tbuckley/cabot-search huggingface dataset:
Stereotactic-body radiotherapy for portal vein tumor thrombosis in hepatocellular carcinoma patients.
Authors: Bae Kwon Jeong, Hoon Sik Choi, Ki Mun Kang, Hojin Jeong, Yun Hee Lee, In Bong Ha, Jin Ho Song
Journal: Journal of Clinical Oncology (2018)

442 Background: Portal vein tumor thrombosis (PVTT) is commonly accompanied by hepatocellular carcinoma (HCC) patients, and in these cases the treatment options became limited and treatment outcome was poor. Stereotactic body radiotherapy (SBRT) is one of the possible treatment options, which can deliver higher doses with highly conformal target have conducted for treatment of PVTT. However, only few studies about the SBRT have reported, even treatment schedules were not consistent. In this study, we report our institutional experience of treating PVTT in HCC patients using SBRT. Methods: 24 HCC patients with PVTT were treated with SBRT at our institution. All patients had unresectable HCC with PVTT, baseline liver function of Child-Pugh class A or B. SBRT was performed by Cyberknife based on 4D-simulation and 4D-planning. The prescription dose was 45 Gy in 3 fractions in 17 (70.8%) patients, and was modified to 39 to 42 Gy in 3 to 4 fractions in 7 (29.2%) patients whose target was large or adjacent to the bowel. After SBRT, transarterial chemoembolization (TACE) was performed in 16 (66.7%) patients within 3 months. Results: There were 2 (8.3%) patients of PVTT showed complete response, and 11 (45.8%) patients showed partial response. Stable disease was found in 7 (29.2%) patients, and progression in 4 (16.7%) patients. The response rate was lower in patients with tumor thrombus at main portal vein than those at branch of portal vein (main, 30% vs. branch, 71.4%, p = 0.052). The 1- and 2-year overall survival (OS) was 67.5%, 48.2%, respectively, with median survival of 20.8 months. The combination SBRT followed by TACE, and presence of grade 3 hepatic toxicities impacted on survival. The 1-year OS was 71.4% in patients whom TACE was combined after SBRT, which was higher than that of 14.6% who were treated with SBRT alone (p &lt; 0.001). The 1-year OS was 81.1% in patients who did not occur grade 3 hepatic toxicity, while 0% in patients who had grade 3 hepatic toxicity (p = 0.002). Conclusions: SBRT is a relatively effective treatment option for HCC patients of PVTT. Especially combined with TACE. Finding an optimal dose schedule which can reduce hepatic toxicity, while keeping the response seems important to increase the survival.
Image Gallery: Symmetrical whirled eschars on the face in mycosis fungoides
Authors: D.J. Lewis, E.J. Kim, M. Duvic
Journal: British Journal of Dermatology (2018)

Journal Article Image Gallery: Symmetrical whirled eschars on the face in mycosis fungoides Get access D.J. Lewis, D.J. Lewis Department of Dermatology The University of Texas MD Anderson Cancer Center Houston TX U.S.ASchool of Medicine Baylor College of Medicine Houston TX U.S.A https://orcid.org/0000-0002-1610-5785 Search for other works by this author on: Oxford Academic Google Scholar E.J. Kim, E.J. Kim Department of Dermatology The University of Texas MD Anderson Cancer Center Houston TX U.S.ASchool of Medicine Baylor College of Medicine Houston TX U.S.A Search for other works by this author on: Oxford Academic Google Scholar M. Duvic M. Duvic Department of Dermatology The University of Texas MD Anderson Cancer Center Houston TX U.S.A https://orcid.org/0000-0002-8971-4565 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 178, Issue 3, 1 March 2018, Page e224, https://doi.org/10.1111/bjd.16234 Published: 01 March 2018
Abstract 19807: Activation of G-Protein Coupled Estrogen Receptor Reduces Cardiac and Skeletal Muscle Dysfunction in Female Rats With Pulmonary Hypertension
Authors: Gisele Zapata-Sudo, Allan N Alencar, Daniele Gabriel-Costa, Ananssa M Silva, Guilherme C Montes, Sabrina T Martinez, Roberto T Sudo
Journal: Circulation (2016)

