Citations

In 2007, the Bárány Society embarked on a project to establish definitions of vestibular syndromes and disorders based on best available evidence, referred to as the International Classification of Vestibular Disorders (ICVD). Since then, numerous publications providing consensus-driven diagnostic criteria for vestibular symptoms, syndromes, and disorders have been published. Here, we reflect on the rationale for developing the ICVD as well as its subsequent achievements, challenges, and outlook. In this summary of the work of the ICVD to date, the authors will focus on practical aspects to help improve the utility and applicability of these diagnostic criteria moving forward.

Abstract Background: Understanding the spatiotemporal dynamics of the tumor microenvironment (TME) during treatment is crucial for improving outcomes in pancreatic ductal adenocarcinoma (PDAC). This study presents a pre-planned spatiotemporal analysis from a phase II trial evaluating neoadjuvant mFOLFIRINOX in resectable PDAC, aimed at elucidating treatment resistance mechanisms and identifying predictive biomarkers. Methods: This multi-institutional, single-arm phase II trial enrolled treatment-naïve patients with histologically confirmed resectable PDAC (NCT05066802) who underwent six cycles of neoadjuvant mFOLFIRINOX followed by surgery. The primary endpoint was the R0 resection rate. Matched pre-treatment tumor biopsies and post-treatment surgical specimens were analyzed from selected responders (R) and non-responders (NR) using high-resolution spatial transcriptomics (10X Genomics Visium). This approach enabled comprehensive mapping of TME evolution and treatment-induced changes. Results: Between May 2020 and February 2022, 27 patients were enrolled. Of these, 24 patients underwent surgery after neoadjuvant treatment (resection rate: 88.9%), and 23 achieved R0 resection (85.2%), meeting the primary endpoint. However, 20 resected patients (83.3%) recurred. Spatiotemporal analysis was performed on matched samples from four R and four NR. In pre-treatment samples from NR group, clusters dominated by fibroblasts (enriched for ECM, EMT, and CAF phenotypes) and B cell subtypes were distinct compared to R group, which exhibited elevated antibody responses and robust T cell and macrophage activity. NR samples showed increased IgM expression but lacked corresponding Fc receptors, suggesting limited immune effector function. Post-treatment NR surgical specimens displayed elevated expression of MUC5AC and CEACAM6 in malignant ductal cells, alongside genes promoting tumor growth. Neoadjuvant mFOLFIRINOX increased fibroblast, while reducing immune cell components. NR tumors formed distinct "resistance niches" after chemotherapy, marked by ECM production, CAF activation, and RTK signaling. Conversely, R tumors showed enhanced epithelial organization with increased type-I hemidesmosome complexes facilitating epithelial adhesion to the basement membrane. Conclusion: Three months of neoadjuvant mFOLFIRINOX was feasible and tolerable for resectable PDAC but associated with high recurrence rate, emphasizing the need for better patient selection. Spatiotemporal analysis revealed critical differences in TME dynamics according to treatment response, including the emergence of resistance niches and distinct pre-treatment spatial signatures. These findings support the integration of spatial biology into future pancreatic cancer trials to improve stratification and therapy. Citation Format: Choong-kun Lee, Changjin Hong, Ho Kyoung Hwang, Min Hwan Kim, Jean Rene Clemenceau, Seock-Jin Chung, Isabel Barnfather, Sumanth Reddy Nakkireddy, Jeong Hwan Park, Ji-Youn Sung, Minji Kim, Yooho Choi, Inyeop Jang, Sunho Park, Sung Hyun Kim, Chang Moo Kang, Hye Jin Choi, Tae Hyun Hwang. Spatiotemporal evolution of the tumor microenvironment predicts treatment response in phase II trial of neoadjuvant chemotherapy for resectable pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 771.

