Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Stereotactic Thermal Ablation of Liver Tumors: 3D Planning, Multiple Needle Approach, and Intraprocedural Image Fusion Are the Key to Success—A Narrative Review

Thermal ablation is an emerging, potentially curative approach in treating primary and metastatic liver cancer. Different technologies are available, with radiofrequency ablation (RFA) and microwave ablation (MWA) being the most widely used. Regardless of the technique, destruction of the entire tumor, including an adequate safety margin, is key. In conventional single-probe US- or CT-guided thermal ablation, the creation of such large necrosis zones is often hampered by technical limitations, especially for large tumors (i.e., &gt;2–3 cm). These limitations have been overcome by stereotactic RFA (SRFA): a multiple needle approach with 3D treatment planning and precise stereotactic needle placement combined with intraprocedural image fusion of pre- and post-interventional CT scans for verification of treatment success. With these sophisticated tools and advanced techniques, the spectrum of locally curable liver malignancies can be dramatically increased. Thus, we strongly believe that stereotactic thermal ablation can become a cornerstone in the treatment of liver malignancies, as it offers all the benefits of a minimally invasive method while providing oncological outcomes comparable to surgery. This article provides an overview of current stereotactic techniques for thermal ablation, summarizes the available clinical evidence for this approach, and discusses its advantages

Comparison of a Robotic and Patient-Mounted Device for CT-Guided Needle Placement: A Phantom Study

Background: Robotic-based guidance systems are becoming increasingly capable of assisting in needle placement during interventional procedures. Despite these technical advances, less sophisticated low-cost guidance devices promise to enhance puncture accuracy compared with the traditional freehand technique. Purpose: To compare the in vitro accuracy and feasibility of two different aiming devices for computed-tomography (CT)-guided punctures. Methods: A total of 560 CT-guided punctures were performed by using either a robotic (Perfint Healthcare: Maxio) or a novel low-cost patient-mounted system (Medical Templates AG: Puncture Cube System [PCS]) for the placement of Kirschner wires in a plexiglass phantom with different slice thicknesses. Needle placement accuracy as well as procedural time were assessed. The Euclidean (ED) and normal distances (ND) were calculated at the entry and target point. Results: Using the robotic device, the ND at the target for 1.25 mm, 2.5 mm, 3.75 mm and 5 mm slice thickness were 1.28 mm (SD &plusmn; 0.79), 1.25 mm (SD &plusmn; 0.81), 1.35 mm (SD &plusmn; 1.00) and 1.35 mm (SD &plusmn; 1.03). Using the PCS, the ND at the target for 1 mm, 3 mm and 5 mm slices were 3.84 mm (SD &plusmn; 1.75), 4.41 mm (SD &plusmn; 2.31) and 4.41 mm (SD &plusmn; 2.11), respectively. With all comparable slice thicknesses, the robotic device was significantly more accurate compared to the low-cost device (p &lt; 0.001). Needle placement with the PCS resulted in lower intervention time (mean, 158.83 s [SD &plusmn; 23.38] vs. 225.67 s [SD &plusmn; 17.2]). Conclusion: Although the robotic device provided more accurate results, both guidance systems showed acceptable results and may be helpful for interventions in difficult anatomical regions and for those requiring complex multi-angle trajectories

Can accurate evaluation of the treatment success after radiofrequency ablation of liver tumors be achieved by visual inspection alone? Results of a blinded assessment with 38 interventional oncologists

Objectives To assess the difficulties in the immediate judgment of treatment success after radiofrequency ablation (RFA) of liver tumors by visual inspection alone and to evaluate whether radiologist’s expertise affects the resultant judgment. Methods Peri-interventional CT-scans of nine patients with nine hepatocellular carcinomas with known outcomes after RFA were presented to 38 participants from 14 different countries. In a total of 342 reads, all interventional oncologists assessed the pre- and immediate post-interventional CT-scans through conventional side-by-side juxtapositioning of images and judged whether complete ablation (i.e., technical success and technique efficacy) was achieved. Results were compared regarding expertise in percutaneous tumor ablation (>50 interventions performed). An ‘overcall’ was defined as insufficient ablation that was misjudged as sufficient, and an ‘undercall’ as an erroneous assessment of complete ablation. Results Overall 3.97 ± 1.27 out of 9 (44.1%) cases per radiologist were misjudged. The mean number of overcalls and undercalls per radiologist were 0.74 ± 0.50 out of 2 (37.0%), and 3.24 ± 1.28 out of 7 (46.3%), respectively. 18/38 (47.4%) participants had considerable experience in percutaneous tumor ablation, with such expertise having no significant influence on the results (overall: p = 0.70; overcalls: p = 0.87; undercalls: p = 0.75). Conclusions Conventional side-by-side evaluation of treatment success after RFA of liver tumors by the juxtaposition of pre- and post-interventional CT-scans is very difficult for experienced radiologists. The implementation of advanced processing techniques such as rigid/non-rigid image fusion with the assessment of the periablational margin is thus likely needed in order to decrease errors and objectively evaluate technical success and predict technique efficacy of liver RFA

