Citations

Abstract Background The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). Methods Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence‐based review, or evidence‐based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. Results The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. Conclusion This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.

AbstractConvalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID‐19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID‐19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID‐19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody‐based therapies.

Introduction: Numerous endovascular tools exist for the treatment of intracranial aneurysms with an increased use of flow-diverting devices in recent years. However, the biological mechanisms leading to aneurysm healing or potential complications such as delayed aneurysm ruptures after flow-diverter treatment are not yet well established. We used RNA-sequencing technology to identify genes relevant for biological impact of coils and flow-diverters in elastase-induced saccular aneurysms in rabbits and to identify genes and pathways of potential clinical interest. Methods: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery. Aneurysms were treated with coils (n=5) or flow-diverters (Pipeline Embolic Device, Covidien, CA) (n=4). Untreated aneurysms (n=6) were used as controls. Messenger RNA and microRNA were isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed using RNA-seq technology. RNA-seq results were analyzed by using the Ingenuity Pathway Analysis tool. Results: Using RNA sequencing for coiled versus non-treated aneurysms, 464 genes were found to be differentially expressed with 58 genes down regulated and 406 genes up regulated. Using the same criteria for the flow-diverter treated aneurysms, 177 genes were found to be differentially expressed with 8 genes down regulated and 169 genes up regulated. Comparing coiled versus flow-diverter treated aneurysms, 13 genes were significantly differentially expressed with 8 down regulated and 5 up regulated genes. Genes identified with the highest interest for aneurysms healing were fibroblast growth factor-23, matrix metalloproteinases (MMP)-1, Scinderin and Basigin (implicated in MMP-2 and MMP-9 regulation). Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions. Conclusions: RNA-sequencing analysis of rabbit aneurysms revealed differential regulation of some key pathways, including inflammation and cellular migration that could explain the different biological mechanisms implicated in aneurysms healing either after coiling or flow-diverter treatments and could explain potential device-related complications.

Background: Obstructive sleep apnea (OSA) imposes an afterload burden on the left ventricle and increases the pressure gradient across the intrathoracic aorta. This might increase the likelihood of aortic dissection (AD). We hypothesized that patients with acute AD would have a high prevalence of previously undiagnosed OSA and a largely nocturnal presentation. Methods: 40 consecutive, consenting subjects with acute AD who survived to hospital discharge were collected from 4 institutions. Mean age was 57 (range 28-75), 24 were male. 25 had type A dissection and 15 type B. 37 completed the modified Berlin Questionnaire and 30 had attended overnight polysomnography. Presenting CT scans had aortic diameter measured at a) the sinotubular junction b) ascending aorta c) origin of innominate d) mid-arch e) origin of left subclavian f) mid-descending aorta g) level of diaphragm; CT scans at 3 months were available in 24 subjects. Results: AHI ranged from 0 - 89; prevalence of OSA (defined by apnea-hypopnea index [AHI] > 5) was 63%. There were no differences in aortic diameter at any level comparing OSA vs non-OSA, regardless of AHI cutoff (>5, >15, >30; figure). Over time aortic diameter decreased at the level of the sinotubular junction and ascending aorta (expected - due to surgery). Whether dissection occurred during overnight hours (10 PM - 7 AM) did not differ by presence/absence of OSA (regardless of AHI cutoff). In those with high-risk Berlin questionnaires (>=2 categories positive) 10/21 (48%) dissections occurred during sleeping hours vs 2/13 (15%) in low risk Berlin group (p = 0.08, Fisher’s exact test). Conclusions: Among patients with acute AD the prevalence of OSA was high. Aortic diameters, however, were not different according to level of AHI. Presence of OSA defined by polysomnography was not associated with a nocturnal presentation in this sample.

AbstractBackgroundAs targeted treatments for amyloid transthyretin cardiomyopathy (ATTR‐CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter‐defibrillator (ICD) utilization, and their impact on survival.MethodsThis is a retrospective cohort study of 130 patients with ATTR‐CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation.ResultsOf 130 patients, 42 had wild‐type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR‐CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF > 40% (67% vs. 28%, p = .001). Thirty‐two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5 vs. 2.8 ± 0.4 years, p = .699).ConclusionsHigh rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR‐CM patients with a high rate of systolic heart failure.

