Citations

Abstract Introduction: Even physicians who routinely work in complex, dynamic practices may be unprepared to optimally manage challenging critical events. High-fidelity simulation can realistically mimic critical clinically relevant events, however the reliability and validity of simulation-based assessment scores for practicing physicians has not been established.Methods: Standardized complex simulation scenarios were developed and administered to board-certified, practicing anesthesiologists who volunteered to participate in an assessment study during formative maintenance of certification activities. A subset of the study population agreed to participate as the primary responder in a second scenario for this study. The physicians were assessed independently by trained raters on both teamwork/behavioral and technical performance measures. Analysis using Generalizability and Decision studies were completed for the two scenarios with two raters.Results: The technical score was not more reliable than the behavioral score. With two raters > 20 scenarios would be required to achieve a reliability estimate of 0.7. Increasing the number of raters would have little effect on reliability.Discussion: The performance of practicing physicians on simulated critical events may be highly context-specific. Realistic simulation-based assessment for practicing physicians is resource-intensive and may be best-suited for individualized formative feedback. Moreover, aggregate data from a population of participants may yield even higher impact if used to identify skill or knowledge gaps to be addressed by training programs and continuing education improvements across the profession.

Abstract So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567/879), we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MGUS. Heritability and genetic estimates yielded 17% (standard error [SE] ±0.04) and 15% (SE ±0.11) for MM and MGUS risk, respectively, and a 55% (SE ±0.30) genetic correlation. The MM-PRS was associated with risk of MM when assessed continuously (odds ratio [OR], 1.17 per SD; 95% confidence interval [CI], 1.13-1.21) or categorically (OR, 1.70; 95% CI, 1.38-2.09 for highest; OR, 0.71; 95% CI, 0.55-0.90 for lowest compared with middle quintile). The MM-PRS was similarly associated with MGUS (OR, 1.19 per SD; 95% CI, 1.14-1.26 as a continuous measure, OR, 1.77, 95%CI: 1.29-2.43 for highest and OR, 0.70, 95%CI: 0.50-0.98 for lowest compared with middle quintile). MM and MGUS associations did not differ by age, sex, or MM immunoglobulin isotype. We validated a 23-SNP MM-PRS in an independent series of MM cases and provide evidence for its association with MGUS. Our results suggest shared common genetic susceptibility to MM and MGUS.

Abstract Background: Berberine (BBR) is a plant-based nutraceutical that has been used for millennia to treat diarrheal infections and in contemporary medicine to improve patient lipid profiles. Reduction in lipids, particularly cholesterol, is achieved partly through up-regulation of bile acid synthesis and excretion into the Gastrointestinal tract. The efficacy of BBR is also thought to be dependent on structural and functional alterations of the gut microbiome. However, knowledge of the effects of BBR on gut microbiome communities is currently lacking. Distinguishing indirect effects of BBR on bacteria through altered bile acid profiles is particularly important in understanding how dietary nutraceuticals alter the microbiome. Results: Germfree mice were colonized with a defined minimal gut bacterial consortium capable of functional bile acid metabolism (Bacteroides vulgatus, Bacteroides uniformis, Parabacteroides distasonis, Bilophila wadsworthia, Clostridium hylemonae, Clostridium hiranonis, Blautia producta; B4PC2). Multi-omics (bile acid metabolomics, 16S rDNA sequencing, cecal metatranscriptomics) were performed in order to provide a simple in vivo model from which to identify network-based correlations between bile acids and bacterial transcripts in the presence and absence of dietary BBR. Significant alterations in network topology and connectedness in function were observed, despite similarity in gut microbial relative abundance between control and BBR treatment. BBR increased cecal bile acid concentrations and altered the taurocholic acid:tauro-β-muricholic acid ratio in the liver. Overall, analysis of correlation networks indicates both bacterial species-specific responses to BBR, as well as functional commonalities among species, such as up-regulation of Na+/H+ antiporter, cell wall synthesis/repair, carbohydrate metabolism and amino acid metabolism. Bile acid concentrations in the gastrointestinal (GI) tract increased significantly during berberine treatment and developed extensive correlation networks with expressed genes in the B4PC2 community. Conclusions: This work has important implications for interpreting the effects of berberine on structure and function of the complex gut microbiome, which may lead to targeted pharmaceutical interventions aimed to achieve the positive physiological effects previously observed with berberine supplementation.

Abstract BACKGROUND Facial nerve schwannomas are rare, challenging tumors to manage due to their nerve of origin. Functional outcomes after stereotactic radiosurgery (SRS) are incompletely defined. OBJECTIVE To analyze the effect of facial nerve segment involvement on functional outcome for these tumors. METHODS Patients who underwent single-session SRS for facial nerve schwannomas with at least 3 mo follow-up at 11 participating centers were included. Preoperative and treatment variables were recorded. Outcome measures included radiological tumor response and neurological function. RESULTS A total of 63 patients (34 females) were included in the present study. In total, 75% had preoperative facial weakness. Mean tumor volume and margin dose were 2.0 ± 2.4 cm 3 and 12.2 ± 0.54 Gy, respectively. Mean radiological follow-up was 45.5 ± 38.9 mo. Progression-free survival at 2, 5, and 10 yr was 98.1%, 87.2%, and 87.2%, respectively. The cumulative proportion of patients with regressing tumors at 2, 5, and 10 yr was 43.1%, 63.6%, and 63.6%, respectively. The number of involved facial nerve segments significantly predicted tumor progression ( P = .04). Facial nerve function was stable or improved in 57 patients (90%). Patients with involvement of the labyrinthine segment of the facial nerve were significantly more likely to have an improvement in facial nerve function after SRS ( P = .03). Hearing worsened in at least 6% of patients. Otherwise, adverse radiation effects included facial twitching (3 patients), facial numbness (2 patients), and dizziness (2 patients). CONCLUSION SRS for facial nerve schwannomas is effective and spares facial nerve function in most patients. Some patients may have functional improvement after treatment, particularly if the labyrinthine segment is involved.

