Citations

Abstract Objective Untreated obstructive sleep apnea (OSA) in the perioperative period confers significant cardiopulmonary risk. However, many otolaryngologists defer restarting positive airway pressure (PAP) therapy following functional endoscopic sinus surgery (FESS) due to perceived risk of epistaxis, mucosal injury, and wound healing. Thus, the objective of this study was to evaluate the immediate resumption of PAP therapy in OSA patients undergoing FESS. Study Design Multicenter prospective controlled study. Setting Academic medical centers. Methods Patients with a history of OSA on PAP therapy scheduled for FESS were prospectively enrolled (OSA/PAP group) along with a control group of non‐OSA FESS patients (non‐OSA group). Patients in the OSA/PAP group restarted PAP therapy on post‐operative Day #0 or #1. The primary outcome was change in Lund‐Kennedy endoscopic scores (LKES); secondary outcomes of interest included change in post‐operative SNOT‐22 scores, Pittsburgh Sleep Quality Index (PSQI) scores, complications, and epistaxis severity scores. Results A total of 100 patients were enrolled, of whom 49 were in the OSA/PAP group, and 51 were in the non‐OSA group. In multivariate adjusted models, early PAP resumption was not independently associated with higher LKES compared to the control group at POV1 or POV2, higher SNOT‐22 compared to the control group at POV1 or POV2, or higher postoperative epistaxis scores compared to the control group. There were no PAP‐related complications such as orbital emphysema or pneumocephalus. Conclusion Early resumption of PAP in OSA patients undergoing FESS does not appear to be associated with worsened post‐operative endoscopic scores, quality‐of‐life scores, or an increased risk of post‐operative epistaxis.

C9orf72 encodes a protein that is important for both typical neurodevelopment and homeostatic processes across the lifespan. Pathogenic C9orf72 repeat expansions constitute the most common genetic cause of frontotemporal lobar degeneration (FTLD). Collectively, preclinical models and clinical neuroimaging studies have observed smaller thalamic volumes in C9orf72-associated FTLD, including in asymptomatic young adult C9orf72 repeat expansion carriers across 18 to 30 years old, supportive of potential neurodevelopmental origins. However, it is unknown whether asymptomatic young adult C9orf72 expansion carriers demonstrate volume differences in specific thalamic nuclei, as reported in older asymptomatic carriers and symptomatic patients; if so, normative transcriptomic patterns could reveal relevant neurodevelopmental and/or FTLD-related neurodegenerative processes. This study investigated volumetric MRI differences of the thalamic nuclei in asymptomatic young adult C9orf72 expansion carriers compared to non-carriers, and examined spatial associations with normative thalamic transcriptomics from 8 weeks post-conception through middle age. Young adult C9orf72 expansion carriers (n=72) and non-carriers (n=48) were enrolled in the Frontotemporal Dementia Prevention Initiative across Europe, Canada, and the USA (ages: 18-30 years; sex: 57% female). Spatial associations between young adult thalamic nuclei volumes and normative transcriptomics from the Allen Human Brain Atlas were examined using complementary data-driven and hypothesis-driven approaches. Spatial expression patterns of transcripts of interest were characterized across prenatal and postnatal neurodevelopment using BrainSpan data. Smaller volumes of the pulvinar, mediodorsal, and lateral nuclei were observed in young adult C9orf72 expansion carriers compared to non-carriers. These nuclei showed higher normative expression of transcripts involved concurrently in neurodevelopmental and C9orf72-associated FTLD neurodegenerative processes (including lysosomal, autophagic, and small GTPase functions), and lower normative expression of CALB1, a marker of prenatal human thalamic development. Normative expression of CALB2 (another human thalamic development marker) yielded positive correlations with C9orf72 across prenatal development to adulthood. These findings identify candidate transcripts that may provide insight into the molecular architecture leading to smaller thalamic nuclei volumes in C9orf72-associated FTLD.

Background Caregiver burden assessments lack clinical uniformity in palliative care. Existing evidence-based interventions often impose resource demands that are prohibitive for smaller programs. Objectives (1) Demonstrate the practical utility of routine caregiver screening paired with an interdisciplinary team (IDT) response protocol. (2) Identify patient and caregiver factors influencing burden. Design Setting: Cross-sectional study in a US outpatient palliative care clinic. Measure ments: The 12-item Zarit Burden Interview (ZBI-12) was administered by a nurse or social worker. Scores guided immediate, point-of-care IDT interventions. Results Of 81 approached caregivers, 74 completed the ZBI-12 (72% female; median age 56). Burden was stratified into mild (n = 37), mild-moderate (n = 22), and high (n = 15) tiers, with median scores increasing significantly (6 vs 16 vs 28; P < 0.001). General counseling was consistent across tiers (∼54%). However, high-intensity supportive interventions rose significantly with burden severity: social work telephone follow-ups increased (0% vs 13.6% vs 33.3%; P < 0.001), support group referrals rose (2.7% vs 31.8% vs 46.7%; P < 0.001), and psychotherapy referrals increased (0% vs 4.5% vs 13.3%; P = 0.030). Multivariable linear regression showed lower patient Palliative Performance Scale (PPS) scores independently predicted higher caregiver burden. Each 10-point decrease in PPS correlated with a 2.4-point increase in total ZBI-12 score (β = −0.240; 95% CI, −0.433 to −0.048; P = 0.015). Conclusion This workflow provides a replicable roadmap to transition caregivers from “invisible patients” to actively supported extensions of the care unit, reinforcing dyadic assessments as standard practice in outpatient palliative medicine.

