Citations

BACKGROUND Thyroid-stimulating hormone (TSH)–secreting pituitary adenomas (TSHomas) are rare lesions that result in secondary hyperthyroidism. MR elastography (MRE) is an emerging imaging modality capable of assessing the mechanical properties of tissues, offering valuable insights into tumor consistency for improved preoperative planning and resection. OBSERVATIONS A 16-year-old female diagnosed with a giant TSHoma underwent endoscopic transnasal transsphenoidal excision. The mechanical properties of TSHoma were assessed using preoperative MRE and in vitro nanoindentation on excised specimen. Collagen content was also evaluated. Based on its appearance on MRE, a neuroradiologist predicted the tumor would be soft, and it was found to be soft during the surgery. Interestingly, the in vitro shear storage and loss moduli closely match the in vivo findings. Additionally, the tumor tissue has up to 20% collagen content in intratumoral areas. LESSONS MRE is a reliable and clinically valuable tool for preoperative evaluation of tumor consistency in rare TSHomas. The strong concordance between MRE findings, intraoperative texture, and in vitro mechanical measurements underscores the potential of MRE to guide surgical planning, reduce operative complexity, and improve clinical outcomes, especially in uncommon and challenging cases. https://thejns.org/doi/10.3171/CASE25402

Purpose Mycobacterium avium complex lung disease (MAC-LD) represents the most common form of nontuberculous mycobacterial lung infection, particularly affecting women and older adults. Clinical management remains challenging, including prediction and differentiation between progressive and non-progressive disease. Overexpression of PD-1 pathways have been reported in progressive disease, and we hypothesize that PD-1 inhibition can restore antigen-specific immune responses detectable by FluoroSpot assay. Methods Peripheral blood mononuclear cells from 22 participants, including progressive and non-progressive MAC-LD patients, healthy controls, and individuals with latent tuberculosis infection (LTBI) were stimulated with nontuberculous mycobacteria and Mycobacterium tuberculosis antigens. Cytokine secretion of interferon-gamma (IFN-γ) and interleukin-2 (IL-2) were quantified using dual FluoroSpot assay, with and without PD-1 blockade. Results Progressive MAC-LD cases demonstrated significant increases in glycopeptidolipid (GPL)- and PPD-stimulated IFN-γ responses following PD-1 blockade, which was not seen in healthy controls, LTBI, or non-progressive MAC-LD patients. After GPL stimulation and in the presence of anti-PD-1, the number of IFN-γ responses increased from 25% to 75% in samples from progressive MAC-LD patients. This supports an association between PD-1–mediated T-cell dysfunction and disease progression. Mycobacterial MTB300 peptide pool antigen failed to discriminate MAC-LD from healthy controls, underscoring antigen specificity. Conclusions Our pilot study demonstrates that IFN-γ FluoroSpot assays, particularly when combining GPL or PPD stimulation and PD-1 inhibition, may help identify progressive MAC-LD. These findings also support other studies reporting that immune checkpoint dysregulation can be present in some patients with progressive and severe MAC-LD patients. Additional studies are warranted to determine its pathogenic role.

Background: Hypoplastic left heart syndrome (HLHS) is defined as “a spectrum of congenital cardiovascular malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch”. Without treatment, HLHS is usually lethal in the neonate. Many hypotheses have been advanced to explain the etiology of HLHS; however, no single theory appears to fully explain the phenotypic variability seen in HLHS. Furthermore, many of these theories offer no explanations regarding the precipitating events which lead to the development of HLHS. Objective: This review considers and critically evaluates the strengths and weaknesses of the leading theories proposed to explain the pathogenesis of HLHS—including hemodynamic disturbances, primary myocardial structural defects, valvar malformations, and genetic or epigenetic alterations that may provoke developmental and anatomic abnormalities. After presenting each model, we propose a novel, comprehensive, and data-driven framework which may assist researchers in developing models for the pathogenesis of the various subtypes of HLHS. Methods: Key findings from human fetal imaging, histopathology, genetic studies, and animal models were considered, as well as the hypothetical contribution of each in observed HLHS phenotypes. The rationales for these findings as causal factors initiating individual HLHS patterns, as well as how they might contribute to HLHS in general, were critically analyzed. Results: The flow theory is strongly supported by animal models and in utero interventions that demonstrate the impact of altered hemodynamics on cardiac morphogenesis. However, the flow theory fails to identify initial causes of disturbed flow or related histological features of HLHS like endocardial fibroelastosis. The myocardial and valve-first models suggest an important role in developmental defects, but do not necessarily have a strong experimental basis that provides explanations for how they mediate HLHS. Genetic studies in patients with HLHS have identified several candidate causal mutations. However, such genetic causes of HLHS exhibit incomplete phenotypic penetrance and clinical impact. A multifactorial framework attempts to integrate these diverse mechanisms and may provide the most coherent explanation that can accommodate the heterogeneity and variable presentation of HLHS. Such a framework may identify multiple forces that drive disease but does not provide useful pathways for future research about HLHS. Conclusions: No single hypothesis has fully explained how HLHS is initiated, progresses, and presents with the clinical conditions that are encountered by cardiac surgeons and cardiologists. The most current models suggest that the spectrum of HLHS reflects acomplex interaction between genetic susceptibility, flow-dependent cardiac remodeling, and environmental factors in utero. A multifactorial model integrates these diverse mechanisms and may provide the most coherent explanation for the various phenotypic variations in HLHS. Based on our analysis of the most current data and the strengths and weaknesses of the current theoretical frameworks, we propose a novel research strategy aimed at identifying specific cardiac progenitor cell populations whose dysregulation may represent a unifying explanation for the etiology of the various phenotypes of HLHS. Based on the arguments made throughout this manuscript that evaluate the various genetic, structural, and hemodynamic models of initiation of disease, we believe that the significant phenotypic variability across the spectrum of HLHS (i.e., the different anatomic subtypes for “classic” HLHS) most likely reflects different underlying etiologies and mechanisms. At the very least, it is very likely that the timing of the insult is critical in determining anatomic subtype. Based on the published data and the arguments within this manuscript, it seems naive to think that there is a single unifying mechanism explain all forms of HLHLS.

