Genicular Artery Embolization, Radiofrequency Ablation, and Corticosteroid Therapy for Knee Osteoarthritis: A Cost-Effectiveness Analysis Using Randomized Clinical Trial Data.

Background: Many patients with symptomatic knee osteoarthritis (KOA) are refractory to traditional nonsurgical treatments such as intraarticular corticosteroid (CS) injection but are not yet eligible for or decline surgery. Genicular artery embolization (GAE) and radiofrequency ablation (RFA) are emerging adjunctive or alternative minimally invasive treatments. Objective: To perform a cost-effectiveness analysis (CEA) comparing CS, GAE, and RFA, for treatment of symptomatic KOA using a Markov model based on a de novo network meta-analysis (NMA) of randomized control trials. Methods: CEA was conducted to compare GAE and RFA to CS using a Markov cohort state-transition model from a U.S. Medicare payer's perspective over a 4-year time horizon. The model incorporated each treatment's success and attrition rates, costs, and utility benefit. Utility benefit values were derived at short-term (0.5-3 months) and long-term (6-12 months) posttreatment follow-up from NMA of published RCTs using an outcome of improved knee pain and/or function. Analyses were conducted at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY). Sensitivity analyses were performed, including when simulating various cost setting scenarios (i.e., office vs hospital outpatient treatment). Results: RFA demonstrated larger treatment effect than GAE, more pronounced at short-term [standardized mean difference (SMD), -1.6688, 95% CI [-2.7806; -0.5571], p=.003] than long-term (SMD -0.3822, 95% CI [-1.9743; 1.2100], p=.64) follow-up. Across cost setting scenarios, incremental cost-effectiveness ratios relative to CS were $561-1563/QALY for GAE versus $76-429/QALY for RFA (not counting scenarios in which RFA was dominated by CS). GAE demonstrated higher cost-effectiveness probability compared to RFA (41.6-54.8% vs. 18.4-29.2%, respectively). GAE was more cost-effective than RFA when the GAE clinical success rate and post-GAE utility value exceeded 32.1-51.0% and 0.562-0.617, respectively, and when the GAE quarterly attrition rate was less than 8.8-17.4%. RFA was more cost-effective when baseline pre-treatment utility values exceeded 0.695-0.713. Neither GAE costs nor RFA costs were sensitive parameters. Conclusion: Across scenarios, GAE was consistently the most likely cost-effective treatment option compared to RFA and CS, although clinical success rates, attrition rates, and utility values impact its cost-effectiveness. Clinical Impact: GAE is likely to be more cost-effective than RFA or CS for treatment of symptomatic KOA.

Quantitative differences in volumetric calculations for radiation dosimetry in segmental Y90 treatment planning using hybrid angiography-CT compared with anatomic segmentation.

OBJECTIVE: To compare treatment volumes reconstructed from hybrid Angio-CT catheter-directed infusion imaging and Couinaud anatomic model as well as the implied differences in Y-90 radiation dosimetry. METHODS: Patients who underwent transarterial radioembolization (TARE) using Y-90 glass microspheres with pretreatment CT or MRI imaging as well as intraprocedural angiography-CT (Angio-CT) were analysed. Treatment volumes were delineated using both tumoural angiosomes (derived from Angio-CT) and Couinaud anatomic landmarks. Segmental and lobar treatment volumes were calculated via semi-automated contouring software. Volume and dose differences were compared by the two-tailed Student t test or Wilcoxon signed-rank test. Factors affecting volume and dose differences were assessed via simple and/or multiple variable linear regression analysis. RESULTS: From September 2018 to March 2021, 44 patients underwent 45 lobar treatments and 38 patients received 56 segmental treatments. All target liver lobes and all tumours were completely included within the field-of-view by Angio-CT. Tumour sizes ranged between 1.1 and 19.5 cm in diameter. Segmental volumes and treatment doses were significantly different between the Couinaud and Angio-CT volumetry methods (316 vs 404 mL, P < .0001 and 253 vs 212 Gy, P < .01, respectively). Watershed tumours were significantly correlated with underestimated volumes by the Couinaud anatomic model (P < .001). There was a significant linear relationship between tumour diameter and percent volume difference (R2 = 0.44, P < .0001). The Couinaud model overestimated volumes for large tumours that exhibited central hypovascularity/necrosis and for superselected peripheral tumours. CONCLUSIONS: Angio-CT may confer advantages over the Couinaud anatomic model and enable more accurate, personalized dosimetry for TARE. ADVANCES IN KNOWLEDGE: Angio-CT may confer advantages over traditional cross-sectional and cone-beam CT imaging for selective internal radiation therapy planning.

Risk Factors for Abscess Development Following Percutaneous Microwave Ablation Therapy of Hepatic Tumors.

PURPOSE: To investigate risk factors associated with post-microwave ablation (MWA) abscess development. MATERIALS AND METHODS: A retrospective case-control analysis was conducted to identify hepatic MWA performed at a single tertiary medical center between January 2010 and January 2022. Case and control patients were defined as those who did or did not develop intrahepatic abscess within 3 months following MWA, respectively. Correlations between risk factors and post-MWA abscess development were assessed by Fisher's exact test. RESULTS: Between 2010 and 2022, 253 patients underwent 376 MWA sessions with post-ablation abscess complication rate of 1.1% (4/376). Complications associated with intrahepatic abscess included bacteremia, empyema, pleural abscess, subcutaneous abscess, cholangitis, bile leak, biliocutaneous and arterio-biliary fistulae, and pseudoaneurysm. One patient expired from septic shock 5 days post-ablation. All abscesses were treated by percutaneous drainage and antibiotics. One patient required concomitant placement of a biliary stent and embolization of a biliocutaneous tract. History of Sphincter of Oddi manipulation (p < 0.01), cholangiocarcinoma (p < 0.05), transarterial radioembolization (TARE) to the index lesion (p < 0.05), and abnormal serum alkaline phosphatase levels (p < 0.05) were significantly correlated with post-MWA abscess. The risk of developing post-MWA abscesses for patients with a history of cholangiocarcinoma or a history of Sphincter of Oddi manipulation were 20.0% and 27.2%, respectively. CONCLUSION: Patients with prior Sphincter of Oddi manipulation, cholangiocarcinoma, or TARE are at greater risk of developing post-MWA abscess.

