The Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties.

Inclusion body myositis (IBM) is an autoimmune and degenerative disorder of skeletal muscle. The B cell infiltrates in IBM muscle tissue are predominantly fully differentiated Ab-secreting plasma cells, with scarce naive or memory B cells. The role of this infiltrate in the disease pathology is not well understood. To better define the humoral response in IBM, we used adaptive immune receptor repertoire sequencing, of human-derived specimens, to generate large BCR repertoire libraries from IBM muscle biopsies and compared them to those generated from dermatomyositis, polymyositis, and circulating CD27+ memory B cells, derived from healthy controls and Ab-secreting cells collected following vaccination. The repertoire properties of the IBM infiltrate included the following: clones that equaled or exceeded the highly clonal vaccine-associated Ab-secreting cell repertoire in size; reduced somatic mutation selection pressure in the CDRs and framework regions; and usage of class-switched IgG and IgA isotypes, with a minor population of IgM-expressing cells. The IBM IgM-expressing population revealed unique features, including an elevated somatic mutation frequency and distinct CDR3 physicochemical properties. These findings demonstrate that some of IBM muscle BCR repertoire characteristics are distinct from dermatomyositis and polymyositis and circulating Ag-experienced subsets, suggesting that it may form through selection by disease-specific Ags.

Assessing Risk of Severe Complications after Endoscopic Transnasal Transsphenoidal Surgery: A Comparison of Frailty, American Society of Anesthesiologists, and Comorbidity Scores.

Objective This study aimed to improve age-independent risk stratification for patients undergoing endoscopic transnasal transsphenoidal (TNTS) approach to pituitary mass resection by investigating the associations between frailty, American Society of Anesthesiologists (ASA), and comorbidity scores with severe complications following TNTS. Design This study is a retrospective review. Setting This review was conducted utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Participants A total of 680 cases of TNTS identified from 2010 to 2013 were included in this study. Main Outcome Measures The modified frailty index (mFI) was calculated to quantify frailty. ASA and Charlson's comorbidity index (CCI) scores were obtained as physiologic status and comorbidity-based prognostic markers. Severe complications were separated into intensive care unit (ICU)-level complications, defined by Clavien-Dindo grade IV (CDIV) criteria, and mortality. Results Overall, 24 CDIV complications (3.5%) and 6 deaths (0.9%) were recorded. Scores for mFI ( p = 0.01, R 2 = 0.97) and ASA ( p = 0.04., R 2 = 0.87) were significantly correlated with CDIV complications. ASA scores were significantly correlated with mortality ( p = 0.03, R 2 = 0.87), as well as independently associated with CDIV complication by multivariable regression models (odds ratio [OR] = 2.96, 95% confidence interval [CI]: 1.35-6.83, p < 0.01), while mFI was not. CCI was not significantly associated with CDIV complications or mortality. A multivariable regression model incorporating ASA had a lower Akaike's Information Criteria (AIC; 188.55) than a model incorporating mFI (195.99). Conclusion Frailty and physiologic status, as measured by mFI and ASA scores respectively, both correlate with ICU-level complications after TNTS. ASA scores demonstrate greater clinical utility than mFI scores; however, as they are more easily generated, uniquely correlated with mortality and independently associated with ICU-level complication risk on multivariable regression analysis.

Adequate short- and long-term pain control with non-opiate analgesics after microdirect laryngoscopy.

