Citations

AbstractObjectiveTo examine associations with changes in quality‐of‐life (QOL) outcomes following treatment of vestibular schwannoma (VS) using stereotactic radiosurgery (SRS).Study DesignProspective longitudinal study.SettingTertiary academic center.MethodsPatients who were treated for sporadic VS using SRS from 2015 to 2022 were included. QOL outcomes were measured using the disease‐specific Penn Acoustic Neuroma QOL (PANQOL) scale.ResultsSeventy‐nine patients with pre‐SRS and at least one post‐SRS PANQOL assessments were available for analysis. The mean change in total PANQOL scores was −2 (SD 13) on a 100‐point scale. The mean duration between assessments was 4.6 years (SD 2.0). Age at SRS, sex, and SRS treatment doses were not significantly associated with changes in total PANQOL scores. Total PANQOL scores improved a mean of 4 points for patients with tumors confined to the internal auditory canal but declined a mean of 5 points for patients with tumors extending into the cerebellopontine angle (P = .01); however, these changes did not exceed the minimum clinically significant threshold of 11 points. The correlation coefficient between treated tumor volume at SRS and change in total PANQOL scores was −0.30 (P = .007). Changes in PANQOL total (P = .5) and hearing domain (P = .3) scores for patients who maintained serviceable hearing or progressed to nonserviceable hearing did not significantly differ.ConclusionTumor extent and treated volume at SRS had a statistically significant but likely not clinically important impact on total PANQOL scores. Progression to nonserviceable hearing did not have a significant impact on PANQOL total or hearing domain scores.

AbstractPurposeThe small and complex space of the intranasal cavity poses a challenge to teaching and learning sinonasal anatomy in undergraduate medical education. Evidence suggests that utilizing 3D‐printed (3DP) models is an effective means to comprehend anatomical structures and their spatial relationships. In this study, we introduce and evaluate the educational value of rigid nasal endoscopy on realistic 3DP and silicone‐cast sinus models as a method to teach medical students intranasal anatomy.MethodsTwelve first‐year medical students participated in an educational rigid‐nasal endoscopy workshop led by Otolaryngology PGY‐2 residents and rhinology consultants. The workshop consisted of (1) an introductory PowerPoint on rigid nasal endoscopy and basic intranasal anatomy, (2) timed trials that tested students' ability to locate intranasal anatomical structures while scoping with a rigid endoscope, and (3) pre‐ and post‐surveys.ResultsParticipants improved in their ability to locate each intranasal anatomical structure during the timed trials. Participants felt that rigid endoscopy of 3DP models was an effective method to learn intranasal anatomy compared to their traditional medical school anatomy course.ConclusionThe results of this study suggest that rigid nasal endoscopy of 3DP sinus models is a potentially high‐value educational method for teaching intranasal anatomy to first‐year medical students. Students enjoyed the opportunity to learn intranasal anatomy while practicing a clinically relevant procedure ‐ rigid nasal endoscopy.

ImportanceSpecialized ophthalmology terminology limits comprehension for nonophthalmology clinicians and professionals, hindering interdisciplinary communication and patient care. The clinical implementation of large language models (LLMs) into practice has to date been relatively unexplored.ObjectiveTo evaluate LLM–generated plain language summaries (PLSs) integrated into standard ophthalmology notes (SONs) in improving diagnostic understanding, satisfaction, and clarity.Design, Setting, and ParticipantsRandomized quality improvement study conducted from February 1, 2024, to May 31, 2024, including data from inpatient and outpatient encounters in a single tertiary academic center. Participants were nonophthalmology clinicians and professionals and ophthalmologists. The single inclusion criterion was any encounter note generated by an ophthalmologist during the study dates. Exclusion criteria were (1) lack of established nonophthalmology clinicians and professionals for outpatient encounters and (2) procedure-only patient encounters.InterventionAddition of LLM-generated plain language summaries to ophthalmology notes.Main Outcomes and MeasuresThe primary outcome was survey responses from nonophthalmology clinicians and professionals assessing understanding, satisfaction, and clarity of ophthalmology notes. Secondary outcomes were survey responses from ophthalmologists evaluating PLS in terms of clinical workflow and accuracy, objective measures of semantic quality, and safety analysis.ResultsA total of 362 (85%) nonophthalmology clinicians and professionals (33.0% response rate) preferred the PLS to SON. Demographic data on age, race and ethnicity, and sex were not collected. Nonophthalmology clinicians and professionals reported enhanced diagnostic understanding (percentage point increase, 9.0; 95% CI, 0.3-18.2; P = .01), increased note detail satisfaction (percentage point increase, 21.5; 95% CI, 11.4-31.5; P < .001), and improved explanation clarity (percentage point increase, 23.0; 95% CI, 12.0-33.1; P < .001) for notes containing a PLS. The addition of a PLS was associated with reduced comprehension gaps between clinicians who were comfortable and uncomfortable with ophthalmology terminology (from 26.1% [95% CI, 13.7%-38.6%; P < .001] to 14.4% [95% CI, 4.3%-24.6%; P > .06]). PLS semantic analysis found high meaning preservation (bidirectional encoder representations from transformers score mean F1 score: 0.85) with greater readability than SONs (Flesch Reading Ease: 51.8 vs 43.6; Flesch-Kincaid Grade Level: 10.7 vs 11.9). Ophthalmologists (n = 489; 84% response rate) reported high PLS accuracy (90% [320 of 355] a great deal) with minimal review time burden (94.9% [464 of 489] ≤1 minute). PLS error rate on ophthalmologist review was 26% (126 of 489). A total of 83.9% (104 of 126) of errors were deemed low risk for harm and none had a risk of severe harm or death.Conclusions and RelevanceIn this study, use of LLM-generated PLSs was associated with enhanced comprehension and satisfaction among nonophthalmology clinicians and professionals, which might aid interdisciplinary communication. Careful implementation and safety monitoring are recommended for clinical integration given the persistence of errors despite physician review.