Introduction There is uncertainty about the number of shark bites on humans in Florida (FL). Methods The International Shark Attack File (ISAF) and Global Shark Attack File (GSAF) databases (2016–2024) were compared with the non-inpatient FL Ambulatory and Emergency Department Patient Data database (AHCA) (2018–2023) and the National Emergency Medical Services (EMS) Information System (NEMSIS) (2016–2024). Results Between 2016–2024 there were 244 FL shark encounters reported in ISAF (mean 27.1 per year), 214 in GSAF (mean 23.8 per year), and 293 in a merged ISAF and GSAF (mean 32.6 per year). Between 2020–2023, there were 373 FL shark encounters reported in AHCA (mean 62.2 per year) compared with 114 encounters reported in NEMSIS (mean 22.8 per year) for 2020–2024. The rate ratio for AHCA FL shark encounters compared to the merged ISAF and GSAF was 1.91 (95% CI 1.64–2.23); p < .001. The percentage of shark encounters in Volusia County, FL, compared with all of FL shark encounters showed no significant differences between the ISAF and GSAF (40.2% and 33.6%, respectively) ( p = .16) and between the AHCA and NEMSIS (7.2% and 7.5%, respectively) ( p = 1.0). However, when comparing either ISAF or GSAF with either AHCA or NEMSIS, there were significant differences ( p < .001 for all). Discussion The AHCA dataset identified about twice as many shark bites as either the ISAF or GSAF. Many FL shark encounters did not require EMS or admission to the hospital. The discrepancy in the number of shark encounters attributed to Volusia County, FL, varied based on the dataset being examined.

Abstract Objective In 2024, the US News and World Report (USNWR)'s Best Hospitals began reporting complications following elective outpatient otolaryngology procedures in its ears, nose, and throat (ENT) ranking. However, this methodology has not been clinically adjudicated in a peer‐reviewed domain. We aimed to conduct manual health record adjudication to assess whether the USNWR methodology accurately attributes complications following elective outpatient otolaryngology procedures. Study Design Case‐cohort. Setting A case‐cohort of n = 80 elective, outpatient otolaryngology procedure/complication pairings from January 2019 to October 2023 across four academic medical centers using the 2024 USNWR otolaryngology procedure subgroups and Solventum Ambulatory Potentially Preventable Complications (AM‐PPC) software. Methods We used the AM‐PPC‐defined complication types as our standard of comparison for our clinical adjudication. Using the electronic health record, we adjudicated: (1) Was there agreement (yes/no) on complication type between our clinical adjudication and the Solventum AM‐PPC software? (2) Was the complication clinically related to, or a sequela of, the index otolaryngology procedure (yes/no)? Results The clinical adjudication agreed on complication type in 59/80 (74%) of patients, and 63/80 (79%) were judged to be clinically related to the index otolaryngology procedure. In total, 50/80 (63%) complications were adjudicated to be in agreement on both the complication type and clinical relatedness to the index procedure, while 9/80 (11%) complications did not agree with the complication type nor were clinically related to the index procedure. Conclusion Outpatient complications reported in the USNWR ENT rating lack the specificity to exclude patients whose complications are sequelae of chronic underlying conditions or related to concurrent, non‐otolaryngology procedures.

