Citations

Objective The objective of this study was to determine whether a triple therapy regimen incorporating twice-daily saquinavir is as effective as a three-times daily regimen. Methods This was an open-label, Phase III, multicentre, 48-week study involving 837 HIV-1-infected patients randomised to one of the following: saquinavir soft gel capsule (SGC) 1200 mg three-times daily, plus two nucleoside reverse transcriptase inhibitors (NRTIs) (arm A); saquinavir SGC 1600 mg twice-daily, plus two NRTIs (arm B); saquinavir SGC 1200 mg twice-daily and nelfinavir 1250 mg twice-daily, plus a single NRTI (arm C). The primary outcome measure was the virological response in arm A versus B and in arm A versus C with respect to the percentage of patients whose plasma HIV-1 RNA levels fell below the level of quantification for the Amplicor assay (<400 copies/ml) at weeks 24 and 48. Results At 48 weeks, the percentage of patients with plasma HIV-1 RNA levels <400 copies/ml was 47.1% (arm A), 45.3% (arm B) and 42.7% (arm C) in the intention-to-treat analysis. The treatment difference between arm B–arm A was -1.8% (95% confidence intervals -10.1, 6.5) and for arm C–arm A was -4.5% (95% confidence intervals -12.7, 3.7) in the intention-to-treat analysis. These differences fell within the maximum allowable difference (±12%) for arm B compared with arm A. At week 24, the percentage of patients with HIV-1 RNA levels <400 copies/ml was 59.6% (arm A), 57.6% (arm B) and 51.3% (arm C). Conclusions A twice-daily triple therapy regimen incorporating saquinavir SGC plus two NRTIs was of equivalent efficacy to the three-times daily regimen studied. All regimens were generally well tolerated.

AbstractDiabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer‐free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF‐mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36‐2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF‐mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19‐1.48). In the case only analysis, BRAF‐mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF‐mutated tumors.

PurposeInversion algorithms used to convert acquired MR elastography wave data into material property estimates often assume that the underlying materials are locally homogeneous. Here we evaluate the impact of that assumption on stiffness estimates in gray‐matter regions of interest in brain MR elastography.MethodsWe describe an updated neural network inversion framework using finite‐difference model–derived data to train convolutional neural network inversion algorithms. Neural network inversions trained on homogeneous simulations (homogeneous learned inversions [HLIs]) or inhomogeneous simulations (inhomogeneous learned inversions [ILIs]) are generated with a variety of kernel sizes. These inversions are evaluated in a brain MR elastography simulation experiment and in vivo in a test–retest repeatability experiment including 10 healthy volunteers.ResultsIn simulation and in vivo, HLI and ILI with small kernels produce similar results. As kernel size increases, the assumption of homogeneity has a larger effect, and HLI and ILI stiffness estimates show larger differences. At each inversion's optimal kernel size in simulation (7 × 7 × 7 for HLI, 11 × 11 × 11 for ILI), ILI is more sensitive to true changes in stiffness in gray‐matter regions of interest in simulation. In vivo, there is no difference in the region‐level repeatability of stiffness estimates between the inversions, although ILI appears to better maintain the stiffness map structure as kernel size increases, while decreasing the spatial variance in stiffness estimates.ConclusionsThis study suggests that inhomogeneous inversions provide small but significant benefits even when large stiffness gradients are absent.

Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this. We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P &lt; 0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test. After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE = 4.44 × 10−6). In this transcriptome-informed genome-wide gene–environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk. Our study suggests a limited role of gene–environment interactions in breast cancer risk.

The use of social media continues to increase in health care and academia. Health care practice, particularly the oncologic field, is constantly changing because of new knowledge, evidence-based research, clinical trials, and government policies. Therefore, oncology trainees and professionals continue to strive to stay up-to-date with practice guidelines, research, and skills. Although social media as an educational and professional development tool is no longer completely new to medicine and has been embraced, it is still under-researched in terms of various outcomes. Social media plays several key roles in professional development and academic advancement. We reviewed the literature to evaluate how social media can be used for professional development and academic promotion of oncology professionals.