Hybrid CT-angiography (Angio-CT) for combined CT and fluoroscopic procedures in interventional radiology enhances utilization.

PURPOSE: To investigate the utilization of an angiography-CT (Angio-CT) system and its advantages for single patient encounters. METHODS: Interventions utilizing both CT and fluoroscopy to perform multiple procedures in a single encounter or single interventions using both were identified. Cases were stratified by complexity (defined by RVUs). Comparative analyses of room (TRoom) and total encounter (TEncounter) times were performed between non-complex bundled cases and controls. RESULTS: Between June 2018 and August 2019, 1108 procedures were performed via the Angio-CT system; 10% (114/1108) used both fluoroscopy and CT. 21% (24/114) Involved more than one procedure in a single encounter that required a CT-only and fluoroscopy-only bundled procedure. 59% (67/114) were non-complex, and 70% (80/114) were non-oncologic. 82.5% (14/17) of non-complex bundled procedures demonstrated TRoom below the mean of their respective controls; 52.8% (9/17) were 2 standard deviations below the control means. Pleural catheter placement following post-lung biopsy pneumothorax was the most common non-complex bundled case with a significant reduction in TRoom when performed via Angio-CT compared to control (99 vs. 163 min, p < 0.0001). There was a significant reduction in TEncounter for abdominopelvic drain placement procedures bundled with either (1) percutaneous nephrostomy tube evaluation with or without replacement, or (2) central venous catheter placement (211 min vs. 344 min, p < 0.001 and 231 min vs. 347 min, p < 0.05, respectively). CONCLUSION: The primary use for the hybrid Angio-CT system was to perform non-oncologic and non-complex cases with potential reduction in TRoom and TEncounter for specific non-complex bundled cases.

Analyzing Radiation Use during Transjugular Intrahepatic Portosystemic Shunt Creation.

Portal vein access during transjugular intrahepatic portosystemic shunt creation was examined in 11 patients. Radiation metrics (kerma area product, reference point air kerma, and fluoroscopy times) during portal vein access were significantly greater for conventional versus intravascular US-guided transjugular intrahepatic portosystemic shunt (54.8 mGy ∙ cm2 ± 27.6 vs 8.4 mGy ∙ cm2 ± 5.0, P = .009; 210.4 mGy ± 109.1 vs 29.5 mGy ± 18.4, P = .009; 19.1 min ± 8.6 vs 8.9 min ± 4.6, P = .04). Wedged hepatic venography is a major contributor to radiation exposure. Intravascular US guidance is associated with significantly reduced radiation use.

Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators.

Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognate diol, eliminating a proresolving signal that potently suppresses IL-8-driven neutrophil transepithelial migration in vitro. Retrospective analyses of samples from patients with CF supported the translational relevance of these preclinical findings. Elevated levels of Cif in bronchoalveolar lavage fluid were correlated with lower levels of 15-epi LXA4, increased IL-8 concentrations, and impaired lung function. Together, these findings provide structural, biochemical, and immunological evidence that the bacterial epoxide hydrolase Cif disrupts resolution pathways during bacterial lung infections. The data also suggest that Cif contributes to sustained pulmonary inflammation and associated loss of lung function in patients with CF.

Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites.

UNLABELLED: Serratia marcescens generates secondary metabolites and secreted enzymes, and it causes hospital infections and community-acquired ocular infections. Previous studies identified cyclic AMP (cAMP) receptor protein (CRP) as an indirect inhibitor of antimicrobial secondary metabolites. Here, we identified a putative two-component regulator that suppressed crp mutant phenotypes. Evidence supports that the putative response regulator eepR was directly transcriptionally inhibited by cAMP-CRP. EepR and the putative sensor kinase EepS were necessary for the biosynthesis of secondary metabolites, including prodigiosin- and serratamolide-dependent phenotypes, swarming motility, and hemolysis. Recombinant EepR bound to the prodigiosin and serratamolide promoters in vitro. Together, these data introduce a novel regulator of secondary metabolites that directly connects the broadly conserved metabolism regulator CRP with biosynthetic genes that may contribute to competition with other microbes. IMPORTANCE: This study identifies a new transcription factor that is directly controlled by a broadly conserved transcription factor, CRP. CRP is well studied in its role to help bacteria respond to the amount of nutrients in their environment. The new transcription factor EepR is essential for the bacterium Serratia marcescens to produce two biologically active compounds, prodigiosin and serratamolide. These two compounds are antimicrobial and may allow S. marcescens to compete for limited nutrients with other microorganisms. Results from this study tie together the CRP environmental nutrient sensor with a new regulator of antimicrobial compounds. Beyond microbial ecology, prodigiosin and serratamolide have therapeutic potential; therefore, understanding their regulation is important for both applied and basic science.

Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation.

Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1ß production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation.