Quantitative Evaluation of Aerosol Generation During In-Office Flexible Laryngoscopy.

Importance: Despite growing scientific knowledge and research, it is still unknown if office flexible laryngoscopy (FL) is aerosol generating and thereby potentially increases the risk of SARS-CoV-2 transmission. The limited literature that exists is conflicting, precluding formal conclusions. Objective: To determine whether FL is aerosol generating. Design, Setting, and Participants: This prospective cohort study included 134 patients seen in the otolaryngology clinic at a single tertiary care academic institution between February and May 2021. Two optical particle sizer instruments were used, quantifying particles ranging from 0.02 µm to 5 µm. Measurements were taken every 30 seconds, with sample periods of 15 seconds throughout the patient encounter. Instruments were located 12 inches from the patient's nares. Timing of events was recorded, including the start and end of physical examination, topical spray administration, start and end of laryngoscopy, and other potential aerosol-generating events (eg, coughing, sneezing). Data analysis was performed from February to May 2021. Exposures: Office examination and office FL. Main Outcomes and Measures: Bayesian online change point detection (OCPD) algorithm was used to detect significant change points (CPs) in this time-series data. The primary outcome was significant CP after FL compared with baseline physiologic variations, such as breathing and phonation. Results: Data were collected from 134 patients between February and May 2021. Ninety-one encounters involved FL. Of this group, 51 patients (56%) wore no mask over their mouth during FL. There was no statistically significant CP in either visits involving FL or visits where FL was not performed. Use of nasal spray did not result in CP in aerosol levels. Overall, neither the number of people present in the examination room, masks over patients' mouth, the duration of the visit, nor the duration of FL were associated with mean aerosol counts, regardless of the exposure. For larger aerosol sizes (≥1 µm), however, rooms with higher air exchange rates had significantly higher reductions in mean aerosol counts for visits involving FL. Conclusions and Relevance: The findings of this cohort study support that FL, including topical spray administration, is not a significant aerosol-generating procedure. The Bayesian OCPD model has a promising application for future aerosol studies in otolaryngology.

Deep sleep and beeps II: Sleep quality improvement project in general surgery patients.

BACKGROUND: Poor sleep leads to poor health outcomes. Phase I of our sleep quality improvement project showed severe sleep disturbance in the ward setting. We implemented a novel PostOp Pack to improve sleep quality. METHODS: Patients underwent elective, general surgery procedures. Fitbit trackers measured total sleep time. Patients completed the inpatient Richards-Campbell Sleep Questionnaire, which combines 5 domains into a cumulative score (0-100). Patients completed the outpatient Pittsburgh Sleep Quality Index preoperatively and postoperatively. Patients received the PostOp Pack, which included physical items and a sleep-protective order set to reduce nighttime awakenings. Patients from phase I served as the historical control. The primary outcome was the percentage of patients with Richards-Campbell Sleep Questionnaire total sleep score ≥50. The secondary outcomes included the mean Richards-Campbell Sleep Questionnaire domain scores and Fitbit total sleep time. RESULTS: A total of 49 patients were compared with 64 historical controls. The percentage of patients with a total sleep score ≥50 was significantly higher in patients receiving a PostOp Pack versus historical control (69% vs. 44%, difference 26%, 95% confidence interval 6.1-45%, P = .01). The mean Richards-Campbell Sleep Questionnaire Total Sleep Score was significantly higher in patients with a PostOp Pack (62 vs 49, mean difference 13, 95% confidence interval 6-21, P ≤ .01). The PostOp Pack Richards-Campbell Sleep Questionnaire domain scores were significantly higher in various areas: Sleep Latency (68 vs 49, P ≤ .01), Awakenings (56 vs 40, P = .01), Sleep Quality (61 vs 49, P = .02), and Noise Disturbance (70 vs 59, P = .04). Of all patients, 92% would use PostOp Pack again in a future hospitalization. No patients had a failure to rescue event with PostOp Pack. The mean total sleep time was significantly improved with PostOp Pack on night 1 (6.4 vs 4.7 hours, P = .03). CONCLUSION: The PostOp Pack improves inpatient sleep quality and is safe.

Non-operative management of biliary complications after Liver Transplantation in pediatric patients: A 30-year experience.

