Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

Differing Characteristics of Human-Shaped Visual Stimuli Affect Clinicians’ Dosage of a Spinal Manipulative Thrust on a Low-Fidelity Model: A Cross-Sectional Study

ObjectiveThe purpose of this study was to determine whether chiropractic clinicians modulate spinal manipulation (SM) thrust characteristics based on visual perception of simulated human silhouette attributes.MethodsWe performed a cross-sectional within-participant design with 8 experienced chiropractors. During each trial, participants observed a human-shaped life-sized silhouette of a mock patient and delivered an SM thrust on a low-fidelity thoracic spine model based on their visual perception. Silhouettes varied on the following 3 factors: apparent sex (male or female silhouette), height (short, average, tall), and body mass index (BMI) (underweight, healthy, obese). Each combination was presented 6 times for a total of 108 trials in random order. Outcome measures included peak thrust force, thrust duration, peak preload force, peak acceleration, time to peak acceleration, and rate of force application. A 3-way repeated measures analysis of variance model was used to for each variable, followed by Tukey's honestly significant difference on significant interactions.ResultsPeak thrust force was reduced when apparent sex of the presented silhouette was female (F_1,7 = 5.70, P = .048). Thrust duration was largely invariant, except that a BMI by height interaction revealed a longer duration occurred for healthy tall participants than healthy short participants (F_4,28 = 4.34, P = .007). Compared to an image depicting obese BMI, an image appearing underweight lead to reduced peak acceleration (F_2,5 = 6.756, P = .009). Clinician time to peak acceleration was reduced in short compared to tall silhouettes (t₇ = 2.20, P = .032).ConclusionVisual perception of simulated human silhouette attributes, including apparent sex, height, and BMI, influenced SM dose characteristics through both kinetic and kinematic measures. The results suggest that visual information from mock patients affects the decision-making of chiropractic clinicians delivering SM thrusts.     

F形空心钉与传统3枚平行钉治疗Pauwels Ⅲ型股骨颈骨折的疗效比较

目的:分析比较"F"形空心钉与传统倒三角3枚平行螺钉内固定治疗青壮年Pauwels Ⅲ型股骨颈骨折的临床疗效。方法：2017年1月至2020年1月收治Pauwels Ⅲ型股骨颈骨折患者38例，根据置入钉方式的不同将其分为两组，其中A组18例，采用"F"形空心钉固定，男12例，女6例，年龄37~55岁，受伤至手术时间1~3 d。B组20例，采用传统倒三角3枚平行拉力螺钉固定，男12例，女8例，年龄35~55岁，受伤至手术时间为1~3 d。比较两组患者骨折不愈合，股骨头坏死，股骨颈短缩，空心螺钉退出情况，髋关节功能Harris评分，疼痛视觉模拟评分（visual analogue scale，VAS）。结果：所有患者获得随访，时间为15~31个月。两组患者在骨折不愈合，股骨颈短缩，股骨头坏死方面差异无统计学意义（P>0.05）；两组患者在螺钉退出方面差异有统计学意义（P<0.05）。两组患者术后12个月时髋关节Harris评分及VAS评分差异均无统计学差异（P>0.05）。结论："F"形与传统倒三角3枚平行空心钉内固定治疗青壮年Pauwels Ⅲ型股骨颈骨折中短期疗效相似，但"F"形空心钉退钉率较低。     

Understanding Hispanic Patient Satisfaction with Telehealth During COVID-19

BackgroundRecent studies have described the use of telehealth for pediatric surgical care during the COVID-19 pandemic. We aimed to evaluate equity in telehealth use by comparing rates of utilization and satisfaction with pediatric surgical telemedicine among Hispanic patients.MethodsWe conducted a retrospective cohort study of patients seen by a surgical subspecialty provider in the outpatient setting at a quaternary pediatric hospital between April 1 and June 30, 2020. Patients evaluated in the same three-month period in 2019 were analyzed as a historic control. Differences in Family Experience Survey (FES) responses based on race and ethnicity and preferred language of care were assessed using univariable and multivariable generalized linear modeling.ResultsThe pandemic cohort included fewer patients of Hispanic ethnicity and fewer Spanish-speakers. After controlling for visit type, comparison of Spanish-speaking and English-speaking patients revealed that Spanish-speaking families had significantly lower scores for FES items that evaluated healthcare provider explaining (IRR 0.74, 95% CI: 0.61–0.90), listening (IRR 0.76, 95% CI: 0.63–0.92), and time spent with the family (IRR 0.73, 95% CI: 0.60–0.89). There were no differences in FES responses based on insurance status or degree of medical complexity.ConclusionsTelehealth services were less commonly used among Hispanic and Spanish-speaking patients. Language may differentially affect family satisfaction with healthcare and telehealth solutions. Strategies to mitigate these inequities are needed and may include strengthening interpreter services and providing language-concordant care.Level of evidenceLevel IV.     

Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen

Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation.