Contralateral Hypertrophy Post Yttrium-90 Transarterial Radioembolization in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombus.

Objectives Contralateral hypertrophy of non-irradiated liver following Yttrium-90 (90Y) transarterial radioembolization (TARE) is increasingly recognized as an option to facilitate curative surgical resection in patients that would otherwise not be surgical candidates due to a small future liver remnant (FLR). This study aimed to investigate the correlation between patient features and liver hypertrophy and identify potential predictors for liver growth in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) undergoing TARE. Methodology Twenty-three patients with HCC and PVTT were included. Contralateral liver hypertrophy was assessed at six months posttreatment based on CT or MRI imaging. Thirteen patient features were selected for statistical and prediction analysis. Univariate Spearman correlation and analysis of variance (ANOVA) tests were performed. Subsequently, four feature-selection methods based on multivariate analysis were used to improve model generalization performance. The selected features were applied to train linear regression models, with fivefold cross-validation to assess the performance of the predicted models. Results The ratio of disease-free target liver volume to spared liver volume and total liver volume showed the highest correlations with contralateral hypertrophy (P-values = 0.03 and 0.05, respectively). In three out of four feature-selection methods, the feature of disease-free target liver volume to total liver volume ratio was selected, having positive correlations with the outcome and suggesting that more hypertrophy may be expected when more volume of disease-free liver is irradiated. Conclusions Contralateral hypertrophy post-90Y TARE can be an option for facilitating surgical resection in patients with otherwise small FLR.

Hepatic Hilar Nerve Block for Adjunctive Analgesia during Percutaneous Thermal Ablation of Hepatic Tumors: A Retrospective Analysis.

PURPOSE: To determine whether hepatic hilar nerve block techniques reduce analgesic and sedation requirements during percutaneous image-guided thermal ablation of hepatic tumors. MATERIALS AND METHODS: A single-center retrospective cohort analysis was performed of 177 patients (median age, 67 years; range, 33-86 years) who underwent percutaneous image-guided thermal ablation of liver tumors. All patients were treated utilizing local anesthetic and moderate sedation between November 2018 and November 2021 at a tertiary level hospital, with or without the administration of a hepatic hilar nerve block. Univariable and multivariable linear regression analyses were performed to determine the relationship between the administration of the hilar nerve block and fentanyl and midazolam dosages. RESULTS: A total of 114 (64%) patients received a hilar nerve block in addition to procedural sedation, and 63 (36%) patients received procedural sedation alone. There were no significant differences in the baseline demographic and tumor characteristics between the cohorts. The procedure duration was longer in the hilar block cohort than in the unblocked cohort (median, 95 vs 82 minutes; P = .0012). The technical success rate (98% in both the cohorts, P = .93) and adverse event rate (11% vs 3%, P = .14) were not significantly different between the cohorts. After adjusting for patient and tumor characteristics, ablation modality, and procedure and ablation durations, hilar nerve blocks were associated with lower fentanyl (-18.4%, P = .0045) and midazolam (-22.7%, P = .0007) dosages. CONCLUSIONS: Hepatic hilar nerve blocks significantly decrease the fentanyl and midazolam requirements during thermal ablation of hepatic tumors, without a significant change in the technical success or adverse event rates.

Nonhealing boils.

It seemed clear that the growth was linked to a recent trip to a tropical location. But the true cause wasn't the one that was originally suspected.

Evaluation of the INDICAID COVID-19 Rapid Antigen Test in Symptomatic Populations and Asymptomatic Community Testing.

