Citations

Candida krusei empyema is a rare but serious manifestation of invasive candidiasis, characterized by intrinsic resistance to fluconazole, biofilm formation, and high mortality, with limited case-level data to inform management. This review aims to systematically identify and synthesize all reported English-language cases of Candida krusei empyema from January 2005 to June 2025 using PubMed, ScienceDirect, OVID MEDLINE, and Gale OneFile and perform descriptive analysis on them. Screening, data extraction, and eligibility assessment were performed, and those articles not clearly meeting eligibility criteria were reviewed by additional reviewers with consensus resolution. Seven publications (six individual cases and two cohorts) were included. We additionally describe the clinical course, management, and outcome of a 70-year-old bilateral lung transplant patient who developed persistent C. krusei empyema despite optimized antifungal therapy. Patients ranged from 11 to 74 years of age (median 62.5 years). Predisposing factors included esophageal perforation (n = 4), post-transplant hemorrhage (n = 1), community-acquired empyema (n = 1), and thoracic surgery (n = 1). Empiric fluconazole was switched to caspofungin (3/4), with others receiving amphotericin B, voriconazole, or combination therapy. Source control varied: chest tube drainage (n = 3), percutaneous catheter (n = 3), and surgical decortication (n = 2). Mortality was 14.3% (1/7). In the absence of clear guidelines and robust literature, the management approach remains heterogeneous. Optimal care requires early recognition, aggressive multimodal antifungal therapy, and effective source control tailored to patient risk. Standardized antifungal protocols and larger case series are needed to guide clinicians in managing this challenging infection.

Immune checkpoint inhibitors (ICIs) are an important class of cancer treatment. Endocrine immune-related adverse events (E-irAEs) account for a significant proportion of irAEs in ICI-treated patients. Diagnosing E-irAEs accurately and timely can be challenging in the absence of clear categorization and standardization across oncology, endocrinology and other specialties. While existing guidelines provide some broad directions to diagnosis and management, they lack clarity on irAE-specific symptom evaluation and work-up, as well as assessment of severity. These limitations can then impact triage, time-sensitive management and care escalation to specialists such as oncoendocrinologists. The objective of this study was to develop consensus-based statements on disease definitions for E-irAEs. A core working group of endocrinologists with expertise in the oncoendocrinology field drafted a survey with statements outlining the general approach to E-irAEs, disease definition and management approach of six specific diagnoses: ir-thyroiditis thyrotoxic phase, ir-thyroiditis hypothyroidism, ir-Graves’ disease, ir-hypophysitis, ir-adrenalitis and ir-type 1 diabetes mellitus. Severity grading tables were drafted for three disease categories—“thyroid”, “pituitary and adrenal”, and “diabetes mellitus”. A two-round modified Delphi process, using the RAND/University of California Los Angeles (RAND/UCLA) Appropriateness Method, was employed. In this process, a 25-member voting panel consisting of endocrinologists, oncologists and other specialists and healthcare providers with experience in management of ICI-treated patients and irAEs was recruited. The panel rated anonymously on usability, accuracy, appropriateness or agreement of 41 items on a 9-point scale in Survey 1, after which a meeting was convened. Statements were modified based on voting results from Survey 1 and Meeting 1, and the process was repeated in Survey 2 and Meeting 2. At the end of this process, consensus was achieved for all statements. Our study findings address the gap in standardized nomenclature, clinical, laboratory and radiological evaluations, and management principles of E-irAEs. With consensus achieved from a panel of experts from a variety of disciplines, we anticipate that the statements can form the basis for standardization of the diagnostic process and improvement of patient care.

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.