Introduction: Patients with concomitant peripheral artery disease (PAD) and heart failure (HF) are known to have increased morbidity and mortality. Though they share common risk factors, the utility of HF screening in patients with PAD remains controversial and without international consensus. We sought to clarify whether PAD is an independent risk factor for HF. Methods: We performed a retrospective analysis of adult patients without a history of heart failure who underwent ankle brachial index (ABI) measurement for any indication between 1995-2020. Patients were then stratified by ABI: PAD with low ABI (<1.10), healthy (ABI= 1.10-1.39), and PAD with elevated ABI (>1.39). The associations between PAD and incident diagnosis of heart failure, systolic dysfunction (HF with reduced ejection fraction, HFrEF), and diastolic dysfunction (HF with preserved ejection fraction, HFpEF) were assessed. All patient and outcomes variables were obtained using the institutional electronic health record. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, hypertension, diabetes, and active tobacco use. Results: The cohort included 36,816 patients (median follow-up 4.21 years), of whom 2,116 (5.7%) were diagnosed with HF. Among HF patients, 1,110 (3.0%) had HFrEF and 1,006 (2.7%) had HFpEF. Both low and elevated ABI groups were associated with an increased risk of HF, both HFrEF, and HFpEF. After multivariable analysis, PAD with elevated ABI was associated with higher overall HF risk (HR, 2.36 [95% CI, 2.03, 2.73]) than low ABI (HR, 1.56 [95% CI, 1.40, 1.74]) when compared to normal ABI. Similarly, PAD with elevated ABI was associated with greater risk of HFrEF (HR, 2.37 [95% CI, 1.93, 2.92]) and HFpEF (HR, 1.82 [95% CI, 1.48, 2.25]) than PAD with low ABI (HFrEF: HR 1.77 [95% CI, 1.52, 2.07], HFpEF: HR 1.31 [95% CI, 1.12, 1.52]). Conclusions: PAD, especially with elevated ABI, is an independent risk factor for heart failure even after adjusting for common HF risk factors. Our findings support HF screening in PAD patients, but longitudinal data on HF morbidity and mortality is necessary to evaluate the value of this practice.

A significant proportion of patients diagnosed with symptomatic severe aortic stenosis (ssAS) do not receive treatment with aortic valve replacement (AVR) despite current ACC/AHA guidelines. Delayed care leads to increased hospitalizations, worsening heart failure and death. Timely referral to a cardiac specialist is a critical step in the treatment pathway. We sought to identify the impact of managing provider type on follow-up care for newly diagnosed patients with severe aortic stenosis (sAS). We analyzed Optum® electronic medical records to identify adults with a new outpatient sAS echo diagnosis in the pre-COVID era (1/2017 - 3/2019). We identified integrated delivery network patients alive 1d post echo excluding those with missing data or AVR within 3d of echo, then selected those managed by a primary care provider (PCP) or a cardiologist (n=5,683). Baseline characteristics were used for covariate-adjusted Cumulative Incidence Function and Fine-Gray subdistribution hazard models. We estimated the impact of managing provider type on the specialist follow-up visit rate (cardiologist, interventional cardiologist and/or cardiothoracic surgeon) for all sAS patients and of surgical or transcatheter AVR for ssAS patients within 1 year of diagnosis. Within 90d of sAS diagnosis, 47% of PCP- vs. 73% of cardiologist-managed patients had a follow-up visit (1-year rates: PCP, 69% vs. cardiologist, 90%; Hazard ratio [HR]=0.54, 95% confidence interval [CI]: 0.49-0.59, p<0.0001). Within 1 year of diagnosis, 36% of PCP- vs. 51% of cardiologist-managed ssAS patients underwent AVR (HR=0.72, CI: 0.63-0.82, p<0.0001) (Figure). Analysis suggests lower referral rates for PCP- than cardiologist-managed patients. In ssAS, 1-year AVR rates were low, particularly for PCPs. These data underscore the importance of timely follow up of all severe AS patients for symptom assessment and appropriate treatment, presenting an opportunity for initiatives to drive behavior change.

