Citations

Abstract Background: Fibroblast activation protein (FAP) is a type II integral membrane glycoprotein, highly expressed on the cell surface of cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers and showing limited expression in normal tissues. Given this expression profile, FAP appears to be a promising target for radioligand therapy that has pan-cancer potential. [177Lu]Lu-NNS309 is a FAP-targeted radiopharmaceutical that shows improved tumor retention and demonstrates promising anti-tumor activity in translationally relevant preclinical models (e.g., PDAC, NSCLC) where FAP is expressed on CAFs. Methods: CFXX489A12101 (NCT06562192) is a first-in-human phase I, open-label, multi-center study of [177Lu]Lu-NNS309 in patients with pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), breast cancer (BC), and colorectal cancer (CRC). The study includes a dose escalation part followed by a dose expansion part. Key eligibility criteria include prior treatment for locally advanced unresectable or metastatic disease and having all measurable lesions (per RECIST 1.1) showing [68Ga]Ga-NNS309 uptake on positron emission tomography/computed tomography (PET/CT). Patients who are eligible for treatment receive one dose of [177Lu]Lu-NNS309 on day 1 of each cycle. A 6-week and a 4-week dosing schedule will be explored. Dosimetry data will be obtained from patients in the dose escalation part after the first dose and will be used to calculate the cumulative radiation exposure. Dose escalation will be guided by a Bayesian hierarchical logistic regression model with overdose control (EWOC) principle, and assessment of all relevant data available from all dose levels including safety, tolerability, clinical dosimetry, pharmacodynamics, and preliminary efficacy. Once the recommended dose(s) (RD) and schedule(s) of [177Lu]Lu-NNS309 are determined, the expansion part may open and will include patients with locally advanced or metastatic PDAC (n∼20), locally advanced or metastatic NSCLC (n∼20), HR+/HER2- ductal BC (n∼15), HR+/HER2- lobular BC (n∼15), and triple negative BC (; n∼24).The primary objectives of the study are to evaluate the safety and tolerability of [177Lu]Lu-NNS309 and to identify the RD(s) and regimen(s) of [177Lu]Lu-NNS309 for further clinical evaluation. Secondary objectives of the study are to evaluate the preliminary anti-tumor activity of [177Lu]Lu-NNS309, characterize the pharmacokinetics of [177Lu]Lu-NNS309 in blood and urine, the radiation dosimetry for organs and tumor lesions, and to evaluate the safety and imaging properties of [68Ga]Ga-NNS309. Conclusion: The study is currently enrolling in the dose escalation part. Citation Format: Ravit Geva, Daniel Juneau, Shadi Abdar Esfahani, Cristiano Ferrario, Farshad Moradi, Amir Iravani, Jordi Ahnert, Ivan Manuel Victoria Ruiz, Thibaud Koessler, Aitana Calvo Ferrandiz, Bernard Doger de Speville, Patrick Flamen, Albiruni Razak, Desiree Deandreis, Laure Al-Mansour, Niklaus Schaefer, James Nagarajah, Hilde Nienhuis, Marco Maccauro, Angelina Filice, Jonathan Goldman, Ken Herrmann, Matthias Eiber, Alexander Drzezga, Martin Heuschkel, Jonathan McConathy, Johnson Geoffrey, Ephraim Parent, Yasutoshi Kuboki, Shizuka Origuchi, Xuan Mai Couillebault, Elisa Garcia Garayoa, Jayarama Naidu Roopa, Christopher Straub, Dominik Hainzl, Xinyu Chen, Fang Yang, Eirini Pectasides, Brandon Mancini. Phase I open-label, multi-center study to evaluate the safety, tolerability, dosimetry, and preliminary activity of FXX489 ([177Lu]Lu-NNS309) in patients with pancreatic, lung, breast and colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT112.