BACKGROUND: To evaluate the efficacy of percutaneous and endoscopic therapeutic interventions for biliary strictures and leaks following LT in children. METHODS: Retrospective analysis of 49 consecutive pediatric liver transplant recipients (27 girls, 22 boys, mean age at transplant 3.9 years) treated at our institution from 1989 to 2019 for biliary leak and/or biliary stricture was performed. Minimally invasive approach was considered clinically successful if it resulted in patency of the narrowed biliary segment and/or correction of the biliary leak. RESULTS: Forty-two patients had a stricture at the biliary anastomosis; seven had a biliary leak. After an average 13.8 years of follow-up, long-term clinical success with minimally invasive treatment (no surgery or re-transplant) was achieved for 24 children (57%) with biliary stricture and 4 (57%) with biliary leaks. Eight patients required re-transplant; however, only one was due to failure of both percutaneous and surgical management. For biliary strictures, failure of non-surgical management was associated with younger age at stricture diagnosis (p < .02). CONCLUSIONS: Percutaneous and endoscopic management of biliary strictures and leaks after LT in children is associated with a durable result in >50% of children.

The use of 3D printing in shared decision making for a juvenile aggressive ossifying fibroma in a pediatric patient.

Juvenile aggressive ossifying fibromas (JAOF) are rare, typically benign pediatric tumors that are locally aggressive and have high recurrence rates. A 7-year old male presented with a palatal mass and a 3D printed model was created and used as a visual aide to highlight the importance of management in terms of functional, cosmetic, and disease-free outcomes with the family. The patient ultimately underwent successful enucleation with final pathology consistent with JAOF. To our knowledge, this is the first description of the use of 3D printing to help in the shared decision-making process for the treatment of this aggressive tumor.

Aspirin Exacerbated Respiratory Disease: Epidemiology, Pathophysiology, and Management.

The correlation between aspirin sensitivity, asthma, and nasal polyposis was recognized in the early 20th century. Today, this classic triad of symptoms, eponymously named Samter's Triad, is known as aspirin exacerbated respiratory disease (AERD). Aspirin exacerbated respiratory disease affects approximately 0.3⁻0.9% of the general population in the USA and approximately 7% of asthmatic patients. The management of AERD is challenging as no single modality has proven to have high rates of symptom control. Consequently, disease management typically involves a multimodality approach across both medical and surgical disciplines. This review describes the epidemiology of AERD and the current state-of-the-art as it relates to the underlying pathophysiologic mechanisms of this disease process. A significant proportion of the review is focused on the appropriate diagnostic workup for AERD patients including the utility of aspirin provocation testing. The spectrum of medical treatments, including aspirin desensitization and recently introduced immunotherapies, are discussed in detail. Furthermore, surgical approaches to disease control, including advanced endoscopic techniques, are reviewed and treatment outcomes presented.

Effect of Nasal Valve Shape on Downstream Volume, Airflow, and Pressure Drop: Importance of the Nasal Valve Revisited.

OBJECTIVES: The relative importance of the nasal valve relative to the remainder of the nasal airway remains unknown. The goal of this article was to objectively measure the shape of the nasal inlet and its effect on downstream airflow and nasal cavity volume using a physical model and a physiologic flow model. METHODS: A patient who had isolated nasal valve surgery and had pre- and postoperative computed tomography scans available for analysis was studied. Nasal inlet shape measurements, computational fluid dynamics, and nasal volume analysis were performed using the computed tomography data. In addition, a physical model was used to determine the effect of nasal obstruction on downstream soft tissue. RESULTS: The postoperative shape of the nasal inlet was improved in terms of length and degree of tortuosity. Whereas the operated-on region at the nasal inlet showed an only 25% increase in cross-sectional area postoperatively, downstream nonoperated sites in the nasal cavity revealed increases in area ranging from 33% to 51%. Computational fluid dynamics analysis showed that airway resistance decreased by 42%, and pressure drop was reduced by 43%. Intraluminal mucosal expansion was found with nasal obstruction in the physical model. CONCLUSION: By decreasing the degree of bending and length at the nasal valve, inspiratory downstream nonoperated sites of the nasal cavity showed improvement in volume and airflow, suggesting that the nasal valve could play an oversized role in modulating the aerodynamics of the airway. This was confirmed with the physical model of nasal obstruction on downstream mucosa.

Correction: Treatment outcomes and HPV characteristics for an institutional cohort of patients with anal cancer receiving concurrent chemotherapy and intensity-modulated radiation therapy.

[This corrects the article DOI: 10.1371/journal.pone.0194234.].

