Citations

Central nervous system (CNS) tumors are the leading cause of cancer-related mortality in children, with prognosis remaining dismal for some of these malignancies. Though the past two decades have seen advancements in surgery, radiation, and targeted therapy, major unresolved hurdles continue to undermine the therapeutic efficacy. These include challenges in suboptimal drug delivery through the blood–brain barrier (BBB), marked intra-tumoral molecular heterogeneity, and the elusive tumor microenvironment. Drug repurposing or re-tasking FDA-approved drugs with evidence of penetration into the CNS, using newer methods of intracranial drug delivery facilitating optimal drug exposure, has been an area of intense research. This could be a valuable tool, as most of these agents have already gone through the lengthy process of drug development and the evaluation of safety risks and the optimal pharmacokinetic profile. They can now be used and tested in clinics with an accelerated and different approach. Conclusions: The next-generation therapeutic strategy should prioritize repurposing oncologic and non-oncologic drugs that have been used for other indication, and have demonstrated robust preclinical activity against pediatric brain tumors. In combination with novel drug delivery techniques, these drugs could hold significant therapeutic promise in pediatric neurooncology.

ABSTRACT The clinical relevance of TP53 mutations ( TP53 MUT ) in myeloproliferative neoplasms (MPN) and their prognostic interaction with MPN subtype designation has not been systematically studied. In the current study, 114 patients with MPN harboring TP53 MUT (VAF ≥ 2%) were evaluated for overall survival (OS), calculated from the time of TP53 MUT detection: chronic phase myelofibrosis (MF‐CP; N = 61); blast‐phase (MPN‐BP; N = 31) or accelerated‐phase (MPN‐AP; N = 16) MPN, and polycythemia vera/essential thrombocythemia (PV/ET; N = 6). Sixty‐five (57%) patients harbored International Consensus Classification (ICC)‐defined multihit TP53 MUT and 56 (49%) monosomal/complex karyotype (MK/CK). Majority of MPN‐BP (90%) and MPN‐AP (81%) while 39% of MF‐CP and none of PV/ET patients harbored multihit TP53 MUT . OS in MPN‐BP and MPN‐AP was equally dismal (median 6 vs. 4.5 months, respectively; p = 1.0), regardless of multihit configuration ( p = 0.44), while OS in TP53 MUT MPN‐BP/AP ( N = 47; median 4 months) was inferior to that of a separate cohort ( N = 49) with TP53 wild‐type MPN‐BP/AP (median 11 months; p < 0.01). OS in MF‐CP was significantly shorter with multihit versus non‐multihit TP53 MUT (median 10 vs. 35 months; HR 2.9; p < 0.01), independent of other MF‐relevant genetic risk factors, including ASXL1/SRSF2/U2AF1 mutations. Multihit TP53 MUT was also associated with inferior survival following allogeneic stem cell transplant (ASCT): median 9 months versus “not reached” in patients with ( N = 9) versus without ( N = 8) multihit TP53 MUT ( p < 0.01). The presence of multihit or non‐multihit TP53 MUT in MPN‐BP/AP or multihit TP53 MUT in MF‐CP is associated with exceptionally poor prognosis and justifies inclusion into the ICC category of “myeloid neoplasms with mutated TP53 .” By contrast, detection of non‐multihit TP53 MUT , by itself, might not endanger short‐term survival in MF‐CP, PV, or ET.

ABSTRACTObjectiveTo assess how patient and caregiver factors influence caregiver readiness for hospital discharge in palliative care patients.Study Setting and DesignThis transitional care study uses cross‐sectional data from a randomized controlled trial conducted from 2018 to 2023 testing an intervention for caregivers of hospitalized adult patients with a serious or life‐limiting illness who received a palliative care consult prior to transitioning out of the hospital.Data Sources and Analytical SampleCaregiver readiness was measured with the Family Readiness for Hospital Discharge Scale (n = 231). Caregiver demographic, intra‐ and interpersonal factors were self‐reported. Patient demographic, comorbidity score, and risk score for complicated discharge planning were extracted from electronic health records. Stepwise regression models estimated variance explained (r2) in caregiver readiness for patient hospital discharge.Principal FindingsPatient demographics and complexity were not statistically associated with caregiver readiness for discharge. Caregiver depressive symptoms, poor caregiver‐patient relationship quality, and fewer hours spent caregiving prior to hospitalization explained 29% of the variance in caregiver readiness.ConclusionsReliance on patient data may not be sufficient for explaining caregiver readiness for discharge. Assessing caregiver factors may be a better alternative for identifying caregivers at risk for low discharge readiness and those in need of additional support.Trial Registration: ClinicalTrials.gov on November 13, 2017, (No. NCT03339271)

