Publications

OBJECTIVE: We investigated the extent of cellular, transcriptional, and translational activation throughout the liver following radiofrequency ablation (RFA).

MATERIALS AND METHODS: RFA of the healthy liver was performed in two 8-10-week-old male C57/Bl6 mice, no/sham procedure in one. One and 7 days after, single-cell RNA sequencing (scRNAseq) was performed on distant, untreated liver to examine > 6,000 genes from normalized datasets of > 6,000 cells/sample, enabling identification of ten major cell populations. We defined cell-to-cell interactions by CellphoneDB and identified active pathways via STRING-db analysis with Markov clustering. Twelve distant liver lobe samples were homogenized on day 3 or day 6 after RFA/sham procedure for SomaLogic proteomic analysis (> 1,300 genes), subsequent STRING-db analysis, and assessment of cellular origin (PanglaoDB-2021).

RESULTS: CellphoneDB identified crosstalk among all ten populations with 4,658 and 4,218 receptor/ligand pairs, identified on day 1 and day 7 post-RFA, respectively. On day 1, 360 differentially expressed genes were identified; on day 7, 430. Activated genes distributed into 16 clusters, including 66 chemokines/cytokines, including Ccl2 and Ccl7; 57 immunomodulators, including Il6, Ctla4 and Pdcd1; and 54 growth factors, including Vegf, Hgf, Pdgf, and Fgf. Angiogenesis pathway genes were observed in endothelial cells and hepatocytes. Pdcd1 and Ctla4 were notably increased transiently in T cells. Proteomic analysis included 228/443 genes (51%) identified by scRNAseq; 73/228 proteins (32%) demonstrated 25% elevation over controls. Overall, 427 proteins were elevated, with 9/10 cell populations contributing to increased protein expression (odds ratio 4.9‒7.0).

CONCLUSION: RFA diffusely activates cellular processes remotely from the ablation zone on both transcriptional and translational levels, altering tumorigenic and immunologic pathways simultaneously.

RELEVANCE STATEMENT: This study offers insights into liver tissue biology after RFA and provides a comprehensive picture of the molecular mechanisms put into motion by this procedure. A better understanding of these processes could provide a potential basis to develop specific biomarkers and effective adjuvant therapies following local tumor ablation.

KEY POINTS: RFA activates a multiplicity of hepatic cellular processes remotely from the ablation zone on a transcriptional and translational level. Single-cell RNA sequencing provides insights into widespread cellular origins of activated pro-immunogenic, pro-tumorigenic, and other pathways detected post-ablation. Consideration of the nature of this response may help achieve the clinical goals of adjuvant therapies and predictive biomarkers.

PURPOSE: To determine clinical and radiographic parameters predictive of interventions and adverse outcomes in patients with spontaneous rectus sheath hematoma.

METHODS: This retrospective, institutional review board approved study identified 261 patients with spontaneous rectus sheath hematoma from January 2000 to August 2021 through CT report searches. Demographics, clinical presentation, comorbidities, medications, and laboratory values were collected. CT scans were reviewed for hematoma characteristics including size, location, density, and active contrast extravasation. The primary outcome was the invasive intervention; and the secondary outcomes included transfusion requirements, length of hospital stay, acute kidney injury, readmission, and mortality. Categorical variables were compared using Fisher's exact test, while continuous variables were analyzed using Student's t-test or Mann-Whitney U test as appropriate based on normality assessment.

RESULTS: The cohort comprised 261 patients (median age 71 (IQR, 60-78) years, 59% female). Invasive treatments were performed in 41 patients (15.7%): 35 underwent angiography with embolization; 6 had surgical exploration. Invasive treatment was significantly more frequent among patients with trans-umbilical extension (25.7% vs 9.4%; p < 0.001), active contrast extravasation (46.7% vs 33.0%, p < 0.001), and hematoma volume > 443.5 cc (31.8% vs 9.6%, p < 0.001)." These patients had higher red blood cell transfusion requirements (85.4% vs. 47.7%, p < 0.001) and longer hospital stays (7 vs. 4 days, p < 0.001). The overall in-hospital mortality was 6.9%, with 1.9% attributable to rectus sheath hematoma.

