Citations

A positive margin following tumor resection (i.e., surgical removal of a cancerous tumor) indicates that cancer may remain in the body and can require a re-operation. This study is part of a larger project designing a technology to support the intraoperative evaluation of margins. This study explores the goals, decisions, information needs, and system requirements of a surgeon performing breast cancer surgery. We conducted semi-structured interviews with 11 breast surgeons to understand how they currently perform resections and then performed a qualitative thematic analysis. We identified three main goals and 13 subgoals. The three main goals are: treating cancer, meeting patient needs, and meeting institutional needs. Surgeons made multiple decisions to accomplish each sub goal and required multiple information elements to make these decisions. Our results will inform the design of the new technology and a sociotechnical systems-based analysis to ensure the technology fits in surgeon workflow.

BACKGROUND: People with narcolepsy are at increased risk for hypertension and cardiovascular disease; excessive sodium intake is linked to both. METHODS: We studied patients with narcolepsy and office systolic blood pressures (BPs) of 130 to 155 mm Hg taking twice-nightly high-sodium oxybate for ≥6 weeks who switched to low-sodium oxybate at the same dosage. The primary end point was the change from baseline in mean 24-hour ambulatory systolic BP at the end of treatment (≈6 weeks after switching). Secondary and exploratory end points included changes in diastolic BP, office BP, and 24-hour sodium excretion. RESULTS: Patients (n=43) had a mean age of 45 years, were 65% female, 33% on antihypertensives, with baseline mean (SD) office BP of 138.0/85.2 (5.7/6.6). Mean (SD) total high- and low-sodium oxybate dosages of 8.0 (1.1) and 8.1 (1.1) g/night, respectively, represented 1456.5 (206.2) and 117.8 (16.3) mg of sodium. The median 24-hour urinary sodium was 4278 mg/d at baseline and 2703 mg/d at the end of treatment (median change, 1288 mg/d). Mean (SE) 24-hour ambulatory systolic BPs at baseline and study end were 132.3 (1.8) and 128.2 (1.8) mm Hg (least-squares mean change, −4.1 [95% CI, −6.9 to −1.4] mm Hg; 1-sided P =0.0019). BP changes by narcolepsy subtype, sex, body mass index, baseline office BP, and baseline antihypertensive use were consistent with the overall effect size. CONCLUSIONS: People with narcolepsy switching from high- to low-sodium oxybate showed substantially reduced daily medication-related sodium intake and significant 24-hour BP reductions. These results demonstrate the importance of reducing pharmaceutical sodium content in this elevated cardiovascular risk patient population. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05869773.

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by aggressive tumor biology, poor vascularization, dense stromal barriers, and profound resistance to chemotherapy. GAIP-interacting protein C-terminus 1 (GIPC1), a PDZ-domain-containing adaptor protein, is highly overexpressed in PDAC and plays a critical role in tumor progression and chemoresistance. This study aimed to develop and evaluate a novel tumor-targeted liposomal siRNA delivery system (LGIPCsi) to silence GIPC1 and enhance the therapeutic efficacy of gemcitabine (GEM) in PDAC; Methods: LGIPCsi nanoparticles were synthesized and optimized for physicochemical stability, siRNA complexation efficiency, and tumor-targeting capability. Their therapeutic efficacy was assessed using in vitro pancreatic cancer cell models and in vivo orthotopic and patient-derived xenograft (PDX) models of PDAC. Biodistribution, tumor uptake, and antitumor efficacy were evaluated following systemic administration. Combination studies were performed to assess the synergistic effects of LGIPCsi and GEM; Results: GIPC1 silencing significantly sensitized pancreatic cancer cells to GEM, resulting in enhanced inhibition of tumor cell proliferation in vitro. In vivo, systemic administration of LGIPCsi achieved efficient intratumoral delivery of siGIPC1, leading to marked tumor growth suppression. Combination therapy with GEM and LGIPCsi produced synergistic antitumor effects, with substantial tumor regression compared to monotherapy groups. Importantly, no significant systemic toxicity was observed in treated animals; Conclusions: This study identifies GIPC1 as a promising therapeutic target in PDAC and demonstrates that tumor-targeted siRNA nanomedicine can effectively overcome chemoresistance when combined with standard chemotherapy. The LGIPCsi platform offers a rational and translational strategy to enhance treatment efficacy in PDAC through targeted RNAi-based combination therapy.