Postoperative surgical draining fluid (SDF) in oral squamous cell carcinoma (OSCC) was reported to contain circulating free DNA and extracellular vesicles (EVs). The potential role of SDF DNA as a cancer biomarker in OSCC patients is investigated. To determine whether EVs contribute to the DNA content of SDF, small EVs (sEVs) were isolated by size exclusion chromatography and compared with those in paired plasma. sEV obtained from a cohort of HPV(+) and HPV(−) patients were evaluated for the endocytic origin, size, vesicular morphology, and the DNA content. The sEV from HPV(+) and HPV(−) SDF were similar. The sEVs from SDF were larger and contained more DNA than the sEV from plasma. Treatments of sEV with the DNase/RNase cocktail established the presence of DNA on the surface and in the sEV lumen. Furthermore, 20 to 30% of the total SDF DNA was associated with sEV. Fragmentomic analyses identified the largest DNA (>10,000 bp) on the vesicle surface. The DNA in the vesicle lumen consisted of smaller (~5000 bp) DNA fragments. Electron microscopy of the enzyme-treated vesicles indicated that surface DNA/RNA may be involved in maintaining vesicular integrity and modulating the vesicle entry into cells. The sEV-carrying surface and luminal DNA emerge as significant contributors to the total SDF DNA and, following validation, might serve as useful biomarkers of disease presence/progression in OSCC.

ABSTRACT Background In chronic liver disease, fat and fibroinflammatory changes often coexist. However, their biomarkers, proton density fat fraction (PDFF) and T 1 , are typically assessed separately. Their reproducibility under mutual confounding remains unclear. Purpose To assess multicenter, multi‐vendor reproducibility of confounder‐corrected chemical shift‐encoded (CSE)‐MRI‐based PDFF mapping and MOLLI‐based T 1 mapping using a combined PDFF‐T 1 phantom. Study Type Prospective phantom study. Phantom Commercial PDFF‐T 1 Phantom (Model 725) with varying PDFF (0%–30%) and T 1 (200–1400 ms) values. Field Strength/Sequence 1.5 T and 3 T multi‐echo, three‐dimensional spoiled‐gradient‐echo (SGRE) sequence for PDFF mapping, and MOLLI sequence (5(3)3 acquisition scheme) using two‐dimensional SGRE readouts for T 1 mapping across four centers and vendors. Assessment PDFF and T 1 maps were acquired using standardized protocols. PDFF maps were reconstructed locally, while T 1 maps were generated using a centralized algorithm. All maps were quantitatively analyzed by a single radiologist using standardized region‐of‐interest placement. Phantom temporal stability was assessed at one center across five sessions over 9 months (baseline, retest, 1 week, 6 and 9 months). Statistical Tests Intraclass correlation coefficients (ICC), reproducibility coefficients (RDC), and linear regression analysis were used. A p value < 0.05 was considered statistically significant. Results PDFF showed overall excellent reproducibility (ICC = 0.987, RDC = 3.7%), with increased variability at higher T 1 values (RDC up to 7.9% at T 1 = 1400 ms). T 1 mapping showed good reproducibility in the absence of fat (RDC 16–161 ms at PDFF = 0%), but moderate to poor reproducibility in the presence of fat, with RDC increasing up to 1553 ms at PDFF 30%. Temporal stability was excellent ICC ≥ 0.998 for both PDFF and T 1 , and RDC of 1.1%–1.3% for PDFF and 52–57 ms for T 1 . Data Conclusion This phantom study demonstrated high reproducibility of PDFF, whereas T 1 reproducibility deteriorated at higher fat and T 1 levels, underscoring the need for fat‐corrected T 1 mapping for reliable assessment of fibroinflammatory changes. Evidence Level N/A. Technical Efficacy Stage 1.

