Comparison of clinical efficacy, subjective user experience, and safety for two different core biopsy needles, the Achieve® and Marquee®.

PURPOSE: To compare clinical efficacy, subjective radiologist preference, and complication rates for two different core biopsy needles, the Achieve® and Marquee®. METHODS: Retrospective review included consecutive patients who underwent 18 gauge non-targeted core liver biopsy, 30 with Achieve® (Merit Medical) and 30 with Marquee® (BD Bard) Pathologist (blinded to needle type) reviewed specimen total length, maximum width, and portal triad count. Sixteen radiologists subjectively rated (1 to 5(best)) each needle for cocking, firing, recoil, chamber exposure, handling, and overall. A medical records search of all (targeted and non-targeted) core liver biopsies 1/1/17-9/30/2020 compared rates of major (requiring transfusion and/or embolization) and minor (self-limited bleeding) hemorrhagic complications. Comparison between needle types was performed using t-test. RESULTS: For Achieve® and Marquee® needles, the respective mean (SD) for total length(mm) was 29.7(7.0) and 31.9(4.6), p = 0.1; max width(mm) was 0.78(0.1) and 0.85(0.1), p < 0.01; and number of portal triads was 15.3(5.3) and 17.3(5.3), p = 0.2. Radiologists subjectively preferred the Marquee® for several measures including cocking, chamber exposure, and overall (p < 0.02 for each), while the needles were rated similarly for firing, recoil, and handling. Review of 800 cases showed no difference in major (1.0% Achieve®, 1.9% Marquee®, p = 0.5) or minor (1.5% Achieve®, 0.5% Marquee®, p = 0.3) rates of hemorrhagic complications. CONCLUSION: Liver biopsy specimens were significantly wider with Marquee® compared to Achieve®. Radiologists preferred the Marquee® for multiple tactile measures, while the major complication rate was not significantly different. While both needles have a similar side-notch design, the Marquee® needle demonstrates better sample quality and higher user preference, without compromising safety.

Molecular Imaging and Therapy for Neuroendocrine Tumors.

OPINION STATEMENT: Neuroendocrine tumors (NETs) are relatively rare, with 12,000-15,000 new cases diagnosed annually in the USA. Although NETs are a diverse group of neoplasms, they share common molecular targets that can be exploited using nuclear medicine techniques for both imaging and therapy. NETs have traditionally been imaged with SPECT imaging using 111In-labeled octreotide analogs to detect neoplasms with somatostatin receptors. In addition, certain NETs (pheochromocytomas, paragangliomas, and neuroblastomas) are also effectively imaged using 123I- or 131I-labeled metaiodobenzylguanidine (MIBG), an analog of guanethidine. More recently, PET imaging with 68Ga-labeled somatostatin receptor (SSR) analogs allows neuroendocrine tumors to be imaged with much higher sensitivity. 68Ga-DOTATATE was approved as a PET tracer by the FDA in June 2016. In addition to imaging, both MIBG and DOTATATE can be labeled with therapeutic radionuclides to deliver targeted radiation selectively to macroscopic and microscopic tumor sites. The incorporation of the same molecular probe for imaging and therapy provides a radio-theranostic approach to identifying, targeting, and treating tumors. Over the years, several centers have experience treating NETs with high-dose 131I-MIBG. 177Lu-DOTATATE was approved by the FDA in 2018 for treatment of gastroenteropancreatic NETs and constitutes a major advancement in the treatment of these diseases. In this paper, we provide an overview of imaging and treating neuroendocrine tumors using MIBG and SSR probes. Although uncommon, neuroendocrine tumors have provided the largest experience for targeted radionuclide imaging and therapy (with the exception of radioiodine treatment for thyroid disease). In addition to benefitting patients with these rare tumors, the knowledge gained provides a blueprint for the development of future paired diagnostic/therapeutic probes for treating other diseases, such as prostate cancer.

