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The need for filtering intravenous infusions has long been recognized in the field of venous access, though hard scientific evidence about the actual indications for in-line filters has been scarce. In the last few years, several papers and a few clinical studies have raised again this issue, suggesting that the time has come for a proper definition of the type of filtration, of its potential benefit, and of its proper indications in clinical practice. The WoCoVA Foundation, whose goal is to increase the global awareness on the risk of intravenous access and on patients’ safety, developed the project of a consensus on intravenous filtration. A panel of experts in different aspects of intravenous infusion was chosen to express the current state of knowledge about filtration and to indicate the direction of future research in this field. The present document reports the final conclusions of the panel.

Abstract Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03–1.13; OR: 3.33, 95% CI, 2.46–4.50; and OR: 1.15, 95% CI, 1.02–1.29, respectively). Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.

Cancer is caused primarily by genomic alterations resulting in deregulation of gene regulatory circuits in key growth, apoptosis, or DNA repair pathways. Multiple genes associated with the initiation and development of tumors are also regulated at the level of mRNA decay, through the recruitment of RNA-binding proteins to AU-rich elements (AREs) located in their 3′-untranslated regions. One of these ARE-binding proteins, tristetraprolin (TTP; encoded by Zfp36 ), is consistently dysregulated in many human malignancies. Herein, using regulated overexpression or conditional ablation in the context of cutaneous chemical carcinogenesis, we show that TTP represents a critical regulator of skin tumorigenesis. We provide evidence that TTP controlled both tumor-associated inflammation and key oncogenic pathways in neoplastic epidermal cells. We identify Areg as a direct target of TTP in keratinocytes and show that EGFR signaling potentially contributed to exacerbated tumor formation. Finally, single-cell RNA-Seq analysis indicated that ZFP36 was downregulated in human malignant keratinocytes. We conclude that TTP expression by epidermal cells played a major role in the control of skin tumorigenesis.

Abstract Age-related chronic inflammation promotes cellular senescence, chronic disease, cancer, and reduced lifespan. In this study, we wanted to explore the effects of a moderate exercise regimen on inflammatory liver disease and tumorigenesis. We used an established model of spontaneous inflammaging, steatosis, and cancer (nfkb1−/− mouse) to demonstrate whether 3 mo of moderate aerobic exercise was sufficient to suppress liver disease and cancer development. Interventional exercise when applied at a relatively late disease stage was effective at reducing tissue inflammation (liver, lung, and stomach), oxidative damage, and cellular senescence, and it reversed hepatic steatosis and prevented tumor development. Underlying these benefits were transcriptional changes in enzymes driving the conversion of tryptophan to NAD+, this leading to increased hepatic NAD+ and elevated activity of the NAD+-dependent deacetylase sirtuin. Increased SIRT activity was correlated with enhanced deacetylation of key transcriptional regulators of inflammation and metabolism, NF-κB (p65), and PGC-1α. We propose that moderate exercise can effectively reprogram pre-established inflammatory and metabolic pathologies in aging with the benefit of prevention of disease.

AbstractBackgroundPrimary mesenteric soft tissue sarcomas (STS) are rare and limited evidence is available to inform management. Surgical resection is challenging due to the proximity of vital structures and a need to preserve enteric function.ObjectivesTo determine the overall survival (OS) and recurrence‐free survival (RFS) for patients undergoing primary resection for mesenteric STS.MethodsThe Trans‐Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) is an intercontinental collaborative comprising specialist sarcoma centers. Data were collected retrospectively for all patients with mesenteric STS undergoing primary resection between 2000 and 2019.ResultsFifty‐six cases from 15 institutions were included. The spectrum of pathology was similar to the retroperitoneum, although of a higher grade. R0/R1 resection was achieved in 87%. Median OS was 56 months. OS was significantly shorter in higher‐grade tumors (p = .018) and extensive resection (p < .001). No significant association between OS and resection margin or tumor size was detected. Rates of local recurrence (LR) and distant metastases (DM) at 5 years were 60% and 41%, respectively. Liver metastases were common (60%), reflecting portal drainage of the mesentery.ConclusionPrimary mesenteric sarcoma is rare, with a modest survival rate. LR and DM are frequent events. Liver metastases are common, highlighting the need for surveillance imaging.

