properties of the short versions of the HLS19-Q47; HLS19-Q12, HLS19-SF12, and HLS19-Q12-NO. A new 12-item short version for measuring HL in YP, HLS19-YP12, is suggested. RESULTS: The HLS19-Q12 did not display sufficient fit to the PCM, and the HLS19-SF12 was not sufficiently unidimensional. Relative to the PCM, some items in the HLS19-Q12, the HLS19-SF12, and the HLS19-Q12-NO discriminated poorly between participants at high and at low locations on the underlying latent trait. We observed disordered response categories for some items in the HLS19-Q12 and the HLS19-SF12. A few items in the HLS19-Q12, the HLS19-SF12, and the HLS19-Q12-NO displayed either uniform or non-uniform differential item functioning. Applying one-factorial CFA, none of the aforementioned short versions achieved exact fit in terms of non-significant model chi-square statistic, or approximate fit in terms of SRMR ≤ .080 and all entries ≤ .10 that were observed in the respective residual matrix. The newly suggested parsimonious 12-item scale, HLS19-YP12, displayed sufficiently fit to the PCM and achieved approximate fit using one-factorial CFA. CONCLUSIONS: Compared to other parsimonious 12-item short versions of HLS19-Q47, the HLS19-YP12 has superior psychometric properties and unconditionally proved its unidimensionality. The HLS19-YP12 offers an efficient and much-needed screening tool for use among YP, which is likely a useful application in processes towards the development and evaluation of health policy and public health work, as well as for use in clinical settings.

A Pilot Study Assessing Retinal Blood Flow Dysregulation in Glaucoma Using Erythrocyte Mediated Velocimetry.

Purpose: The purpose of this study was to compare autoregulation of retinal arteriolar and venular blood flow in patients with glaucoma, glaucoma suspect participants, and control participants using erythrocyte mediated velocimetry. Methods: This prospective cohort pilot study included 7 eyes of 5 participants with glaucoma, 15 eyes of 8 glaucoma suspect participants, and 11 eyes of 6 control participants. Mean erythrocyte velocity in retinal arterioles and venules was measured using erythrocyte mediated velocimetry at room air and after oxygen supplementation. Change in erythrocyte velocity was compared among all groups using generalized estimating equations. Results: In total, 64 vessels (18 with glaucoma, 31 that were glaucoma suspect, and 15 controls) of 33 eyes of 19 participants were analyzed. There was no significant difference in baseline velocities in arterioles or venules among the three groups. With induction of hyperoxia, mean arterial erythrocyte velocity decreased in glaucoma (-7.2 ± 13.7%), which differed from controls and glaucoma suspects where erythrocyte velocity increased with hyperoxia by 4.6 ± 13.3% (P = 0.002) and 7.2 ± 21.7% (P = 0.03), respectively. A higher baseline arteriolar velocity (ß = -3.9% per mm/s, P = 0.002), glaucoma diagnosis (ß = -21.1%, P = 0.03), and White race (ß = -20.0%, P = 0.01) were associated with decreased velocity in response to arterial hyperoxia. Conclusions: Hyperoxia increased erythrocyte velocity in control and glaucoma suspect participants, but decreased erythrocyte velocity in glaucoma participants, possibly due to impaired autoregulation. Baseline velocity, glaucoma diagnosis, and White race were associated with a decrease in velocity with induction of hyperoxia. Translational Relevance: The European Medicines Agency (EMA) permits precision measurements of blood flow which may aid in the development of biomarkers of glaucoma-related dysregulation of blood flow.

HLS19-NAV-Validation of a New Instrument Measuring Navigational Health Literacy in Eight European Countries.

To manoeuvre a complex and fragmented health care system, people need sufficient navigational health literacy (NAV-HL). The objective of this study was to validate the HLS19-NAV measurement scale applied in the European Health Literacy Population Survey 2019-2021 (HLS19). From December 2019 to January 2021, data on NAV-HL was collected in eight European countries. The HLS19-NAV was translated into seven languages and successfully applied in and validated for eight countries, where language and survey method differed. The psychometric properties of the scale were assessed using confirmatory factor analysis (CFA) and Rasch modelling. The tested CFA models sufficiently well described the observed correlation structures. In most countries, the NAV-HL data displayed acceptable fit to the unidimensional Rasch partial credit model (PCM). For some countries, some items showed poor data-model fit when tested against the PCM, and some items displayed differential item functioning for selected person factors. The HLS19-NAV demonstrated high internal consistency. To ensure content validity, the HLS19-NAV was developed based on a conceptual framework. As an estimate of discriminant validity, the Pearson correlations between the NAV-HL and general health literacy (GEN-HL) scales were computed. Concurrent predictive validity was estimated by testing whether the HLS19-NAV, like general HL measures, follows a social gradient and whether it forms a predictor of general health status as a health-related outcome of general HL. In some countries, adjustments at the item level may be beneficial.

Combined Transcranial and Endoscopic Endonasal Approach for Resection of a Complex Sinonasal Squamous Cell Carcinoma: Two-Dimensional Operative Video.

Sinonasal squamous cell carcinoma (SCC) is a rare head-and-neck neoplasm that has a propensity to locally invade vital structures. Currently, the combination of surgical resection and radiation remains the optimal treatment. 1 However, the extent of disease burden and involvement of surrounding anatomy may make these inoperable. Here, we demonstrate the successful application of multidisciplinary approach for surgical resection of a large, complex SCC lesion centered at the superior nasal cavity with extension into the eye orbits and brain. A two-step approach was performed; transcribiform, endoscopic piecemeal resection with reconstruction of the skull base, followed by a bifrontal craniotomy. Reconstruction was achieved using an inlay of DuraMatrix allograft (Stryker Inc., Kalamzoo, Michigan, United States) followed by an inlay of AlloDerm (Allergan Inc., Irvine, California, United States), anchored anteriorly and posteriorly with wide wings placed over the respective orbital roofs. Major steps include (1) a summary of the patient presentation and preoperative imaging, (2) resection of the tumor endonasally, (3) resection of the tumor intracranially from a bifrontal craniotomy, and (4) a review of the postoperative imaging. The patient tolerated the procedure ( Fig. 1 ) well, returned to his baseline with no new neurologic deficits, and was placed on 6-week antibiotics regimen for osteomyelitis discovered during the operation. Approximately, 2 months after discharge, the patient unfortunately returned with altered mental status, was found to have sepsis, and expired shortly thereafter. This operative video illustrates the technical steps and capabilities of surgical treatment, achieving near-complete gross total resection of a complex SCC lesion using a multidisciplinary approach. The link to the video can be found at: https://youtu.be/8ffckKIuBzM .

A microengineered Brain-Chip to model neuroinflammation in humans.

Species differences in brain and blood-brain barrier (BBB) biology hamper the translation of findings from animal models to humans, impeding the development of therapeutics for brain diseases. Here, we present a human organotypic microphysiological system (MPS) that includes endothelial-like cells, pericytes, glia, and cortical neurons and maintains BBB permeability at in vivo relevant levels. This human Brain-Chip engineered to recapitulate critical aspects of the complex interactions that mediate neuroinflammation and demonstrates significant improvements in clinical mimicry compared to previously reported similar MPS. In comparison to Transwell culture, the transcriptomic profiling of the Brain-Chip displayed significantly advanced similarity to the human adult cortex and enrichment in key neurobiological pathways. Exposure to TNF-α recreated the anticipated inflammatory environment shown by glia activation, increased release of proinflammatory cytokines, and compromised barrier permeability. We report the development of a robust brain MPS for mechanistic understanding of cell-cell interactions and BBB function during neuroinflammation.