Citations

BACKGROUND Perineural spread (PNS) of colorectal carcinoma (CRC) is a rare and challenging diagnosis. Its clinical and radiological presentation is often subtle and can overlap with radiation-induced neuropathy and malignant nerve tumors, complicating timely diagnosis. The role of circulating tumor DNA (ctDNA) in the detection of PNS has not been previously described. OBSERVATIONS A 48-year-old man with a history of rectal cancer and perineural invasion presented with progressive, refractory sciatic neuropathic pain. Conventional surveillance imaging was initially negative despite subtle rising of carcinoembryonic antigen and ctDNA levels. Subsequent MRI revealed abnormalities of the lumbosacral plexus and sciatic nerve, and fascicular biopsy confirmed metastatic CRC involving the sciatic nerve, establishing the diagnosis of PNS. LESSONS This case highlights PNS as a rare but important consideration in patients with focal neuropathic symptoms and prior CRC. Circulating tumor DNA positivity may serve as an early indicator of occult tumor activity even within the nerves when imaging is equivocal. However, currently histopathological confirmation remains the only definitive method to distinguish PNS from alternative diagnoses and is essential to guide appropriate management. https://thejns.org/doi/10.3171/CASE25997

Background: Although cochlear implant surgery, along with subsequent speech therapy, is the gold standard for rehabilitating children with severe to profound hearing loss, it is an expensive process. The motivation and involvement of caregivers play a crucial role in achieving successful outcomes following implantation. However, there is a lack of research in India examining the specific challenges faced by caregivers in this context. This pilot study was designed to explore and assess the burden experienced by caregivers of children who have undergone cochlear implantation. Materials and Methods: A pilot observational study was conducted at a tertiary hospital in South India, involving children with bilateral severe to profound hearing loss. The study included children who underwent cochlear implantation and subsequent auditory rehabilitation through the state comprehensive health insurance scheme. Caregivers were interviewed using a semi-structured questionnaire, and their responses were evaluated using the social burden scale and the caregiver burden scale. Results: Twenty cochlear implantees were included in the study. On the social burden scale, 26% of caregivers reported experiencing a severe overall burden, while 71% indicated a moderate burden. According to the caregiver burden scale, most caregivers experienced a mild-to-moderate burden in the emotional domain, whereas the physical, social, and financial domains were associated with low-to-mild levels of burden. Conclusions: Caregivers of cochlear implantees experience a significant degree of emotional and social burden. Therefore, enhancing both financial and psychological support for caregivers is essential. Such improvements will contribute to more effective and comprehensive hearing rehabilitation programs.

Management of locoregionally advanced human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV(+) OPSCC) can include induction chemotherapy followed by definitive chemoradiation. The standard induction regimen of cisplatin, docetaxel, and 5-fluorouracil (TPF) is associated with high toxicity. Given the chemosensitivity of HPV(+) OPSCC, platinum doublets are frequently used as induction therapy with potentially less toxicity. This retrospective study aimed to compare outcomes between treatment-naive HPV(+) OPSCC patients receiving induction TPF and those receiving an induction platinum doublet. Data collected included tumor characteristics, response after chemoradiation, hospitalization rates, and overall survival (OS). Fifty-five patients (18 TPF and 37 platinum doublet) were included. There was no significant difference in response after completion of definitive chemoradiation (TPF: CR 83.3%, PR 5.6%, progression or metastasis 11.1% vs. platinum doublet: CR 75.7%, PR 16.2%, progression or metastasis 8.1%; p = 0.5241). There were also no differences in hospitalizations for adverse events (38.9% in TPF vs. 40.5% in platinum doublet, p = 0.907) or recurrence (11.1% in TPF vs. 2.7% in platinum doublet, p = 0.198). The 5-year OS was 84.6% in the TPF group and 81.5% in the platinum doublet group (p = 0.581). Induction platinum doublet regimens offer comparable OS, response, and hospitalization rates to TPF in locally advanced HPV(+) OPSCC. Induction with a platinum doublet may be a viable de-escalation strategy for patients who are not candidates for TPF.

