Impact of COVID-19 Pandemic on Sex and Racial Disparities in Chest Pain Presentation and Management Through the Emergency Department.

Background: Sex and racial disparities in the presentation and management of chest pain persist, however, the impact of coronavirus disease 2019 (COVID-19) on these disparities have not been studied. We sought to determine whether the COVID-19 pandemic contributed to pre-existing sex and racial disparities in the presentation, management, and outcomes of patients presenting to the emergency department (ED) with chest pain. Methods: We conducted an observational cohort study with retrospective data collection of patients between January 1, 2016, and May 1, 2022. This was a single study conducted at a quaternary academic medical center of all patients who presented to the ED with a complaint of chest pain or chest pain equivalent symptoms. Patient were further segregated into different groups based on sex (male, female), race, ethnicity (Asian, Black, Hispanic, White, and other), and age (18 - 40, 41 - 65, > 65). We compared diagnostic evaluations, treatment decisions, and outcomes during prespecified time points before, during, and after the COVID-19 pandemic. Results: This study included 95,764 chest pain encounters. Total chest pain presentations to the ED fell about 38% during the early pandemic months. Females presented significantly less than males during initial COVID-19 (48% vs. 52%, P < 0.001) and Asian females were least likely to present. There was an increase in the total number of troponins and echocardiograms ordered during peak COVID-19 across both sexes, but females were still less likely to have these tests ordered across all timepoints. The number of coronary angiograms did not increase during peak COVID-19, and females were less likely to undergo coronary angiogram during all timepoints. Finally, females with chest pain were less likely to be diagnosed with acute myocardial infarction (AMI) during all timepoints, while in-hospital deaths were similar between males and females during all timepoints. Conclusions: During COVID-19, females, especially Asian females, were less likely to present to the ED for chest pain. Non-White patients were less likely to present to the ED compared to White patients prior to and during the pandemic. Disparities in management and outcomes of chest pain encounters remained similar to pre-COVID-19, with females receiving less cardiac workup and AMI diagnoses than males, but in-hospital mortality remaining similar between groups and timepoints.

Nanosensor-based monitoring of autophagy-associated lysosomal acidification in vivo.

Autophagy is a cellular process with important functions that drive neurodegenerative diseases and cancers. Lysosomal hyperacidification is a hallmark of autophagy. Lysosomal pH is currently measured by fluorescent probes in cell culture, but existing methods do not allow for quantitative, transient or in vivo measurements. In the present study, we developed near-infrared optical nanosensors using organic color centers (covalent sp3 defects on carbon nanotubes) to measure autophagy-mediated endolysosomal hyperacidification in live cells and in vivo. The nanosensors localize to the lysosomes, where the emission band shifts in response to local pH, enabling spatial, dynamic and quantitative mapping of subtle changes in lysosomal pH. Using the sensor, we observed cellular and intratumoral hyperacidification on administration of mTORC1 and V-ATPase modulators, revealing that lysosomal acidification mirrors the dynamics of S6K dephosphorylation and LC3B lipidation while diverging from p62 degradation. This sensor enables the transient and in vivo monitoring of the autophagy-lysosomal pathway.

P-selectin-targeted nanocarriers induce active crossing of the blood-brain barrier via caveolin-1-dependent transcytosis.

Medulloblastoma is the most common malignant paediatric brain tumour, with ~30% mediated by Sonic hedgehog signalling. Vismodegib-mediated inhibition of the Sonic hedgehog effector Smoothened inhibits tumour growth but causes growth plate fusion at effective doses. Here, we report a nanotherapeutic approach targeting endothelial tumour vasculature to enhance blood-brain barrier crossing. We use fucoidan-based nanocarriers targeting endothelial P-selectin to induce caveolin-1-dependent transcytosis and thus nanocarrier transport into the brain tumour microenvironment in a selective and active manner, the efficiency of which is increased by radiation treatment. In a Sonic hedgehog medulloblastoma animal model, fucoidan-based nanoparticles encapsulating vismodegib exhibit a striking efficacy and marked reduced bone toxicity and drug exposure to healthy brain tissue. Overall, these findings demonstrate a potent strategy for targeted intracranial pharmacodelivery that overcomes the restrictive blood-brain barrier to achieve enhanced tumour-selective penetration and has therapeutic implications for diseases within the central nervous system.

Otolaryngology Patient Satisfaction with In-Office Appointments and Virtual Visits Due to COVID-19.

BACKGROUND: The COVID-19 pandemic forced otolaryngologists to seek new methods of providing patient care in a remote setting. The effect of this paradigm shift on patient satisfaction, however, remains unelucidated. This study compares patient satisfaction with telehealth visits during the COVID-19 pandemic to that with in-office visits during the same period in 2019. METHODS: Press Ganey survey responses of patients seen by otolaryngologists within a large, academic, multicenter hospital system were gathered. Responses were included in analyses if they corresponded with a visit that occurred either in clinic March to December 2019 or via telehealth March to December 2020. Chi-Square Test of Independence and Fisher's Exact Test were employed to detect differences between years. Binary logistic regressions were performed to detect the factors most predictive of positive telehealth experiences. RESULTS: Patient overall satisfaction with in-office and telehealth visits did not differ significantly (76.4% in 2019 vs 78.0% in 2020 rated visit overall as "very good," P = .09). Patients seen by a Head and Neck (odds ratio 4.13, 95% confidence interval 1.52-11.26, P = .005), Laryngology (OR 5.96, 95% CI 1.51-23.50, P = .01), or Rhinology (OR 4.02, 95% CI 1.55-10.43, P = .004) provider were significantly more likely to report a positive telehealth experience. CONCLUSIONS: Patients seen via telehealth during COVID-19 reported levels of satisfaction similar to those seen in-office the year prior. These telehealth satisfaction levels, however, are contextualized within the expected confines of a pandemic. Further research is required to determine whether satisfaction remains consistent as telemedicine becomes a ubiquitous component of medical practice.

Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta.

Amyloid-beta (Aß) deposition occurs in the early stages of Alzheimer's disease (AD), but the early detection of Aß is a persistent challenge. Herein, we engineered a near-infrared optical nanosensor capable of detecting Aß intracellularly in live cells and intracranially in vivo. The sensor is composed of single-walled carbon nanotubes functionalized with Aß wherein Aß-Aß interactions drive the response. We found that the Aß nanosensors selectively responded to Aß via solvatochromic modulation of the near-infrared emission of the nanotube. The sensor tracked Aß accumulation in live cells and, upon intracranial administration in a genetic model of AD, signaled distinct responses in aged mice. This technology enables the interrogation of molecular mechanisms underlying Aß neurotoxicity in the development of AD in living systems.

Ergonomic Analysis of Functional Endoscopic Sinus Surgery Using Novel Inertial Sensors.

OBJECTIVES/HYPOTHESIS: Suboptimal ergonomics during endoscopic sinus surgery can lead to considerable physical discomfort and fatigue for the surgeon. The purpose of this pilot study is to objectively evaluate the ergonomic positions of trainee and attending surgeons while performing functional endoscopic sinus surgery (FESS). STUDY DESIGN: Pilot prospective trial. METHODS: Six surgeons (two attendings and four trainees) performed FESS while wearing 11 inertial measurement units (IMUs) affixed to either side of each major joint. Screen placement was standardized to be 1 m directly in front of the surgeon and on the patient's left, 0-15° declined from the surgeons' eyes. Bed height was standardized such that the workspace was 0 to 10 cm below the elbows. IMU data were analyzed to calculate joint angles. Ideal joint angles (i.e., <10° for neck and trunk) were determined by the validated Rapid Entire Body Assessment tool. Subjects subsequently completed a modified National Aeronautics and Space Administration Task Load Index to assess cognitive and physical burden and pain. Student's t-test was employed to detect differences between groups. RESULTS: Trainees adopted positions involving significantly greater neck flexion (9.90° vs. -6.48°, P = .03) and reported significantly higher frustration levels (3.04 vs. 1.33, P = .02) while operating than attendings. For both cohorts, increased operative time was significantly correlated with greater back flexion (r = 0.90, P = .02; r = 0.55, P = .04, respectively). CONCLUSIONS: Our data suggest that trainees operate with higher risk neck postures than do attendings. These data indicate high-risk operative postures may be borne of inexperience and present an opportunity for postural interventions at an early stage of training. LEVEL OF EVIDENCE: NA Laryngoscope, 132:1153-1159, 2022.

Sinonasal Issues After Maxillectomy With Free Flap Reconstruction: Incidence and Clinical Approach.

OBJECTIVE: To characterize the clinical features associated with sinonasal complaints after maxillectomy with free flap reconstruction as well as propose a screening and treatment algorithm. METHODS: Retrospective review of patients who underwent maxillectomy and free flap reconstruction at a tertiary care center. RESULTS: Fifty-eight patients were included, 25 (43.1%) of them had documented sinonasal complaints postoperatively. Eleven patients subsequently underwent revision surgery for sinonasal complaints. Among the 25 patients with sinonasal complaints, 22 patients (88.0%) had nasal crusting, 17 (68.0%) had nasal obstruction, 12 (48.0%) had rhinorrhea, 9 (36.0%) had facial pain or pressure, and 7 (28.0%) had foul odor. Twenty-two patients (88.0%) had multiple sinonasal complaints. There was a higher incidence of both sinonasal complaints and surgical intervention in patients who underwent adjuvant radiation, but this was not statistically significant (47.7% vs 28.6%, P = .235; 29.4% vs 7.1%, P = .265). CONCLUSIONS: Sinonasal complaints are common following free flap reconstruction for a maxillectomy defect and should be screened for at postoperative visits, with early referral to a rhinologist for consideration of endoscopic sinus surgery. Nonsurgical treatment strategies include large-volume nasal saline irrigations, xylitol irrigations for persistent inflammatory symptoms, and culture-directed antibiotic irrigations for persistent infectious symptoms. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:67-72, 2022.

Clinical Features of Parosmia Associated With COVID-19 Infection.

OBJECTIVE: To characterize the clinical features, risk factors, symptom time-course, and quality of life implications for parosmia among coronavirus disease (COVID)-related olfactory dysfunction patients. METHODS: Individuals with olfactory dysfunction associated with laboratory-confirmed or clinically suspected COVID-19 infection were recruited from otolaryngology and primary care practices over a period from August 2020 to March 2021. Participants completed olfactory dysfunction and quality of life surveys. RESULTS: A total of 148 (64.1%) of 231 respondents reported parosmia at some point. Parosmia developed within 1 week of any COVID-19 symptom onset in 25.4% of respondents, but more than 1 month after symptom onset in 43.4% of respondents. Parosmia was associated with significantly better quantitative olfactory scores on Brief Smell Identification Test (8.7 vs. 7.5, P = .006), but demonstrated worse quality of life scores, including modified brief Questionnaire of Olfactory Dysfunction-Negative Statements and Sino-Nasal Outcome Test-22 scores (12.1 vs. 8.5, P < .001; 26.2 vs. 23.2, P = .113). Participants who developed parosmia at any point were significantly younger and less likely to have history of chronic sinusitis than those who did not develop parosmia (40.2 vs. 44.9 years, P = .007; 7.2% vs. 0.7%, P = .006). CONCLUSION: COVID-19-associated olfactory dysfunction is frequently linked with development of parosmia, which often presents either at onset of smell loss or in a delayed fashion. Despite better quantitative olfactory scores, respondents with parosmia report decreased quality of life. A majority of respondents with persistent parosmia have sought treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:633-639, 2022.

Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury.

Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy.

Prevalence and Clinical Significance of Radiographic Sinus Disease on Preoperative Computed Tomography Imaging in the Endoscopic Skull Base Surgery Population.

INTRODUCTION: Endoscopic skull base surgery (ESBS) provides a safe, minimally invasive approach to treat benign and malignant skull base lesions. The significance of concomitant sinonasal pathology on imaging in patients undergoing ESBS and its effect on perioperative management is not well described. We sought to identify the prevalence and clinical significance of incidentally found radiographic sinus disease on preoperative imaging in patients undergoing ESBS and provide a protocol for management of these patients. DESIGN: A retrospective chart review was performed of consecutive patients who underwent ESBS from January 1, 2016 to June 30, 2018. Preoperative computed tomography (CT) scans were reviewed and scored using the Lund-Mackay (LM) staging system. Preoperative nasal endoscopy findings were analyzed. Any preoperative treatment based on these findings and changes in intraoperative management were examined. RESULTS: A total of 156 patients (81 women, 74 men) who underwent ESBS were reviewed. The average LM score was 2 ± 2.7 (range: 0-12). A total of 94 patients (60.3%) had evidence of radiographic sinus disease (LM score > 0) and 23 patients (14.7%) had presence of sphenoid sinus disease. Seven patients (4.5%) were treated preoperatively based on CT and/or nasal endoscopy findings. All patients who received preoperative treatment had evidence of sinus disease on imaging with an average score of 4.7 and were evaluated and treated within 1-2 weeks prior to ESBS. One patient had ESBS postponed until endoscopic sinus surgery was performed for extensive chronic rhinosinusitis (CRS) findings on imaging. CONCLUSION: A review of preoperative imaging in patients undergoing ESBS can help identify concurrent sinonasal disease, which has the potential to alter preoperative as well as intraoperative management in these patients. We report a diligent but conservative approach for the treatment of concomitant CRS in the ESBS population with decision for preoperative treatment guided by various factors.

Using the Middle Turbinate to Protect the Skull Base in Endoscopic Transsphenoidal Surgery: A Cadaver Study.

OBJECTIVES: Inadvertent intracranial injury from nasogastric tube (NGT) placement is a described and potentially fatal complication following endoscopic transsphenoidal hypophysectomy (TSH). This cadaver study assessed the role of middle turbinate (MT) preservation and medialization in preventing accidental skull base injury from NGT insertion after TSH. Methods: Standard approach for TSH was performed on 3 human cadavers. MTs were placed into neutral position (MTN), then medialized via suture pexy to the septum (MTP), and subsequently resected (MTR). After each stage, 3 blinded individuals passed a 10 F Dobhoff and a 16 F NGT on each side of each cadaver (5 passes per side). Using endoscopic visualization, each pass was scored by a blinded reviewer based on the first contact point of the tube (0 = nasopharynx, 1 = inferior sphenoid face, 2 = sphenoid sinus), with higher scores suggestive of increased risk of intracranial injury. Results: There were 270 Dobhoff and 270 NGT passes scored. Data was divided into 3 groups based on presence and position of the MT. Significant differences were demonstrated between all three groups [one-way ANOVA: Dobhoff F(2,267) = 6.981, p = 0.001], [NGT F(2,267) = 17.582, p < 0.001]. There were significant differences between means for MTN versus MTP groups [Dobhoff (0.43 vs 0.22, p = 0.007), NGT (0.73 vs 0.28, p < 0.001)] and MTP versus MTR groups [Dobhoff (0.22 vs 0.55, p < 0.001), NGT (0.28 vs 0.81, p < 0.001)], indicating that the presence and position of the MT can significantly affect the accessibility of the sphenoid sinus interior after TSH. There was a trend toward lower means in the MTN group compared to the MTR group. Conclusion: MT preservation and deliberate medialization against the septum may reduce risk of inadvertent intracranial NGT injury in postop TSH patients. This simple maneuver should be considered in all routine TSH procedures.

