Citations

Alcohol use disorder (AUD) is a preventable non-communicable disease that affects multiple organs and organ systems across all age groups, including the fetus and is a risk factor for developing certain cancers. Furthermore, alcohol intoxication can result in physical trauma to oneself and others, and is a contributing factor in road accidents. Early recognition of AUD is critical for improving diagnosis, management, and outcomes. Accurate diagnosis relies on comprehensive clinical evaluation and patient history. However, denial of AUD, inebriation, and lack of awareness of problems associated with AUD, can prevent early identification of the disease. AUD-associated organ damage manifests in several ways and can be recognized on imaging modalities including ultrasound, CT, and MRI. Detection of these imaging features is useful in raising suspicion of AUD or diagnosing chronic alcohol use. Radiologists should be aware of the manifestations of alcohol's effects across various organ systems and aid in the early detection and treatment of AUD. In this two-part review, the authors present a comprehensive image-based review illustrating the effects of AUD on different organ systems at various stages. This second part focuses on the imaging manifestations in the central nervous system, fetal health, cardiovascular system, and musculoskeletal system. Additionally, a brief overview of secondary imaging manifestations of alcohol use, associated with trauma and cancers, will be presented.

Objective: To explore the existing evidence on novel imaging modalities that may aid in prognostication of vestibular schwannoma (VS) clinical outcomes across various management approaches. Study design: Scoping review. Setting: Not applicable. Patients: Individuals diagnosed with VS. Interventions: Novel imaging techniques. Main outcome measures: Tumor growth and response to medical therapy. Results: A total of 18 articles were included in this review. Of these, 7 focused on pretreatment prognosis, 6 evaluated radiosurgery outcomes, 4 examined microsurgery outcomes, and 1 assessed response to bevacizumab. The imaging modalities investigated included radiomics (n = 10), positron emission tomography (PET; n = 2), dynamic contrast-enhanced MRI (DCE-MRI; n = 2), both PET and DCE-MRI (n = 1), magnetic resonance elastography (MRE; n = 1), contrast-enhanced CT (CE-CT; n = 1), and slip interface imaging (SII; n = 1). Radiomic studies yielded encouraging results in predicting tumor growth after wait-and-scan and radiosurgery, with reported accuracies ranging from 52% to 88%, sensitivities from 13% to 95%, specificities from 50% to 94%, and area under the curves from 0.65 to 0.99. PET studies identified several promising ligands associated with tumor growth during wait-and-scan, suggesting a potential role in prognostication. DCE-MRI also demonstrated associations with tumor growth and treatment response to bevacizumab. Studies on MRE, CE-CT, and SII identified novel imaging parameters associated with tumor stiffness and adhesion. Conclusions: Several emerging imaging modalities hold potential for improving clinical outcome prognostication in VS. Techniques such as radiomics, PET, and DCE-MRI have shown promising results; however, the supporting evidence is still limited and heterogeneous. Further research is necessary to validate and refine these approaches to enhance their clinical utility.

Abstract Patients at risk for progression from myeloid precursor states (idiopathic cytopenia of undetermined significance [ICUS] and clonal cytopenia of undetermined significance [CCUS]) to myelodysplastic syndrome (MDS) are not well defined. Epidemiologic risk factors, clonal changes for MDS development, and evolution from one MDS state to another were available in the MDS Natural History Study (NHS), a prospective cohort enrolled at diverse US sites. Extensive clinical data and biospecimens were collected at baseline and follow-up. A total of 1177 (56%) individuals with MDS or MDS-related precursor conditions (ICUS/idiopathic dysplasia of undetermined significance [IDUS], CCUS, and MDS/myeloproliferative neoplasm overlap) were enrolled and diagnosed in the MDS NHS. The median age was 74 years, with 89% aged ≥60 years, and most were male patients. Median follow-up time was 1.6 years and was similar among ICUS/IDUS, CCUS, and MDS. During follow-up period, 68% of participants terminated the study, 35% died, and 38% had disease progression. Using a refined clinical definition of progression, the greatest proportion of progression was observed among higher-risk-MDS (116 [73%]), followed by lower-risk-MDS (170 [52%]); fewer progression events were observed among participants with CCUS (65 [22%]) and ICUS/IDUS (46 [17%]). Predictors of progression are delineated, including female sex, higher quantity of mutations, the presence of TP53 mutation, and poor/very poor cytogenetic score. Based on these prospective data, guidelines for clinical management including monitoring and surveillance are outlined. The MDS NHS provides real-world data to illustrate how clinical and genotypic differences inform the classification, disease course, and approach to therapy, with informed monitoring guidelines for patients. This trial was registered at www.ClinicalTrials.gov as NCT02775383.