Treatment outcomes and HPV characteristics for an institutional cohort of patients with anal cancer receiving concurrent chemotherapy and intensity-modulated radiation therapy.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) has been used to limit treatment-related toxicity for patients with anal squamous cell carcinoma (SCC). The treatment outcomes and HPV characteristics for a cohort of patients receiving definitive concurrent chemotherapy and IMRT are reported. MATERIALS AND METHODS: 52 patients with anal SCC were treated with IMRT and concurrent chemotherapy. Radiation was delivered sequentially to the pelvis and inguinal lymph nodes (45 Gy) and anal tumor (median dose, 54 Gy). Multiplex real-time PCR for 7 high-risk HPV subtypes (n = 22) and p16 immunohistochemistry (n = 21, rated on a 0, 1, and 2+ scale) were performed on available specimens. Survival was estimated using Kaplan-Meier analysis, and toxicities were recorded. RESULTS: Median follow-up was 33 months. Three-year freedom from locoregional failure (FFLRF), freedom from distant metastasis (FFDM), freedom from colostomy (FFC), and overall survival (OS) were 94%, 85%, 91%, and 90%, respectively. Acute grade 2+ skin, GI, and GU toxicities occurred in 83%, 71%, and 19% of evaluable patients, respectively. The rates of late grade 2+ GI and GU toxicities for evaluable patients (n = 32) were 28% and 9%, respectively. Of patients with available pathology, 91% and 71% were positive for HPV and p16 (2+), respectively. HPV genotypes included 16 (n = 17), 33 (n = 2), 18 (n = 1), and 45 (n = 1). HPV and p16 status were associated on Chi-square analysis (p = 0.07). Neither HPV nor p16 status was significantly associated with any clinical outcome. For HPV+ patients, 3-year FFLRF, FFDM, FFC, and OS were 100%, 69%, 100%, and 88%, respectively. CONCLUSIONS: In this patient cohort, disease control was excellent for anal SCC treated with definitive concurrent chemotherapy and IMRT, and treatment was well tolerated. HPV and p16 status were not prognostic for treatment outcomes which may be related to our small sample size.

Nonstandardized Terminology to Describe Focal Liver Lesions in Patients at Risk for Hepatocellular Carcinoma: Implications Regarding Clinical Communication.

OBJECTIVE: The purpose of this study is to determine the correlation between malignancy risk of focal liver observations in patients at risk for hepatocellular carcinoma (HCC) implied by phrases used in nonstructured radiology reports with the risk inferred by hepatologists. MATERIALS AND METHODS: We performed a retrospective review of nonstructured radiology reports issued before Liver Imaging and Reporting Data System (LI-RADS) adoption from four-phase liver CT examinations of patients at risk for HCC. The phrase used by the radiologist in the report impression to describe each focal liver observation was recorded. Five hepatologists independently inferred the LI-RADS category from each phrase. Two abdominal radiologists independently reviewed the images and, blinded to all other information, assigned a LI-RADS category to each observation. Discrepancies were resolved by consensus. RESULTS: One hundred five observations in 77 patients were reported by 23 radiologists using 29 phrases. The most common phrase, "consistent with HCC" (n = 20), was applied to radiologist-assigned LR-3 (n = 1), LR-4 (n = 5), LR-5 (n = 11), and LR-5V (n = 3) observations. Eleven phrases were used more than once. Sixteen phrases were associated with LR-4 or higher observations; among these, hepatologists misinterpreted 37% of LR-4 or lower observations as definitely HCC and 46% of LR-5 and LR-5V observations as not definitely HCC. Overall, there was modest correlation (r = 0.69) between radiologist-assigned and hepatologist-inferred categories. CONCLUSION: Nonstandardized terminology results in inaccurate communication of HCC risk. Structured reporting systems such as LI-RADS may improve communication by conveying unambiguous estimates of malignancy risk.

Improving Rhinology Skills with Simulation.

The convergence of technology and medicine has led to many advances in surgical training. Novel surgical simulators have led to significantly improved skills of graduating surgeons, leading to decreased time to proficiency, improved efficiency, decreased errors, and improvement in patient safety. Endoscopic sinus surgery poses a steep learning curve given the complex 3-dimensional anatomy of the nasal and paranasal cavities, and the necessary visual-spatial motor skills and bimanual dexterity. This article focuses on surgical simulation in rhinological training and how innovative high-fidelity and low-fidelity simulators can maximize resident training and improve procedural skills before operating in the live environment.