Abstract Transgender and gender diverse (TGD) individuals face significant barriers to accessing health care. Recent introductions of regulatory policies at state and federal levels raise concerns over the politicization of gender-affirming health care, the risks of further restricting access to quality care, and the potential criminalization of healthcare professionals who care for TGD patients. The Endocrine Society and the Pediatric Endocrine Society have published several news articles and comments in the last couple of years supporting safe and effective gender-affirming interventions as outlined in the 2017 Endocrine Society’s Clinical Practice Guidelines. The Endocrine Society Position Statement on Transgender Health also acknowledges the rapid expansion in understanding the biological underpinning of gender identity and the need for increased funding to help close gaps in knowledge about the optimal care of TGD individuals. This Policy Perspective affirms these principles in the context of pending and future legislation attempting to discriminate against TGD patients while also stressing the need for science and health care experts to inform health policies.

This report presents the American Society of Clinical Oncology’s (ASCO’s) evaluation of the adaptations in care delivery, research operations, and regulatory oversight made in response to the coronavirus pandemic and presents recommendations for moving forward as the pandemic recedes. ASCO organized its recommendations for clinical research around five goals to ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality. The specific goals are: (1) ensure that clinical research is accessible, affordable, and equitable; (2) design more pragmatic and efficient clinical trials; (3) minimize administrative and regulatory burdens on research sites; (4) recruit, retain, and support a well-trained clinical research workforce; and (5) promote appropriate oversight and review of clinical trial conduct and results. Similarly, ASCO also organized its recommendations regarding cancer care delivery around five goals: (1) promote and protect equitable access to high-quality cancer care; (2) support safe delivery of high-quality cancer care; (3) advance policies to ensure oncology providers have sufficient resources to provide high-quality patient care; (4) recognize and address threats to clinician, provider, and patient well-being; and (5) improve patient access to high-quality cancer care via telemedicine. ASCO will work at all levels to advance the recommendations made in this report.

AbstractBackgroundThe abrupt loss of ovarian hormones before menopause, induced by oophorectomy, has been associated with accelerated aging, multimorbidity, and Alzheimer’s disease (AD). We investigated the impact of prolonged loss of ovarian hormones on AD progression in a transgenic mouse model of amyloid pathology using in vivo diffusion tensor MRI, resting‐state functional MRI (rsfMRI) and spectroscopy (MRS).MethodFemale 3.5‐month‐old TG2576 (TG) (N=27) and wild‐type (WT) (N=27) mice were ovariectomized (TGOVX) or sham‐operated (TGSHAM). When they became 18‐month‐old, 1‐H MRS (ROIs: hypothalamus, hippocampus, and cerebral cortex), DTI and rsfMRI was performed. ROI based analysis was performed on rsfMRI and DTI (Fractional anisotropy (FA), axial diffusivity (AxD), mean diffusivity, and radial diffusivity). The brain samples were then evaluated by histology and ELISA to assess Aβ load and activated glial cells. The loss of ovarian hormones via OVX was validated with elevated plasma luteinizing hormone level: OVX>SHAM (p<0.05). Two‐way ANOVA and post‐hoc (Student’s‐t) tests were used for statistical analysis. P values were adjusted for multiple comparisons (FDR‐p).ResultThe multimodel imaging data showed that there was a significant increase in taurine and total creatine (markers for inflammation and energy metabolism) in the hypothalamus, decrease in FA and AxD (markers for white matter integrity) in the white matter regions, and decrease in the functional connectivity between the prefrontal cortex and the hippocampus and dorsal and ventral hippocampus regions (a neural marker of network activity and integrity) (FDR‐p <0.05 (Figure 1)) in TGOVX mice compared to TGSHAM mice (post‐hoc t‐test). rsFMRI showed a significant increase in rsfMRI connectivity in WTOVX mice compared to WTSHAM mice. Complementary histological (and ELISA) analysis revealed no differences in Aβ load (plaque and soluble) and activated glial cells between the TG groups.ConclusionThe MRI results suggest that inflammatory response was elevated, energy metabolism was disrupted and white matter and network integrity decreased after prolonged ovarian hormone loss. These MRI results support other data from human and animal studies suggesting that abrupt hormonal changes associated with premenopausal removal of ovaries may increase the risk factors of AD, and accelerate the disease progression by causing abnormalities in brain structure, function and metabolism.