As the COVID-19 pandemic progresses, there is an increasing need for rapid, accessible assays for SARS-CoV-2 detection. We present a clinical evaluation and real-world implementation of the INDICAID COVID-19 rapid antigen test (INDICAID rapid test). A multisite clinical evaluation of the INDICAID rapid test using prospectively collected nasal (bilateral anterior) swab samples from symptomatic subjects was performed. The INDICAID rapid test demonstrated a positive percent agreement (PPA) and negative percent agreement (NPA) of 85.3% (95% confidence interval [95% CI], 75.6% to 91.6%) and 94.9% (95% CI, 91.6% to 96.9%), respectively, compared to laboratory-based reverse transcriptase PCR (RT-PCR) using nasal specimens. The INDICAID rapid test was then implemented at COVID-19 outbreak screening centers in Hong Kong as part of a testing algorithm (termed "dual-track") to screen asymptomatic individuals for prioritization for confirmatory RT-PCR testing. In one approach, preliminary positive INDICAID rapid test results triggered expedited processing for laboratory-based RT-PCR, reducing the average time to confirmatory result from 10.85 h to 7.0 h. In a second approach, preliminary positive results triggered subsequent testing with an onsite rapid RT-PCR, reducing the average time to confirmatory result to 0.84 h. In 22,994 asymptomatic patients, the INDICAID rapid test demonstrated a PPA of 84.2% (95% CI, 69.6% to 92.6%) and an NPA of 99.9% (95% CI, 99.9% to 100%) compared to laboratory-based RT-PCR using combined nasal/oropharyngeal specimens. The INDICAID rapid test has excellent performance compared to laboratory-based RT-PCR testing and, when used in tandem with RT-PCR, reduces the time to confirmatory positive result. IMPORTANCE Laboratory-based RT-PCR, the current gold standard for COVID-19 testing, can require a turnaround time of 24 to 48 h from sample collection to result. The delayed time to result limits the effectiveness of centralized RT-PCR testing to reduce transmission and stem potential outbreaks. To address this, we conducted a thorough evaluation of the INDICAID COVID-19 rapid antigen test, a 20-minute rapid antigen test, in both symptomatic and asymptomatic populations. The INDICAID rapid test demonstrated high sensitivity and specificity with RT-PCR as the comparator method. A dual-track testing algorithm was also evaluated utilizing the INDICAID rapid test to screen for preliminary positive patients, whose samples were then prioritized for RT-PCR testing. The dual-track method demonstrated significant improvements in expediting the reporting of positive RT-PCR test results compared to standard RT-PCR testing without prioritization, offering an improved strategy for community testing and controlling SARS-CoV-2 outbreaks.

Asian and African/Caribbean AQP4-NMOSD patient outcomes according to self-identified race and place of residence.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by aquaporin-4 antibodies, whose prognosis is influenced by onset age, race, environmental exposures and immunosuppression. Distinguishing the contribution of environment from genetics is challenging. We aimed to compare neuromyelitis optica spectrum disorder (NMOSD) patient outcomes according to self-identified racial group and place of residence. METHODS: This retrospective analysis of prospectively collected data included non-white anti-aquaporin-4 antibody positive NMOSD patients under follow-up from 15 centers [United Kingdom, France, Germany, Denmark, Martinique, United States of America, Japan, South Korea, Singapore, Thailand, China (including Hong Kong) and India]. Racial groups were designated: African/Caribbean; South Asian; East Asian (including Southeast Asia). Patients from these racial groups residing outside Africa/Caribbean or Asia were compared with those living in the Caribbean or the Asian areas. Kaplan-Meier survival curves and Cox models were generated using time to sustained Expanded Disability Status Scale≥6.0 or death; time to sustained Kurtzke Visual Function Score≥3.0 or a composite endpoint of all three. RESULTS: Among 821 patients, African/Caribbean patients (n = 206) had the shortest time to immunosuppression and higher visual disability at onset. South Asian patients (n = 65) were younger, had lower visual disability at onset and higher mortality rate. East Asians (n = 550) had the lowest relapse rate and lowest accrued motor disability. Survival analysis of African/Caribbean outside Africa/Caribbean vs those in the Caribbean showed a significant difference in the composite endpoint (p = 0.024,log-rank test), not apparently related to treatment differences. No significant differences between native and those residing outside Asia were found for other racial groups. CONCLUSION: This NMOSD study reports the effects of place of residence on the outcomes in different races. Place of residence may not be a significant driver of disability among Asian patients, while it may influence African/Caribbean patient outcomes. Validating these findings could help distinguish between genetic causes and potentially modifiable environmental factors.

Characterization of LY2775240, a selective phosphodiesterase-4 inhibitor, in nonclinical models and in healthy subjects.