Reliability of Stereotactic Radiofrequency Ablation (SRFA) for Malignant Liver Tumors: Novice versus Experienced Operators

Purpose: To compare the results of a novice with those of experienced interventional radiologists (IRs) for stereotactic radiofrequency ablation (SRFA) of malignant liver tumors in terms of safety, technical success, and local tumor control. Methods: A database, including all SRFA procedures performed in a single center between January 2011 and December 2018 was retrospectively analyzed. A total of 39 ablation sessions performed by a novice IR were compared to the results of three more experienced IRs. Comparative SRFA sessions were selected using propensity score matching considering tumor type, age, sex, tumor size, and tumor number as matching variables. Overall, 549 target tumors were treated in 273 sessions. Median tumor size was 2.2 cm (1.0–8.5 cm) for 178 hepatocellular carcinomas (HCCs) and 3.0 cm (0.5–13.0 cm) for 371 metastases. A median of 2 (1–11) tumors were treated per session. Results: No significant differences were observed when comparing the results of more experienced IRs with those of a novice IR regarding the rates of major complications (6.8% [16/234] vs. 5.1% [2/39]; p = 0.477), mortality (1.3% [2/234] vs. 0% [0/39]; p = 0.690), primary technical efficacy (98.5% [525/533] vs. 98.9% [94/95]; p = 0.735), and local recurrence (5.6% [30/533] vs. 5.3% [5/95]; p = 0.886). However, the median planning/placement time was significantly shorter for the experienced IRs (92 min vs. 119 min; p = 0.002). Conclusions: SRFA is a safe, effective, and reliable treatment option for malignant liver tumors and favorable outcomes can be achieved even by inexperienced operators with minimal supervision

Endogenous pararetroviral sequences in tomato (<it>Solanum lycopersicum</it>) and related species

Abstract Background Endogenous pararetroviral sequences (EPRVs) are a recently discovered class of repetitive sequences that is broadly distributed in the plant kingdom. The potential contribution of EPRVs to plant pathogenicity or, conversely, to virus resistance is just beginning to be explored. Some members of the family Solanaceae are particularly rich in EPRVs. In previous work, EPRVs have been characterized molecularly in various species of Nicotiana including N.tabacum (tobacco) and Solanum tuberosum (potato). Here we describe a family of EPRVs in cultivated tomato (Solanum lycopersicum L.) and a wild relative (S.habrochaites). Results Molecular cloning and DNA sequence analysis revealed that tomato EPRVs (named LycEPRVs) are most closely related to those in tobacco. The sequence similarity of LycEPRVs in S.lycopersicum and S.habrochaites indicates they are potentially derived from the same pararetrovirus. DNA blot analysis revealed a similar genomic organization in the two species, but also some independent excision or insertion events after species separation, or flanking sequence divergence. LycEPRVs share with the tobacco elements a disrupted genomic structure and frequent association with retrotransposons. Fluorescence in situ hybridization revealed that copies of LycEPRV are dispersed on all chromosomes in predominantly heterochromatic regions. Methylation of LycEPRVs was detected in CHG and asymmetric CHH nucleotide groups. Although normally quiescent EPRVs can be reactivated and produce symptoms of infection in some Nicotiana interspecific hybrids, a similar pathogenicity of LycEPRVs could not be demonstrated in Solanum L. section Lycopersicon [Mill.] hybrids. Even in healthy plants, however, transcripts derived from multiple LycEPRV loci and short RNAs complementary to LycEPRVs were detected and were elevated upon infection with heterologous viruses encoding suppressors of PTGS. Conclusion The analysis of LycEPRVs provides further evidence for the extensive invasion of pararetroviral sequences into the genomes of solanaceous plants. The detection of asymmetric CHH methylation and short RNAs, which are hallmarks of RNAi in plants, suggests that LycEPRVs are controlled by an RNA-mediated silencing mechanism.</p

Multidisciplinary Treatment of Liver Metastases from Intracranial SFTs/HPCs: A Report of Three Consecutive Cases

In the 2016 WHO classification of tumors of the central nervous system, hemangiopericytomas (HPCs) and solitary fibrous tumors (SFTs) were integrated into a new entity (SFT/HPC). Metastases to bone, liver, lung, and abdominal cavity are of concern. Only 37 cases of patients with liver metastases due to intracranial SFTs/HPCs have been reported. Herein, we present our experience in the management of patients with liver metastases from intracranial SFTs/HCPs. All consecutive patients who were treated for liver metastases from intracranial SFTs/HPCs from January 2014 to December 2020 were enrolled. Overall, three patients were treated for liver metastasis from SFTs/HPCs with curative intent. Two patients with bilobar metastases at presentation required surgical resection, transarterial embolization, stereotactic radiofrequency ablation (SRFA) and systemic therapy. One patient with a singular right liver lobe metastasis was treated with SRFA alone. This patient shows no evidence of liver metastases 39 months following diagnosis. Of the two patients with bilobar disease, one died 89 months following diagnosis, while one is still alive 73 months following diagnosis. Long-term survival can be achieved using a multimodal treatment concept, including surgery, loco-regional and systemic therapies. Referral to a specialized tertiary cancer center and comprehensive long-term follow-up examinations are essential