Publications by Year: 2026

Imaging and intervention for spinal facetogenic pain has evolved continuously, with radiologists at the helm of several new advanced techniques including CT-guided interventions to ensure accurate needle placement, biologic therapies including platelet-rich plasma, and new noninvasive therapies such as MR-guided focused ultrasound. Though advances have been made in both imaging localization of painful facet joints and therapies offered, awareness of these techniques and the reimbursement landscape are varied. We hope to elucidate the current state of practice for both diagnosis and treatment of this common painful ailment, and highlight the ways that radiologists are at the forefront of advancement in these techniques.

BACKGROUND: Pan-fibroblast growth factor receptor (FGFR) inhibitors, targeting FGFR1-3 or FGFR1-4, are Food and Drug Administration-approved for FGFR2-driven cholangiocarcinoma. However, acquired resistance and dose-limiting toxicities from systemic FGFR inhibition constrain efficacy. Lirafugratinib (RLY-4008), a first-in-class FGFR2-selective inhibitor with activity against resistance-associated FGFR2 kinase domain mutations, shows promise in patients with FGFR2-altered solid tumors (ReFocus trial, NCT04526106). Defining acquired resistance mechanisms to selective FGFR2 targeting is essential for therapeutic development.

PATIENTS AND METHODS: Circulating tumor DNA (ctDNA) samples from 28 patients treated with lirafugratinib (16 FGFR inhibitor-naive, 12 FGFR inhibitor-refractory) were analyzed using targeted next-generation sequencing. Genomic alterations observed were compared with those reported in prior studies of pan-FGFR inhibitor resistance and validated in preclinical models.

RESULTS: Polyclonal FGFR2 kinase domain mutations and receptor tyrosine kinase-mitogen activated protein kinase (RTK-MAPK) bypass alterations emerged as common lirafugratinib resistance mechanisms in the FGFR inhibitor-naive context (8/16 and 9/16 patients, respectively). Resistance profiles differed markedly from pan-FGFR inhibitors, with decreased FGFR2 V565F/L and N550H/K mutations, increased M538I and L618F mutations, and more frequent RTK-MAPK bypass alterations. The variant allele fraction was typically higher for FGFR2 kinase domain mutations, consistent with these alterations serving as primary resistance drivers. Preclinical studies confirmed differential sensitivity of these FGFR2 mutations to lirafugratinib. Importantly, lirafugratinib demonstrated clinical efficacy in the FGFR inhibitor-refractory setting, with ctDNA dynamics showing resolution of multiple FGFR2 mutations and persistence or emergence of others.

CONCLUSIONS: Lirafugratinib retains activity against multiple mutations that confer clinical resistance to pan-FGFR inhibitors. However, diverse resistance mechanisms, including various kinase domain mutations and RTK-MAPK bypass alterations, remain challenges in the treatment of FGFR2-altered tumors, even with selective FGFR2 kinase inhibition.

The preclinical neuroscience course is widely regarded as one of the most conceptually challenging components of medical education and is often associated with the emergence of "neurophobia." Rather than continuing to focus solely on reducing fear, it is time to cultivate "neuro-curiosity" a mindset of inquiry, relevance, and connection. Grounded in self-determination theory, which emphasizes autonomy, competence, and relatedness as drivers of intrinsic motivation, this review outlines four core pillars for curriculum reform: clinical relevance, neuroanatomy through imaging, case-based learning, and digital engagement. Together, these strategies promote deeper learning, emotional engagement, and diagnostic reasoning. With neurologic disease burden rising and a projected shortage of neurologists, early, engaging exposure to neuroscience is critical to building a robust future workforce. The preclinical neuroscience course presents a unique opportunity not only to teach foundational knowledge, but also to inspire sustained interest in neurology from the very start of medical training.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used to treat obesity and metabolic diseases, yet their early impact on body composition and circulating regulators of muscle and bone remain unclear. This study aimed to assess early effects of liraglutide on total and regional body composition and associated changes in circulating markers of muscle and bone metabolism.