LY2775240 is a highly selective, potent and orally-administered inhibitor of phosphodiesterase 4 (PDE4), and is being investigated as a treatment option for inflammatory disorders, such as psoriasis. LY2775240 was investigated in rodent and rhesus monkey nonclinical models. Treatment with LY2775240 led to significant reductions in TNFα production, a marker of PDE4 engagement upon immune activation, in both nonclinical models. In the first part of a 2-part first-in-human randomized study, a wide dose range of LY2775240 was safely evaluated and found to be well-tolerated with common adverse events (AEs) of nausea, diarrhea, and headache. No serious AEs were reported. The pharmacokinetic profile of LY2775240 was well-characterized, with a half-life that can support once-a-day dosing. An ex vivo pharmacodynamic (PD) assay demonstrated dose-dependent PDE4 target engagement as assessed by reduction in TNFα production. A 20 mg dose of LY2775240 led to near-maximal TNFα inhibition in this PD assay in the first part of the study and was selected for comparison with the clinical dose of apremilast (30 mg) in the crossover, second part of this study. The 20 mg dose of LY2775240 demonstrated sustained maximal (50%-80%) inhibition of TNFα over all timepoints over the 24-h duration. The comparator apremilast achieved peak inhibition of ~ 50% at only 4 h postdose with a return to about 10% inhibition within 12 h of dosing. In summary, the nonclinical data and safety, tolerability, and PK/PD data in healthy subjects supports further investigation of LY2775240 in inflammatory indications. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Phosphodiesterase 4 (PDE4) inhibitors, such as apremilast, are currently approved to treat autoimmune disorders, such as psoriasis. LY2775240 is an oral PDE4 inhibitor being developed for treatment of a variety of inflammatory disorders. The degree of enzymatic inhibition achieved by PDE4 inhibitors clinically is poorly understood. WHAT QUESTION DID THIS STUDY ADDRESS? This study investigated single ascending doses of LY2775240, a highly selective oral PDE4 inhibitor, in healthy subjects. LY2775240 was well-tolerated over the dose range evaluated, and pharmacokinetic/pharmacodynamic (PD) profiles were well-characterized. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? This study evaluated different doses of LY2775240 and subsequently compared a selected LY2775240 dose with the clinical dose of apremilast with an ex vivo assay. This information builds a connection between target engagement and clinical efficacy. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This is the first report of an ex vivo PD assay that has been systematically implemented in a PDE4 inhibitor Phase 1 study. Early investigation of exposure-response relationships versus a comparator can support evaluation of clinically meaningful doses of investigational agents.

Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance.

OBJECTIVE: Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine. DESIGN: We performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples. RESULTS: We characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1ß and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease. CONCLUSION: Our work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn's disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1ß-targeting therapies upstream of IL-23.

Palliative care needs and utilisation of different specialist services in the last days of life for people with lung cancer.

OBJECTIVES: To (a) compare palliative care needs of lung cancer patients on their final admission to community-based and inpatient palliative care services; and (b) explore whether and how these care needs affect their utilisation of different palliative care services in the last days of life. METHODS: Descriptive study involving 17,816 lung cancer patients who received the last episode of palliative care from specialist services and died between 1 January 2013 and 31 December 2018. RESULTS: Both groups of patients admitted to community-based and inpatient palliative care services generally experienced relatively low levels of symptom distress, but high levels of functional impairment and dependency. "Unstable" versus "stable" palliative care phase (Odds ratio = 11.66; 95% Confidence Interval: 9.55-14.24), poorer functional outcomes and severe levels of distress from many symptoms predicted greater likelihood of use of inpatient versus community-based palliative care. CONCLUSIONS: Most inpatient palliative care admissions are not associated with high levels of symptom severity. To extend the period of home care and rate of home death for people with lung cancer, additional investment is required to improve their access to sufficiently skilled palliative care staff, multi-disciplinary teams and 24-hour home support in community settings.

Efficacy and Prognostic Factors for Y-90 Radioembolization (Y-90) in Metastatic Neuroendocrine Tumors with Liver Metastases.