ABSTRACT Objective Pituitary carcinoma (PC) is defined by the presence of metastasis from a pituitary tumour. PC is rare, therefore information regarding survival and factors influencing survival are limited. We sought to assess overall survival following the diagnosis of PC and to determine factors associated with outcome. Design Retrospective case series. Patients Patients with PC who attended the Mayo clinic between 1997 and 2025. Measurements Information regarding patient demographics, tumour characteristics, management and outcomes were extracted. Results In total 25 patients (11 women, 44%) were diagnosed with PC (median age 56 years, range, 44–78). The most common cell type was a corticotroph tumour ( n = 15, 60%). All but one patient had pituitary directed surgery and all received pituitary adenoma (PA) directed radiation therapy. Metastases were identified a median 6 years (range, 1–32) after initial PA diagnosis. At last follow‐up, 10 (40%) patients were alive, 12 (48%) died of PC, and 3 (12%) died from other causes. The median survival time of patients from PC diagnosis was 3 years. The 1‐, 5‐ and 10‐year survival rates were 59%, 37% and 15%, respectively. Increased survival probability was associated with temozolomide treatment ( n = 9) at some point in treatment plan ( p = 0.026), the use of systemic therapy vs locoregional treatment ( p = 0.045), female sex ( p = 0.011), and in nonfunctional tumours ( p = 0.023). Conclusion PC carries a poor prognosis, with a median survival of only 3 years. Improved survival was associated with temozolomide exposure, female sex, and nonfunctional tumour subtype and underscores the prognostic relevance of tumour biology and treatment approach.

Abstract Cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) can yield density maps whose molecular identities are unknown. Predicted-structure databases enable proteome-scale searches, but distinguishing the correct candidates remains challenging, particularly for intermediate-resolution maps without clear side-chain features. We developed CryoAssign, an automated framework that combines large-scale structure matching with learning-to-rank prioritization. CryoAssign searches intact density maps without prior segmentation and integrates complementary measures of map–model agreement. On held-out benchmark maps, CryoAssign robustly prioritized the correct candidates. It also identified proteins or narrowed the set of candidates in previously unassigned cryo-EM maps and recovered multiple components from complex cryo-EM and cryo-ET maps. Controlled low-pass filtering showed generally robust recovery across a broad range of intermediate resolutions. CryoAssign provides a scalable approach for identifying proteins from cryo-EM and cryo-ET density maps.

ABSTRACT Periprosthetic joint infection (PJI) is a devastating complication of total joint arthroplasty that can be challenging to diagnose and treat. Neutrophils are a prominent feature in PJI, with neutrophil extracellular traps (NETs) known to be present; little is known, however, about the physiology of PJI-associated NETs. Here, the proteomes of PJI and non-infectious arthroplasty failure (NIAF), analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS) and proximity extension assay (PEA)-based profiling of fluids derived from sonication of arthroplasty components removed from patients who had undergone revision arthroplasty, were compared, with a focus on NET formation. In addition, in vitro effects of synovial fluid components on Staphylococcus aureus- induced NET formation were characterized. LC-MS/MS (PJI n = 85, NIAF n = 26) and PEA (PJI n = 95, NIAF n = 39) showed NET formation and neutrophil degranulation to be associated with PJI, with the complement cascade and platelet activation pathways identified as potential contributors. In vitro studies showed delayed NET formation in artificial synovial fluid compared to standard cell culture media conventionally used to evaluate NETs. Together, these results demonstrate the presence of NETs in PJI, identify potential pathways involved in PJI-associated NETosis, and point to an influence of synovial components on NET formation during PJI. IMPORTANCE Periprosthetic joint infection (PJI) is a major complication of joint replacement, placing a significant burden on patients and the healthcare system. Our research reveals that neutrophils and their antimicrobial “traps” are dominant features of the immune response at the infection joint site. Importantly, we found that the unique environment of the joint delays the formation of these traps, potentially contributing to the pathogenesis of PJI. By establishing a new experimental platform tailored for the infected joint, this work provides a foundational platform for probing these mechanisms and supports the development of improved diagnostic and therapeutic strategies.

Purpose: This study examined whether phoneme-level posterior probabilities generated by an articulatory-informed deep learning model (Phonet) can serve as interpretable and sensitive markers of articulatory impairment in motor speech disorders (MSDs). The goal was to determine whether these features distinguish individuals with and without MSDs and reflect varying severity levels of articulatory impairment. Method: A total of 676 participants (199 with MSDs, 477 without MSDs) completed a remotely captured word repetition task. Speech recordings were phonetically aligned, and posterior probabilities were extracted using a retrained version of the Phonet model, which estimates frame-level probabilities for 23 phonological classes. Segment-level posterior values were computed and compared across groups and severity levels using linear mixed-effects regression models. Results: Posterior probabilities were significantly reduced in the MSD group across all phoneme types. Within the MSD group, posterior probabilities decreased progressively with greater clinical severity, as measured by both perceptual sound distortion ratings and a cumulative articulation error score. Segment-specific analyses revealed systematic differences across phoneme classes, indicating that posterior probabilities capture distinct patterns of articulatory degradation associated with motor speech impairment. Conclusions: Phoneme-level posterior probabilities serve as interpretable, segment-specific indicators of articulatory impairment in MSDs. These features differentiate clinical status and reflect gradations of severity, making them promising tools for augmenting traditional perceptual speech assessments. Their linguistic transparency and scalability support future clinical applications in diagnosis, monitoring, and targeted intervention.