Visual and semiquantitative analysis of 82Rb uptake in malignant tumors on PET/CT: first systematic analysis.

OBJECTIVE: The objective of this study was to analyze the uptake of rubidium in malignant tumors. PARTICIPANTS AND METHODS: Sixteen malignant lesions were included. Two radiologists compared each lesion to four references (subcutaneous fat, lung, mediastinal blood pool, and liver) at rest and stress and scored as 1-4. Maximum standardized uptake value (SUV) in each lesion and four references, as well as ratios of lesion SUV to SUV of each of the references, were calculated at rest and stress. We assessed an agreement for scores of reader 1 versus reader 2 (inter-reader) at rest and stress, scores at rest versus stress (intrapatient) for reader 1 and reader 2, and lesion SUV and respective ratios at rest and stress using paired t-test and Bland-Altman analyses. RESULTS: Fifteen (94%) out of 16 lesions had a score of 3 or 4 at rest or stress or both by at least one reviewer. We did not find evidence of inter-reader bias at rest or stress or intrapatient (rest vs. stress) bias for either reader. SUV ranged from 1.0 to 8.1 at rest and from 0.7 to 6.7 at stress. There was an excellent agreement between ratios of lesion SUV to lung SUV at rest versus stress. On the extreme, there was a poor agreement between ratios of lesion SUV to liver SUV at rest versus stress. Otherwise, the agreement was good for the majority of the results, and moderate for a few others. CONCLUSION: Malignant tumors can be readily depicted and quantified on rubidium PET/CT. Further research is needed.

Comparative Analysis of Cone-Beam CT Angiogram and Conventional CT Angiogram for Prostatic Artery Identification Prior to Embolization.

Pre-prostatic artery embolization (PAE) cone-beam computed tomography (CT) angiograms (n = 31; mean age: 62.4 ± 9.75 years) and conventional CT angiograms (n = 32; mean age: 62.5 ± 7.2 years) were retrospectively compared. Mean signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), radiation exposure, and prostatic artery (PA) identification scores (0-4) for cone-beam CT angiogram and conventional CT angiogram were 33.19 (± 14.31) and 18.13 (± 5.38) (P < .01); 27.42 (± 13.39) and 14.78 (± 4.92) (P < .01); 14.57 mSv (±2.5) and 19.25 mSv (±3.7) (P < .01); 3.36 (± 0.89) and 3.16 (± 0.95) (P = .08), respectively. Pre-PAE cone-beam CT angiogram allows for PA identification with improved SNR and CNR and less radiation dose compared to conventional CT angiogram.

Comparison of Type II Endoleak Embolizations: Embolization of Endoleak Nidus Only versus Embolization of Endoleak Nidus and Branch Vessels.

PURPOSE: To compare outcomes of type II endoleak embolization involving embolization of the endoleak nidus only vs embolization of the endoleak nidus and branch vessels in patients treated with endovascular repair of abdominal aortic aneurysms. MATERIALS AND METHODS: Twenty-nine consecutive patients (mean age, 77.9 y; range, 63-88 y) with type II endoleak who underwent embolization from 2004 to 2015 were retrospectively reviewed. Patients were divided into 2 groups: embolization of endoleak nidus only (group A) and embolization of endoleak nidus and branch vessels (group B). Mean follow-up intervals were 20.5 months ± 14.7 in group A and 24.3 months ± 18.5 in group B. Outcomes were compared between groups by Mann-Whitney U and Pearson χ2 tests. RESULTS: Mean interval from endovascular aneurysm repair to embolization was 47.6 months ± 42.9, and mean presentation time of endoleak before embolization was 23.1 months ± 25.8. Coils (n = 28) and liquid embolic agents (n = 23) were used for embolization. There were no significant differences in rates of residual endoleak (50% vs 53.8%; P = .96) or sac decrease/stabilization (62.5% vs 61.5%; P = .64). Procedure time and radiation exposure in group B (132.3 min ± 78.1; 232.4 Gy·cm2 ± 130.7) were greater than in group A (63.4 min ± 11.9; 61.5 Gy·cm2 ± 35.5; P < .01). There were no procedure-related complications. CONCLUSIONS: Embolization of the endoleak nidus and branch vessels is not superior to embolization of only the nidus in terms of occlusion of type II endoleak and change in sac size despite requiring longer procedure times and resulting in greater patient radiation exposure.