Background: Yttrium-90 (Y-90) can be an effective liver-directed therapy for patients with metastatic neuroendocrine tumors (NETs), but population-based data are limited. We characterized the use of Y-90 in NET patients and identified factors associated with response. Methods: We identified 49 patients with metastatic liver-dominant NETs across BC Cancer's six regional centres who received Y-90 between June 2011 and January 2017 in British Columbia, Canada. Baseline characteristics, radiographic responses, and outcomes were summarized. Results: Of the 49 patients who received Y-90, the median age was 56 years (range 21-78), 49% were male, and 94% had an ECOG performance status of 0-1. The primary location of the NET included pancreas (31%), small bowel (41%), large bowel (6%), unknown (14%), and others (12%). 69% of these patients had liver metastases alone, and tumors were graded as G1 (61%), G2 (25%), G3 (2%), and unknown (12%). Prior therapies included surgery (63%), local ablative therapy (25%), somatostatin analogue (69%), and systemic therapy (35%). The median Y-90 dose was 2.2 GBq (range 0.8-3.6), as SIR-spheres (69%) or TheraSpheres (29%). Median time to Y-90 from diagnosis of metastases measured 1.54 years. 88% received segmental Y-90, with 1 (69%), 2 (29%), and 3 (2%) treatments. Y-90 resulted in partial response (53%), stable disease (33%), and progressive disease (12%). Y-90 was well-tolerated, with infrequent grade 3-4 biochemical toxicities (2%) and grade 3 abdominal pain (6%). Longer overall survival (OS) was associated with resection of primary tumor, well-differentiated histology, and low Ki-67. Median OS was 27.2 months (95% CI 8.0-46.5). Conclusions: In our population-based cohort, Y-90 was well-tolerated in patients with metastatic liver-dominant NETs. Prior surgical resection was an important predictor of OS.

Safety and Efficacy of a Truncated Deflation Algorithm for Distal Transradial Access.

PURPOSE: To assess safety and efficacy of a modified rapid hemostasis protocol for distal transradial access (TRA). MATERIALS AND METHODS: A single-center retrospective study of patients undergoing percutaneous image-guided procedures from a distal TRA with rapid deflation hemostasis protocol was performed. Between March 2017 and August 2019, 593 procedures in 434 patients were performed. Mean patient age was 63.5 y (range, 18-94 y). RESULTS: The most common procedures were transarterial chemoembolization (218; 36.8%), abdominal and pelvic embolization (116; 19.6%), yttrium-90 mapping (115; 19.4%), yttrium-90 administration (84; 14.2%), and diagnostic angiography (44; 7.4%). Mean (range) values for clotting parameters were international normalized ratio 1.2 (0.9-3.2), partial thromboplastin time 33.5 s (26-44 s), and platelets 23.4 × 109/L (37-552 × 109/L). A hematoma developed in 7 (1.2%) patients. No radial artery occlusions were encountered during follow-up. Nursing intensity was defined as the number of minutes after the procedure required for assessing and managing the access site for bleeding. The mean nursing intensity was 25.1 min (range, 25-40 min). CONCLUSIONS: The rapid deflation hemostasis protocol for distal TRA at the anatomical snuffbox was feasible and safe. No significant difference or association was found between hematoma formation and clotting parameters after the procedure or type of vascular access equipment used.

Palliative care needs and utilization of specialist services for people imminently dying with dementia: A national population-based study.