Abstract Chronically elevated circulating excess free fatty acids (ie, lipotoxicity) is a pathological process implicated in several metabolic disorders, including obesity-driven type 2 diabetes (T2D). Lipotoxicity exerts detrimental effects on pancreatic islet β-cells by reducing glucose-stimulated insulin secretion (GSIS), altering β-cell transcriptional identity, and promoting apoptosis. While β-cell-derived small extracellular vesicles (sEV) have been shown to contribute to β-cell failure in T2D, their specific role in lipotoxicity-mediated β-cell failure remains to be elucidated. In this work, we demonstrate that lipotoxicity enhances the release of sEVs from β-cells, which exhibit altered proteomic and lipidomic profiles. These palmitate (PAL)-exposed extracellular vesicles (EVs) induce β-cell dysfunction in healthy mouse and human islets and trigger significant islet transcriptional changes, including the upregulation of genes associated with the TGFβ/Smad3 pathway, as noted by RNA sequencing. Importantly, pharmacological inhibition of the TGFβI/II receptor improved PAL EV-induced β-cell dysfunction, underscoring their involvement in activating the TGFβ/Smad3 pathway during this process. We have comprehensively characterized lipotoxic β-cell sEVs and implicated their role in inducing β-cell functional failure in T2D. These findings highlight potential avenues for therapeutic interventions targeting sEV-mediated pathways to preserve β-cell health in metabolic disorders.

ABSTRACT Presented is a 76-year-old man with metastatic melanoma that was successfully treated with pembrolizumab, an immune checkpoint inhibitor (ICI). He underwent 20 months of ICI treatment without dose limiting side effects. Nearly 18 months after ICI discontinuation, the patient developed intermittent epigastric pain and diarrhea. Owing to mild symptoms, he was not immediately evaluated. Three years after ICI cessation, he was diagnosed with stricturing, jejunal Crohn's disease. He was treated with vedolizumab and displayed clinical and radiographic response to treatment. This case serves as an example of potential gastrointestinal-related, long-term autoimmune implications of ICI therapy, even in patients without acute side effects.

Purpose of review Liver transplantation for metastatic colorectal cancer has been shown to be efficacious in the well selected patient. In the United States, there remains controversy on the appropriate selection criteria and optimal graft type to be utilized in these patients. Our group advocates for strict recipient selection and early access to quality grafts for these recipients. Recent findings In the past two years, there has been an explosion of centers reporting outcomes after liver transplantation for colorectal liver metastases. In North America, the publications have focused on single center experiences. The group in Oslo has reported their long-term outcomes of all transplanted patients. The TransMet randomized controlled trial has demonstrated efficacy of liver transplantation with chemotherapy over chemotherapy alone. Summary Liver transplantation for metastatic colorectal cancer is an efficacious procedure for the well selected patient. Regardless of graft type, potential liver transplant recipients with liver limited unresectable colorectal liver metastases should be evaluated with a strict criterion to determine eligibility. Once eligible, patients should receive early access to high quality grafts.

To address the limitations of existing instruments, the authors developed the Vestibular Schwannoma Quality of Life (VSQOL) Index. The Index captures the multifaceted impacts of vestibular schwannoma (VS) on daily life across eight categories: hearing problems; dizziness and imbalance; pain, discomfort, and tinnitus; problems with face or eyes; impact on physical, emotional, and social well-being; difficulty with thinking and memory; satisfaction or regret; and impact on employment. Initially developed in English, this digital supplement of the Journal of Neurosurgery presents translations of the VSQOL Index to Simplified Chinese, Spanish, Japanese, Arabic, French, and Norwegian. These translations aim to improve access to VS quality of life (QOL) research globally with enhanced racial, ethnic, and geographic representation. The goal is to comprehensively evaluate the impact of VS diagnosis and management on well-being and QOL by offering the VSQOL Index in patients’ native, or first-learned, languages. The English version and these translations may be used for noncommercial research, clinical, or educational purposes without written permission from the authors. Investigators interested in translating the VSQOL Index to other languages should contact the corresponding author for translation methodology instructions.