Introduction:  Pulmonary hypertension (PH) is a disease of women (female-to-male ratio 4:1) and is associated with cardiac and skeletal muscle dysfunction.   Hypothesis:  Herein, the activation of a new estrogen receptor (GPR30) by the agonist G1 was evaluated in monocrotaline (MCT)-induced PH female rats.   Methods:  Depletion of estrogen was induced by bilateral oophorectomy (OVX) in female Wistar rats (12 wks old). Experimental groups included the SHAM or OVX that received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction followed by administration of vehicle or G1, (400 μg/kg/day s.c.) for 14 days after the onset of disease (n=7 per group). Hemodynamic parameters were determined by transthoracic echocardiography. The effects of G1 in the maintenance of exercise capacity and skeletal muscle function were investigated using a treadmill test to observe the time to exhaustion and evaluating the contractile properties of electrically stimulated soleus (SOL) muscle.   Results:  MCT injection and estrogen loss led to a significant decrease in pulmonary acceleration time (PAT) and an increase in RV free wall thickness and MCT-related changes were attenuated by treatment with G1 (Table 1). Right ventricular systolic pressure (RVSP) was higher in MCT-injected rats and the magnitude of this increase in OVX group was significantly higher than that in SHAM group and G1 normalized it (Table 1). Combination of estrogen loss and MCT also reduced treadmill time to exhaustion in PH rats ( P   P     Conclusions:  G1 reversed PH-related cardiopulmonary dysfunction and exercise intolerance in female rats, a finding that may have important implications for the ongoing clinical evaluation of new drugs for the treatment of the disease in aging females.
David Cooper: brought HIV research and treatment to resource- poor settings
Authors: Bob Roehr
Journal: BMJ (2018)

David Cooper was a leader in the fight against AIDS, from its early days until the time of his death at age 68. His initial work took place in Sydney, but it soon expanded to all of Australia and then to a global setting: for four years he served as president of the International AIDS Society (IAS), which organises the International AIDS Conferences and other meetings.

More than anything, Cooper was a clinician and humanitarian who cared deeply about his patients and realised the importance of research to their care.

Cooper was born in Sydney to Jewish parents, who had fled eastern Europe on the cusp of the second world war. This, he said, helped shape his views on discrimination, medicine, and service. He entered the University of Sydney at age 15 and graduated with a medical degree in 1972, reaping honours and publishing papers along the way.

He trained in cancer immunology at St Vincent’s Hospital in Sydney, married Dorrie (the love of his life), and started a family. In the early 1980s, while on a fellowship at the Dana-Farber Cancer Institute in Boston, he read about and saw some of the first patients with what would come to be known as AIDS.

St Vincent’s …
Continuous Glucose Monitors for Insulin Dosing
Authors: Roy W. Beck
Journal: JAMA (2018)

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Patterns of care in treating childhood neuroblastoma: Evidence from a population level study (SEER) in the United States.
Authors: Diarmuid Coughlan, Charles Lynch, Matthew Gianferante, Jennifer Stevens, Linda C Harlan
Journal: Journal of Clinical Oncology (2017)

e22011 Background: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors. This heterogeneity is reflected in the sequence and variety of treatment modalities administered. We describe the treatment pattern and survival of childhood neuroblastoma patients using population-based data in the United States. Methods: Using the National Cancer Institute’s (NCI) Patterns of Care data, we examined treatment provided to childhood neuroblastoma patients newly diagnosed in 2010 and 2011 and registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries. Data were re-abstracted from hospital records and treating physicians were contacted to verify the treatment given. Stratifying by the Children’s Oncology Group (COG)’s 3-level (low, intermediate and high) neuroblastoma risk classification system for therapeutic decision-making, gave a snapshot of community-based treatment patterns. Kaplan-Meier survival analyses were also performed. Results: The majority of 250 patients (76%) were enrolled on an open/active clinical trial. All low-risk patients received surgery with/without chemotherapy. The majority of intermediate-risk patients (77%) received chemotherapy regimen that included carboplatin, etoposide, cyclophosphamide and doxorubicin. High-risk patients received extensive, multimodal treatment consisting of chemotherapy, surgery, high dose chemotherapy with stem cell rescue (transplant), radiation, immunotherapy (dinutuximab), and isotretinoin therapy. Cyclophosphamide was the most utilized chemotherapy agent (94%) in high-risk patients. Survival with a maximum follow-up of 48 months, was lowest (68%) for patients diagnosed with high-risk disease. Conclusions: The majority of childhood neuroblastoma patients are registered on a risk-based open/active clinical trial. Variation in modality, systemic agents and sequence of treatment reflects the heterogeneity of therapy for childhood neuroblastoma patients.
Pyruvate kinase M2 fuels multiple aspects of cancer cells: from cellular metabolism, transcriptional regulation to extracellular signaling
Authors: Ming-Chuan Hsu, Wen-Chun Hung
Journal: Molecular Cancer (2018)