BACKGROUND: There is a growing emphasis on the importance of availability of specialist palliative care for people living with dementia. However, for people imminently dying with dementia, we still have little knowledge about their palliative care needs and utilization of different specialist services. OBJECTIVES: To (i) assess palliative care needs and other clinical and social characteristics of people imminently dying with dementia on their last admission in the context of community and inpatient palliative care services before death; (ii) compare care needs between patients requiring community-based and inpatient services; (iii) determine how and whether such care needs affect utilization of different palliative care services. DESIGN: Observational study using data from the Australian Palliative Care Outcomes Collaboration. SETTINGS: Specialist palliative care services across Australia registered in the Palliative Care Outcomes Collaboration. PARTICIPANTS: A total of 3361 people who required specialist palliative care principally for dementia (including Alzheimer's disease and other dementias), and whose death occurred between 1 January 2013 and 31 December 2018. METHODS: Five validated clinical instruments were used to collect point-of-care outcomes on each individual's function (Resource Utilisation Groups - Activities of Daily Living & Australia-modified Karnofsky Performance Status), symptom distress (Symptoms Assessment Scale & Palliative Care Problem Severity Score) and other clinical characteristics (Palliative Care Phases). We fitted multivariate logistic regression models to examine the association between these clinical outcomes and utilization of different specialist palliative care services. RESULTS: The majority of people imminently dying with dementia had absent or mild levels of symptom distress but experienced high levels of functional decline and needed substantial assistance with basic tasks of daily living in their last days of life. Large disparities in symptoms distress and functional decline between inpatient and community groups were not observed although differences in assessment scores were often statistically significant. Poor functional outcomes (odds ratio = 1.77, 95% confidence interval: 1.24-2.52) and "non-stable" palliative care phases (odds ratio =24.51, 95% confidence interval: 12.03-49.96) were positively associated with use of inpatient versus community palliative care, whereas there was no clear association between the majority of symptoms and use of different care services. CONCLUSIONS: The majority of people imminently dying with dementia could potentially benefit from greater access to supportive services in the community. Development of a dementia-specific palliative care pathway is needed to promote needs-based palliative care delivery models. TWEETABLE ABSTRACT: the majority of people imminently dying with dementia could potentially benefit from greater access to supportive services in community.

Left Distal Transradial Access (ldTRA): A Comparative Assessment of Conventional and Distal Radial Artery Size.

PURPOSE: To assess left radial artery size, technical feasibility and safety of ldTRA in the anatomical snuffbox for percutaneous image-guided procedures. MATERIALS AND METHODS: A retrospective single-center study was performed from November 2016 to June 2018 on all patients undergoing ldTRA for interventional radiology procedures. RESULTS: A total of 287 patients (91 female and 196 male), aged 18-94 years (mean age 64 years), were included. 389 procedures were performed which included hepatic chemoembolization (n = 161), selective internal radiation therapy Y-90 mapping (n = 74), selective internal radiation therapy Y-90 administration (n = 48), diagnostic angiography (n = 34), mesenteric and pelvic embolization (n = 59), stent insertion (n = 8) and miscellaneous (n = 5). Mean sonographic measurement of the left radial artery size at the conventional site at the wrist was 2.55 mm (range 1.4-3.3 mm) and 2.34 mm (range 1.4-3.2 mm) at the anatomical snuffbox (p < 0.001). Technical success rate was 100%, a single small hematoma occurred in the first patient (0.3%). 74.2% of patients had follow-up for radial artery patency (mean 46 days, range 0-66 days), which did not reveal radial artery occlusions or pseudoaneurysm formation. CONCLUSION: The left distal radial artery in the anatomical snuffbox is smaller in comparison with the conventional access site at the wrist. The difference however is small and does not require intentional downsizing of vascular access equipment to facilitate utilization of ldTRA. Assessment of the vessel size is imperative for appropriate equipment selection and optimizing procedural success. This study supports that ldTRA is technically feasible and safe.

Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy.

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin's target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our late-stage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies.

Ablative Transarterial Radioembolization Improves Survival in Patients with HCC and Portal Vein Tumor Thrombus.

PURPOSE: Patients with hepatocellular carcinoma and portal vein tumor thrombus have a poor prognosis and limited therapeutic options. We sought to compare survival, tolerability, and safety in such patients treated with conventional yttrium-90 transarterial radioembolization dosimetric techniques or ablative transarterial radioembolization. MATERIALS AND METHODS: This retrospective, single-center cohort study included patients with hepatocellular carcinoma and right, left, and/or main portal vein tumor thrombus, preserved liver function (Child-Pugh class ≤ B7), and good performance status (Eastern Cooperative Oncology Group score ≤ 1) treated with yttrium-90 microspheres from 2011 to 2018 with ablative intent transarterial radioembolization (A-TARE), or conventional technique (cTARE). Statistical models were used to compare overall survival, post-treatment survival, toxicities, and prognosticators of response. RESULTS: Fifty-seven patients were included (21 [36.8%] ablative and 36 [63.2%] conventional intent). Median overall survival was 15.7 months. Compared to conventional treatment, ablative radioembolization was associated with longer median overall survival (45.3 vs 18.2 months; P = 0.003), longer post-treatment survival (19.1 vs 4.9 months; P = 0.005), a 70% lower risk of death (hazard ratio 0.30; 95% confidence interval, 0.13-0.70; P = 0.005), and improved 4-year survival (53.9% vs 11.2%). Overall survival did not differ significantly between treatment with resin and glass microspheres (27.5 vs 22.2 months; P = 0.62). Acceptable hepatic toxicities were observed after yttrium-90 administration, without statistical differences between the groups. CONCLUSION: In patients with advanced hepatocellular carcinoma and portal vein tumor thrombus, A-TARE is associated with longer survival than cTARE. Neither modality is associated with deleterious effects on liver function.

Prospective Study on Total Fluoroscopic Time in Patients Undergoing Uterine Artery Embolization: Comparing Transradial and Transfemoral Approaches.

PURPOSE: Comparing total fluoroscopy time (FT) to perform uterine artery embolization (UAE) with transradial approach (TRA) versus transfemoral approach (TFA). Our hypothesis was that there would be no significant procedural time penalty incurred, despite the learning curve associated with adopting a new approach. MATERIALS AND METHODS: A cohort study was undertaken including 66 consecutive patients undergoing UAE with either TRA/TFA between January and September 2015. Total FT was recorded prospectively for each procedure, and data subsequently analyzed retrospectively. Each operator had at least 2 years of experience as an interventional radiologist having performed at least 200 TFA UAEs. All operators had recently incorporated TRA into their practice. RESULTS: A total of 39 TFA and 27 TRA cases were included in the study; mean age for TFA group was 44.4 years (± 4.9) and for TRA group was 45.1 years (± 4.9) (p = 0.59). Mean FTs were comparable between the two groups (p = 0.86) despite a learning curve associated with TRA: The mean total FT with TFA was 20.36 min (± 9.48) compared to TRA 20.12 min (± 7.67). CONCLUSIONS: FTs for TRA UAE were comparable to TFA UAE, even though TRA had been recently adopted as a new approach. Despite the learning curve associated with developing a novel technique, operators should not expect the efficiency of their service to be significantly compromised. Introducing this safe and effective method of vascular access should therefore be considered.

Management of Acute Contrast Reactions-Understanding Radiologists' Preparedness and the Efficacy of Simulation-Based Training in Canada.

PURPOSE: Acute radiologic emergencies, primarily severe contrast reactions, are rare but life-threatening events. Given a generalized paucity of formalized or mandated training, studies have shown that radiologists and trainees perform poorly when acutely managing such events. Moreover, skill base, knowledge, and comfort levels precipitously decline over time given the infrequent occurrence of these events during one's daily practice. The primary aim of this study was to assess radiologists' preparedness for managing acute radiologic emergencies and to determine the efficacy of a high-fidelity simulation based training model in an effort to provide a rationale for similar programs to be implemented on a provincial or national level. METHODS: This was a prospective, observational study of radiology residents and attending radiologists throughout the province who were recruited to attend a full-day simulation-based course presenting various cases of acute radiologic emergencies. Participant demographics were collected at the time of commencement of the workshop. Course materials were disseminated 4 weeks prior to the workshop, and a 17-question knowledge quiz was administered before and after the workshop. Likert-type questionnaires were also distributed to survey comfort levels and equipment familiarity. The knowledge quiz and questionnaire were redistributed at 3- and 6-month intervals for acquisition of follow-up data. RESULTS: A total of 14 attending radiologists and 7 residents attended the workshop, with all participants completing the preworkshop questionnaire and 90.5% (19 of 21) completing the post-workshop questionnaire. Participants' principle locations of practice were as follows: academic institutions (50%), community hospitals (36.9%), and private clinics (13.1%). A significant increase in knowledge was demonstrated, with average scores of 10 out of 17 (59%) and 14.5 out of 17 (85%) (P < .001) before and after the workshop, respectively. A significant increase in participants' comfort levels in recognizing acute anaphylactic reactions (3.5; 4.7, P < .001), commencing initial management for acute radiologic emergencies (3.3; 5.0, P < .001), and administering the correct dose for anaphylactic reactions (2.5; 4.8, P < .001) was also demonstrated. Moreover, participants became increasingly familiar with the contents and equipment found within contrast reaction kits (2.8; 3.8, P < .01). Repeat evaluations at 3 and 6 months found an average knowledge test score of 13.8 out of 17 (81%) and 10.8 out of 17 (64%), respectively. Comfort levels were also reassessed in recognizing acute anaphylactic reactions (4.5; 4.1), commencing initial management (4.0; 3.9) and administering the correct dose of medication (4.0; 3.7) at 3- and 6-month intervals. CONCLUSIONS: Acute radiologic emergencies are rare but life-threatening events that require rapid diagnosis and treatment to mitigate associated morbidity and mortality. Simulation-based workshops are a highly efficacious training model to increase knowledge, comfort levels, and equipment familiarity for radiologists and trainees alike; however, retraining at regular intervals is required.

Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement.

Intraprocedural Parenchymal Blood Volume Is a Predictor of Treatment Response for Chemoembolization in Hepatocellular Carcinoma: Results of a Prospective Study.

PURPOSE: To evaluate cone-beam parenchymal blood volume (PBV) before and after embolization as a predictor of radiographic response to transarterial chemoembolization in unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A phase IIa prospective clinical trial was conducted in patients with HCCs > 1.5 cm undergoing chemoembolization; 52 tumors in 40 patients with Barcelona Clinic Liver Criteria stage B disease met inclusion criteria. Pre- and postembolization PBV analysis was performed with a semiquantitative best-fit methodology for index tumors, with a predefined primary endpoint of radiographic response at 3 months. Analyses were conducted with Wilcoxon signed-rank tests and one-way analysis of variance on ranks. RESULTS: Mean tumoral PBV measurements before and after embolization were 170 mL/1,000 mL ± 120 and 0 mL/100 mL ± 130, respectively. Per modified Response Evaluation Criteria In Solid Tumors, 25 tumors (48%) exhibited complete response (CR), 13 (25%) partial response (PR), 3 (6%) stable disease (SD), and 11 (21%) progressive disease (PD). Statistically significant changes in median PBV (ΔPBV) were identified in the CR (P = .001) and PR (P = .003) groups, with no significant difference observed in SD (P = .30) and PD groups (P = .06). A statistically significant correlation between ΔPBV and tumor response was established by one-way analysis of variance on ranks (P = .036; CR, 200 mL/100 mL ± 99; PR, 240 mL/100 mL ± 370; SD, 64 mL/100 mL ± 99; PD, 88 mL/100 mL ± 129). CONCLUSIONS: Intraprocedural PBV can be used as a predictor of response in index HCC tumors of > 1.5 cm.

Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma: imaging evaluation post treatment.

Surgical resection, when feasible, is the standard of care for hepatocellular carcinoma. However, many tumours are not resectable at the time of diagnosis. Recently, stereotactic body radiation therapy (SBRT) has emerged as a non-invasive local therapy for both non-resectable primary hepatic malignancies as well as hepatic metastases. Knowledge of the expected hepatic parenchymal appearance post treatment, as well as potential pitfalls and complications, is essential for accurate evaluation of treatment response. This pictorial review provides a fundamental description of the SBRT technique, outlines the expected cross-sectional imaging appearances of tumour response, and highlights potential pitfalls in interpretation. The expected liver parenchymal changes post-SBRT are also reviewed, along with some common radiation-induced complications.

Contrast-Enhanced Ultrasound of the Liver: Optimizing Technique and Clinical Applications.

OBJECTIVE: The purpose of this article is to review the general principles, technique, and clinical applications of contrast-enhanced ultrasound of the liver. CONCLUSION: Proper technique and optimization of contrast-enhanced ultrasound require a balance between maintaining the integrity of the microbubble contrast agent and preserving the ultrasound signal. Established and emerging applications in the liver include diagnosis of focal lesions, aiding ultrasound-guided intervention, monitoring of therapy, and aiding surgical management.