We present an interesting case of a 74‐year‐old female who presented with spinal accessory neuropathy following an ipsilateral right‐sided carotid endarterectomy 6 months after the initial injury. Subsequent surgical exploration revealed a surgical clip that had been placed directly across the spinal accessory nerve. Clip removal and neurolysis was subsequently performed, leaving the nerve intact. After surgical intervention, she immediately demonstrated increased bilateral shoulder shrug motion and continues to improve her function with physical therapy. This case demonstrates a fascinating case of cranial nerve recovery after delayed intervention in the context of existing literature. Laryngoscope, 135:2073–2075, 2025

Background. Early allograft dysfunction (EAD) affects outcomes in liver transplantation (LT). Existing risk models developed for deceased-donor LT depend on posttransplant factors and fall short in living-donor LT (LDLT), where pretransplant evaluations are crucial for preventing EAD and justifying the donor’s risks. Methods. This retrospective study analyzed data from 2944 adult patients who underwent LDLT at 17 centers between 2016 and 2020. We developed a logistic regression model to predict EAD based on this development cohort. We used data from 1020 patients at the King Faisal Transplant Center for external validation. Results. In the development cohort, 321 patients (10.9%) experienced EAD. These patients had poorer health status, more liver decompensation, and higher requirements of hospitalization than those without EAD. Multivariable logistic regression identified independent pretransplant predictors of EAD: laboratory Model for End-Stage Liver Disease score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.09), the necessity for hospitalization at the time of transplant (OR, 2.58; 95% CI, 2.00-3.30), and graft weight in kilogram (OR, 0.27; 95% CI, 0.17-0.45). Using these predictors, we developed the model for EAD after LDLT, which demonstrated strong discriminative ability in the development cohort with an area under the curve (AUC) of 0.71 (95% CI, 0.68-0.74). The model maintained high discrimination during internal validation (AUC, 0.70; 95% CI, 0.67-0.73) and showed a modest reduction in discriminative power in external validation (AUC, 0.65; 95% CI, 0.61-0.68). Conclusions. EAD post-LDLT is influenced by the recipient’s pretransplant health condition and the graft weight. Integrating the model for EAD after LDLT into the pretransplant process of pairing donors and recipients can enhance the safety and efficacy of LDLT.

This study aimed to explore contextual elements of the cancer experience that are consistently distressing and/or psychologically traumatic, as well as explore perceptions of Accelerated Resolution Therapy® (ART®) and its influence on the cancer experience. Using a qualitative descriptive design, semi-structured interviews were completed by 12 participants following the completion of ART. Interview data were analyzed using content analysis to identify major themes and patterns. Four themes included: (a) Cancer as the straw that broke the camel’s back, (b) ART® is different from previous therapy, (c) Don’t need to always be looking in the rearview mirror, and (d) Importance of early psychological intervention. Participants perceived that ART® was different and potentially more effective than other types of therapy they had previously received. Results support the diagnosis of cancer and the cumulative effects of previous life events and cancer-related stressors as traumatic events.

AbstractDefining the CSF cytokine/chemokine and injury biomarker signature of glial fibrillary acidic protein (GFAP) autoimmunity can inform immunopathogenesis. CSF GFAP‐IgG‐positive samples (N = 98) were tested for 17 cytokines/chemokines, neurofilament light chain (NfL), and GFAP (ELLA, Bio‐Techne). Controls included non‐inflammatory (N = 42), AQP4‐IgG‐positive (N = 83), CNS infections (N = 13), and neurosarcoidosis (N = 32). IL5, IL6, IL10, IL8/CXCL8, CXCL9, CXCL10, CXCL13, BAFF, GM‐CSF, IFN‐gamma, and TNF‐alpha concentrations were higher compared to non‐inflammatory controls (P < 0.01). GFAP concentrations were similar to those of AQP4‐IgG‐positive patients; NfL was higher (P < 0.001) and correlated with MRI changes and outcomes. CSF cytokine/chemokine findings in GFAP autoimmunity correlate with histopathology; GFAP and NfL hold promise as disease biomarkers.