tbuckley/cabot-search huggingface dataset:
Diagnostic and prognostic awareness among patients with metastatic solid cancer in a public cancer center in Mexico.
Authors: Mirza Alcalde Castro, Yanin Chavarri Guerra, Wendy Alicia Ramos-Lopez, Alfredo Covarrubias-Gómez, Sofia Sanchez, Paulina Quiroz, Africa Navarro-Lara, Andrea Medina-Campos, María Luisa Moreno-García, Sergio Contreras-Garduño, Viridiana Pérez-Montessoro, Paul E. Goss, Enrique Soto Perez De Celis
Journal: Journal of Clinical Oncology (2018)

42 Background: Patient awareness regarding diagnosis and prognosis may lead to improved treatment shared decision making and improve satisfaction with treatment choices. We assessed the diagnostic and prognostic awareness among newly diagnosed patients with metastatic solid tumors in a public cancer center in Mexico City. Methods: Patients with metastatic cancer enrolled in a randomized clinical trial of patient navigation to improve access to supportive care in a public cancer center in Mexico City (NCT03293849) were included. At baseline, demographic, social, and clinical characteristics were collected. Patients answered open-ended questions regarding knowledge about their diagnosis and prognosis, as well as on patient-physician communication. We analyzed prognostic and diagnostic awareness using descriptive statistics, and explored if patients reporting worse patient-physician communication were less aware of their diagnosis and prognosis. Results: 125 patients were included between 08/17 and 04/18. Median age was 61 years (range 23-93; 52% male); 88.8% lived in urban areas; 41.6% had less than high school education; and 57.6% were married or partnered. 61% had gastrointestinal, 14% genitourinary, and 25% other tumors. Although all patients had had at least one consultation with an oncologist, 3% did not know what their diagnosis was. 77% of patients considered they had prognostic awareness; however, only 14% considered that their disease had a bad prognosis, and 2% considered they could be cured. 6.5% of the patients believed the information given by their oncologist was insufficient, and 8% felt they had trouble getting information about their disease. We found no statistically significant relationship between perceived barriers to patient-physician communication and diagnostic (p = 0.28) or prognostic (p = 0.18) awareness. Conclusions: Although most patients understood their oncologic diagnosis, a significant proportion were unaware of their prognosis. Communication strategies, tailored to the specific characteristics of each patient population and aimed at improving prognostic awareness, are fundamental for optimal shared decision making.
Depletion of Ars2 inhibits cell proliferation and leukemogenesis in acute myeloid leukemia by modulating the miR-6734-3p/p27 axis
Authors: Xiaoye Hu, Shuangnian Xu, Yibiao Chen, Ziyi Gao, Yunong Li, Jinjiao Hu, Xiuning Huang, Yanhao Zhang, Xiuxing Jiang, Lirong Li, Chong Yang, Jieping Chen, Ning Gao
Journal: Leukemia (2018)

Ars2 is a component of the nuclear cap-binding complex (CBC) that contributes to microRNA biogenesis and is required for cellular proliferation. Little is known regarding the functional role of Ars2 in cell proliferation and leukemogenesis of acute myeloid leukemia. Here, we show that the elevated expression of Ars2 was observed in acute myeloid leukemia (AML) cell lines and bone marrow samples from AML patients and was correlated with poorer overall survival. Overexpression of Ars2 promoted cell proliferation and colony formation in AML cells, whereas depletion of Ars2 inhibited cell proliferation and colony formation. Mechanistic studies reveal that depletion of Ars2 suppressed the interaction of Ars2 with CBC and led to alterations in miRNA processing. Furthermore, Ars2 depletion reduced the levels of miR-6734-3p, resulting in upregulation of p27 and culminating in cell cycle arrest at the G1 phase. In vivo studies indicate that depletion of Ars2 significantly reduced leukemic cell burden and prolonged the survival time of the leukemia-bearing mice. These findings indicate that Ars2 may not only play a crucial role in the regulation of cell proliferation and leukemogenesis, but could also be identified as a critical therapeutic target for treatment of AML.
Telbivudine-Induced Myopathy Incidentally Detected by FDG PET/CT Imaging in a Patient With History of Hepatocellular Carcinoma
Authors: Sijuan Zou, Zhaoting Cheng, Shuang Song, Dongling Zhu, Xiaohua Zhu
Journal: Clinical Nuclear Medicine (2018)