AbstractPrior case reports have suggested that treating thoracic outlet syndrome (TOS) may relieve intractable migraine headaches, but there has been no case series large enough to show when underlying TOS should be suspected as a contributor to migraine burden. This observational followed by questionnaire study was performed in an outpatient neurology practice to identify clinical features of patients with migraine in which TOS contributed to migraine burden. We report the clinical features of 50 consecutive patients (48 women, 2 men, age = 43.9+/12.7 years) who were treated for chronic migraine and TOS (20 migraine with aura, 28 migraine without aura, two hemiplegic migraines). Headaches had become chronic within 1 year of onset in 21 patients (42%) with characteristics as follows (percentages are based on known data): greater severity ipsilateral to TOS limb pain (38/50=76%), presence of limb swelling (32/48=67%), and worsened by recumbency (32/38=84%). Thirty‐two patients eventually needed surgery, which included percutaneous transluminal venoplasty, 1st rib removal, scalenectomy, pectoralis minor tenotomy, and/or vein patching. The mean improvement of headaches on the treated side was 72 ± 26.7%; 12 patients experienced complete resolution of headaches after treatment of TOS (follow‐up 7.2 ± 5.2 months). Questionnaire responders reported significant reductions in headache days (18.3 ± 8.6 to 11.1 ± 10.8 days/month, p < 0.0016), severity (7.8+/2.5 to 5.4 ± 2.9, p < 0.00079), and need for emergency care (3.6 ± 4.0 to 0.71 ± 1.3 visits/year, p < 0.0029). Chronic migraines can be important manifestations of TOS. Early transition to a chronic state, lateralized limb pain, and headaches worsened by recumbency are clues to the contribution of TOS pathology. Addressing the TOS contribution to migraine can significantly reduce migraine headache burden.

The CRISPR-Cas9 system has enabled researchers to precisely modify/edit the sequence of a genome. A typical editing experiment consists of two steps: (1) editing cultured cells; (2) cell cloning and selection of clones with and without intended edit, presumed to be isogenic. The application of CRISPR-Cas9 system may result in off-target edits, whereas cloning will reveal culture-acquired mutations. We analyzed the extent of the former and the latter by whole genome sequencing in three experiments involving separate genomic loci and conducted by three independent laboratories. In all experiments we hardly found any off-target edits, whereas detecting hundreds to thousands of single nucleotide mutations unique to each clone after relatively short culture of 10–20 passages. Notably, clones also differed in copy number alterations (CNAs) that were several kb to several mb in size and represented the largest source of genomic divergence among clones. We suggest that screening of clones for mutations and CNAs acquired in culture is a necessary step to allow correct interpretation of DNA editing experiments. Furthermore, since culture associated mutations are inevitable, we propose that experiments involving derivation of clonal lines should compare a mix of multiple unedited lines and a mix of multiple edited lines.

Objective: Investigate the performance of multiparametric MRI radiomic features, alone or combined with current standard-of-care methods, for pulmonary nodule classification. Assess the impact of segmentation variability on feature reproducibility and reliability. Methods: Radiomic features were extracted from 74 pulmonary nodules of 68 patients who underwent nodule resection or biopsy after MRI exam. The MRI features were compared with histopathology and conventional quantitative imaging values (maximum standardized uptake value [SUVmax] and mean Hounsfield unit [HU]) to determine whether MRI radiomic features can differentiate types of nodules and associate with SUVmax and HU using Wilcoxon rank sum test and linear regression. Diagnostic performance of features and four machine learning (ML) models were evaluated with area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CIs). Concordance correlation coefficient (CCC) assessed the segmentation variation impact on feature reproducibility and reliability. Results: Elevn diffusion-weighted features distinguished malignant from benign nodules (adjusted p < 0.05, AUC: 0.73–0.81). No features differentiated cancer types. Sixty-seven multiparametric features associated with mean CT HU and 14 correlated with SUVmax. All significant MRI features outperformed traditional imaging parameters (SUVmax, mean HU, apparent diffusion coefficient [ADC], T1, T2, dynamic contrast-enhanced imaging values) in distinguishing malignant from benign nodules with some achieving statistical significance (p < 0.05). Adding ADC and smoking history improved feature performance. Machine learning models demonstrated strong performance in nodule classification, with extreme gradient boosting (XGBoost) having the highest discrimination (AUC = 0.83, CI=[0.727, 0.932]). We found good to excellent inter- and intrareader feature reproducibility and reliability (CCC≥0.80). Conclusion: Eleven MRI radiomic features differentiated malignant from benign lung nodules, outperforming traditional quantitative methods. MRI radiomic ML models demonstrated good nodule classification performances with XGBoost superior to three others. There was good to excellent inter- and intrareader feature reproducibility and reliability. Advances in knowledge: Our study identified MRI radiomic features that successfully differentiated malignant from benign lung nodules and demonstrated high performance of our MR radiomic feature-based ML models for nodule classification. These new findings could help further establish thoracic MRI as a non-invasive and radiation-free alternative to standard practice for pulmonary nodule assessment.