ABSTRACT Symmorphosis is a concept of economy of biological design, whereby structural properties are matched to functional demands. According to symmorphosis, biological structures are never over designed to exceed functional demands. Based on this concept, the evolution of the diaphragm muscle (DIAm) in mammals is a tale of two structures, a membrane that separates and partitions the primitive coelomic cavity into separate abdominal and thoracic cavities and a muscle that serves as a pump to generate intra‐abdominal (P ab ) and intrathoracic (P th ) pressures. The DIAm partition evolved in reptiles from folds of the pleural and peritoneal membranes that was driven by the biological advantage of separating organs in the larger coelomic cavity into separate thoracic and abdominal cavities, especially with the evolution of aspiration breathing. The DIAm pump evolved from the advantage afforded by more effective generation of both a negative P th for ventilation of the lungs and a positive P ab for venous return of blood to the heart and expulsive behaviors such as airway clearance, defecation, micturition, and child birth. © 2019 American Physiological Society. Compr Physiol 9:715‐766, 2019.

Abstract The mammalian neuromuscular junction (NMJ) comprises a presynaptic terminal, a postsynaptic receptor region on the muscle fiber (endplate), and the perisynaptic (terminal) Schwann cell. As with any synapse, the purpose of the NMJ is to transmit signals from the nervous system to muscle fibers. This neural control of muscle fibers is organized as motor units, which display distinct structural and functional phenotypes including differences in pre‐ and postsynaptic elements of NMJs. Motor units vary considerably in the frequency of their activation (both motor neuron discharge rate and duration/duty cycle), force generation, and susceptibility to fatigue. For earlier and more frequently recruited motor units, the structure and function of the activated NMJs must have high fidelity to ensure consistent activation and continued contractile response to sustain vital motor behaviors (e.g., breathing and postural balance). Similarly, for higher force less frequent behaviors (e.g., coughing and jumping), the structure and function of recruited NMJs must ensure short‐term reliable activation but not activation sustained for a prolonged period in which fatigue may occur. The NMJ is highly plastic, changing structurally and functionally throughout the life span from embryonic development to old age. The NMJ also changes under pathological conditions including acute and chronic disease. Such neuroplasticity often varies across motor unit types. © 2022 American Physiological Society. Compr Physiol 12: 3731–3766, 2022.

Abstract Background: Resilience, quantified by the brief resilience scale (BRS), has been recognized for its role in pain and symptomatology in musculoskeletal conditions. The role of psychological factors in the clinical presentation and outcomes of FAI surgery continues to be poorly understood. Methods: This is a prospective multicenter study of FAI patients undergoing primary hip arthroscopy. PROMs were administered at baseline, 3-, and 6-months post-op and included the Patient Reported Outcomes Measurement Information System (PROMIS) domains of anxiety and depression, as well as Hip Disability and Osteoarthritis and Outcome Score (HOOS), modified Harris Hip Score (mHHS), and International Hip Outcome Tool (iHOT-12). Resilience was characterized by BRS score and divided into low (“L”, score<3), normal (“N”, score 3-4.3), and high resilience (“H”, score>4.3). Results: 675 patients were included with a mean age of 24.9±7.8 years and female predominance (56%). Mean BRS scores were 3.7±0.7 (1.5-5.0). 13.8% (n=93) had low resilience, 65.9% (n=445) had normal resilience, and 20.3% (n=137) had high resilience. Lower resilience had more severe symptoms in HOOS pain (p<0.001), HOOS sports (p=0.003), HOOS ADL (p<0.001), HOOS QoL (p<0.001), iHOT-12 (p=0.002), and mHHS (p<0.001). Anxiety (L: 50.5%/N: 14.4%/H: 2.2%) and depression (L: 38.7%/N: 8.8%/H: 2.9%) were higher in lower resilience groups (all p<0.001) and this trend stayed consistent in female and male sub-analyses with females having greater anxiety and depression symptoms. The follow-up cohort with 3- and 6-months follow-up was 487 patients and had similar baseline characteristics as the baseline cohort. Lower resilience had lower postoperative PROs (with similar change) (p<0.05). After treatment, rates of anxiety or depression decreased from 22.1% to 15.6% with the low resilience group having the highest change from 62.9% to 45.9%. Conclusion: Low resilience correlates with more severe symptoms and predicts anxiety/depression in FAI. 13.8% had low resilience while 20.3% had high resilience. Lower resilience had worse postoperative PROs. Particularly in patients with low resilience at presentation, rates of anxiety or depression symptoms decreased postoperatively. Further studies are needed to understand the role of resilience in longer-term outcomes of FAI and whether concurrent psychological treatment will help improve patient outcomes after hip arthroscopy for FAI.