Myopathy is an adverse effect of telbivudine. We describe a case of telbivudine-induced myopathy visualized on FDG PET/CT in a 75-year-old man with history of chronic HBV infection and hepatocellular carcinoma. FDG PET/CT images demonstrate no abnormal uptake characteristic of hypermetabolic malignancy. However, intense hypermetabolic activity in muscles of the abdominal wall was noted. Three months after telbivudine withdrawal, a second FDG PET/CT showed normal muscle activity in the abdominal wall.
<i>In vivo</i> [<sup>64</sup>Cu]CuCl<sub>2</sub> PET imaging reveals activity of Dextran-Catechin on tumor copper homeostasis
Authors: Arvind Parmar, Giancarlo Pascali, Florida Voli, Luigi Lerra, Eugene Yee, Aria Ahmed-Cox, Kathleen Kimpton, Giuseppe Cirillo, Andrew Arthur, David Zahra, Gita Rahardjo, Guo Jun Liu, Nigel Lengkeek, Federica Saletta, Arnaud Charil, Maria Kavallaris, Orazio Vittorio
Journal: Theranostics (2018)

Given the strong clinical evidence that copper levels are significantly elevated in a wide spectrum of tumors, copper homeostasis is considered as an emerging target for anticancer drug design.Monitoring copper levels in vivo is therefore of paramount importance when assessing the efficacy of copper-targeting drugs.Herein, we investigated the activity of the copper-targeting compound Dextran-Catechin by developing a [ 64 Cu]CuCl2 PET imaging protocol to monitor its effect on copper homeostasis in tumors.Methods: Protein expression of copper transporter 1 (CTR1) in tissue microarrays representing 90 neuroblastoma patient tumors was assessed by immunohistochemistry.Western blotting analysis was used to study the effect of Dextran-Catechin on the expression of CTR1 in neuroblastoma cell lines and in tumors.A preclinical human neuroblastoma xenograft model was used to study anticancer activity of Dextran-Catechin in vivo and its effect on tumor copper homeostasis.PET imaging with [ 64 Cu]CuCl2 was performed in such preclinical neuroblastoma model to monitor alteration of copper levels in tumors during treatment.Results: CTR1 protein was found to be highly expressed in patient neuroblastoma tumors by immunohistochemistry. Treatment of neuroblastoma cell lines with Dextran-Catechin resulted in decreased levels of glutathione and in downregulation of CTR1 expression, which caused a significant decrease of intracellular copper.No changes in CTR1 expression was observed in normal human astrocytes after Dextran-Catechin treatment.In vivo studies and PET imaging analysis using the neuroblastoma preclinical model revealed elevated [ 64 Cu]CuCl2 retention in the tumor mass.Following treatment with Dextran-Catechin, there was a significant reduction in radioactive uptake, as well as reduced tumor growth.Ex vivo analysis of tumors collected from Dextran-Catechin treated mice confirmed the reduced levels of CTR1.Interestingly, copper levels in blood were not affected by treatment, demonstrating potential tumor specificity of Dextran-Catechin activity.Conclusion: Dextran-Catechin mediates its activity by lowering CTR1 and intracellular copper levels in tumors.This finding further reveals a potential therapeutic strategy for targeting copper-dependent cancers and presents a novel PET imaging method to assess patient response to copper-targeting anticancer treatments.
Prevalence of Eating Disorders Among US Children Aged 9 to 10 Years
Authors: Kaitlin Rozzell, Da Yeoun Moon, Patrycja Klimek, Tiffany Brown, Aaron J. Blashill
Journal: JAMA Pediatrics (2018)

From the Adolescent Brain Cognitive Development (ABCD) StudyEating disorders (EDs) are associated with significant morbidity and mortality. 1The prevalence of early-onset EDs has increased in the past several decades, with younger children more likely than adolescents to experience psychiatric comorbidity.The single nationally representative study that has reported 12-month prevalence rates of EDs among children aged 8 to 15 years found 0.1% total for children aged 8 to 11 years, with 0.3% for girls and 0.1% for boys aged 8 to 15 years old. 2 However, this previous study used Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria and did not report the prevalence of specific ED diagnoses.The aims of the present study were to report the prevalence rates of anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and other specified feeding and eating disorders (OSFED) in addition to a global "any ED" diagnosis, using
A pilot study assessing the burden of caregivers of elderly patients at University College Hospital UCH.
Authors: Eunice Nkechi Omoyeni
Journal: Journal of Clinical Oncology (2018)