The dynamic field of radiopharmaceuticals is currently experiencing an explosion of growth due in part to excitement over the emerging field of theranostics (therapy and diagnostics). Radiopharmaceuticals use physiological targeting methods to deliver radionuclides with medically relevant decay properties to disease biomarkers for diagnosis and treatment, offering opportunities for early disease imaging and radiation therapy treatment in disease pathologies that are inoperable or refractory to other forms of radiotherapy. Sustaining this rapidly growing field depends heavily on the continued design and production of novel, effective radiopharmaceuticals. Effective therapeutic radiopharmaceuticals cause complex and varied cellular responses, and to choose radionuclides that maximize therapeutic response, researchers must understand radiation biology. Cellular radiation response depends heavily on factors including linear energy transfer (LET), dose, dose rate, targeted location, direct or indirect energy deposition mechanisms, the broader cellular matrix, cellular stress signaling pathways, and endogenous radiation protection mechanisms. Because of the extensive application of low-LET external beam radiation on clinical cancer treatments, biological responses to low-LET form the basis of radiation biology and are generally considered transferable to high-LET radiopharmaceuticals. However, increased focus on high-LET, radiopharmaceutical therapy-specific radiation biology is motivated by differences between low- and high-LET radiation, external beam versus radiopharmaceutical therapy-induced biological response, and the observed varied clinical responses to radiopharmaceutical therapies. This review article summarizes historical understanding of low- and high-LET radiation responses within cells, with emphasis on radiopharmaceutical-specific responses when available, and discusses current gaps in understanding in the radiation biology of radiotheranostic pharmaceuticals.

ABSTRACT Sodium glucose co‐transporter 2 inhibitors (SGLT2i) and glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are nephroprotective and their use is recommended for adults with chronic kidney disease (CKD). The role of SGLT2i and GLP‐1 RAs in patients with acute kidney injury (AKI) is unknown. This systematic review aimed to estimate the effect of SGLT2i or GLP‐1 RAs on clinical outcomes in AKI. We systematically searched Embase, MEDLINE, Scopus, Web of Science Core Collection, and clinical trials registries for observational studies and clinical trials from database inception to July 3, 2025. Included studies evaluated adults (≥ 18 years) with AKI during a hospitalization and compared patients subsequently exposed to either SGLT2i or GLP‐1 RAs to a non‐exposed control group. Random effects meta‐analyses were performed. Six studies related to SGLT2i (five observational, one randomized trial) and one related to GLP‐1 RAs (one observational) met eligibility criteria ( N = 432,048 patients). SGLT2i/GLP‐1 RA exposure was associated with lower odds of major adverse kidney events (MAKE) (OR 0.63, 95% CI 0.46–0.86) and all‐cause mortality [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.21–0.62] compared to controls. The odds for kidney replacement therapy were lower with SGLT2i therapy in the three studies where it was evaluated (OR 0.61, 95% CI 0.40–0.93). Sensitivity analyses restricted to SGLT2i data were consistent with the overall findings [MAKE OR 0.63 (95% CI 0.42–0.95); Mortality OR 0.34 (95% CI 0.18, 0.65)]. Exposure to SGLT2i or GLP‐1 RAs after AKI, examined primarily in observational studies, was associated with improved clinical outcomes. These findings are promising and warrant evaluation in randomized clinical trials.

ABSTRACT Sudden sensorineural hearing loss (SSNHL) is most often idiopathic or related to benign conditions such as Meniere's disease. However, SSNHL caused by vertebrobasilar ischemia is rare and may precede life‐threatening neurological deficits. We present the case of a 67‐year‐old male with hypertension and hyperlipidemia who developed acute vertigo, left‐sided hearing loss, dysarthria, right facial droop, and right‐sided weakness. Initial non‐contrast CT was unremarkable, but computed tomography angiography (CTA) revealed a near‐occlusive thrombus in the mid‐basilar artery. MRI showed an acute infarct in the left cerebellum within the anterior inferior cerebellar artery (AICA) distribution, which supplies the internal auditory artery. Subsequent audiometry confirmed bilateral SSNHL, more severe on the left. The patient was outside the thrombolysis window but underwent cerebral angiography, which confirmed chronic left vertebral occlusion and high‐grade basilar stenosis. He was started on dual antiplatelet therapy and high dose statin therapy and discharged to rehabilitation with residual vertigo and hearing loss. This case emphasizes that SSNHL and vertigo can be early signs of posterior circulation stroke. High‐grade basilar stenosis affecting AICA flow may compromise perfusion to the auditory and vestibular systems. Clinicians should maintain a high index of suspicion for vertebrobasilar ischemia in patients presenting with audiovestibular symptoms, even in the absence of classic stroke findings. Early imaging with MRI and CTA is critical for diagnosis. Recognizing these atypical presentations enables timely management and may reduce long‐term neurologic impairment.

