Yttrium-90 Transarterial Radioembolization for Chemotherapy-Refractory Intrahepatic Cholangiocarcinoma: A Prospective,Observational Study

PurposeTo evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC).MethodsA prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS).ResultsSixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6–18.1). Overall survival was 8.7 months (95% CI, 5.3–12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6–3.1), and LPFS was 3.1 months (95% CI, 1.3–4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1–2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3.ConclusionsPatients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes.     

An Exploratory Cost-Effectiveness Analysis of the Connected Health Intervention to Improve Care for People with Dementia: A Simulation Analysis

Many people with dementia live in the community; thus, supporting informal caregivers is critical. The Connected Health intervention facilitates collection and sharing of patient data among informal caregivers and providers to identify emerging patient needs and support rapid decision-making. This study estimates the costs of care of dementia using time-driven activity based costing of an exemplar patient. Intervention costs and health utility values were derived from a feasibility study of the intervention. A Markov model produced estimates of the cost-effectiveness of the intervention under four scenarios: (1) a minimal effect of the intervention on disease progression; (2) moderate effects on disease progression, and minimal effects on quality of life (QOL) and cost; (3) minimal effects on disease progression and QOL, and a moderate effect on cost; (4) moderate effects on disease progression and cost, with minimal effects on QOL. Cost estimates of formal and informal care ranged from €3713 to €7614 per month. Intervention costs were €484 per month. Under scenarios 2, 3 and 4, the cost per quality-adjusted life year of the intervention falls below €45,000, the threshold below which the Health Information and Quality Authority in Ireland generally accepts interventions as cost-effective. The results suggest that the intervention would be cost-effective with limited reductions in rates of disease progression and cost of care, and with minimal improvements in quality of life. Future research should consider the specific experiences of intervention patients.     

Improving blood donor recruitment and retention: integrating theoretical advances from social and behavioral science research agendas

BACKGROUND: Increasing blood donor recruitment and retention is of key importance to transfusion services. Research within the social and behavioral science traditions has adopted separate but complementary approaches to addressing these issues. This article aims to review both of these types of literature, examine theoretical developments, identify commonalities, and offer a means to integrate these within a single intervention approach. STUDY DESIGN AND METHODS: The social and behavioral science literature on blood donor recruitment and retention focusing on theory, interventions, and integration is reviewed. RESULTS: The role of emotional regulation (anticipated anxiety and vasovagal reactions) is central to both the behavioral and the social science approaches to enhancing donor motivation, yet although intentions are the best predictor of donor behavior, interventions targeting enactment of intentions have not been used to increase donation. Implementation intentions (that is, if-then plans formed in advance of acting) provide a useful technique to integrate findings from social and behavioral sciences to increase donor recruitment and retention. CONCLUSION: After reviewing the literature, implementation intention formation is proposed as a technique to integrate the key findings and theories from the behavioral and social science literature on blood donor recruitment and retention.     

A recurrent pathogenic variant in TPM2 reveals further phenotypic and genetic heterogeneity in multiple pterygium syndrome-related disorders

Multiple pterygium syndrome (MPS) disorders are a phenotypically and genetically heterogeneous group of conditions characterized by multiple joint contractures (arthrogryposis), pterygia (joint webbing) and other developmental defects. MPS is most frequently inherited in an autosomal recessive fashion but X-linked and autosomal dominant forms also occur. Advances in genomic technologies have identified many genetic causes of MPS-related disorders and genetic diagnosis requires large targeted next generation sequencing gene panels or genome-wide sequencing approaches. Using the Illumina TruSightOne clinical exome assay, we identified a recurrent heterozygous missense substitution in TPM2 (encoding beta tropomyosin) in three unrelated individuals. This was confirmed to have arisen as a de novo event in the two patients with parental samples. TPM2 mutations have previously been described in association with a variety of dominantly inherited neuromuscular phenotypes including nemaline myopathy, congenital fibre-type disproportion, distal arthrogryposis and trismus pseudocamptodactyly, and in a patient with autosomal recessive Escobar syndrome and a nemaline myopathy. The three cases reported here had overlapping but variable features. Our findings expand the range of TMP2-related phenotypes and indicate that de novo TMP2 mutations should be considered in isolated cases of MPS-related conditions.     

Modified C-Reactive Protein Is Expressed by Stroke Neovessels and Is a Potent Activator of Angiogenesis In Vitro

Native C-reactive protein (nCRP) is a pentameric oligo-protein and an acute phase reactant whose serum expression is increased in patients with inflammatory disease. We have identified by immunohistochemistry, significant expression of a tissue-binding insoluble modified version or monomeric form of CRP (mCRP) associated with angiogenic microvessels in peri-infarcted regions of patients studied with acute ischaemic stroke. mCRP, but not nCRP was expressed in the cytoplasm and nucleus of damaged neurons. mCRP co-localized with CD105, a marker of angiogenesis in regions of revascularisation. In vitro investigations demonstrated that mCRP was preferentially expressed in human brain microvessel endothelial cells following oxygen-glucose deprivation and mCRP (but not column purified nCRP) associated with the endothelial cell surface, and was angiogenic to vascular endothelial cells, stimulating migration and tube formation in matrigel more strongly than fibroblast growth factor-2. The mechanism of signal transduction was not through the CD16 receptor. Western blotting showed that mCRP stimulated phosphorylation of the key down-stream mitogenic signalling protein ERK1/2. Pharmacological inhibition of ERK1/2 phosphorylation blocked the angiogenic effects of mCRP. We propose that mCRP may contribute to the neovascularization process and because of its abundant presence, be important in modulating angiogenesis in both acute stroke and later during neuro-recovery.     

Future directions for the Cancer Information Service and cancer education

From its beginnings in the 1970s, the National Cancer Institute’s (NCI’s) Cancer Information Service (CIS) has developed as a vibrant program for providing health care professionals and the public with relevant cancer-related information through telephone, mail, and online communication. The CIS has become an important contributor to health communication and health education research. Through its network of community partnerships, it has disseminated relevant cancer information and health promotion programs to vulnerable and hard-to-reach populations. It has become a model for the development of health information and education programs around the world. However, the CIS is still growing; it is continually innovating and refining its programs and services. This concluding article examines the potential for increasing CIS contributions to cancer education and cancer control in the future.