Chimeric antigen receptor (CAR) T-cell therapy has demonstrated promising efficacy results in CNS lymphomas, with reassuring rates of acute neurotoxicity. However, the neurologic outcome of these brain-injured patients remains unknown beyond the short term. Our objective was to report on the medium-term neurocognitive evolution.

We retrospectively selected isolated CNS lymphomas treated with CAR T cells (June 2021-April 2024) at Pitié-Salpêtrière Hospital who had neuropsychological follow-up as part of routine care (various tests evaluating main cognitive domains: language, memory, executive functions, visuospatial abilities, and overall functioning). We collected the results of the various cognitive tests from the patients' medical records at baseline, in the absence of tumoral progression; 6 weeks (W6); 6 months (M6); and 12 months (M12) after CAR T-cell therapy. We used paired Student t tests to compare follow-up values of neurocognitive variables with their baseline values. The primary outcome was the difference in Montreal Cognitive Assessment (MoCA) scores between baseline and M12.

Thirty patients (43% female, 57% male) were included, of whom 21 had neuropsychological assessment up to M12. Their median age was 61 years (range 30-82). At baseline, MoCA score was 23.5 (range 11-29) and 34%-80% of patients had abnormal scores in the main cognitive domains. Nineteen (63%) patients experienced acute neurotoxicity (6 (20%) of grade ≥3). Twenty-one patients (70%) maintained or improved their MoCA score at W6, while 9 (30%) worsened theirs. The occurrence and severity of neurotoxicity were significantly associated with these 2 types of initial trajectories (p = 0.003, 95% CI 1.78-1,227.01). There was a significant improvement of MoCA score at M6 (mean 24.7 vs 22.6, p = 0.002, 95% CI 0.92-3.37) and M12 (mean 25.4 vs 22.1, p < 0.001, 95% CI 2.12-4.92) compared with baseline. Language score significantly improved between baseline and M12 (mean Z-score of -0.6 vs -0.1; p = 0.02, 95% CI 0.08-0.9). Scores addressing memory, executive functions, visuo-spatial functions, and anxiety/depression were stable or improved, although not significantly.

Midterm neurocognition follow-up in patients with CNS lymphoma treated by CAR T cells seems reassuring, with no significant cognitive worsening, and even an improvement in general cognitive functioning, even in patients who experienced severe acute neurotoxicity. These results should be confirmed with longer follow-up.

We aim to quantify the dosimetric benefits of daily online adaptive (DOA) carbon ion stereotactic radiotherapy (CISR) in hepatocellular carcinoma (HCC).

13 patients received 4 × 10.5 Gy (RBE-weighted dose) CISR to 14 HCC lesions in challenging locations (N = 10: liver dome, N = 3: < 1 cm from intestines). All patients underwent daily in-room CT, with forward calculation of the baseline plan. Additionally, four patients were shuttled to a 1.5 Tesla MR scanner in treatment position for MRI simulation. Based on visual review of all data, the physician decided to treat or to perform offline plan adaptation and treat another day. We compare the dosimetry properties of four scenarios per fraction: (1) baseline plan, (2) no adaptation, (3) occasional offline adaptation (OOA), (4) DOA.

Baseline planning target volume (PTV) and internal target volume (ITV) coverage by the prescribed dose (median coverage: PTV: 97%, ITV: 100%) significantly decreased for no adaptation (PTV: 87.6%, p = 0.0001; ITV: 97.7%, p = 0.007) and OOA (PTV: 87.8%, p = 0.0001; ITV: 97.7%, p = 0.007), while DOA maintained high PTV coverage (PTV: 95.7%, p = 0.17; ITV: 100%, p = 0.53). Frequent violations of organs-at-risk (OAR) dose constraints occurred for no adaptation and OOA (both 20/52 fractions, 38.5%). They affected the bowel, heart and esophagus up to 6 cm from the PTV. DOA led to considerably fewer (6/52 fractions, 11.5%) and less intense violations of OAR dose constraints.