Comparison of Traditional Upper Airway Surgery and Upper Airway Stimulation for Obstructive Sleep Apnea.

OBJECTIVE: To compare patients with moderate-severe obstructive sleep apnea (OSA) undergoing traditional single and multilevel sleep surgery to those undergoing upper airway stimulation (UAS). STUDY DESIGN: Case control study comparing retrospective cohort of patients undergoing traditional sleep surgery to patients undergoing UAS enrolled in the ADHERE registry. SETTING: 8 multinational academic medical centers. SUBJECTS AND METHODS: 233 patients undergoing prior single or multilevel traditional sleep surgery and meeting study inclusion criteria were compared to 465 patients from the ADHERE registry who underwent UAS. We compared preoperative and postoperative demographic, quality of life, and polysomnographic data. We also evaluated treatment response rates. RESULTS: The pre and postoperative apnea hypopnea index (AHI) was 33.5 and 15 in the traditional sleep surgery group and 32 and 10 in the UAS group. The postoperative AHI in the UAS group was significantly lower. The pre and postoperative Epworth sleepiness scores (ESS) were 12 and 6 in both the traditional sleep surgery and UAS groups. Subgroup analysis evaluated those patients undergoing single level palate and multilevel palate and tongue base traditional sleep surgeries. The UAS group had a significantly lower postoperive AHI than both traditional sleep surgery subgroups. The UAS group had a higher percentage of patients reaching surgical success, defined as a postoperative AHI <20 with a 50% reduction from preoperative severity. CONCLUSION: UAS offers significantly better control of AHI severity than traditional sleep surgery. Quality life improvements were similar between groups.

Endoscopic Orbital Decompression: Technical Pearls and Pitfalls of an Evolving Technique.

BACKGROUND: First described in the early 1990s, endoscopic orbital decompression has become increasingly popular and has been shown to be a safe and effective approach for surgical decompression of the medial and inferior orbit. METHODS: We present our preferred technique for performing an endoscopic orbital decompression, highlighting key pearls and pitfalls. RESULTS: An endoscopic wide maxillary antrostomy and sphenoethmoidectomy is performed in standard fashion. We prefer to resect the middle turbinate for optimal exposure and access. The medial orbital wall is skeletonized and the lamina papyracea is carefully elevated, preserving the underlying periorbita. The orbital floor medial to the infraorbital nerve is resected. Once the periorbita is fully exposed, parallel axial incisions along the medial orbit and orbital floor are made from posterior to anterior using a sickle knife, taking care not to bury the tip to avoid injuring underlying orbital contents. The remaining fibrous bands are incised and prolapse of orbital fat is observed. Post extubation bag mask ventilation is limited to avoid subcutaneous emphysema. CONCLUSION: Compared to open techniques, endoscopic orbital decompression provides superior visualization of critical anatomical landmarks, assures healthy sinus functioning post procedure, offers a lower complication rate, and avoids external incisions.

Snapshot Impact of COVID-19 on Mental Wellness in Nonphysician Otolaryngology Health Care Workers: A National Study.