Background: Medicaid reimbursement to physicians is often perceived to be lower than Medicare, but little is known about orthopaedic foot and ankle reimbursement. This study sought to compare Medicare and Medicaid reimbursement for the 20 most common foot and ankle procedures. Methods: Medicare reimbursement rates for common foot and ankle codes were obtained from the online Centers for Medicare & Medicaid fee schedule, while Medicaid rates were found from individual state fee schedule websites. Medicaid rates were compared by state and pooled to obtain national differences. The Medicare Wage Index was used to adjust Medicaid rates by state wages to ensure a more accurate comparison. Variability between states was measured using state percentages of Medicare and coefficient of variation values. Results: Medicaid reimbursed physicians higher than Medicare in 31 states overall, with average reimbursement ranging from 37% to 324% of Medicare. Nationally, Medicaid reimbursed 8.8% higher than Medicare, but Medicare reimbursed 3.7% higher when adjusted for the Medicare Wage Index. The Current Procedural Terminology ( CPT ) codes with the highest ratio of Medicaid to Medicare reimbursement were CPT 28002 for incision and drainage of the foot (176.6%) and CPT 28820 for toe amputation (167.6%). Five codes had lower relative Medicaid reimbursement on average: CPT 27687 for repair procedures on the leg and ankle joint, CPT 28810 for amputation procedures on the foot and toes, CPT 28010 for toe tenotomy, CPT 28005 for incision procedures on the foot and toes, and CPT 28470 for closed treatment of a metatarsal fracture. The coefficient of variation values ranged from 0.34 to 0.84 in the Medicaid group and 0.40 to 0.78 in the adjusted group, indicating high variability between states and between procedures. Conclusion: Medicaid reimbursement is highly inconsistent between states, ranging from 37% to 324% of Medicare. Medicaid reimbursed more than Medicare overall, which is in contrast with most published findings that tend to show higher reimbursement for Medicare when compared to Medicaid. When adjusting for wage differences between states, Medicare reimbursed slightly higher than Medicaid. Level of Evidence: Level IV, economic analysis.

Introduction Although osteosarcoma represents the most common primary malignant bone tumor in children, they comprise only 0.2% of all cancers. Osteosarcoma frequently involves long bones; however, 8% of osteosarcomas involve the skull or mandible. Osteosarcoma is generally categorized based on location within the bone (central, surface, or extraskeletal) and histological grade (high-grade or low-grade). Osteoblastic osteosarcoma is a central, high-grade subtype and may be difficult to diagnose; it may present similarly to osteoblastoma, another rare, but benign, type of osteoblastic bone tumor. In this report, we present a rare case of osteoblastic osteosarcoma involving the temporal-occipital skull. Study design Case report and systematic review. Setting Tertiary referral center. Results A 21-year-old male presented for assessment of a mass appearing over his left mastoid region, first noticed within the previous 12 months. He experienced growth of the lesion and pain that increased when pressure was applied to the mass. Results from fine needle aspiration and CT-guided core biopsy were positive for osteosarcoma, osteoblastic-type. Magnetic resonance imaging of the brain and skull base revealed the mass to be 2.8 cm in maximal diameter. Given a somewhat favorable location, the tumor could be completely excised en bloc with negative margins, and the patient subsequently received adjuvant chemotherapy. The patient is doing well at last follow-up 10 months after surgery, with no evidence of recurrence to date. Conclusion The temporal bone is an uncommon location for a primary osteosarcoma, and there are numerous conditions that could present in a similar manner. This case highlights this rare occurrence of osteoblastic osteosarcoma of the temporal bone without previous exposure to radiation. There are a limited number of similar cases in the literature, and our report serves to bring awareness to this potential diagnosis and considerations related to treatment.

Background We undertook this study to evaluate the efficacy of an on-table extubation protocol and to assess the magnitude of benefits when implemented as a routine practice in a developing country. Methods This prospective observational study at a single tertiary care referral hospital was designed to determine the efficacy of an on-table extubation protocol when applied to children undergoing cardiac surgery in the developing world. The study included 226 patients who were 1 month to 18 years of age undergoing cardiac surgery (including grown-up congenital heart disease [GUCHD] patients). Patients with RACHS score ≥ 4, neonates, preoperatively ventilated children, and emergency surgeries were excluded from the study. All pediatric elective cardiac surgical patients belonging to RACHS 1, 2, and 3 categories were considered as potential candidates for on-table extubation. Trial registration: Clinical Trials Registry of India (CTRI/2020/07/026567). Results Among the 226 children who underwent elective cardiac surgeries, we were able to extubate 142 patients (62.83%) in the operating room. This included 46.6% (54/116) infants, 80.8% (38/47) children less than 5 years of age, 79.3% (46/58) children between 5 years to 18 years age, and 80% (4/5) GUCHD. The duration of intensive care unit (ICU) stay, hospital stay, and hospital cost were significantly less in the on-table extubation group (23 [20, 26] hours; 102 [97, 125] hours; INR 2,09,011 [181032, 244298]) as compared with those patients extubated in the ICU within 6 hours (28 [22, 46] hours; 122 [100, 168] hours; INR 2,25,430 [162203, 273831]) and beyond 6 hours (71 [45, 121] hours; 184 [127, 243] hours; INR 2,53,541 [226838, 306871]). Conclusions This protocol shows a significant reduction in ICU stay, hospital stay, and total hospital cost when compared with either extubation within 6 h in the ICU or delayed extubation (beyond 6 h) in patients undergoing pediatric cardiac surgery.