Daily CT- and MR-guided CISR is feasible in the liver, and demonstrates frequent violations of initial treatment planning objectives when non-adaptive or offline adaptive approaches are followed. DOA could improve target coverage and OAR protection, while particularities of carbon ions such as overdoses far from the target should be considered.

The present study explores the potential of sorafenib (SOR) and atorvastatin (ATST) to induce a ferroptosis and apoptosis-based hybrid cell death mechanism. The synergistic ATST + SOR combination was delivered through Glutamine-tagged PLGA nanoparticles (ATST + SOR/G-PLGA NPs) to promote intratumoral specificity. The formulation was optimized using DesignExpert® software by adopting Box-Behnken design (BBD). The optimized ATST + SOR/G-PLGA NPs had a spherical particle size of ~ 178.3 ± 12.6 nm, a PDI of 0.151 ± 0.08, and a Z-potential of -24.8 ± 5.8 mV. The formulation revealed a biphasic sustained release with higher release at acidic pH. In-vitro biological assessment showed a dose-dependent decrease in cell viability with reduced IC₅₀ values. In the presence of ferrostatin-1, the IC₅₀ value was significantly increased. The exposure to ATST + SOR/G-PLGA NPs led to elevated levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), increased late apoptotic/necrotic cells, and mitochondrial membrane depolarization. Pharmacokinetic study revealed a 2.63- and 2.93-fold improved AUC_0-∞, and 2.58- and 2.84-fold improvement in MRT as compared to free SOR and ATST. Preclinical efficacy study showed a marked reduction in tumor volume and a higher inhibition rate. Toxicity assessment revealed no signs of systemic or organ toxicity, implying suitability of formulation for in-vivo delivery. In a nutshell, the proposed strategy offers a powerful avenue to manage advanced malignancies by inducing a hybrid cell death mechanism. Also, the nutrient transporter targeted polymeric nanosystems present an effective approach, which warrants further investigation.

Wilms tumor is the most common pediatric renal neoplasm. The diagnosis of Wilms tumor is made on imaging when the radiological features and age of presentation are typical. Percutaneous biopsy is reserved for cases with atypical imaging appearance or older age at presentation, as the biopsy itself upgrades Wilms tumor to stage III. This is more relevant when it comes to the International Society of Pediatric Oncology (SIOP) guideline, which states that chemotherapy should be given before surgery, when compared to the Children's Oncology Group (COG) guideline, which recommends surgery, without neoadjuvant chemotherapy for the initial stages. Few uncommon renal neoplasms may have typical imaging and clinical characteristics, which can help to differentiate them from Wilms tumor. While upfront nephrectomy or nephron-sparing surgery can be done for small masses confined within the kidney and non-aggressive or benign histological types, preoperative chemotherapy with or without biopsy is required for most atypical renal neoplasms. Pseudomasses can mimic atypical renal tumors, but with a few distinguishing imaging features. This review describes the atypical imaging appearances of Wilms tumor and the typical imaging appearance of uncommon renal neoplasms and pseudomasses.

Today, magnetic resonance imaging (MRI) is considered the diagnostic tool of choice for eye and orbital pathologies. In this article, the MR image characteristics of relevant pathologies are illustrated using case-based examples in the context of clinical findings.Vascular pathologies (such as capillary hemangioma and cavernous venous malformation), inflammatory diseases (such as endocrine orbitopathy), and neoplasms (such as lymphoma, uveal melanoma, retinoblastoma, and ocular/orbital metastasis) are described. Additionally, the role of MRI in acute clinical settings and trauma is discussed.The text explains technical aspects of MRI encompassing field strength and the utilization of receiver coils to optimize image quality and achieve high spatial resolution.Alongside common sequences (T1- and T2-weighted sequences) used in standard anatomic imaging (sAI), the article demonstrates the potential of "multiparametric" imaging techniques (diffusion-weighted imaging, DWI, and dynamic contrast-enhanced imaging, DCE). These innovative MRI sequences depict functional tissue characteristics in addition to morphology alone and thus facilitate radiological assessment.

Inflammatory rhabdomyoblastic tumor (IRMT) is a rare myogenic neoplasm with a morphologic spectrum and incompletely defined clinical behavior. It is characterized by a prominent inflammatory infiltrate, skeletal muscle differentiation, and recurrent near-haploidization, with occasional progression to rhabdomyosarcoma. Its relationship with neurofibromatosis type 1 (NF1) remains incompletely understood, despite recurrent NF1 alterations and reports of IRMT arising in patients with NF1. We analyzed five IRMTs: three conventional tumors, one tumor with increased mitotic activity without overt malignant features, and one malignant tumor. Two arose in patients with clinically overt NF1 and Targeted next-generation sequencing identified pathogenic NF1 alterations in four out of five tumors, supporting an association between IRMT and NF1. Whole-genome sequencing demonstrated near-haploid genomes in conventional IRMTs, whereas the malignant tumor showed whole-genome duplication, genome-wide loss of heterozygosity, and homozygous CDKN2A inactivation. When included with other genomically characterized and published conventional IRMTs and malignant progressions, integrated data supports a view in which near-haploidization represents the genomic background of conventional IRMT, with complete CDKN2A inactivation and whole-genome duplication as candidate contributors to malignant progression. Although this small retrospective series cannot establish temporal sequence or causality, our findings provide additional clinicopathologic and molecular support for an association between IRMT and NF1 and further characterize the genomic alterations associated with malignant progression. Complete CDKN2A loss and whole-genome duplication should be regarded as candidate progression-associated findings requiring validation in larger cohorts and longitudinal and functional studies.

The 2018 American Joint Committee on Cancer (AJCC) classification for laryngeal cancer defines staging based on anatomical invasion but does not formally incorporate prior tracheostomy. Discrepancies between clinical staging (cT) and pathological staging (pT) often complicate therapeutic decision-making. The objective of this study was to determine if the clinical necessity of a prior tracheostomy serves as an independent preoperative predictor of pT4a staging in patients undergoing primary total laryngectomy, thereby assisting in clinical planning.

This retrospective study reviewed the histopathological records of patients surgically treated for advanced laryngeal squamous cell carcinoma over a 20-year period. Eligibility criteria required a preoperative clinical staging indicative of extensive disease justifying total laryngectomy, without the presence of prior chemoradiotherapy or partial laryngeal surgeries. Data regarding pathological staging, nodal involvement, and microscopic characteristics were extracted. Associations were assessed using Fisher's Exact Test, and the magnitude of effect was calculated using multivariate logistic regression, yielding an Odds Ratio (OR).

The final cohort comprised 96-patients (93.75% male; median age 65-years). A prior tracheostomy was required in 39.6% of the cohort. A statistically significant association was established between pT4a staging and prior tracheostomy, with 86.8% of tracheostomized patients revealing pT4a disease on final pathology (p = 0.013). Multivariate logistic regression confirmed that advanced pathological staging (T4a) was the sole independent predictor of the need for prior tracheostomy (OR = 4.41, 95% CI; p = 0.010). Other variables, including nodal staging, histological grade, perineural invasion, and angiolymphatic invasion, did not show significant independent associations with the requirement for prior tracheostomy.

The clinical requirement of a tracheostomy prior to definitive total laryngectomy is a robust, independent predictor of pT4a staging. In the context of ambiguous clinical imaging, prior tracheostomy serves as a surrogate marker for extensive anatomical compromise, providing critical adjunctive data to support multidisciplinary tumor boards in decisions favoring primary surgical resection.