Preoperative 18F-FDG-PET/CT vs Contrast-Enhanced CT to Identify Regional Nodal Metastasis among Patients with Head and Neck Squamous Cell Carcinoma.

Objective Our objective was to compare the accuracy of preoperative positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in detecting cervical nodal metastases in patients treated with neck dissection and to scrutinize the ability of each modality to determine nodal stage. Study Design Case series with chart review. Setting Montefiore Medical Center, Bronx, New York. Subjects and Methods Patients who underwent neck dissection at our institution for primary treatment of head and neck squamous cell carcinoma (HNSCC) and had received preoperative PET/CT and CECT were included in this study. Imaging studies were reinterpreted by 3 specialists within the field and compared for interreader agreement. Concordance between radiology and histopathology was measured using neck levels and sides, along with patient nodal stage. Sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and agreement coefficients were calculated. Results Seventy-three patients were included in the study. Sensitivity was 0.69 and 0.94 (level and side) for PET/CT vs 0.53 and 0.66 for CECT ( P = .056, P = .001). Specificity was 0.86 and 0.56 for PET/CT vs 0.91 and 0.76 for CECT ( P = .014, P = .024). No significant difference was found in overall accuracy ( P = .33, P = .88). The overall agreement percentages between N stage called by imaging modality and pathology were 52% and 55% for PET/CT and CECT, respectively. Conclusion No significant difference in sensitivity was found between PET/CT and CECT. CECT was found to have superior specificity compared with PET/CT. The information gleaned from each modality in the pretreatment evaluation of HNSCC appears to be complementary.

Hematologic Nadirs During Chemoradiation for Anal Cancer: Temporal Characterization and Dosimetric Predictors.

PURPOSE: Pelvic bone marrow (BM) constraints may offer a means to reduce the toxicity commonly associated with chemoradiation for anal cancer. We conducted a bi-institutional analysis of dose-volume metrics in a time-sensitive fashion to devise practical metrics to minimize hematologic toxicity. METHODS AND MATERIALS: Fifty-six anal cancer patients from 2 institutions received definitive radiation therapy (median primary dose of 54 Gy) using intensity modulated radiation therapy (IMRT, n=49) or 3-dimensional (3D) conformal therapy (n=7) with concurrent 5-fluorouracil (5-FU) and mitomycin C. Weekly blood counts were retrospectively plotted to characterize the time course of cytopenias. Dose-volume parameters were correlated with blood counts at a standardized time point to identify predictors of initial blood count nadirs. RESULTS: Leukocytes, neutrophils, and platelets reached a nadir at week 3 of treatment. Smaller volumes of the pelvic BM correlated most strongly with lower week 3 blood counts, more so than age, sex, body mass index (BMI), or dose metrics. Patients who had ≥750 cc of pelvic BM spared from doses of ≥30 Gy had 0% grade 3+ leukopenia or neutropenia at week 3. Higher V40 Gy to the lower pelvic BM (LP V40) also correlated with cytopenia. Patients with an LP V40 >23% had higher rates of grade 3+ leukopenia (29% vs 4%, P=.02), grade 3+ neutropenia (33% vs 8%, P=.04), and grade 2+ thrombocytopenia (32% vs 7%, P=.04) at week 3. On multivariate analysis, pelvic BM volume and LP V40 remained associated with leukocyte count, and all marrow subsite volumes remained associated with neutrophil counts at week 3 (P<.1). CONCLUSIONS: Larger pelvic BM volumes correlate with less severe leukocyte and neutrophil nadirs, suggesting that larger total "marrow reserve" can mitigate cytopenias. Sparing a critical marrow reserve and limiting the V40 Gy to the lower pelvis may reduce the risk of hematologic toxicity.

Induction Chemotherapy Followed by Concurrent Full-dose Gemcitabine and Intensity-modulated Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma.