VEXAS (Vacuoles, E1 ubiquitin-activating enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a systemic disorder characterized by an overlap of hematologic and inflammatory features. Most patients require chronic use of moderate-to-high doses of glucocorticoids (GCs) to maintain disease control. Data on GC-sparing therapies is limited, and there have been no prospective pharmacotherapeutic trials in VEXAS syndrome published to date. Pacritinib, an oral inhibitor of IRAK1, JAK2, and ACVR1, has emerged as a promising therapeutic option for VEXAS syndrome. The PAXIS trial is the first prospective, randomized pharmacotherapeutic study conducted in this rare and severe disease. Utilizing a novel study design and disease-specific endpoints, the trial will evaluate the efficacy and safety of two dose levels of pacritinib compared with placebo in patients with VEXAS syndrome (NCT06782373, EUCTR: 2024-516347-41-00).

Objective: Cochlear implantation (CI) under local anesthesia facilitates intraoperative behavioral patient feedback to potentially improve acoustic hearing preservation and limit intracochlear trauma. Patient feedback during electrode insertion is potentially confounded by loudness adaptation, a perception of tone decrease despite stable presentation, or insufficient intensity discrimination, a failure to detect a change in hearing despite one actually occurring. Both loudness adaptation and intensity discrimination are critical factors for awake CI and have not been systematically studied in the CI candidate population. Patients: Adult candidates for CI. Interventions: Under routine audiometric testing conditions in a soundproof booth, a standard behavioral audiogram, audiogram obtained in recorded ambient operating room (OR) noise, loudness adaptation to sustained suprathreshold (+10 and +20 dB) pure tones at 500, 1000, 2000, and 4000 Hz in both quiet and in ambient OR noise, and intensity discrimination to sustained suprathreshold (+10 and +20 dB) pure tones at 500, 1000, 2000, and 4000 Hz were performed. Main outcome measures: Pure tone average (PTA) in quiet and in ambient OR noise, proportion of patients reporting loudness adaptation at different suprathreshold levels and frequencies, and reliability of intensity discrimination. Results: In total, 20 ears were included for study. The median PTA was similar between testing in quiet (68 dB, IQR: 63 to 73) and in ambient OR noise (68 dB, IQR: 62 to 73). Most participants (n = 11, 55%) reported loudness adaptation when testing at +10 dB suprathreshold intensity, with a decreased proportion (n = 8, 40%) demonstrating adaptation at the higher tone intensity (+20 dB suprathreshold). Loudness adaptation varied among frequencies, with a trend toward increasing adaptation at higher frequencies at both testing intensities. Participants demonstrated excellent intensity discrimination, detecting a 5 dB difference when testing at +10 dB both in quiet and with background OR noise in 82 of the 85 (96%) tests performed across the frequency range, although with lower intensity discrimination at +20 dB, particularly in background OR noise. Conclusions: For CI candidates, pure tone audiometric performance did not significantly differ in background OR noise, confirming the reliability of intraoperative audiometric testing. For optimal tone presentation, there is decreasing loudness adaptation with increased tone presentation (+20 dB suprathreshold) and in lower frequencies of tone presentation. Intensity discrimination was reliable at a 5 dB increment across a range of testing parameters.