OBJECTIVE: In otolaryngology, it is important to minimize the use of opioids for post-operative analgesia given the rise in opioid abuse and mortality due to overdose in the United States. We sought to quantitatively determine the efficacy of non-opiate analgesia in postoperative pain management after microdirect laryngoscopy (MDL). METHODS: This is a single institution prospective study monitoring post-operative pain using a visual analog scale (VAS, 1-10). Patients with a history of vocal fold lesions, paralysis, and stenosis who underwent MDL were surveyed for one month following their procedure (daily for the first week and weekly thereafter). Student's t-test was used to determine whether short (1 week) and long term (1 month) pain was controlled by over-the-counter (OTC) medications. We defined adequate pain control as an average daily VAS score below 4 for the first 4 days and below 1 in the following 3 weeks and hypothesized that patients would report adequate pain control without the use of opioids. RESULTS: Post-operative pain after MDL was generally mild. The average daily VAS score was 2.16 (95% CI [0.0-5.2], P = 0.0014) in the first 4 days post-procedure and 0.28 (95% CI [0.0-1.3], P = 0.0007) in the 3 weeks post-procedure confirming our hypothesis. On average, patients used 3.14 (CI: [0.0-12.8]) pills of acetaminophen and 0.57 (CI: [0.0-4.7]) pills of an NSAID per day in the first week. Only three patients required opioid analgesia, all of whom used opioids in the first 48 h. CONCLUSIONS: OTC analgesics provide sufficient pain control after microdirect laryngoscopy for most patients. Given the potential for substance abuse from opioid medications, this study demonstrates that adequate pain control requires, at most, 48 h of opioid medications. Further study is needed to determine factors that contribute to increased pain after laryngoscopy.

Factors Affecting Posterior Glottic Stenosis Surgery Outcomes: Systematic Review and Meta-analysis.

OBJECTIVES: To investigate surgical adjuncts (stents) and previous surgeries on outcomes from posterior glottic stenosis (PGS). METHODS: PubMED/Medline, CINAHL, EMBASE, and Web of Science were searched for publications on adult patients undergoing surgery for PGS. Decannulation and need for additional surgeries were evaluated as outcomes. Linear mixed-effects (with random effects and fixed effects) models were used for multivariate testing. RESULTS: In total, 516 abstracts were reviewed and 26 articles were considered for systematic review. Of these, 19 articles with 140 pooled patient cases were extracted for meta-analysis. On multivariate meta-analysis analysis accounting for study-specific variation and use of open procedures, prior surgeries were associated with additional surgeries (RR = 3.76 [1.39-3.86], P = .038) and the use of a stent was associated with a lower likelihood of decannulation (RR = 0.42 [0.09-0.98], P = .044). CONCLUSION: Minimizing repeat surgery is a predictor for avoiding additional future surgeries and use of a stent was correlated with poor outcomes. These 2 findings may assist providers in patient counseling regarding the need for further surgical interventions. Further, this study is the first to compare the efficacy of surgical approaches for the resolution of PGS, and highlights the importance of avoiding repeat procedures and stents for the management of PGS.

CD4+ follicular regulatory T cells optimize the influenza virus-specific B cell response.

CD4+ follicular regulatory T (Tfr) cells control B cell responses through the modulation of follicular helper T (Tfh) cells and germinal center development while suppressing autoreactivity; however, their role in the regulation of productive germinal center B cell responses and humoral memory is incompletely defined. We show that Tfr cells promote antigen-specific germinal center B cell responses upon influenza virus infection. Following viral challenge, we found that Tfr cells are necessary for robust generation of virus-specific, long-lived plasma cells, antibody production against both hemagglutinin (HA) and neuraminidase (NA), the two major influenza virus glycoproteins, and appropriate regulation of the BCR repertoire. To further investigate the functional relevance of Tfr cells during viral challenge, we used a sequential immunization model with repeated exposure of antigenically partially conserved strains of influenza viruses, revealing that Tfr cells promote recall antibody responses against the conserved HA stalk region. Thus, Tfr cells promote antigen-specific B cell responses and are essential for the development of long-term humoral memory.

A Manufacturer and User Facility Device Experience Analysis of Upper Aerodigestive Endoscopy Contamination: Is Flexible Laryngoscopy Different?