Research describing the match and specific positional demands during match play in women’s collegiate soccer is limited. The purpose of the study was to quantify the match demands of National Collegiate Athletic Association (NCAA) Division III soccer and assess position differences in movement kinematics, heart rate (HR), and energy expenditure. Twenty-five Division III women soccer players (height: 1.61 ± 0.3 m; body mass: 66.7 ± 7.5 kg; fat-free mass: 50.3 ± 6.5 kg; body fat%: 25.6 ± 5.1%) were equipped with a wearable global positioning system to assess the demands of 22 matches throughout a season. Players were categorized by position (goal keepers (GK), center defenders (CB), flank players (FP), forwards (F), and center midfielders (CM)). Players covered 9807 ± 2588 m and 1019 ± 552 m at high speeds (>249.6 m·m−1), with an overall average speed of 62.85 ± 14.7 m·m−1. This resulted in a mean HR of 74.2 ± 6% HR max and energy expenditure of 1259 ± 309 kcal. Significant and meaningful differences in movement kinematics were observed across position groups. CM covered the most distance resulting in the highest training load. FP covered the most distance at high speeds and mean HR values were highest in CM, CB, and FP positions.

Podcasts are online digital audio programs that are disseminated via online subscription that are easily accessible through computers or smartphones. Increasingly, residents and medical students are prioritizing podcasts for asynchronous medical education due to ease of use, convenience (eg, use while exercising or commuting), and repeatability. Some trainees have found podcasts more useful than traditional didactic lectures. Given the increasing requirements of social distancing and the need for distance medical education platforms, podcast production can serve as a useful tool to complement resident and medical student education and is a resource that will remain accessible in perpetuity. An otolaryngology specialty podcast, “Headmirror’s ENT in a Nutshell,” was created to augment asynchronous learning and address the acute need for distance learning opportunities. Over the first 7 weeks of production, 50 episodes were created. Episodes were posted on www.headmirror.com, with subscription services available through Apple Podcast, Spotify, and other platforms.

Objective: Recurrent laryngeal nerve injury is a potential complication of cardiothoracic surgery and cause of unilateral vocal fold paralysis (UVFP). Injection laryngoplasty (IL) is an intervention offered to patients with UVFP to alleviate symptoms including dysphagia, dysphonia and weak cough. There is no definitive evidence that IL prevents pneumonia. In this study, we compare rates of pneumonia in patients with UVFP secondary to cardiothoracic surgery who did or did not undergo IL. Methods: A retrospective chart review identified patients diagnosed with UVFP by an otolaryngologist using flexible laryngoscopy following cardiothoracic surgery from January 1, 2008 to December 31, 2017. Each subject was grouped by IL status and assessed for subsequent pneumonia within 6 months of their diagnosis of UVFP. The association of IL with pneumonia was evaluated using Cox proportional hazards regression. Results: Of 92 patients who met inclusion criteria, 35 (38%) underwent IL and 57 (62%) did not. Twenty patients developed pneumonia, four who had undergone IL and 16 who had not; 12 patients developed aspiration pneumonia including two having undergone IL and 10 who had not. Those who had IL were less likely to develop total pneumonia compared to those who had not (HR = 0.33, P = .045). The protective effect of IL was not as clearly sustained when measuring for aspiration pneumonia, specifically (HR = 0.34; P = .10). Discussion: Injection laryngoplasty may reduce the risk of pneumonia in patients with UVFP secondary to cardiothoracic surgery; however, further research is needed to quantify the potential protective nature of IL in this patient population. Level of evidence: 3 (A retrospective cohort study).

Background Immune checkpoint inhibitors (ICIs) to date have demonstrated limited activity in advanced ovarian cancer (OC). Folate receptor alpha (FRα) is overexpressed in the majority of OCs and presents an attractive target for a combination immunotherapy to potentially overcome resistance to ICI in OCs. The current study sought to examine clinical and immunologic responses to TPIV200, a multiepitope FRα vaccine administered with programmed death ligand 1 (PD-L1) inhibitor durvalumab in patients with advanced platinum-resistant OC. Methods Following Simon two-stage phase II trial design, 27 patients were enrolled. Treatment was administered in 28-day cycles (intradermal TPIV200 and granulocyte-macrophage colony-stimulating factor (GM-CSF) for 6 cycles and intravenous durvalumab for 12 cycles). Primary endpoints included overall response rate and progression-free survival at 24 weeks. Translational parameters focused on tumor microenvironment, PD-L1 and FRα expression, and peripheral vaccine-specific immune responses. Results Treatment was well tolerated, with related grade 3 toxicity rate of 18.5%. Increased T cell responses to the majority of peptides were observed in all patients at 6 weeks (p<0.0001). There was one unconfirmed partial response (3.7%) and nine patients had stable disease (33.3%). Clinical benefit was not associated with baseline FRα or PD-L1 expression. One patient with prolonged clinical benefit demonstrated loss of FRα expression and upregulation of PD-L1 in a progressing lesion. Despite the low overall response rate, the median overall survival was 21 months (13.5–∞), with evidence of benefit from postimmunotherapy regimens. Conclusions Combination of TPIV200 and durvalumab was safe and elicited robust FRα-specific T cell responses in all patients. Unexpectedly durable survival in this heavily pretreated population highlights the need to investigate the impact of FRα vaccination on the OC biology post-treatment.