Originally identified as a metabolic enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway, pyruvate kinase M2-type (PKM2) has been shown to exhibit novel biological activities in the nucleus and outside the cells. Although cell-based studies reveal new non-canonical functions of PKM2 in gene transcription, epigenetic modulation and cell cycle progression, the importance of these non-canonical functions in PKM2-mediated tumorigenesis is still under debate because studies in genetically modified mice do not consistently echo the findings observed in cultured cancer cells. In addition to regulation of gene expression, the existence of PKM2 in exosomes opens a new venue to study the potential role of this glycolytic enzyme in cell-cell communication and extracellular signal initiation. In this review, we briefly summarize current understanding of PKM2 in metabolic switch and gene regulation. We will then emphasize recent progress of PKM2 in extracellular signaling and tumor microenvironment reprogramming. Finally, the discrepancy of some PKM2's functions in vitro and in vivo, and the application of PKM2 in cancer detection and treatment will be discussed.
Abstract 18086: Rates of Cardiovascular Events in Patients Receiving High-Intensity Statin Therapy in the United Kingdom
Authors: Benjamin Taylor, Mark Danese, Guilllermo Villa, Mickael Lothgren, Kamlesh Khunti, Kausik Ray
Journal: Circulation (2015)

Background: Cardiovascular (CV) event rates have declined, in part due to extensive use of treatments such as statin therapy, but rates in specific real-world populations are unknown. Our aim was to provide contemporary estimates of CV event rates across five high-risk cohorts receiving high-intensity statin therapy in the UK. Hypothesis: CV event rates will vary by cohort and over time. Methods: Five cohorts receiving high-intensity statins were studied in the Clinical Practice Research Datalink: (1) high-risk primary prevention (HRPP - diabetes with no other CV event), (2) evident CV disease (ECVD - CV disease excluding acute coronary syndrome (ACS), ischemic stroke (IS), and heart failure (HF)), (3) incident ACS, (4) incident IS, and (5) incident HF (in patients with ACS or IS). Patients were followed from 1/1/2005 (HRPP, ECVD) or qualifying index event (ACS/IS/HF) until the next CV event, death, or end of observation (12/31/2011). Outcome CV events were based on hospitalization primary diagnoses and cause of death data. These were combined to form a composite endpoint (ACS, IS, HF, or CV death) for all cohorts. For HRPP, the ECVD conditions were included as outcomes. Crude rates were estimated at 2-month intervals over time. Results: Cohort sizes ranged from 414 patients for IS to 9,411 for ECVD. Observation time ranged from 3.6 years for HF to 7.0 years for HRPP. Mean, unadjusted composite CV event rates per 1,000 person years were 37 for HRPP, 43 for ECVD, 107 for IS, 135 for ACS, and 201 for HF (Figure). The rates for secondary prevention cohorts were highest after the index CV event and then declined and became stable by one year. Conclusions: In the incident cohorts, event rates were highest in the first year and declined over time. However, rates were higher than the prevalent cohorts even at 1500 days after the index event. These rates are higher than in clinical trials and further research should identify methods of reducing CV risk in these high intensity statin patients.
Endothelial C-Type Natriuretic Peptide Acts on Pericytes to Regulate Microcirculatory Flow and Blood Pressure
Authors: Katarina Špiranec, Wen Chen, Franziska Werner, Viacheslav O. Nikolaev, Takashi Naruke, Franziska Koch, Andrea Werner, Petra Eder-Negrin, Rodrigo Diéguez-Hurtado, Ralf H. Adams, Hideo A. Baba, Hannes Schmidt, Kai Schuh, Boris V. Skryabin, Kiavash Movahedi, Frank Schweda, Michaela Kuhn
Journal: Circulation (2018)