AbstractBackgroundAfrican Americans are at higher risk of developing Alzheimer’s disease (AD) and AD‐related dementia. They are also more likely to live in communities with fewer dementia resources. The 2011 National Alzheimer’s Project Act calls for special attention to dementia‐related health disparities in high risk groups. Ensuring access to dementia‐specific information is one tactic for addressing disparities; however, the method by which information is delivered may play a role in how effectively that information is understood and retained over time.MethodWe delivered the same dementia education presentation to two comparable, predominantly African American neighborhoods in Jacksonville, FL. In one (intervention) community, the presentation was followed by an hour‐long focus group on what makes a community “dementia friendly”, using modified materials from the Dementia Friendly America (DFA) toolbox. In the other (control) community, the presentation was followed by a social hour allowing participants to interact with presenters and ask questions informally. Our primary objective was to assess the impact of the different conditions on AD knowledge.ResultsA 7‐item scale assessing AD knowledge was administered to immediately before and after the educational presentation (pre‐test, immediate post), and again two months later (Intervention group n=40; Control n=37). Additional, one‐year follow‐up was completed on the intervention community (n=21). Groups did not differ in AD knowledge at pre‐test (M=4.5 vs. 4.2, p=NS). At immediate post‐test, both groups improved their scores, but there was again no difference between groups (M=5.8 vs. 5.4, p=NS). At two‐month post‐testing, both groups declined in their knowledge score, but the control group declined more precipitously, yielding a significant group mean difference (M= 5.4 vs. 4.7, p=0.02). At one year follow‐up, a subsample of the intervention group (n=21) was re‐examined and demonstrated no significant decline in knowledge scores as compared to 2‐month follow‐up (M=5.7 vs. 5.4, p=0.36).ConclusionResults suggest that focus group discussion following dementia education as per the DFA model may contribute to greater retention of information and exert a sustainable impact on AD knowledge over time in an African American community setting.

Abstract PURPOSE We investigated the long term impact of SRS and WBRT in two large prospective phase III trials. METHODS Patients with 1–4 BMs +/- resection were randomized to SRS or WBRT. Cognitive deterioration was a drop of &gt;1 standard deviation from baseline in &gt;2/6 cognitive measures (CM). Quality of life (QOL) scores were scored 0–100 point scale. CM and QOL scores were modeled using baseline adjusted Linear Mixed Models (LMM) with uncorrelated random intercept for subject and random slopes for time. Differences over time between groups and the effect of &gt;2 cognitive scores with &gt;2 SD change from baseline were assessed. RESULTS 88 patients were included with median follow up of 24 months. We observed decreasing CM over time (SRS: 4/6; WBRT: 5/6). Mean CM was significantly higher in SRS for Total recall and Delayed Recall at 3, 6, 9, 12 months. More patients in WBRT arm declined 1 SD in &gt;1 and &gt;2 CM at the 3, 6, 9, and 12 months. A 1 SD decline in &gt;3 CM at 1 year was 21% SRS vs 47% WBRT (p=0.02). SRS had fewer patients with a 2 SD decline in &gt;1 CM at every time point. SRS had fewer patients with a 2 SD decline at &gt;2 and &gt;3 CM. WBRT had lower QOL at 3 months, but switched to SRS having lower QOL at 24 months for PWB, EWB, FWB, FactG, BR, and FactBR (p&lt; 0.05). A 2 SD decline in cognition decreased mean FWB by 6.4 units (95% CI: -11, -1.75; p=0.007) and decreased QOL by 5.1 units (95% CI: -7.7, -2.5; p&lt; 0.001). CONCLUSIONS We report the first pooled prospective study demonstrating the long term outcomes of patients with BMs after cranial radiation. WBRT was associated with worse cognitive outcomes. Impaired cognition is associated with worse QOL.