12 Background: Caregiver burden is defined as “the perception of stress and fatigue caused by the sustained effort required in caring for persons with chronic illness or other conditions with special needs for care”. It is a type of stress or strain experienced by caregivers, which is directly/ indirectly related to the challenges/problems they face as a result of the health status of the person cared for. Stucki et al. 2000, described the carers burden as “strain or load borne by a person who cares for a chronically ill, disabled, or elderly family member”. Caregiver burden is response to physical, psychological, emotional, social, and financial stressors associated with the caregiving in a multidimensional way. It is the psychosocial and physical reaction to the imbalance of demands placed on the caregiver by various factors, including personal time, multiple roles, physical and emotional states, financial resources, and formal care resources. The caregiver's perception of the burden, rather than the perception of other family members or healthcare providers, determines the impact of this burden on his or her life. Methods: Caregivers of elderly patients attending the geriatric and medical outpatient’s clinics at UCH completed a caregiver strain index scale, over a 2 month period. Demographic information regarding gender, age, were obtained and scaled questions were ticked. Data was analysed using IBM SPSS statistics 21. Results: Eighty-five participants completed the caregiver strain index scale. The socio-demographic data described age and gender. Most participants fell in the 31 - 40 and 41 - 50 age groups (41.2% for each group). Fifty-eight (68.2%) were females while 27 (31.8%) were males. Most common strain variable was demand on time with percentage 54.1% (46). Twenty-nine (34.1%) had moderate level of stress (4 - 6) , while 32 (37.6%) had mild level of stress, and 17 (20.0%) had high level of stress. One participant had the highest score index was 11 while 13 (15.3%) had scores of 3 and 13 (15.3%) had scores of 5. Conclusions: The study showed that caregivers of elderly patients have high burden in the demand on their time and need supportive/collaborative systems which includes palliative care to help with the task of caring for these elderly ones.
Symptom science research conducted in NCI community programs over the past decade.
Authors: Diane C. St. Germain, Ann M. O'Mara
Journal: Journal of Clinical Oncology (2018)

220 Background: With the rising number of survivors across many cancer sites, increasing attention is being paid to assessing, preventing, and managing cancer and treatment related symptoms. This presentation will discuss the breadth of the symptom management portfolio within the community research programs funded by the NCI: The Community Clinical Oncology Program (CCOP) and the NCI Community Oncology Research Program (NCORP) from 2008 to 2018. Trends in types of symptoms and study designs will be described to identify research gaps. Methods: Symptom management research was operationally defined as any clinical study focusing on cancer and treatment related symptoms and/or related psychological, social and spiritual problems. The primary endpoint is measured by a patient reported outcome (PRO). Using this definition, a search was conducted of the NCI database to capture clinical studies implemented in the CCOP and NCORP networks from 2008 to 2018. Results: Between 2008 and 2018, 68 clinical studies were conducted in the NCI community research programs that met this definition. During this period of time, the most frequently studied symptom was neurotoxicities (n = 13), comprised of chemotherapy induced peripheral neuropathy (n = 3), neurocognition (n = 9) and ototoxicity (n = 1). Gastrointestinal symptoms (n = 10), pain (n = 9) and fatigue (6) were the following most frequent. The least studied symptoms included genitourinary symptoms (n = 1), vaginal health (n = 1), sexual desire (n = 1), psychosocial (n = 2) and lymphedema (n = 2). The predominant trial design was phase II or III randomized clinical trial with the remaining longitudinal, cohort design. Further delineation of these data will be presented. Conclusions: The prevalence of the symptoms studied within the NCI community programs mirrors the symptom literature in terms of frequency. Cancer survivors have reported a number of symptoms not adequately addressed by their clinicians such as sexual health and psychosocial issues. This gap also mirrors the frequency of research conducted in the community networks. Future research in the network focusing on these understudied areas should be considered by investigators.
Detection of Osteomyelitis Associated With Diabetic Foot Ulcers-Reply
Authors: Lisa G. Newman
Journal: JAMA (1992)