Background: Although prophylactic antibiotics are considered the standard of care, data with regard to the comparative efficacy of specific antibiotics in the prevention of periprosthetic joint infection (PJI) have remained limited. This study evaluated whether perioperative antibiotic choice affects rates of PJI development in shoulder arthroplasty. Methods: From 2000 to 2019, all primary shoulder arthroplasty types (hemiarthroplasty, anatomic total shoulder arthroplasty, reverse shoulder arthroplasty) performed for elective and trauma indications with perioperative antibiotic data and a minimum follow-up of 2 years were identified from a single institution. Demographic characteristics, PJI risk factors, and PJI-free survivorship data were retrieved. Multivariable analyses were conducted to determine the association between the antibiotic administered and the development of PJI. Results: Of 7,713 shoulder arthroplasties, cefazolin was administered in 6,879 procedures (89.2%) and non-cefazolin antibiotics consisting of vancomycin (465 procedures [6.0%]), clindamycin (345 procedures [4.5%]), and alternative regimens (24 procedures [0.31%]) were administered in 834 procedures (10.8%). PJIs occurred in 101 shoulder arthroplasties (1.3%), with Cutibacterium acnes as the most common pathogen (44 procedures [43.6%]). PJI-free survivorship was greater in shoulder arthroplasties in which cefazolin was administered compared with those in which non-cefazolin antibiotics were administered, with 0.91% greater survival free of PJI at 1 month, 1.4% at 1 year, and 2.7% at 15 years (p < 0.001). Cefazolin administration, compared with non-cefazolin administration, was associated with a 69% reduction in all-cause PJI risk and a 78% reduction in C. acnes PJI risk (p < 0.001). A higher risk of PJI for both groups was observed with vancomycin; the hazard ratio [HR] was 2.32 (95% confidence interval [CI], 1.22 to 4.40; p = 0.010) for all-cause PJI and 2.94 (95% CI, 1.12 to 7.49; p = 0.028) for C. acnes PJI. A higher risk of PJI was also observed for both groups for clindamycin; the HR was 5.07 (95% CI, 2.83 to 9.05; p < 0.001) for all-cause PJI and 8.01 (95% CI, 3.63 to 17.42; p < 0.001) for C. acnes PJI. Conclusions: In primary shoulder arthroplasty, cefazolin administration was associated with a significantly lower rate of PJI compared with non-cefazolin alternatives, including both vancomycin and clindamycin. These risk discrepancies were observed across all infectious pathogens and may be considered even greater when C. acnes was the infecting bacterium. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Case: We present a case of a 71-year-old woman with history of left-sided shoulder arthritis who underwent standard total shoulder arthroplasty using a novel hybrid glenoid component. After 3 years, she sustained traumatic dissociation of the interface between the polyethylene face and central titanium post, a unique failure mechanism of the hybrid glenoid component. This was successfully corrected through conversation to reverse shoulder arthroplasty (RSA). Follow-up after 2 years demonstrated marked improvement in pain and function. Conclusion: Hybrid glenoid components present a unique failure mechanism as compared to traditional glenoid loosening and can be effectively corrected with RSA.

We present diagnostic criteria for mal de débarquement syndrome (MdDS) for inclusion into the International Classification of Vestibular Disorders. The criteria include the following: 1] Non-spinning vertigo characterized by an oscillatory perception (‘rocking,’ ‘bobbing,’ or ‘swaying’) present continuously or for most of the day; 2] Onset occurs within 48 hours after the end of exposure to passive motion, 3] Symptoms temporarily reduce with exposure to passive motion (e.g. driving), and 4] Symptoms persist for >48 hours. MdDS may be designated as “in evolution,” if symptoms are ongoing but the observation period has been less than 1 month; “transient,” if symptoms resolve at or before 1 month and the observation period extends at least to the resolution point; or “persistent” if symptoms last for more than 1 month. Individuals with MdDS may develop co-existing symptoms of spatial disorientation, visual motion intolerance, fatigue, and exacerbation of headaches or anxiety. Features that distinguish MdDS from vestibular migraine, motion sickness, and persistent postural perceptual dizziness (PPPD) are reviewed. Motion-moderated oscillatory vertigo can also occur without a motion trigger, typically following another vestibular disorder, a medical illness, heightened psychological stress, or metabolic disturbance. Terminology for this non-motion triggered presentation has been varied as it has features of both MdDS and PPPD. Further research is needed into its phenomenological and biological relationship to MdDS, PPPD, and other vestibular disorders.