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Abstract Background Effective treatment options for nonresectable hepatic carcinoma (HC) in dogs are limited. Hypothesis/Objective Objectives were to report outcomes, complications, and tumor responses via computed tomography (CT) assessment after drug-eluting bead transarterial chemoembolization (DEB-TACE) for nonresectable HC in dogs. The authors hypothesized that major complications would be uncommon and short-term CT assessment would demonstrate stable disease or partial response. Animals Client-owned dogs (n = 16) with nonresectable HC. Methods Prospective, single-arm clinical trial. Drug-eluting bead transarterial chemoembolization was performed to varying levels of blood flow stasis. Computed tomography imaging was compared before and approximately 12 weeks after initial treatment. Results Drug-eluting bead transarterial chemoembolization was successfully administered in all attempts. Based on percent change in elliptical tumor volume response (mL), stable disease (8/13; 62%) was the most common outcome followed by partial response (3/13; 23%) and progressive disease (2/13; 15%) with a median of 74 days (range, 39-125) after initial treatment. Median tumor volume (mL) after DEB-TACE decreased in volume by 13% (range, 56% decrease to 77% increase). Mild complications consistent with postembolization syndrome occurred after 7/27 (26%) treatments. Major complications occurred after 3/27 (11%) treatments: hepatic abscess/septicemia (2) and cholecystitis/death (1), resulting in treatment-induced death after 2/27 (7%) treatments. Median survival time after treatment was 337 days (range, 22-1061). Dogs with a presenting complaint of weight loss (P = .02) had a significantly shorter median survival time (126 days; range, 46-337) than those dogs without prior history of weight loss (582 days; range, 22-1061). Conclusions Drug-eluting bead transarterial chemoembolization for nonresectable HC is a feasible procedure, which promoted stable disease or partial response in 85% of dogs in this study sample.

Background Breast cancer is the most diagnosed cancer among women in the United States. While rates of advanced-stage breast cancer have declined overall, incidence is rising among Korean American women. Advanced-stage breast cancer is more frequent among Korean women compared to other Asian ethnic groups, largely attributed to low adherence to breast cancer screening. Church settings offer important opportunities for education as most Korean American women over age 50 regularly attend church services. The objective of this trial is to evaluate the efficacy of a culturally tailored intervention Faith in Action! on breast cancer screening adherence rates among Korean American women. Methods A parallel cluster randomized trial with staggered roll-out was designed to evaluate the efficacy of the Faith in Action! intervention, a church-based small group education and lay health navigator program, delivered by trained church members, on breast cancer screening among Korean American women (NCT05298605). The study was designed and will be conducted in partnership with our center’s Community Outreach and Engagement (COE), which formed a Community Advisory Board. Twenty-four total Korean churches in Los Angeles will be randomized within blocks of 8 churches to either intervention or waitlist control conditions in a 1:1 ratio. Using a train-the-trainer approach, lay navigators from the Korean Church community nominated by church leadership will be trained by COE and certified to deliver the Faith in Action! intervention to study participants over a 6-month program period. Participants at churches randomized to the waitlist control group receive an educational presentation on physical activity and nutrition and, after 6-month follow-up, are invited to receive the Faith in Action! intervention. Eligible participants include women, ages 45–75 years, who attend a participating church in Los Angeles County, do not have a breast cancer diagnosis, and did not receive a mammogram in the last 2 years. The primary outcome is adherence to breast cancer screening guidelines within 6 months from the end of the intervention. Secondary outcomes include adherence to breast cancer screening within 1 year and knowledge on breast cancer screening. Discussion This study addresses a current need for developing and testing culturally tailored interventions to increase breast cancer screening adherence among Korean American women. Leveraging faith-based organizations and delivering the intervention through trained lay health navigators, if found to be effective, has the potential to provide a scalable and sustainable strategy for increasing screening rates and ultimately improve health and well-being as well as reduce cancer-related disparities in this population. Trial registration ClinicalTrials.gov NCT05298605 . Registered on March 17, 2022.

Hypothesis testing in contingency tables is usually based on asymptotic results, thereby restricting its proper use to large samples. To study these tests in small samples, we consider the likelihood ratio test (LRT) and define an accurate index for the celebrated hypotheses of homogeneity, independence, and Hardy-Weinberg equilibrium. The aim is to understand the use of the asymptotic results of the frequentist Likelihood Ratio Test and the Bayesian FBST (Full Bayesian Significance Test) under small-sample scenarios. The proposed exact LRT p-value is used as a benchmark to understand the other indices. We perform analysis in different scenarios, considering different sample sizes and different table dimensions. The conditional Fisher's exact test for 2 × 2 tables and the Barnard's exact test are also discussed. The main message of this paper is that all indices have very similar behavior, except for Fisher and Barnard tests that has a discrete behavior. The most powerful test was the asymptotic p-value from the likelihood ratio test, suggesting that is a good alternative for small sample sizes.