<h3>In Reply.</h3> —Our conclusion that leukocyte scanning can distinguish between soft tissue and bone infection is supported by the low false-positive (10%) and false-negative (7%) rates found in our study when these scans were compared with bone biopsy, as well as by others.<sup>2</sup>As noted in our "Methods" section, osteomyelitis was diagnosed only when focal uptake was seen on<i>both</i>plantar and dorsal views. As the ulcers were confined to the plantar surface, uptake would not be expected on the dorsal view if only the soft tissues were infected. Orthogonal views may be necessary only in the case of tarsal osteomyelitis as the thickness of the foot alone may preclude increased uptake on both plantar and dorsal views even when bony infection is present. These views were performed in the three patients with calcaneus osteomyelitis in our study. We agree that bone scans may not be accurate in
Long-Term Protection After Fractional-Dose Yellow Fever Vaccination
Authors: Anna H.E. Roukens, Karlijn van Halem, Adriëtte W. de Visser, Leo G. Visser
Journal: Annals of Internal Medicine (2018)

Background: Outbreaks of yellow fever and a frequently depleted vaccine stock increase demand for a dose-sparing strategy. A fractional dose of 17D yellow fever virus (17D-YFV) vaccine has been shown to be noninferior to the standard dose in inducing seroprotection. Objective: To evaluate whether fractional-dose vaccination can confer long-term immunity. Design: 10-year follow-up of a subgroup of a randomized, controlled, noninferiority trial. (Dutch Trial Register: NTR7094 [current study] and ISRCTN46326316 [original study]) Setting: The Netherlands. Participants: Seventy-five of 155 participants in the original trial provided a blood sample for this study. These 75 participants had received primary vaccination with 17D-YFV vaccine 10 years before. Forty received a 0.1-mL fractional dose intradermally, and 35 received the standard 0.5-mL dose subcutaneously. Measurements: Virus-neutralizing antibody responses were measured by a plaque reduction neutralization test. Results: Thirty-nine of 40 (98% [95% CI, 89% to 100%]) participants had protective levels of yellow fever–neutralizing antibodies more than 10 years after receiving a fractional dose of 17D-YFV vaccine compared with 34 of 35 (97% [CI, 87% to 100%]) in the standard-dose group. Limitation: Only 48% of participants from the original trial participated in this study. Conclusion: Intradermal administration of a one-fifth dose of yellow fever vaccine induced a protective immune response that lasted for 10 years after vaccination. Persons receiving a fractional dose of yellow fever vaccine do not require a booster vaccination for long-term protection against yellow fever. Primary Funding Source: Leiden University Medical Center and the International Society of Travel Medicine.
Immune cells and CNS physiology: Microglia and beyond
Authors: Geoffrey T. Norris, Jonathan Kipnis
Journal: The Journal of Experimental Medicine (2018)

Recent advances have directed our knowledge of the immune system from a narrative of “self” versus “nonself” to one in which immune function is critical for homeostasis of organs throughout the body. This is also the case with respect to the central nervous system (CNS). CNS immunity exists in a segregated state, with a marked partition occurring between the brain parenchyma and meningeal spaces. While the brain parenchyma is patrolled by perivascular macrophages and microglia, the meningeal spaces are supplied with a diverse immune repertoire. In this review, we posit that such partition allows for neuro–immune crosstalk to be properly tuned. Convention may imply that meningeal immunity is an ominous threat to brain function; however, recent studies have shown that its presence may instead be a steady hand directing the CNS to optimal performance.
Priority Setting Is More Than Resource Allocation: Reflecting on the Content of Funders’ Duties and Their Implications for Current Practice
Authors: Bridget Pratt, Adnan A. Hyder
Journal: The American Journal of Bioethics (2018)

Pierson and Millum (2018) examine an important area in much need of attention by bioethicists: the moral responsibilities of funders in health research priority setting. Much work in bioethics has ...
Helen Salisbury: The third presence
Authors: Helen Salisbury
Journal: BMJ (2018)

As students we’re taught not only scientific and clinical facts but also how to consult with patients: how to build a rapport, how to listen so that patients know that they’re heard, how to explain and be understood, and how to share decisions.