CONCLUSION: While most rectus sheath hematomas are managed conservatively, specific CT findings-trans-umbilical extension, larger volume, and active contrast extravasation-predict invasive intervention and guide clinical decision-making.

The central principle of the theory of constraints is that in any complex system there are only a few constraints that limit the performance (ie, "throughput") of the system. These constraints are rate-limiting steps to throughput. Once the constraint or bottleneck is identified, resources are used to improve the utilization rate at the point of the constraint to make the process as productive as possible. Others in the organization also must work to maintain the high utilization rate at the constraint. Strategies such as buffers are used to increase throughput at the constraints. Although it was initially developed in manufacturing, the theory of constraints has been applied to many industries. By using the theory of constraints to evaluate the radiologic workflow, constraints can be identified through targeted process improvement projects for optimization at steps that affect the total throughput of the system. Constraints can be physical, such as equipment or space (eg, imaging units or recovery room beds), or related to personnel. Because radiology is currently in a resource-constrained environment, targeted interventions with highly effective processes could improve productivity or flow. Given the workforce shortages in radiology, determining whether the constraint is equipment- or personnel-related may lead to different improvement projects.

BACKGROUND: Calciprotein particles (CPP) are nanoparticles that play an important role in the pathogenesis of chronic kidney disease-mineral and bone disorder (CKD-MBD).

HYPOTHESIS/OBJECTIVES: Identification of plasma CPP and preliminary exploration of the relationships among CPP concentrations, calcification propensity (T50), and CKD-MBD variables in cats with azotemic CKD.

ANIMALS: Cats with azotemic CKD (n = 52) stabilized on a phosphate-restricted diet (PRD).

METHODS: Total CPP (T-CPP), low-density CPP (L-CPP), and high-density CPP (H-CPP) were measured in heparinized plasma using a fluorescent bisphosphonate (OsteoSense) after gel filtration. Standardized linear regression models evaluated associations among CPP, T50, and CKD-MBD variables. Generalized estimating equations compared preprandial and postprandial CPP concentrations. Calciprotein particle changes (ΔCPP) between visits were compared between cats with different ionized calcium (iCa) trajectories using independent samples t-test or Mann-Whitney U tests.

RESULTS: Fibroblast growth factor-23 (standardized coefficient [sβ], 0.35; P = .04) and parathyroid hormones (sβ, -0.34; P = .042) were significantly associated with preprandial T-CPP concentrations in cats fed a PRD, whereas phosphate was significantly associated with postprandial T-CPP (sβ, 0.72; P = .003) and L-CPP (sβ, 0.75; P = .003) concentrations before dietary phosphate restriction. ΔT-CPP was significantly greater in cats with CKD with uptrend iCa compared to those with downtrend iCa after PRD stabilization (14 105 ± 36 299 AU vs -29 495 ± 49 664 AU; P = .036).

CONCLUSIONS AND CLINICAL IMPORTANCE: Calciprotein particle measurement is possible in cats and adds to the assessment of CKD-MBD, particularly the risk of soft tissue mineralization. The trajectory of iCa after PRD might influence CPP concentrations in cats with CKD.

PURPOSE: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality in sub-Saharan Africa, with most cases arising from chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. Despite Rwanda's national hepatitis guidelines recommending biannual surveillance with abdominal ultrasound (US) and alpha-fetoprotein (AFP) testing, the extent of adherence remains unknown. This study aimed to assess adherence to HCC surveillance guidelines among HBV- and HCV-infected patients at a national referral hospital in Rwanda.

METHODS: We conducted a retrospective descriptive study of HBV- and HCV-infected patients attending the Rwanda Military Referral and Teaching Hospital between January 2022 and December 2024. Surveillance adherence was assessed based on the proportion of time covered by abdominal US and AFP testing, with coverage categorized as optimal (100%), intermediate (50%-99%), or poor (<50%).