Objective To analyze the use of electrical field imaging (EFI) in the detection of extracochlear electrodes in cochlear implants (CI) Study Design Retrospective cohort study Setting Tertiary academic medical center Methods EFI patterns from 6 recipients with extracochlear electrodes were compared with 10 recipients with all intracochlear electrodes to identify differences in EFI patterns between these two groups. For the extracochlear group, EFI patterns were analyzed using two methods: visual inspection and calculation of the average impedance difference (AID) between specific EFI curves. These results were then compared with information from CT and plain film imaging, surgical notes, and audiology tests to confirm the placement of the electrodes in each recipient. Results An average AID of 0.06 kΩ was calculated from the EFI patterns for recipients with complete electrode insertion, whereas an average AID of 0.15 kΩ was calculated from the EFI curves measured for the extracochlear electrodes. Visual analysis of the EFI impedance curves for extracochlear electrodes showed a distinct separation from those measured for intracochlear electrodes. Based on AID analysis and visual inspection the EFI, patterns were in close agreement with the number of extracochlear electrodes detected based on either imaging, intraoperative surgical note, or audiological findings. Conclusion EFI is a noninvasive, inexpensive, and time-efficient measurement that can be used to detect extracochlear electrodes and monitor electrode migration from the cochlea.

AbstractBackgroundEarly‐onset Alzheimer’s disease (EOAD) occurs before age 65 and has more diverse disease presentations than late‐onset AD. To improve our understanding of phenotypic heterogeneity among EOAD individuals, we analyzed cognitive scores using data‐driven statistical analysis.MethodBaseline cognitive data from 286 sporadic EOAD individuals from the Longitudinal EOAD study (LEADS) were transformed to z‐scores using data from 95 cognitively normal (CN) individuals. Cognitive composites were generated for domains of memory, language, speed/attention, visuospatial, and executive function. Residuals from linear regression models on Z‐scores adjusted for age, sex, and education were obtained. Cluster analysis using the Ward method on the cognitive domain residuals was performed and scree plot using the pseudo T‐squared determined the optimal number of clusters for the EOAD sample. We also compared gray matter density (GMD) of each EOAD cluster to CN participants using voxel‐wise multiple linear regressions.ResultsThree clusters of cognitive performance were identified from the EOAD sample. Disease duration was not significantly different across clusters. Using a z‐score of ‐1.5 SD as the impairment threshold, all clusters were impaired across most domains (Table 1). Cluster‐3 was more impaired than cluster‐2 in all domains (Table 2; all p<.0001), and in all domains except episodic memory compared to cluster‐1 (all p<.01). Cluster‐1 (n = 71; 85.9% amnestic) was most impaired in executive function, visuospatial, and speed/attention. Cluster‐2 (n = 133; 88.7% amnestic) was most impaired in episodic memory. Cluster‐3 (n = 82; 69.5% amnestic) was most impaired in executive function, visuospatial, and speed/attention (Table 1). 3D‐comparisons showed all EOAD clusters had reduced GMD compared to CN. Cluster‐1 and cluster‐3 both showed widespread atrophy, with cluster‐3 being more severe. Cluster‐2 showed the most atrophy in the temporal and parietal lobes (Figure 1).ConclusionWe identified heterogeneity in cognitive patterns among sporadic EOAD individuals. Cluster‐3 appeared to reflect widespread impairment, and cluster‐2 represented an amnestic‐only presentation. Despite comparable disease duration, some EOAD patients progress faster, while some are more resilient. 3D‐comparisons showed neurodegenerative changes affecting brain regions responsible for respective impaired cognitive functions in each cluster (e.g., cluster‐2 is primarily amnestic‐impaired and has temporoparietal atrophy). Future work should explore amyloid‐PET and tau‐PET burden.