Background: The growing focus on subjective patient experiences has created an increase in popularity for physician rating websites. The purpose of this study was to characterize extremely negative reviews of pediatric orthopaedic surgeons. Methods: Pediatric orthopaedic surgeons were randomly selected using the Pediatric Orthopaedic Society of North America comprehensive list of surgeons. A search was then performed on Healthgrades.com, Vitals.com, and Yelp.com for 1-star reviews. Reviews were classified into clinical and nonclinical categories. Statistical analyses were performed regarding the frequency of reviews and complaints for each respective category. Results: Of the 279 one-star reviews categorized, 248 reviews (88.9% of reviews) included nonclinical complaints, and 182 reviews (65.2% of reviews) included clinical complaints. Nonsurgical patients were associated with 255 reviews, and the remaining 24 were related to surgical patients. Of the 430 comments within reviews, 248 referenced nonclinical aspects of care, and 182 referenced clinical care. Clinical factors most frequently noted included clinical disagreement (37%), unclear treatment plan (25%), complication (17%), misdiagnosis (15%), uncontrolled pain (13%), and delay in care (8%). The most addressed nonclinical factors included physician bedside manner (68%), time spent with provider (21%), wait time (18%), unprofessional staff (17%), scheduling issues (9%), cost (8%), and billing (8%). Compared with surgical reviews, nonsurgical reviews were more likely to contain nonclinical complaints (rate ratio: 1.5; P<0.05) and less likely to contain clinical complaints (rate ratio: 0.7; P<0.05). The most common complaint by surgical patients was complications (91.7%). Conclusions: To our knowledge, this is the first study to examine the factors associated with negative reviews of pediatric orthopaedic surgeons. The majority of reviews of pediatric orthopaedic surgeons were left by nonsurgical patients and were related to nonclinical aspects of care. We also found surgeon-dependent factors such as poor physician bedside manner, unclear treatment plan, or parents’ disagreement with treatment plan were the most common reasons for negative reviews. Level of Evidence: Level IV.

AbstractBackgroundObstructive sleep apnea (OSA) imposes an afterload burden on the left ventricle and increases the pressure gradient across the aortic wall. Thus, OSA may increase the risk for aortic dissection (AD).MethodsThis study enrolled 40 subjects with acute AD from four institutions; 37 completed the modified Berlin Questionnaire and 31 underwent attended overnight polysomnography. Aortic diameter was measured on a computed tomography scan at seven locations from the sinotubular junction to the diaphragm.ResultsTwenty‐seven subjects had type A dissection; 13 had type B. In those who had polysomnography apnea–hypopnea index (AHI) ranged from 0.7 to 89. Prevalence of OSA (AHI ≥ 5) was 61%. Nocturnal presentation (10 p.m.–7 a.m.) did not differ by presence/absence of OSA. The modified Berlin Questionnaire was not predictive of the presence of OSA. Among type A subjects with polysomnography (n = 23), aortic diameters at all locations were greater in the OSA group though differences were not statistically significant. Summating aortic diameters at the seven locations also yielded a numerically larger mean value in the OSA group versus the non‐OSA group.ConclusionsIn this sample of patients with acute dissection, OSA was prevalent but was not associated with a nocturnal presentation. The presence of underlying OSA may be associated with larger aortic diameters at the time of dissection compared to patients without OSA. Though differences did not meet statistical significance the current series is limited by small numbers.