Background One of the potentially important applications of three-dimensional (3D) intracranial vessel wall (IVW) cardiovascular magnetic resonance (CMR) is to monitor disease progression and regression via quantitative measurement of IVW morphology during medical management or drug development. However, a prerequisite for this application is to validate that IVW morphologic measurements based on the modality are reliable. In this study we performed comprehensive reliability analysis for the recently proposed whole-brain IVW CMR technique. Methods Thirty-four healthy subjects and 10 patients with known intracranial atherosclerotic disease underwent repeat whole-brain IVW CMR scans. In 19 of the 34 subjects, two-dimensional (2D) turbo spin-echo (TSE) scan was performed to serve as a reference for the assessment of vessel dimensions. Lumen and wall volume, normalized wall index, mean and maximum wall thickness were measured in both 3D and 2D IVW CMR images. Scan-rescan, intra-observer, and inter-observer reproducibility of 3D IVW CMR in the quantification of IVW or plaque dimensions were respectively assessed in volunteers and patients as well as for different healthy subjectsub-groups (i.e. < 50 and ≥ 50 years). The agreement in vessel wall and lumen measurements between the 3D technique and the 2D TSE method was also investigated. In addition, the sample size required for future longitudinal clinical studies was calculated. Results The intra-class correlation coefficient (ICC) and Bland-Altman plots indicated excellent reproducibility and inter-method agreement for all morphologic measurements (All ICCs > 0.75). In addition, all ICCs of patients were equal to or higher than that of healthy subjects except maximum wall thickness. In volunteers, all ICCs of the age group of ≥50 years were equal to or higher than that of the age group of < 50 years. Normalized wall index and mean and maximum wall thickness were significantly larger in the age group of ≥50 years. To detect 5% - 20% difference between placebo and treatment groups, normalized wall index requires the smallest sample size while lumen volume requires the highest sample size. Conclusions Whole-brain 3D IVW CMR is a reliable imaging method for the quantification of intracranial vessel dimensions and could potentially be useful for monitoring plaque progression and regression.

Heart Failure is a chronic syndrome affecting over 5.7 million in the US and 26 million adults worldwide with nearly 50% experiencing depressive symptoms. The objective of the study is to compare the effects of two evidence-based treatment options for adult patients with depression and advanced heart failure, on depressive symptom severity, physical and mental health related quality of life (HRQoL), heart-failure specific quality of life, caregiver burden, morbidity, and mortality at 3, 6 and 12-months. Trial design. Pragmatic, randomized, comparative effectiveness trial. Interventions. The treatment interventions are: (1) Behavioral Activation (BA), a patient-centered psychotherapy which emphasizes engagement in enjoyable and valued personalized activities as selected by the patient; or (2) Antidepressant Medication Management administered using the collaborative care model (MEDS). Participants. Adults aged 18 and over with advanced heart failure (defined as New York Heart Association (NYHA) Class II, III, and IV) and depression (defined as a score of 10 or above on the PHQ-9 and confirmed by the MINI International Neuropsychiatric Interview for the DSM-5) selected from all patients at Cedars-Sinai Medical Center who are admitted with heart failure and all patients presenting to the outpatient programs of the Smidt Heart Institute at Cedars-Sinai Medical Center. We plan to randomize 416 patients to BA or MEDS, with an estimated 28% loss to follow-up/inability to collect follow-up data. Thus, we plan to include 150 in each group for a total of 300 participants from which data after randomization will be collected and analyzed. The current trial is the first to compare the impact of BA and MEDS on depressive symptoms, quality of life, caregiver burden, morbidity, and mortality in patients with depression and advanced heart failure. The trial will provide novel results that will be disseminated and implemented into a wide range of current practice settings. ClinicalTrials.Gov Identifier: NCT03688100.

IntroductionPhysical activity (PA) promotes significant physical and psychosocial benefits for breast cancer survivors. While evidence exists regarding recommendations for the frequency, duration and intensity of exercise that optimise PA benefits for cancer survivors, the role of the environment in achieving optimal outcomes has yet to be determined. This paper presents a protocol for a clinical trial to evaluate the feasibility of a 3-month nature-based walking programme for breast cancer survivors. Secondary outcomes assessed include the impact of the intervention on fitness, quality of life outcomes, and biomarkers of ageing and inflammation.Methods and analysisThe trial is a 12-week single-arm pilot study. Twenty female breast cancer survivors will engage in a supervised moderate intensity walking intervention in small groups in a nature reserve for 50 minutes three times per week. Data will be collected at baseline and end of study, and include assessment of inflammatory cytokines and anti-inflammatory myokines (TNF-α, IL-1ß, IL-6, CRP, TGF-ß, IL-10, IL-13), as well as ageing (DNA methylation, ageing genes) biomarkers; surveys (Patient-Reported Outcomes Measurement Information System-29, Functional Assessment of Cancer Therapy-General, Post-Traumatic Growth Inventory); and fitness assessments (6 min Walk Test, Grip-Strength, One Repetition-Maximum Leg Press). Participants will also complete weekly surveys assessing social support and participate in an exit interview. This is an important first step for future research on the influence of exercise environment on cancer survivor PA outcomes.Ethics and disseminationThis study was approved by the Cedars Sinai Medical Center Institutional Review Board (IIT2020-20). Findings will be disseminated through academic manuscripts, conferences, and community presentations.Trial registration numberNCT04896580.

Background Upregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), but also exposes HER3 as a target for immune attack. We generated an adenovirus encoding full length human HER3 (Ad-HER3) to serve as a cancer vaccine. Previously we reported the anti-tumor efficacy and function of the T cell response to this vaccine. We now provide a detailed assessment of the antitumor efficacy and functional mechanisms of the HER3 vaccine-induced antibodies (HER3-VIAs) in serum from mice immunized with Ad-HER3. Methods Serum containing HER3-VIA was tested in complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) assays and for its effect on HER3 internalization and degradation, downstream signaling of HER3 heterodimers and growth of metastatic HER2+ (BT474M1), HER2 therapy-resistant (rBT474), and triple negative (MDA-MB-468) breast cancers. Results HER3-VIAs mediated CDC and ADCC, HER3 internalization, interruption of HER3 heterodimer-driven tumor signaling pathways, and anti-proliferative effects against HER2+ tumor cells in vitro and significant antitumor effects against metastatic HER2+ BT474M1, treatment refractory HER2+ rBT474 and triple negative MDA-MB-468 in vivo. Conclusions In addition to the T cell anti-tumor response induced by Ad-HER3, the HER3-VIAs provide additional functions to eliminate tumors in which HER3 signaling mediates aggressive behavior or acquired resistance to HER2-targeted therapy. These data support clinical studies of vaccination against HER3 prior to or concomitantly with other therapies to prevent outgrowth of therapy-resistant HER2+ and triple negative clones.

ImportanceWomen with angina due to suspected ischaemia referred for coronary angiography often have no obstructive coronary artery disease (ANOCA/INOCA).ObjectiveTo determine if intensive medical treatment (IMT) reduces major ischaemic events (major adverse cardiovascular event, MACE) among women with suspected ANOCA/INOCA.DesignRandomised, prospective, blinded-outcomes evaluation.Setting71 sites in the USA.Participants2476 women with suspected ANOCA/INOCA.InterventionsIMT-high intensity statin, ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) and aspirin versus usual care (UC).Main outcomes and measuresPrimary: all cause death, myocardial infarction, stroke/transient ischaemic attack, hospitalisation for angina or heart failure (MACE). Secondary: components of the primary, quality of life and win ratio.ResultsRecruitment was lower than planned (n=2476), yielding an aged population (mean, 64 years) with well-controlled blood pressure and low-density lipoprotein cholesterol at baseline, and relatively high rates of statin and ACEI/ARB use. At 2.5 years, 421 events occurred (221 in IMT, 200 in UC) with no difference in the primary outcome (HR=1.13 (95% CI 0.94 to 1.37) for IMT vs UC, p=0.20) or secondary outcomes. Hospitalisations for angina were the dominant contributor to MACE. Sensitivity analysis of contamination provided an estimated HR for IMT versus UC of 0.74 95% CI (0.352 to 1.558), p=0.43.Conclusions and relevanceAmong women with suspected ANOCA/INOCA, outcomes were dominated by chest pain and IMT did not improve outcomes, although limited power precludes concluding that it may not be helpful. The findings support the need for more investigation in this population with high burden of angina hospitalisation, health resource consumption and poor quality of life.Trial registration numberNCT03417388.

To perform statistical inference for time series, one should be able to assess if they present deterministic or stochastic trends. For univariate analysis, one way to detect stochastic trends is to test if the series has unit roots, and for multivariate studies it is often relevant to search for stationary linear relationships between the series, or if they cointegrate. The main goal of this article is to briefly review the shortcomings of unit root and cointegration tests proposed by the Bayesian approach of statistical inference and to show how they can be overcome by the Full Bayesian Significance Test (FBST), a procedure designed to test sharp or precise hypothesis. We will compare its performance with the most used frequentist alternatives, namely, the Augmented Dickey–Fuller for unit roots and the maximum eigenvalue test for cointegration.

Adjuvant chemotherapy improves breast cancer survival but is associated with bothersome short- and long-term toxicity. Factors associated with toxicity, especially subacute toxicity up to 2 years following chemotherapy, have not been fully elucidated. The NRG Oncology/NSABP B-30 clinical trial compared 3 different doxorubicin-, cyclophosphamide-, and docetaxel-based chemotherapy regimens given over 3–6 months. Patients with hormone receptor-positive breast cancer received subsequent adjuvant endocrine therapy. From baseline through 24 months, 2156 patients completed questionnaires serially. We used multivariable probabilistic index models to identify factors associated with acute (>0–12 months) and subacute (>12–24 months) difficulties with pain, cognition, vasomotor symptoms, and vaginal symptoms. For all symptom domains, presence of symptoms prior to chemotherapy initiation were associated with symptoms in the subacute period (all p < 0.001). In addition, different combinations of patient factors and breast cancer treatments were associated with increased likelihood of pain, vasomotor, and vaginal symptoms in the subacute period. Consideration of pre-treatment symptoms and patient factors, as well as treatments for breast cancer, can facilitate identification of groups of patients that may experience symptoms following completion of chemotherapy. This information may be important for treatment-decision-making when alternative regimens are equivalent in benefit.