BackgroundLocalized regions of left–right image intensity asymmetry (LRIA) were incidentally observed on T2‐weighted (T2‐w) and T1‐weighted (T1‐w) diagnostic magnetic resonance imaging (MRI) images. Suspicion of herpes encephalitis resulted in unnecessary follow‐up imaging. A nonbiological imaging artifact that can lead to diagnostic uncertainty was identified.PurposeTo investigate whether systematic LRIA exist for a range of scanner models and to determine if LRIA can introduce diagnostic uncertainty.Study TypeA retrospective study using the Alzheimer's Disease Neuroimaging Initiative (ADNI) data base.SubjectsOne thousand seven hundred fifty‐three (median age: 72, males/females: 878/875) unique participants with longitudinal data were included.Field Strength3T.SequencesT1‐w three‐dimensional inversion‐recovery spoiled gradient‐echo (IR‐SPGR) or magnetization‐prepared rapid gradient‐echo (MP‐RAGE) and T2‐w fluid‐attenuated inversion recovery (FLAIR) long tau fast spin echo inversion recovery (LT‐FSE‐IR). Only General Electric, Philips, and Siemens' product sequences were used.AssessmentLRIA was calculated as the left–right percent difference with respect to the mean intensity from automated anatomical atlas segmented regions. Three neuroradiologists with 37 (**), 32 (**), and 3 (**) years of experience rated the clinical impact of 30 T2‐w three‐dimensional FLAIR exams with LRIA to determine the diagnostic uncertainty. Statistical comparisons between retrospective intensity normalized T1m and original T1‐w images were made.Statistical TestsFor each image type, a linear mixed effects model was fit using LRIA scores from all scanners, regions, and participants as the outcome and age and sex as predictors. Statistical significance was defined as having a P‐value <0.05.ResultsLRIA scores were significantly different from zero on most scanners. All clinicians were uncertain or recommended definite diagnostic follow‐up in 62.5% of cases with LRIA >10%. Individuals with acute brain pathology or focal neurologic deficits are not enrolled in ADNI; therefore, focal signal abnormalities were considered false positives.Data ConclusionLRIA is system specific, systematic, creates diagnostic uncertainty, and impacts IR‐SPGR, MP‐RAGE, and LT‐FSE‐IR product sequences.Level of Evidence: 2Technical Efficacy Stage: 3

Abstract Using vaccine data combined with electronic health records, we report that mRNA boosters provide greater protection than a 2-dose regimen against SARS-CoV-2 infection and related hospitalizations. The benefit of a booster was more evident in the elderly and those with comorbidities.

AbstractBackgroundThe U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is a 2‐year randomized controlled trial to evaluate the effect of lifestyle interventions in older adults (60‐79 years) who are cognitively unimpaired but at increased risk for cognitive decline/dementia due to factors such as cardiovascular disease and family history. The POINTER Imaging ancillary study is collecting PET and MRI data to evaluate neuroimaging biomarkers of AD and cerebrovascular pathophysiology in this at‐risk sample.MethodPOINTER Imaging is actively enrolling 1250 participants, 23% from under‐represented racial/ethnic groups (URG), recruited from five U.S. POINTER clinical sites. Participants have undergone PET imaging with [18F]Florbetaben (FBB) to measure Aβ and [18F]MK‐6240 to measure tau burden, as well as MRI to measure brain morphometry, white matter hyperintensities and cerebral blood flow. FBB and MK‐6240 data were quality checked, pre‐processed, and quantified using previously validated methods. PET images were coregistered to a structural MRI, which was also used to create FreeSurfer‐defined reference regions and regions of interest. We examined PET imaging measures (global Aβ, regional tau) and basic demographic (age, sex, race/ethnicity) characteristics of the sample.Result96 participants (mean age 69.3±5.0) have been enrolled in POINTER Imaging. Of these, 59 (61%) are women and 22 (23%) are URG, which is similar to rates of women (75%) and URG (22%) in the main trial. This dataset is <10% of targeted enrollment, was predominantly recruited from 2/5 clinical sites and may not represent the final imaging cohort. FBB quantification (N=20) revealed a mean cortical summary SUVR of 1.09±0.12 (19.6±18.4 centiloids) (whole cerebellum normalization; previously validated positivity threshold=1.08), and 8/20 (40%) of these participants were Aβ+ (Fig. 1A). MK‐6240 quantification (N=23) showed predominantly no/minimal binding with a few exceptions in medial and lateral temporal lobes (Fig. 1B&C).ConclusionThe POINTER imaging study is meeting the target URG enrollment and representative of the main U.S. POINTER trial. Higher frequency of Aβ positivity than published in population cohorts coupled with greater cardiovascular risk factors among POINTER participants highlights our success in recruiting individuals at increased risk of cognitive decline.