Background: Decreases in Medicare reimbursement have been noted among many medical specialties. An in-depth analysis of the subspecialty of orthopaedic sports medicine is needed to determine changes in Medicare reimbursement in this field. Purpose/Hypothesis: The purpose was to elucidate the trends in inflation-adjusted Medicare reimbursement for orthopaedic sports medicine procedures between 2000 and 2020. It was hypothesized that Medicare reimbursement decreased substantially during the study period. Study Design: Economic decision and analysis; Level of evidence, 4. Methods: The Physician Fee Schedule Look-up Tool was used to extract Medicare reimbursement information between 2000 and 2020 for 67 procedures related to orthopaedic sports medicine. These values were adjusted for inflation using the Consumer Price Index. The compound annual growth rate (CAGR) was calculated to measure the annual rate of change, and descriptive analyses were performed using the Student t test. Results: Between 2000 and 2020, inflation-adjusted Medicare reimbursement for the 67 included procedures decreased by an average of 33% (CAGR = –2.2%; R 2 = 0.78). Reimbursement decreased for procedures related to the shoulder and elbow by 34% (CAGR = –2.3%; R 2 = 0.80), for hip-related procedures by 23% (CAGR = –1.4%; R 2 = 0.77), for knee-related procedures by 31% (CAGR = –2.0%; R 2 = 0.81), and for procedures relating to the foot and ankle by 38% (CAGR = –2.5%; R 2 = 0.79). Conclusion: Study findings indicated that inflation-adjusted Medicare reimbursement decreased substantially between 2000 and 2020 for orthopaedic sports medicine procedures, ranging from a 23% decrease for hip-related procedures to a 38% decrease for foot and ankle–related procedures. The results of this study could be used to provide further context for health care policy decisions and help ensure sustainable financial environments for orthopaedic sports medicine surgeon.

Abstract Background Diffuse Midline Glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis. Methods We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n = 24) underwent serial lumbar puncture for cell-free tumor DNA (cf-tDNA) analysis and patients on all arms at the University of Michigan underwent serial plasma collection. We performed digital droplet polymerase chain reaction (ddPCR) analysis of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI). Results Change in H3.3K27M VAF over time (“VAF delta”) correlated with prolonged PFS in both CSF and plasma samples. Nonrecurrent patients that had a decrease in CSF VAF displayed a longer progression free survival (P = .0042). Decrease in plasma VAF displayed a similar trend (P = .085). VAF “spikes” (increase of at least 25%) preceded tumor progression in 8/16 cases (50%) in plasma and 5/11 cases (45.4%) in CSF. In individual cases, early reduction in H3K27M VAF predicted long-term clinical response (&gt;1 year) to ONC201, and did not increase in cases of later-defined pseudo-progression. Conclusion Our work demonstrates the feasibility and potential utility of serial cf-tDNA in both plasma and CSF of DMG patients to supplement radiographic monitoring. Patterns of change in H3K27M VAF over time demonstrate clinical utility in terms of predicting progression and sustained response and possible differentiation of pseudo-progression and pseudo-response.

Summary Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists. Questions focused on management of patients from presentation to post-endoscopy follow-up. The survey was administered to a list of eligible candidates provided by societies of gastroenterology. A total of 308 endoscopists completed the questionnaire. The majority (83%) practiced in Europe and treated adults (78%). Most agreed patients should be advised to seek emergency care (66%) within 1 to 2 hours (41% agreement). There was agreement that medications to induce vomiting should be avoided (84%) and that blood tests or imaging studies were usually not required before endoscopy. By contrast, there was more variability in the type of sedation recommended and the need for endotracheal intubation, especially when comparing more experienced with less experienced EoE-endoscopists. Overall, fewer than half (43%) respondents recommended obtaining esophageal biopsies during the initial endoscopy. However, there were significant differences in the proportion who recommended biopsies based on level of EoE-experience (25, 52, 77%, P &lt; 0.001; less vs. moderate vs. very experienced) and comparing pediatric and adult endoscopists (32, vs. 79%, P &lt; 0.001; adult vs. pediatric). There exists heterogeneity among endoscopists in recommendations to manage EFI in patients with EoE. These findings support development of clinical guidelines and new studies to clarify the rationale for best practices. Key summary: Established knowledge—The optimal management of patients with esophageal food impaction due to eosinophilic esophagitis from presentation at the emergency department to postendoscopy care is unclear. New findings—Considerable recommendation variation exists in the management of EFI in patients with EoE. Our findings provide a rationale for the creation of consensus practice guidelines and further study into best practices.