Abstract Histones variant composition and post-translational modifications (PTMs) of core and linker histones jointly orchestrate chromatin architecture and tissue-specific gene regulation. However, capturing the full complexity of the “histone code” in native human tissues remains challenging. Here we present a human cardiac histone proteoform atlas—comprising intact histone variants with combinatorial PTMs—enabled by a streamlined top‑down proteomics workflow. In a single one‑dimensional reversed‑phase liquid chromatography (LC)-mass spectrometry (MS) run, we achieve baseline separation of all four core histone families (H2A, H2B, H3, and H4) together with the linker histone H1 directly from human myocardium. Notably, this intact-protein analysis preserves the connectivity of co-occurring PTMs to individual histone molecules to reveal the combinatorial histone code, enabling proteoform‑level quantification of histone‑variant composition and PTM stoichiometry at the chromatographic scale. Targeted MS/MS directly resolves co-occurring PTM combinations and distinguishes highly homologous histone isoforms. Using this approach, we assemble the first comprehensive cardiac histone proteoform atlas and uncover previously unobserved histone proteoforms. More broadly, this top-down proteomics workflow provides a robust framework for proteoform-resolved analysis of histone variants and PTMs in complex biological systems.

BACKGROUND AND OBJECTIVES: En bloc spondylectomies are essential for controlling malignant spinal tumors, but existing classification systems are often complex and impractical. This study introduces the Column, Line-of-Sight, Margins, Ring (CLiMR) framework, a novel system simplifying and standardizing en bloc spondylectomy planning and classification. METHODS: A retrospective review of patients who underwent single- or multistage en bloc spinal tumor resections was conducted at a single academic center (October 2019-December 2024). The CLiMR framework assigns scores to 4 components: Column (osteotomies/diskectomies for tumor release), Line-of-Sight (approach for circumferential access), Margin (adjacent structures sacrificed), and Ring (size of the vertebral ring window for safe delivery of neural tissue). Scores were applied using operative notes and imaging. RESULTS: Column scores ranged from 0.5 to 4.5. Of the patients included, 40.9% underwent sagittal split osteotomies, 22.7% radical diskectomies, 18.2% horizontal osteotomies, and the remaining 18.2% combinations of previous osteotomies . A posterior-only approach (Line-of-Sight score = 1) was used in 45.4% of cases, whereas 45.4% required a multistage approach (score = 2). Margin scores reflected increasing morbidity: 31.8% (n = 7) involving chest wall/pleura resection (grade 3), 40.9% (n = 9) requiring eloquent nerve sacrifice (grade 6), and 9.1% (n = 2) necessitating limb sacrifice (grade 7). The majority (86.4%, n = 19) of ring scores were grade 1, requiring laminectomies/facetectomies. The mean CLiMR score was 9.36 ± 2.43, with higher scores correlating with longer hospital stays (R = 0.64, P = .0012), longer case durations (R = 0.61, P = .0023), and increased blood loss (R = 0.40, P = .067). Patients with local recurrence, positive margins, or complications trended toward greater CLiMR scores. CONCLUSION: The CLiMR framework provides a novel, user-friendly method for planning and communicating en bloc spondylectomies. By addressing technical complexities and morbidity, CLiMR enables standardized assessment, facilitates surgical decision-making, and supports future research. This study demonstrates feasibility and lays the foundation for future validation studies.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate are intended to serve as a resource for health care providers to identify individuals who may benefit from cancer risk assessment and genetic counseling and testing; help guide decisions related to genetic testing; and facilitate a multidisciplinary approach in the comprehensive care of individuals at increased risk for hereditary breast, ovarian, pancreatic, and prostate cancer. The current guidelines focus primarily on assessment of pathogenic and likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants associated with increased risk of these cancers. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding screening for prostate cancer and pancreas cancer, as well as testing criteria for nonepithelial ovarian cancer.