Background: Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular tone, but the target cells remain controversial. The cGMP-producing guanylyl cyclase–B (GC-B) receptor for CNP is expressed in vascular smooth muscle cells (SMCs). However, whereas endothelial cell–specific CNP knockout mice are hypertensive, mice with deletion of GC-B in vascular SMCs have unaltered blood pressure. Methods: We analyzed whether the vasodilating response to CNP changes along the vascular tree, ie, whether the GC-B receptor is expressed in microvascular types of cells. Mice with a floxed GC-B ( Npr2 ) gene were interbred with Tie2-Cre or PDGF-Rβ-Cre ERT2 lines to develop mice lacking GC-B in endothelial cells or in precapillary arteriolar SMCs and capillary pericytes. Intravital microscopy, invasive and noninvasive hemodynamics, fluorescence energy transfer studies of pericyte cAMP levels in situ, and renal physiology were combined to dissect whether and how CNP/GC-B/cGMP signaling modulates microcirculatory tone and blood pressure. Results: Intravital microscopy studies revealed that the vasodilatatory effect of CNP increases toward small-diameter arterioles and capillaries. CNP consistently did not prevent endothelin-1–induced acute constrictions of proximal arterioles, but fully reversed endothelin effects in precapillary arterioles and capillaries. Here, the GC-B receptor is expressed both in endothelial and mural cells, ie, in pericytes. It is notable that the vasodilatatory effects of CNP were preserved in mice with endothelial GC-B deletion, but abolished in mice lacking GC-B in microcirculatory SMCs and pericytes. CNP, via GC-B/cGMP signaling, modulates 2 signaling cascades in pericytes: it activates cGMP-dependent protein kinase I to phosphorylate downstream targets such as the cytoskeleton-associated vasodilator-activated phosphoprotein, and it inhibits phosphodiesterase 3A, thereby enhancing pericyte cAMP levels. These pathways ultimately prevent endothelin-induced increases of pericyte calcium levels and pericyte contraction. Mice with deletion of GC-B in microcirculatory SMCs and pericytes have elevated peripheral resistance and chronic arterial hypertension without a change in renal function. Conclusions: Our studies indicate that endothelial CNP regulates distal arteriolar and capillary blood flow. CNP-induced GC-B/cGMP signaling in microvascular SMCs and pericytes is essential for the maintenance of normal microvascular resistance and blood pressure.
Alerting relatives about heritable risks: the limits of confidentiality
Authors: Anneke Lucassen, Roy Gilbar
Journal: BMJ (2018)

Are there situations when sharing a patient’s genetic information with relatives without consent is acceptable? Anneke Lucassen and Roy Gilbar discuss John has recently received a diagnosis of Huntington’s disease. This serious hereditary condition has no cure and early death (aged 40-60) is likely. An affected person has a 50% chance of passing the condition on to their children. Those who inherit the causative mutation (a triplet repeat or “stutter” in the DNA) are likely to develop the disease in mid-life, or earlier if the stutter has enlarged, which can sometimes happen if it is inherited paternally. John’s daughter, Clare, knows her father is ill but not that his condition is heritable. She is pregnant and mentions this to John’s clinicians. They wonder whether she has a right to know that he has a heritable condition, but John worries about Clare and that she might terminate her pregnancy. He therefore refuses consent for Clare to be told. This scenario, recently discussed by English courts in ABC v St George’s Healthcare NHS Trust and others (box 1),1 raises questions that clinicians increasingly face—namely, whether, and how, genetic information discovered in one patient might be communicated to relatives at risk of inheriting it. Tensions around confidentiality and responsibilities to others are well described in practices around, for example, sexually transmitted diseases (STDs), yet for heritable risks the prevailing discourse remains one that gives prominence to patient confidentiality. This is presumably because, until recently, few treatments were available to prevent or ameliorate the course of genetic conditions. Box 1 ### the ABC case ABC is the first case in English law to deal with non-disclosure of a patient’s genetic information to a relative.222324 Similar to our scenario of John and Clare, in ABC, a daughter claimed that her father’s clinicians were negligent for not … RETURN TO TEXT
Presenting Systolic Blood Pressure and Outcomes in Patients With Acute Aortic Dissection
Authors: Eduardo Bossone, Riccardo Gorla, Troy M. LaBounty, Toru Suzuki, Dan Gilon, Craig Strauss, Andrea Ballotta, Himanshu J. Patel, Arturo Evangelista, Marek P. Ehrlich, Stuart Hutchison, Eva Kline-Rogers, Daniel G. Montgomery, Christoph A. Nienaber, Eric M. Isselbacher, Kim A. Eagle
Journal: Journal of the American College of Cardiology (2018)
Recruitment of feces donors among blood donors: Results from an observational cohort study
Authors: Simon Mark Dahl Jørgensen, Christian Erikstrup, Khoa Manh Dinh, Lars Erik Lemming, Jens Frederik Dahlerup, Christian Lodberg Hvas
Journal: Gut Microbes (2018)

As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58%) were excluded mainly due to having an allergy, being overweight, or presenting gastrointestinal complaints. Among the remaining 58 (37%) donors, complete blood and feces screenings were obtained from 46 (79%). Of these 46 donors, 15 (33%) were excluded primarily due to abnormal blood results or the presence of apathogenic intestinal parasites. Overall, 31 (20%; 95% confidence interval 14–27%) of the 155 blood donors qualified as feces donors. In conclusion, blood donors constitute a suitable and motivated population for a continuous recruitment of voluntary feces donors. We found that a stepwise recruitment procedure was feasible and that 20% of the blood donors were eligible for feces donation.