OBJECTIVE: To evaluate the outcomes and toxicity of concurrent full-dose gemcitabine and intensity-modulated radiation therapy (IMRT) for patients with borderline resectable and locally advanced pancreatic adenocarcinoma after induction chemotherapy. MATERIALS AND METHODS: From 2009 to 2012, 32 patients were treated with concurrent gemcitabine and IMRT for borderline resectable or locally advanced pancreatic adenocarcinoma. All patients received induction FOLFIRINOX or gemcitabine-based chemotherapy before chemoradiation. The radiotherapy volume was limited to the primary tumor, and the median dose was 55 Gy in 25 fractions. Gemcitabine was administered weekly during radiotherapy on days 1, 8, 22, and 29 at a median weekly dose of 800 mg/m². RESULTS: Twenty-five patients had locally advanced disease and 7 had borderline resectable disease. The median follow-up time was 14.6 months. The median progression-free and overall survival were 13.9 and 23.1 months, with a trend toward improved overall survival for patients receiving induction FOLFIRINOX compared with gemcitabine-based therapy. A radiographic complete or partial response was achieved in 13 patients (41%), with 4 (13%) having complete radiographic responses. Surgical resection was performed in 10 patients (31%)--6 patients with locally advanced disease and 4 with borderline resectable disease. Grade 3/4 hematologic toxicity during and up to 6 weeks after chemoradiation occurred in 12 patients (38%); grade 3 nonhematologic toxicity occurred in 7 patients (22%), with no grade 4 or 5 toxicity. All patients completed their radiotherapy. CONCLUSIONS: Concurrent full-dose gemcitabine and limited-field IMRT after induction chemotherapy for the treatment of borderline resectable and locally advanced pancreatic cancer is promising with acceptable toxicity rates.

A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver.

UNLABELLED: Identification of microRNAs (miRNAs) that regulate lipid metabolism is important to advance the understanding and treatment of some of the most common human diseases. In the liver, a few key miRNAs have been reported that regulate lipid metabolism, but since many genes contribute to hepatic lipid metabolism, we hypothesized that other such miRNAs exist. To identify genes repressed by miRNAs in mature hepatocytes in vivo, we injected adult mice carrying floxed Dicer1 alleles with an adenoassociated viral vector expressing Cre recombinase specifically in hepatocytes. By inactivating Dicer in adult quiescent hepatocytes we avoided the hepatocyte injury and regeneration observed in previous mouse models of global miRNA deficiency in hepatocytes. Next, we combined gene and miRNA expression profiling to identify candidate gene/miRNA interactions involved in hepatic lipid metabolism and validated their function in vivo using antisense oligonucleotides. A candidate gene that emerged from our screen was lipoprotein lipase (Lpl), which encodes an enzyme that facilitates cellular uptake of lipids from the circulation. Unlike in energy-dependent cells like myocytes, LPL is normally repressed in adult hepatocytes. We identified miR-29a as the miRNA responsible for repressing LPL in hepatocytes, and found that decreasing hepatic miR-29a levels causes lipids to accumulate in mouse livers. CONCLUSION: Our screen suggests several new miRNAs are regulators of hepatic lipid metabolism. We show that one of these, miR-29a, contributes to physiological lipid distribution away from the liver and protects hepatocytes from steatosis. Our results, together with miR-29a's known antifibrotic effect, suggest miR-29a is a therapeutic target in fatty liver disease.

Segmentation precision of abdominal anatomy for MRI-based radiotherapy.

The limited soft tissue visualization provided by computed tomography, the standard imaging modality for radiotherapy treatment planning and daily localization, has motivated studies on the use of magnetic resonance imaging (MRI) for better characterization of treatment sites, such as the prostate and head and neck. However, no studies have been conducted on MRI-based segmentation for the abdomen, a site that could greatly benefit from enhanced soft tissue targeting. We investigated the interobserver and intraobserver precision in segmentation of abdominal organs on MR images for treatment planning and localization. Manual segmentation of 8 abdominal organs was performed by 3 independent observers on MR images acquired from 14 healthy subjects. Observers repeated segmentation 4 separate times for each image set. Interobserver and intraobserver contouring precision was assessed by computing 3-dimensional overlap (Dice coefficient [DC]) and distance to agreement (Hausdorff distance [HD]) of segmented organs. The mean and standard deviation of intraobserver and interobserver DC and HD values were DC(intraobserver) = 0.89 ± 0.12, HD(intraobserver) = 3.6mm ± 1.5, DC(interobserver) = 0.89 ± 0.15, and HD(interobserver) = 3.2mm ± 1.4. Overall, metrics indicated good interobserver/intraobserver precision (mean DC > 0.7, mean HD < 4mm). Results suggest that MRI offers good segmentation precision for abdominal sites. These findings support the utility of MRI for abdominal planning and localization, as emerging MRI technologies, techniques, and onboard imaging devices are beginning to enable MRI-based radiotherapy.