Background: A critical component of conducting systematic reviews or meta-analyses is assessing the methodological quality and bias of included studies. Several methodological quality assessment tools have been developed; however, these tools may not be relevant to observational sports medicine research, which carries numerous unique nuances and biases. Purpose: To develop the Sport Publication Observational Research Tool (SPORT), which evaluates and scores the methodological quality of observational sports medicine research. Study Design: Consensus statement. Methods: SPORT was developed through a modified Delphi approach involving members from the Herodicus Society and The FORUM. All active members were invited to participate in the process aimed at building consensus on SPORT content and scoring. After finalizing SPORT, a power analysis led to the independent selection of 55 observational clinical sports medicine studies, which were scored twice by 4 reviewers of varying training levels. Interrater and intrarater reliability for SPORT was assessed using intraclass correlation coefficients (ICCs). The distribution and percentiles for total SPORT score across the 55 studies were calculated. SPORT was also compared with the methodological index for non-randomized studies (MINORS), a commonly utilized quality assessment tool. Results: A total of 51 members participated and achieved 100%, 100%, 98.0%, and 98.0% completion rates for rounds 1 through 4, respectively. The final SPORT included 19 subscores related to methodological quality and bias and achieved 94% consensus approval. Mean SPORT completion time was 6 minutes and 19 seconds per study, which varied significantly by reviewer training level. The subscore "peer review" demonstrated unacceptable reliability and was removed. The remaining 18 subscores exhibited ICC ranges of 0.599 to 0.955 for interrater reliability and 0.530 to 0.936 for intrarater reliability. Total SPORT score demonstrated excellent agreement, for interrater (ICC, 0.967) and intrarater reliability (ICC, 0.966). Median SPORT score across the 55 studies was 20.0 and skewed toward lower scores. There was a moderate significant correlation between SPORT and MINORS ( r [53] = 0.575; P < .001). Conclusion: An objective tool to assess the methodologic quality of observational sports medicine research (SPORT) was successfully developed through a modified Delphi approach with numerous content experts in the field. This tool may be useful in assessing the methodological quality of primary observational sports medicine studies included in systematic reviews and meta-analyses.

Abstract Diffuse hemispheric glioma, H3 G34‐mutant (DHG‐H3 G34) has been primarily molecularly characterized by methylation profiling and sequencing studies. We describe an integrated histomolecular evaluation including high‐resolution copy number profiling of a series of 60 DHG‐H3 G34 to further our understanding of the spectrum of genetic changes associated with this tumor type. Cases were clinically tested using an 187‐gene mutation and fusion targeted neuro‐oncology next‐generation sequencing panel ( n = 60) and Oncoscan chromosomal microarray ( n = 26) by a single laboratory (2018–2022). A subset of cases had immunohistochemical results for OLIG2 ( n = 42), p53 ( n = 48), and ATRX ( n = 46), and methylation array data ( n = 8). Median age at testing was 21 years (range, 12–50). No significant difference was noted in clinical, histopathological, and mutational profile between pediatric and adult patients. H3‐3A G34 mutations included G34R ( n = 56; 94%), G34V ( n = 3), and a non‐canonical G34E ( n = 1). Concurrent mutations most often involved TP53 ( n = 55; 92%), ATRX ( n = 50; 83%), and PDGFRA ( n = 34; 57%). A reportedly primary tumor was confirmed to be hypermutant and had a PMS2 mutation. A single case also showed an FGFR3::FAM184B fusion. All cases with available chromosomal microarray data had unbalanced genomes, which were often complex (14/26; 54%). The most frequent recurrent copy number abnormalities were losses involving 3q, 4q, 10q, 13q, and 18q, and 17p copy‐neutral loss of heterozygosity (cnLOH) encompassing TP53 . This copy number profile was reminiscent of that seen in Grade 4 IDH‐mutant astrocytomas. Collectively, a TP53 abnormality at copy number (12/26, all cnLOH), sequence (55/60) and protein expression (46/48) level was detected in all 60 cases. In conclusion, integrated high‐resolution copy number and histomolecular analysis expanded the spectrum of genetic changes associated with DHG‐H3 G34, including the presence of universal TP53 abnormalities with frequent cnLOH—a copy number abnormality that has been largely unrecognized—for this new 2021 World Health Organization central nervous system tumor type.