Abstract Background Molecular breast imaging (MBI) has shown utility as a supplement to mammography in women with dense breasts. Background parenchymal uptake (BPU), which describes the level of Tc-99m sestamibi in fibroglandular tissue on MBI, varies among women with similar density. Higher BPU is associated with greater breast cancer risk. The goal of this work is to investigate the histological correlations of BPU that may explain this association with risk. Methods We compared histologic features of prospectively collected benign breast tissue biopsies from healthy women who had a region of dense tissue on mammography exhibiting one of the extreme categories of BPU on MBI: either photopenic or marked. Tissue composition of specimens was assessed by measuring area of epithelium, stroma, and fat and counting lobules. Lobular involution status was assessed by an expert pathologist as either none, partial, or complete. Ki-67 index and estrogen receptor-alpha expression were also assessed. Results Biopsies were performed in 48 women (mean age 54.9 years [SD 11.1 years]), including 20 with marked BPU and 28 with photopenic BPU. Women with marked BPU were younger (mean age 49.9 vs. 58.4 years, p = 0.004), had higher body mass index ( p = 0.01), and were more likely premenopausal ( p = 0.005). Marked BPU specimens had a higher proportion of epithelium (14.5% vs. 2.2%, p < 0.001), lower stromal content (44.8% vs. 84.2%, p = 0.005), similar fat (18.9% vs. 12.9%, p = 0.41), and greater lobule counts (15.5 vs. 6.3, p < 0.001) compared to photopenic specimens. Complete lobular involution was less frequent in marked tissue than in photopenic tissue (10.5% vs. 76%, p < 0.001). Ki-67 index was higher in marked BPU tissues (5.4% vs. 1.6%, p = 0.006), though the difference was attenuated after adjustment for epithelial area (p = 0.26). Estrogen receptor-alpha expression did not differ between marked and photopenic groups (25.6% vs. 28.4%, p = 0.12). Conclusions Marked BPU on MBI is associated with greater epithelial content, less lobular involution, and higher proliferative activity—features characteristic of tissue at elevated risk for malignant transformation. These findings suggest that BPU provides functional information beyond mammographic density, supporting its role as an imaging biomarker for breast cancer risk in women with dense breasts. Trial Registration: NCT01240278 and NCT01588834

Summary: Peripheral Artery Disease (PAD) is a significant global health concern, leading to morbidity through progressive stenosis and eventually occlusion of the lower extremity arterial vasculature. Advanced imaging modalities play a major role in diagnosing PAD, in planning endovascular as well as surgical interventions, and in monitoring post-treatment outcomes. This review highlights the current major imaging techniques, including duplex ultrasound, computed tomography angiography (CTA) and magnetic resonance angiography (MRA). It provides insights into their applications, advantages, limitations and the importance of individualized imaging strategies for optimizing patient outcomes.

The TransMet trial and Norwegian studies have shown excellent outcomes in highly selected patients undergoing liver transplant (LT) for unresectable colorectal liver metastases (uCRLM). Our aim is to provide an updated analysis of the current state of LT for uCRLM in the United States. Adult patients with a diagnosis of uCRLM listed for LT between December 2017 and March 2025 were identified from the United Network for Organ Sharing database and analyzed. An analysis of living donor LT (LDLT) and deceased donor LT (DDLT) was performed. During this period, 222 patients were listed, and 158 received an LT across 33 centers. Of these, 76 (48.1%) underwent LDLT, and 82 patients (51.9%) underwent DDLT. Of the 82 deceased donors, 56 (68.2%) were out-of-sequence offers. Overall, the 3-year survival and disease-free survival rates were 66.7% and 44.0%, respectively. The 3-year survival for LDLT and DDLT was 74.1% and 57.3% ( p =0.04), respectively. While these results have not yet reached the acceptable threshold established for other LT indications, they have improved and are expected to continue improving after the implementation of prioritization points. Given the potential variability of oncologic selection criteria and graft quality, we call for the standardization of nationally accepted selection criteria for listing patients for LT with uCRLM and for providing early access to high-quality organs. To achieve this, it is imperative to create, update, and maintain national databases that allow for the collection of more granular oncological variables.