RESULTS: Among 388 patients (mean age, 41.9 years; 73.4% male), 82.7% were HBV-infected. Over one third (31.4%) and nearly half (44.6%) of the patients never received an US or AFP test, respectively. Only 15.5% achieved optimal US coverage, and 12.1% had optimal AFP coverage. Surveillance coverage was worse in patients age 31-50 years and those residing in Kigali. Paradoxically, patients from rural provinces demonstrated better adherence. Thirteen patients (3.4%) had liver lesions detected on US, although lesion status was undocumented in 44.6% of cases.

CONCLUSION: Adherence to HCC surveillance guidelines in Rwanda is suboptimal, with significant gaps across age groups and regions. These findings underscore the need for integrating HCC surveillance into routine hepatitis care and leveraging Rwanda's decentralized health system to improve early cancer detection.

Glioblastoma (GB) is one of the most aggressive brain tumours, with a high mortality rate. Tumour heterogeneity, GB's invasive nature, the blood-brain barrier (BBB) and resistance development offer significant challenges in devising an effective strategy to manage GB. Clinicians rely on tumour resection, radiotherapy and temozolomide (TMZ) chemotherapy, but their efficacy is hindered due to poor BBB penetration. EGFR (epidermal growth factor receptor), NF-κB, angiogenic pathways, RAS/RAF/MAPK, PI3K/Akt/mTOR, etc., play an important role in GB progression. Development in nanotechnology, pharmaceutical science and genetic engineering enables the design of drug candidates with superior efficacy and safety profiles. This review delves into recent advancements in nanoparticles, hydrogels, extracellular vesicles, microneedles and other drug delivery platforms used in GB treatment. These novel drug delivery systems achieved superior BBB penetration, tumour targeting, and controlled release and better survival outcomes in preclinical setups. This review also discusses the major translational challenges, including those of large-scale production, tumour heterogeneity, off-target effects and M2 macrophage induction. Innovative strategies focusing on drug delivery as a biological decision-making process, integrating tumour stress responses into drug carrier and system-level design principles, are discussed, outlining future prospects.

This study is to determine peripheral sample collection timing impact on selectivity index (SI) and success of unstimulated adrenal venous sampling (AVS) for primary aldosteronism (PA) subtyping. In this study, a retrospective discovery and a prospective validation arm were conducted. 74 patients undergoing AVS before and after-ACTH stimulation were reviewed. Discovery dataset was divided into 1) "pre" group, peripherals collected 30-min before AVS and 2) "post" group, peripherals collected 1-min after AVS. SIs were calculated using 30-min-pre and 1-min-post values. Patients with samples having SIs < 2 and SIs ≥ 5 on before and after-ACTH were classified as false negative and those with SI ≥ 2 and SI ≥ 5 on before and after-ACTH as true positive. Data was analyzed using Chi-squared test. For validation, 27 patients were enrolled prospectively as a paired group. In each, two peripherals were collected approximately 30 min before and 1 min after AVS. Cortisol was compared using Wilcoxon matched-pair signed rank test. Retrospectively, 38% of "30 min-pre" patients had SI < 2 in right adrenals, compared to 14% in "1 min-post" patients (P = 0.007). For the left, 45.9% of "30 min pre" patients had SIs < 2 compared to 13.5% in "1 min-post" patients, (P = 0.002). Prospectively, peripheral cortisol 1 min post decreased by 28% compared to 30-min pre (median, 6.4 to 4.6 μmol/L; P < 0.001). SIs increased 40% bilaterally (P < 0.001). In conclusion, in unstimulated AVS, collecting peripheral samples after sampling the adrenal veins is more likely to give more accurate SI than before sampling the adrenal veins.

Preprocedural chest or cardiac imaging for cardiothoracic surgery is focused on the imaging necessary to inform the performance of a surgical procedure after an initial diagnosis and the decision to operate has been made with consideration of patient comorbidities and anesthesia risk. The diverse range of noncoronary cardiac surgeries, coronary cardiac surgeries, and thoracic surgeries each have their own unique surgical techniques, risks, and complications, which can further vary between patients undergoing first time or repeat cardiothoracic surgery. This document reviews the literature for preprocedural chest or cardiac imaging in patients with and without a history of cardiothoracic surgery. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.