METHODS: Twenty adults with obesity received liraglutide 3.0 mg/day or placebo for 35 days in this crossover randomized controlled trial. In this secondary analysis, body composition was assessed by dual-energy X-ray absorptiometry at the end of each phase, while hormones were measured by ELISA at baseline and at each of 6 weekly visits over 5 weeks.

RESULTS: Liraglutide reduced body weight, BMI, and total and regional mass (trunk, hip, and extremities). Absolute fat-free mass was slightly but significantly lower. Absolute lean mass in the trunk and extremities decreased, whereas relative lean mass and fat-free mass percentages remained stable at treatment completion.

CONCLUSIONS: Short-term liraglutide treatment reduces total and regional mass without altering relative body composition. Further research is warranted to confirm and clarify the clinical significance of these changes, to further study hormonal changes and identify strategies to preserve muscle mass during weight loss.

The mammalian cerebral cortex comprises a complex neuronal network that maintains a precise balance between excitatory pyramidal neurons and inhibitory interneurons. Accumulating evidence indicates that specific interneuron subtypes form stereotyped microcircuits with distinct pyramidal neuron classes1-3. Here we show that pyramidal neurons have an active role in this process by promoting the survival and terminal differentiation of their associated interneuron subtypes. In the wild-type cortex, interneuron subtype abundance mirrors the prevalence of their pyramidal neuron partners. In Fezf2 mutants, which lack L5b pyramidal neurons and are expanded in L6 intratelencephalic neurons, corresponding subtype-specific shifts occur through two distinct mechanisms: somatostatin interneurons adjust their programmed cell death, whereas parvalbumin interneurons switch their subtype identity. Silencing neuronal activity or blocking vesicular release in L5b pyramidal neurons revealed that their communication with interneurons does not require voltage-gated synaptic activity but engages both tetanus toxin-sensitive and tetanus toxin-insensitive pathways. Moreover, a targeted bioinformatic screen for ligand-receptor pairs displaying subtype-specific expression and reduced expression of pyramidal neuron-derived ligand in Fezf2 mutants identified candidate secreted factors and adhesion molecules. These findings reveal distinct, pyramidal neuron-driven mechanisms for sculpting interneuron diversity and integrating them into local cortical circuits.

Evening residential illumination possesses the capacity to impair sleep quality via the suppression of endogenous melatonin production, a process largely driven by short-wavelength (blue) light. In this investigation, we characterized the light emissions from 52 distinct examples across three common lamp technologies: light-emitting diodes (LED), incandescent, and compact fluorescent (CFL) lamps. To estimate the differential circadian impact of these sources, we determined the Melatonin Suppression Value (MSV), melanopic illuminance, and photopic illuminance for each. Our findings reveal that "cool" white LED (median 12.3% MSV) and "cool" white CFL (12.1% MSV) lamps induce considerably greater melatonin suppression than "warm" white LED (3.6%), "warm" white CFL (2.6%), or traditional incandescent (1.5%) lamps. As potential countermeasures, we examined the efficacy of tunable Correlated Color Temperature (CCT) lamps and "blue-light-filtering" (BLF) lenses. The four tunable LED lamps demonstrated a profound ability to mitigate circadian disruption, reducing estimated melatonin suppression from 10% at a 5700 K (cool white) setting to 0.1% at 2100 K (warm white). An analysis of eight BLF lenses identified variable performance; while six had moderate impacts compared to uncorrected vision, their benefit was limited relative to standard clear lenses. Only two BLF lenses, distinguished by a "brown" tint, proved highly effective, reducing estimated suppression to below 0.3%. These results suggest that cool white CFL and LED lamps may exert a greater disruptive influence on sleep physiology than other lamp types. Conversely, tunable lamps adjusted to warm settings and "brown"-tinted BLF lenses represent beneficial strategies for ameliorating this effect. (Detailed measurement methodologies are available in a previously published study, with supplementary calculations provided separately).