Conformationally selective RNA aptamers allosterically modulate the ß2-adrenoceptor.

G-protein-coupled receptor (GPCR) ligands function by stabilizing multiple, functionally distinct receptor conformations. This property underlies the ability of 'biased agonists' to activate specific subsets of a given receptor's signaling profile. However, stabilizing distinct active GPCR conformations to enable structural characterization of mechanisms underlying GPCR activation remains difficult. These challenges have accentuated the need for receptor tools that allosterically stabilize and regulate receptor function through unique, previously unappreciated mechanisms. Here, using a highly diverse RNA library combined with advanced selection strategies involving state-of-the-art next-generation sequencing and bioinformatics analyses, we identify RNA aptamers that bind a prototypical GPCR, the ß2-adrenoceptor (ß2AR). Using biochemical, pharmacological, and biophysical approaches, we demonstrate that these aptamers bind with nanomolar affinity at defined surfaces of the receptor, allosterically stabilizing active, inactive, and ligand-specific receptor conformations. The discovery of RNA aptamers as allosteric GPCR modulators significantly expands the diversity of ligands available to study the structural and functional regulation of GPCRs.

A photocrosslinking assay for reporting protein interactions in polyketide and fatty acid synthases.

Understanding protein-protein interactions that occur between ACP and KS domains of polyketide synthases and fatty acid synthases is critical to improving the scope and efficiency of combinatorial biosynthesis efforts aimed at producing non-natural polyketides. Here, we report a facile strategy for rapidly reporting such ACP-KS interactions based on the incorporation of an amino acid with photocrosslinking functionality. Crucially, this photocrosslinking strategy can be applied to any polyketide or fatty acid synthase regardless of substrate specificity, and can be adapted to a high-throughput format for directed evolution studies.

A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome.

OBJECTIVE: Infants with meconium aspiration syndrome (MAS) have marked surfactant dysfunction. Airways and alveoli of affected neonates contain meconium, inflammatory cells, inflammatory mediators, edema fluid, protein, and other debris. The objective of this study was to compare treatment with bronchoalveolar lavage using dilute Surfaxin with standard therapy in a population of newborn infants with MAS. METHODS: Inclusion criteria were 1) gestational age > or =35 weeks, 2) enrollment within 72 hours of birth, 3) diagnosis of MAS, 4) need for mechanical ventilation, and 5) an oxygenation index > or =8 and < or =25. Subjects were randomized to either lavage with Surfaxin or standard care (2:1 proportion). In lavaged infants, a volume of 8 mL/kg dilute Surfaxin (2.5 mg/mL) was instilled into each lung over approximately 20 seconds followed by suctioning after 5 ventilator breaths. The procedure was repeated twice. The third and final lavage was with a more concentrated solution (10 mg/mL) of Surfaxin. RESULTS: Twenty-two infants were enrolled (15 Surfaxin and 7 control). Demographic characteristics were similar. There were trends (not significant) for Surfaxin-lavaged infants to be weaned from mechanical ventilation earlier (mean of 6.3 vs 9.9 days, respectively), as well as to have a more rapid decline in their oxygenation indexes compared with control infants, the latter difference persisting for the 96-hour-long study period. The therapy was safe and generally well tolerated by the infants. CONCLUSIONS: Dilute Surfaxin lavage seems to be a safe and potentially effective therapy in the treatment of MAS. Data from this investigation support future prospective, controlled clinical trials of bronchoalveolar lavage with Surfaxin in neonates with MAS.