OBJECTIVE: Nonphysician health care workers are involved in high-risk patient care during the COVID-19 pandemic, placing them at high risk of mental health burden. The mental health impact of COVID-19 in this crucial population has not been studied thus far. Thus, the objective of this study is to assess the psychosocial well-being of these providers. STUDY DESIGN: National cross-sectional online survey (no control group). SETTING: Academic otolaryngology programs in the United States. SUBJECTS AND METHODS: We distributed a survey to nonphysician health care workers in otolaryngology departments across the United States. The survey incorporated a variety of validated mental health assessment tools to measure participant burnout (Mini-Z assessment), anxiety (Generalized Anxiety Disorder-7), distress (Impact of Event Scale), and depression (Patient Health Questionnaire-2). Multivariable logistic regression analysis was performed to determine predictive factors associated with these mental health outcomes. RESULTS: We received 347 survey responses: 248 (71.5%) nurses, 63 (18.2%) administrative staff, and 36 (10.4%) advanced practice providers. A total of 104 (30.0%) respondents reported symptoms of burnout; 241 (69.5%), symptoms of anxiety; 292 (84.1%), symptoms of at least mild distress; and 79 (22.8%), symptoms of depression. Upon further analysis, development of these symptoms was associated with factors such as occupation, practice setting, and case load. CONCLUSION: Frontline otolaryngology health care providers exhibit high rates of mental health complications, particularly anxiety and distress, in the wake of COVID-19. Adequate support systems must be put into place to address these issues.

Mental health among otolaryngology resident and attending physicians during the COVID-19 pandemic: National study.

BACKGROUND: Otolaryngologists are among the highest risk for COVID-19 exposure. METHODS: This is a cross-sectional, survey-based, national study evaluating academic otolaryngologists. Burnout, anxiety, distress, and depression were assessed by the single-item Mini-Z Burnout Assessment, 7-item Generalized Anxiety Disorder Scale, 15-item Impact of Event Scale, and 2-item Patient Health Questionnaire, respectively. RESULTS: A total of 349 physicians completed the survey. Of them, 165 (47.3%) were residents and 212 (60.7%) were males. Anxiety, distress, burnout, and depression were reported in 167 (47.9%), 210 (60.2%), 76 (21.8%), and 37 (10.6%) physicians, respectively. Attendings had decreased burnout relative to residents (odds ratio [OR] 0.28, confidence interval [CI] [0.11-0.68]; P = .005). Females had increased burnout (OR 1.93, CI [1.12.-3.32]; P = .018), anxiety (OR 2.53, CI [1.59-4.02]; P < .005), and distress (OR 2.68, CI [1.64-4.37]; P < .005). Physicians in states with greater than 20 000 positive cases had increased distress (OR 2.01, CI [1.22-3.31]; P = .006). CONCLUSION: During the COVID-19 pandemic, the prevalence of burnout, anxiety, and distress is high among academic otolaryngologists.

Predictive value of the ACS NSQIP calculator for head and neck reconstruction free tissue transfer.

BACKGROUND: Predictive models to forecast the likelihood of specific outcomes after surgical intervention allow informed shared decision-making by surgeons and patients. Previous studies have suggested that existing general surgical risk calculators poorly forecast head and neck surgical outcomes. However, no large study has addressed this question while subdividing subjects by surgery performed. OBJECTIVES: To determine the accuracy of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator in estimating length of hospital stay and risk of postoperative complications after free tissue transfer surgery. STUDY DESIGN: A retrospective chart review of patients at one institution was performed using Current Procedural Terminology codes for anterolateral thigh (ALT) flap, fibula free flap (FFF), and radial forearm free flap (RFFF) reconstruction. Output data from the ACS NSQIP surgical risk calculator were compared with the observed rates in our patients. METHODS: Incidences of cardiac complications, pneumonia, venous thromboembolism, return to the operating room, and discharge to skilled nursing facility (SNF) were compared to predicted incidences. Length of stay was also compared to the predicted length of stay. RESULTS: Three hundred thirty-six free flap reconstructions with 197 ALT flaps, 85 RFFFs, and 54 FFFFs were included. Brier scores were calculated using ACS NSQIP forecast and actual incidences. No Brier score was <0.01 for the entire sample or any subgroup, which indicates that the NSQIP risk calculator does not accurately forecast outcomes after free tissue reconstruction. CONCLUSION: The ACS NSQIP failed to accurately forecast postoperative outcomes after head and neck free flap reconstruction for the entire sample or subgroup analyses. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:679-684, 2020.

Impact of perforation size and predictive factors for successful pediatric gelfoam myringoplasty.

OBJECTIVES: Rates of success with pediatric myringoplasty range from 35 to 95%. The objective of this study is to evaluate the impact of perforation size on successful closure of the tympanic membrane (TM) after gelfoam myringoplasty. We also aim to identify variables that affect perforation closure rates and define predictive factors for successful TM closure. METHODS: A retrospective chart review of all patients that underwent gelfoam myringoplasty by a single surgeon from August 2008 through January 2015 was performed. RESULTS: One hundred fifty-nine patients met inclusion criteria and underwent a total of 219 procedures. Overall, gelfoam myringoplasty had an 83.1% rate of successful closure. Average perforation size was 15.31%. Classification tree analysis separated our cohort into three groups based on perforation size: Group 1 (<16.25%) had a 91% closure rate, group 2 (16.25% to <31.25%) had a 66.0% closure rate and group 3 (≥31.25%) had a 30.0% closure rate. Smaller perforations (P ≤0.001) were associated with increased success rates. Other factors associated with successful closure of the TM included younger age at the time of myringoplasty (P ≤0.001), fewer number of prior tympanostomy tubes (P = 0.016), and lesser duration of tube retention (P = 0.003). CONCLUSION: Gelfoam myringoplasty provides good overall TM closure rates and may be considered as a potential first-line option for repair of perforations, including those involving up to 40% of the TM. Younger patients with smaller perforations, fewer sets of tubes, shorter length of tube retention are more likely to have successful closure of the tympanic membrane.

Synthetic molecular recognition nanosensor paint for microalbuminuria.

Microalbuminuria is an important clinical marker of several cardiovascular, metabolic, and other diseases such as diabetes, hypertension, atherosclerosis, and cancer. The accurate detection of microalbuminuria relies on albumin quantification in the urine, usually via an immunoturbidity assay; however, like many antibody-based assessments, this method may not be robust enough to function in global health applications, point-of-care assays, or wearable devices. Here, we develop an antibody-free approach using synthetic molecular recognition by constructing a polymer to mimic fatty acid binding to the albumin, informed by the albumin crystal structure. A single-walled carbon nanotube, encapsulated by the polymer, as the transduction element produces a hypsochromic (blue) shift in photoluminescence upon the binding of albumin in clinical urine samples. This complex, incorporated into an acrylic material, results in a nanosensor paint that enables the detection of microalbuminuria in patient samples and comprises a rapid point-of-care sensor robust enough to be deployed in resource-limited settings.

Electroporation-induced changes in tumor vasculature and microenvironment can promote the delivery and increase the efficacy of sorafenib nanoparticles.

Blood vessels, the extracellular space, and the cell membrane represent physiologic barriers to nanoparticle-based drug delivery for cancer therapy. We demonstrate that electroporation (EP) can assist in the delivery of dye stabilized sorafenib nanoparticles (SFB-IR783) by increasing the permeability of endothelial monolayers, improving diffusion through the extracellular space in tumorspheres, and by disrupting plasma membrane function in cancer cells. These changes occur in a dose-dependent fashion, increasing proportionally with electric field strength. Cell death from irreversible electroporation (IRE) was observed to contribute to the persistent transport of SFB-IR783 through these physiologic barriers. In a model of mice bearing bilateral xenograft HCT116 colorectal tumors, treatment with EP resulted in the immediate and increased uptake of SFB-IR783 when compared with the untreated contralateral tumor. The uptake of SFB-IR783 was independent of direct transfection of cells through EP and was mediated by changes in vascular permeability and extracellular diffusion. The combination of EP and SFB-IR783 was observed to result in 40% reduction in mean tumor diameter when compared with sham treatment (p < .05) at the time of sacrifice, which was not observed in cohorts treated with EP alone or SFB-IR783 alone. Treatment of tumor with EP can augment the uptake and increase the efficacy of nanoparticle therapy.