In the classroom, teaching scenarios usually involve one doctor and one patient (often an actor). In reality, consulting is frequently more complicated: the wife who keeps interrupting and speaks for her husband; the toddlers intent on emptying your cupboards while you try to consult with their parent.

But even in consultations that are ostensibly one to one, a third presence is always in the room, distracting me if I’m not careful, stealing …
Soluble immune checkpoints in cancer: production, function and biological significance
Authors: Daqian Gu, Xiang Ao, Yu Yang, Zhuo Chen, Xiang Xu
Journal: Journal for ImmunoTherapy of Cancer (2018)

Immune checkpoints play important roles in immune regulation, and blocking immune checkpoints on the cell membrane is a promising strategy in the treatment of cancer. Based on this, monoclonal antibodies are having much rapid development, such as those against CTLA-4 (cytotoxic T lymphocyte antigen 4) and PD-1 (programmed cell death protein 1).But the cost of preparation of monoclonal antibodies is too high and the therapeutic effect is still under restrictions. Recently, a series of soluble immune checkpoints have been found such as sCTLA-4 (soluble CTLA-4) and sPD-1 (soluble PD-1). They are functional parts of membrane immune checkpoints produced in different ways and can be secreted by immune cells. Moreover, these soluble checkpoints can diffuse in the serum. Much evidence has demonstrated that these soluble checkpoints are involved in positive or negative immune regulation and that changes in their plasma levels affect the development, prognosis and treatment of cancer. Since they are endogenous molecules, they will not induce immunological rejection in human beings, which might make up for the deficiencies of monoclonal antibodies and enhance the utility value of these molecules. Therefore, there is an increasing need for investigating novel soluble checkpoints and their functions, and it is promising to develop relevant therapies in the future. In this review, we describe the production mechanisms and functions of various soluble immune checkpoint receptors and ligands and discuss their biological significance in regard to biomarkers, potential candidate drugs, therapeutic targets, and other topics.
Identification of a Genetic Signature Enriching for Response to Ibrutinib in Relapsed/Refractory Follicular Lymphoma in the Dawn Phase 2 Trial
Authors: Sriram Balasubramanian, Brendan Hodkinson, Stephen J. Schuster, Nathan H. Fowler, Judith Trotman, Georg Hess, Bruce Cheson, Michael Schaffer, Shean-Sheng Wang, Sanjay Deshpande, Jessica Vermeulen, Gilles Salles, Ajay K. Gopal
Journal: Blood (2018)
An invitation to complete: Making advance directives part of the new patient process.
Authors: Susan Ash-Lee, Leslie T. Busby, Sami Diab, Cynthia B. Taniguchi, Ami Gorsky
Journal: Journal of Clinical Oncology (2018)

7 Background: In Colorado, there is no legal designation as to who is authorized to make healthcare decisions for an adult unable to make decisions for themselves. Completing an advance directive is increasingly associated with better end-of-life outcomes. Failure to complete an advance directive leads to fewer days on hospice and expensive, end-of-life care. It was hypothesized that patients who completed a Medical Durable Power of Attorney (MDPOA) document early may have higher adoption of advance care planning and earlier hospice at end-of-life. Methods: The Rocky Mountain Cancer Centers (RMCC) is the largest private oncology group in Colorado with multiple offices across the state. The RMCC-Pueblo clinic developed and piloted a new patient process where, at registration, all new patients were invited to complete a MDPOA while also completing other new patient forms. The Medical Durable Power of Attorney (MDPOA) is a document that appoints a healthcare decision maker (“healthcare agent”). Data on 4,441 patients from Nov. 1, 2017, to June 30, 2018, were extracted from the electronic health record (EHR), including code status, advance care planning counseling appointment, advance directive completion, and outcomes. Results: During this pilot, advance directive capture within the EHR rose from 15.4% to 21.4%. While the number of patients who elected hospice enrollment at the end of life was about the same, the length of hospice stay increased from an average of 14 to over 20 days, a 50% improvement. Conclusions: A MDPOA as a routine part of the new patient intake process is feasible and scalable. It opens the door to future ACP discussions and improved hospice utilization. Because of these findings, we are currently expanding this process to all RMCC practice sites. The results suggest that early completion of an Advance Directive lead to ongoing and healthy discussions about the patient’s end-of-life preferences for care, including appropriate hospice enrollment.