Abstract Systemic light chain amyloidosis (AL) arises from monoclonal immunoglobulin light chains, but determinants of progression from precursor states remain poorly defined. In a cross-sectional cohort comprising 1950 systemic AL patients diagnosed 2010-2024, 258 (13.2%) patients with a previously diagnosed plasma cell disorder (PCD) were compared to patients with no prior PCD diagnosis. Patients with monoclonal gammopathy of undetermined signficance (MGUS) and smoldering multiple myeloma (SMM) in the former group had lower difference between involved and uninvolved FLCs (dFLC), higher M-protein, and lower rates of t(11;14) at AL diagnosis. Patients developing AL from SMM had a shorter time to AL (median 34.2 versus 61.3 months) and higher dFLC (median 28.9 versus 11.0 mg/dl) compared to those from MGUS. Patients developing AL after known multiple myeloma (MM) or lymphoplasmacytic lymphoma (LPL) commonly lacked deep hematologic response before AL (≤ very good partial response in 78% of MM, 100% of LPL patients). We additionally studied longitudinally followed cohorts of 3,966 MGUS and 426 (SMM) patients with longitudinal FLC measurements and matched follow-up, in which 1.8% of MGUS and 7.2% of SMM patients developed AL. Those patients who developed AL showed markedly higher dFLC at MGUS/SMM diagnosis and more frequent λ restriction and rates of t(11;14). Higher dFLC was associated with progressively earlier AL development; a 10% cumulative risk occurred at 20 months for patients with a dFLC >80 mg/dL but was not reached if dFLC <10 mg/dL at an estimated median follow-up of 86 months. In multivariable analysis, dFLC >6.4 mg/dL (HR 11.3) and λ isotype (HR 3.6) independently predicted AL, whereas heavy chain secretion was associated with lower risk (HR 0.2 for IgG). These findings indicate that AL risk is primarily driven by cumulative light chain exposure, refining our knowledge of AL pathophysiology and providing guidance for follow-up of patients with elevated dFLC.

Purpose To assess how comfortable patients with cancer are in responding to intimate questions on sexual orientation and gender identity (SOGI) and to examine whether question sequencing alters patient-reported comfort. Patients and Methods Patients with cancer were asked to respond to one of two surveys that were provided to patients in a randomized manner and that included seven identical SOGI questions but differed in sequence of responses (upfront vs later debated terms, e.g. “genderqueer”). Using a Likert scale (1 = very uncomfortable to 5 = very comfortable), patients rated comfort. The primary endpoint was the percentage of patients comfortable with the question, “Do you consider yourself to be… [12 response options, including genderqueer]”. Secondary endpoints included differences in comfort based on question sequence or demographics. Write-in comments were captured. Results 74% of patients (95% CI: 70%, 78%) were comfortable when reviewing the primary endpoint SOGI question. Similar comfort levels were reported for the other questions. No significant differences in comfort were observed based on question sequence or demographics. Four themes emerged from write in comments 1) emotional reactions to the questions (“uncomfortable because this question is essentially gender binary”) 2) emotional reactions toward SOGI (“bending over backwards to be politically correct”); 3) concern for privacy and relevance to cancer care (“not sure why this information is needed/necessary”); and 4) constructive remarks (“didn’t know what cisgender was - please define”). Conclusions Most patients with cancer are comfortable in answering SOGI questions. However, their comfort might be enhanced with slight question/response modifications.

Abstract Pulmonary fibrosis (PF) involves excessive collagen accumulation, yet mechanisms shifting the balance of synthesis and degradation toward net deposition remain unclear. Myeloperoxidase (MPO) inversely correlates with survival in PF. Using the bleomycin model, we found MPO knockout (MPOko) mice were protected from fibrosis, and pharmacological MPO inhibition after peak inflammation (day 7) recapitulated this protection. MPO persisted in lung tissue 21 days post-injury despite neutrophil efflux, linking acute inflammation to sustained remodeling. Mechanistically, we identified that MPO inhibits Cathepsin K (CatK), a potent collagenolytic enzyme involved in fibrosis resolution. Notably, CatK gene expression ( CTSK ) is elevated in PF, suggesting post-translational inhibition of CatK. MPOko and inhibitor-treated mice exhibited elevated CatK activity after bleomycin; exogenous addition of pathophysiologic concentrations of MPO reduced CatK activity in mouse precision-cut lung slices and human fibroblasts. Biochemically, MPO reduced CatK activity to 33% of control. In two distinct cohorts of PF patients, we observed significantly increased MPO protein levels in platelet poor plasma and in lung tissue. In PF patients, 62% had MPO levels in platelet poor plasma exceeding healthy controls, while lung tissue from other PF patients showed significantly elevated MPO staining. Plasma levels were inversely correlated with decreased survival, FVC, and DLCO. These findings establish MPO as a post-translational inhibitor of CatK-mediated collagenolysis, revealing a mechanism linking acute inflammation to sustained fibrosis and suggest a patient subpopulation that may benefit from MPO-targeted therapy. Graphical Abstract Myeloperoxidase persists in lung tissue after injury and inhibits cathepsin K activity, impairing collagen degradation and promoting extracellular matrix accumulation during pulmonary fibrosis.