Aberrant metabolism, a hallmark of cancer, reveals vulnerabilities across human tumors. Here, we demonstrate that transcriptomic alterations of metabolism-related genes (metabolic transcriptome) in multiple myeloma (MM), classify patients into six metabolic-transcriptional groups characterized by specific metabolic pathways and cytogenetic alterations, independent of currently described myeloma risk groups. Interestingly, hyperdiploid patients clustered into 2 groups (MM5 and MM6) with significantly distinct Progression-Free and Overall Survival. The MM5 group, with worse prognosis, showed a significant enrichment in myeloid and dormant cell signatures. Regulon analysis identified myeloid transcription factors (TFs) as regulators of metabolic, myeloid, and dormant genes in MM5. In addition to myeloid genes acting as potential biomarkers and therapeutic targets, the metabolic gene ACSL1 plays a crucial role in MM5, decreasing cell proliferation by affecting metabolism and mitochondrial function, sensitizing MM to BCL-2 family inhibitors. These findings highlight ACSL1 as a promising therapeutic target for MM5 and provide new insights into MM metabolic heterogeneity that may guide future precision medicine strategies.

Russia's war against Ukraine has renewed discussion about a possible NATO Article 5 collective defense scenario in Europe. In such a situation, Germany would function as key logistical and medical hub, placing substantial strain on its healthcare system. Experience from the COVID-19 pandemic suggests that health system resilience not only depends on infrastructure but also on availability and commitment of health professionals. This study examined willingness of future health professionals in Germany to contribute beyond routine duties in such a crisis and assessed preparedness, ownership, and awareness as potential determinants.

Between 20 May and 15 July 2025, a cross-sectional online survey was conducted among German medical, nursing, and paramedic students (n = 514). Data were collected on demographics and self-assessed individual preparedness, perceived institutional preparedness, voluntary engagement as major indicator of ownership, and awareness regarding a NATO collective defense scenario. Willingness to contribute beyond routine practice was assessed across preparatory activities, crisis-specific medical tasks, and modified working conditions. Composite scores were calculated for awareness, individual and institutional preparedness, and willingness. Associations with willingness were examined using multivariable linear regression adjusted for predefined covariates.

Overall, 48.8% considered a NATO collective defense scenario by 2030 likely, 83.3% anticipated negative effects on the German healthcare system, and 94.5% perceived the healthcare system as poorly prepared. Individual preparedness was low (median: 3 on 0-12 scale; IQR: 1-5), while recent voluntary engagement, including voluntary work during studies or apprenticeships in general or in civil aid organizations specifically, was common (59.1%). Participants showed high willingness to engage in preparatory measures and to provide care in Germany, but lower willingness to initiate trainings or to provide care for German or allied soldiers abroad. In adjusted regression analyses, higher perceived institutional preparedness, voluntary engagement, and awareness were significantly associated with greater willingness (all: p < 0.01).

Willingness of future health professionals to support the German healthcare system in a NATO collective defense scenario was associated with perceived institutional preparedness, awareness, and voluntary engagement. Widespread perceptions of insufficient preparedness raise concerns about system resilience, and the associated factors might represent potential targets for policy interventions.

This study aimed to assess hyperoxic lung injury (HLI) during a heliox dive based on the unit pulmonary toxic dose (UPTD), K index, and equivalent surface oxygen time (ESOT).

The UPTD, K index, and ESOT values of each schedule in the Helium-Oxygen Decompression Table of China were calculated. Based on the recommended thresholds, the risk of lung injury was analyzed, and suggestions were proposed to modify certain schedules.

The K index and ESOT were more conservative than UPTD in predicting HLI. After a deeper dive, the UPTD, K index, and ESOT values were generally higher than the recommended thresholds. For schedules in which the UPTD, K index, and ESOT values do not exceed the thresholds, we recommend prolonging time on oxygen with or without reducing time on air, or recommending oxygen inhalation after surfacing, which may improve safety without increasing the risk of lung injury. For most schedules, the lung injury may resolve within 12 hours after surfacing, according to the K index.

Decompression schedules can be adjusted in real time according to K or ESOT values, which may improve safety while effectively controlling the risk of HLI.