OBJECTIVES/HYPOTHESIS: Several recent studies have observed a high incidence of duodenoscope microbial contamination and an association of contamination with healthcare-acquired infections. This study sought to quantify nasopharyngoscope microbial contamination relative to that of other endoscope categories and characterize the manufacturers, outcomes, and microbial profiles associated with these cases. STUDY DESIGN: Retrospective, cross-sectional study. METHODS: A total of 3,865 adverse events were collected from 2013 to 2019 using the US Food and Drug Administration Manufacturer and User Facility Device Experience database. The fraction of total device failures associated with contamination was quantified for nasopharyngoscopes, bronchoscopes, duodenoscopes, and gastroscopes. Odds ratios of nasopharyngoscope contamination compared to that of bronchoscopes, duodenoscopes, or gastroscopes were calculated, and significance was assessed by χ2 analysis. The Kruskal-Wallis test was used for nonparametric testing of significance. RESULTS: Nasopharyngoscope device failures were reported at an incidence of 0.646 per month; 34.1% involved contamination, comparable to the frequency observed for bronchoscopes (23.4%, P = .118), duodenoscopes (29.2%, P = .493), and gastroscopes (45.3%, P = .178). The frequency of device contamination was observed to be significantly higher for a particular endoscope manufacturer regardless of endoscope category (Kruskal-Wallis P = .021). In instances of contamination, nasopharyngoscopes were significantly less associated with patient harm or death than bronchoscope (odds ratio [OR] = 10.2) and duodenoscope (OR = 4.81) cases. CONCLUSIONS: Although the rates of contamination were comparable across all endoscope categories, nasopharyngoscope contamination was less commonly associated with patient harm or death. In an era of rising healthcare costs, determining adequate disinfection standards for nasopharyngoscopes and their impact on patient safety is crucial. LEVEL OF EVIDENCE: NA Laryngoscope, 131:598-605, 2021.

A Review of Telemedicine Applications in Otorhinolaryngology: Considerations During the Coronavirus Disease of 2019 Pandemic.

OBJECTIVE/HYPOTHESIS: Review the published literature of telemedicine's use within otorhinolaryngology (ORL), highlight its successful implementation, and document areas with need of future research. STUDY DESIGN: State of the Art Review. METHODS: Three independent, comprehensive searches for articles published on the subject of telemedicine in ORL were conducted of literature available from January 2000 to April 2020. Search terms were designed to identify studies which examined telemedicine use within ORL. Consensus among authors was used to include all relevant articles. RESULTS: While several, small reports document clinical outcomes, patient satisfaction, and the cost of telemedicine, much of the literature on telemedicine in ORL is comprised of preliminary, proof-of-concept reports. Further research will be necessary to establish its strengths and limitations. CONCLUSIONS: Particularly during the coronavirus disease of 2019 pandemic, telemedicine can, and should, be used within ORL practice. This review can assist in guiding providers in implementing telemedicine that has been demonstrated to be successful, and direct future research. Laryngoscope, 131:744-759, 2021.

Sequencing of Sclerosing Microcystic Adenocarcinoma Identifies Mutational Burden and Somatic Variants Associated With Tumorigenesis.

BACKGROUND/AIM: Sclerosing microcystic adenocarcinoma (SMA) is a rare oral cavity neoplasia, histologically resembling microcystic adnexal carcinoma (MAC) of the skin. Only nine SMA cases have been reported in the literature, frequently in the context of immunosuppression; SMA has not been recognized in the most recent WHO tumor classification. We sought to identify potential molecular mechanisms of tumorigenesis in a case of SMA relative to those known for MAC. CASE REPORT: A 41-year-old female with psoriatic arthritis undergoing immunosuppression therapy presented with a tongue mass. Biopsy revealed a diagnosis of SMA. Partial glossectomy and neck dissection showed no residual tumor or nodal disease. RESULTS: whole exome sequencing revealed moderate mutational burden and putative loss of function mutations in CDK11B but no overlap with known MAC mutations. CONCLUSION: We characterized the genomic profile of SMA for the first time, identifying both mutational burden and unique somatic variants associated with tumorigenesis.