Abstract Background Human granulocytic anaplasmosis (HGA) can cause severe illness requiring intensive care, but factors associated with critical illness among hospitalized patients are incompletely described. Method We performed a retrospective multicenter cohort study of adults hospitalized with PCR-confirmed HGA at Mayo Clinic Rochester and affiliated Mayo Clinic Health System sites in Minnesota and Wisconsin from 2014 through 2024. Patients who required ICU-level care were compared with those managed on general medical wards using exploratory univariate analyses (Fisher exact and Kruskal–Wallis tests). Results Among 101 hospitalized patients, 12 (12%) required ICU-level care. Symptoms documented at hospital presentation/admission were more frequent in ICU patients, including vomiting (64% vs 30%) and abdominal pain (55% vs 26%). On admission, ICU patients had lower sodium (mean 128.8 vs 132.3 mmol/L) and higher total bilirubin (mean 1.3 vs 0.8 mg/dL). Platelet nadir during hospitalization was lower in ICU patients (mean 54.8 × 109/L vs 84.1 × 109/L). Peak ferritin, measured in a subset, was markedly higher in ICU patients (median 21 666 vs 961 µg/L). The composite endpoint of HGA-related complications or serious treatment-related adverse events occurred more often in ICU patients (75% vs 17%); one death occurred in the ICU group. Conclusions In hospitalized adults with HGA, ICU-level care was associated with gastrointestinal symptoms at presentation/admission, admission hyponatremia and hyperbilirubinemia, lower platelet nadir, and marked hyperferritinemia when measured. Because these findings were derived from univariate group-level comparisons with substantial overlap between groups, they should be viewed as hypothesis-generating rather than individually predictive or sufficient as stand-alone triage criteria.

Regenerative rehabilitation combines rehabilitation science with regenerative medicine approaches to achieve synergistic and more effective outcomes. Within the field of regenerative medicine, there has been a growing number of cell and gene therapies (CGTs) that are either approved for clinical use or actively undergoing clinical trials. Many of these therapies—especially those targeting neurological and musculoskeletal disorders—use functional outcomes as primary or secondary endpoints, prompting discussion about how physical medicine and rehabilitation (PM&R) physicians can support the integration of CGTs into clinical care. In this perspective article, we explain why physicians specializing in PM&R could take a leading role in advancing the clinical translation of CGTs. Currently, CGTs are not confined to a single medical specialty, presenting a timely opportunity for PM&R—working collaboratively with neurology, hematology, and other disciplines—to assume greater leadership and influence the development and implementation of these transformative treatments. To our knowledge, this is the first publication within PM&R literature to emphasize the importance of our specialty serving as a leader and driving force in the adoption of these therapies.

Abstract Background Vorasidenib is Food and Drug Administration‐approved for treatment of grade 2 isocitrate dehydrogenase (IDH)–mutant gliomas and has demonstrated a benefit in progression‐free survival compared to a placebo. This study assessed the cost‐effectiveness of this treatment strategy compared to standard treatment: observation or chemoradiation (CRT). Methods The authors used an integrated Markov model to compare quality‐adjusted life‐years (QALY) gained and cost‐effectiveness of patients with IDH‐mutated low‐grade glioma (LGG) treated with vorasidenib, observation, or CRT. Outcomes were expressed as incremental cost‐effectiveness ratios (ICERs) per QALY gained. Treatment is considered cost‐effective if it meets the commonly accepted willingness‐to‐pay threshold of $100,000 per QALY gained. Results Based on model parameters, vorasidenib demonstrated an ICER of $356,756 per QALY when compared to CRT. When compared to observation, vorasidenib demonstrated an improved ICER of $215,191 per QALY. On one‐way sensitivity analysis compared to observation, median cost of vorasidenib and median overall survival were most likely to affect ICER with only marginal changes on analysis of other model factors. For ICER to become ≤$100,000 compared to observation, the cost of vorasidenib would need to drop to below $14,072 monthly or have a median survival gain of at least 11.9 years. The probabilistic sensitivity analysis demonstrated that vorasidenib was favored in none of 5000 Monte Carlo iterations. Conclusion Using the best available data, the current price of vorasidenib does not meet commonly accepted cost‐effectiveness thresholds in treatment of IDH‐mutated LGGs.