tbuckley/cabot-search huggingface dataset:
Oncology education for internal medicine residents: The value of participating in a medical oncology rotation.
Authors: Nancy Alice Nixon, Yoo-Joung Ko, Howard John Lim, Christine Elser, Vincent Channing Tam
Journal: Journal of Clinical Oncology (2016)

e18175 Background: Despite the high incidence and prevalence of cancer, medical oncology (MO) rotations are not mandatory in a majority of Canadian internal medicine (IM) training programs. The purpose of this study was to clarify the value of a MO rotation for IM residents. Methods: IM residents scheduled for a MO rotation at BC Cancer Agency (BCCA, Vancouver), Princess Margaret Cancer Centre (PMCC, Toronto), Sunnybrook Odette Cancer Centre (SOCC, Toronto), Tom Baker Cancer Centre (TBCC, Calgary) were asked by e-mail to participate in pre- and post-rotation surveys regarding attitudes toward a MO rotation and general cancer knowledge. Responses pre- versus post-rotation were compared. Results: Between January 2013 and December 2015 68 IM residents completed the pre-rotation survey and 48 (71%) the post-rotation survey. Responses were received from 22 IM residents at TBCC, 9 BCCA, 9 SOCC and 8 PMCC. Residents spent 78% of their rotation in outpatient clinics, 15% with inpatient care and 7% emergency room assessments. Cancer-related learning during the rotations was mostly acquired from MO physicians in clinic (36%), while self-directed learning accounted for 34%. 52% of IM residents believed MO should be a mandatory rotation. When asked to rate their comfort level in dealing with cancer patients and patients at end-of-life (out of 5), mean scores improved from 3.2 to 4.0 (p < 0.001) and 3.6 to 4.0 (p = 0.003), respectively. Mean score on the knowledge assessment improved from 77% pre-rotation to 85% post-rotation (p = 0.003). The most important topics to be learned during an MO rotation are: 1) Common complications of cancer/oncologic emergencies; 2) Common complications of cancer treatment; 3) General approach to diagnosis in a patient with suspected cancer; 4) General principles of treating cancer; 5) Management of common malignancies. Conclusions: A MO rotation for IM residents improves comfort level in dealing with cancer patients and patients at end-of-life. Overall cancer-specific knowledge also improved. Given these benefits, IM training programs should consider a mandatory MO rotation.
Abstract 83: Autophagy Protects the Heart Against Pressure Overload Induced Heart Failure
Authors: Akihiro Shirakabe, Yoshiyuki Ikeda, Toshiro Saito, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation Research (2016)

Autophagy is an important mechanism for the degradation of cytosolic proteins and organelles. We investigated how autophagy is regulated in the heart in response to pressure overload (PO). Mice were subjected to transverse aortic constriction (TAC) at multiple time points between 1 hours and 30 days. Left ventricular (LV) weight/tibial length (TL) was significantly elevated at Day 5 (6.21 ± 0.10 vs 4.59 ± 0.10, p&lt;0.05) and thereafter. Ejection fraction (EF) was maintained at Day 7 (82.1±3.4 vs 78.4±3.2%), but gradually decreased thereafter (at Day 30; 51.0±4.5, p&lt;0.05). The level of LC3II was rapidly increased and peaked at 3 hour (2.4 fold , p&lt;0.05), returned to normal by 24 hours, and then significantly decreased at Day 5 (-40.0%, p&lt;0.05) and thereafter. Autophagic flux was evaluated with tandem fluorescent LC3. At 6 hours, both GFP/RFP double positive (yellow) dots and RFP dots were significantly increased in the TAC group compared to the sham group with or without chloroquine (CQ) (yellow 12±2 vs 4±0 CQ(-), 23±3 vs 9±1 CQ(+); RFP 13±2 vs 5±1 CQ(-), 19±1 vs 13±1 CQ(+)). On the other hand, both yellow and RFP dots were significantly decreased at Day7 and thereafter in the TAC group compared to the sham group with or without CQ. These data suggest that autophagic flux is activated transiently after TAC, but is inactivated after Day 5. To examine the functional significance of autophagy during PO, beclin1 heterozygous KO ( beclin1 -hetKO) mice, atg7 cardiac specific KO (Atg7-CKO) mice, and cardiac-specific U6-shRNA beclin1 (U6shRNA beclin1 ) mice were subjected to TAC. At Day 7 or 14, decreases in EF (60.7 ± 4.8%, 53.8 ± 2.1% and 46.7 ± 5.9%, p&lt;0.05) and increases in lung weight/TL (8.43 ± 0.87, 11.04 ± 4.16 and 18.76 ± 3.77, p&lt;0.05) were exacerbated in beclin1 -hetKO, atg7 -CKO and U6shRNA beclin1 mice compared to in control mice. These results suggest that PO inhibits autophagy after Day5, which coincides with the development of cardiac dysfunction. Since heart failure is exacerbated by further suppression of autophagy, autophagy during PO protects the heart from cardiac dysfunction.
Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta‐analysis
Authors: Laura Kulik, Julie K. Heimbach, Feras Zaiem, Jehad Almasri, Larry J Prokop, Zhen Wang, M. Hassan Murad, Khaled Mohammed
Journal: Hepatology (2017)

Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down-staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow-up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06-1.85; I2 = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060-2.370; I2 = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down-staging therapy versus no downstaging, and this showed a significant increase in 1-year (two studies, RR, 1.11; 95% CI, 1.01-1.23) and 5-year (1 study, RR, 1.17; 95% CI, 1.03-1.32) post-LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision.In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (Hepatology 2018;67:381-400).
NICE urges GPs to diagnoses endometriosis more quickly
Authors: Jacqui Wise
Journal: BMJ (2017)

GPs are being urged to look out for the symptoms of endometriosis as, on average, women wait 7.5 years between first seeing a doctor and getting a confirmed diagnosis, according to the National Institute for Health and Care Excellence.

The new guidelines say that doctors should suspect endometriosis in women and teenage girls presenting with one or more of the following signs or symptoms1 …
Enhanced endothelium epithelial sodium channel signaling prompts left ventricular diastolic dysfunction in obese female mice
Authors: Guanghong Jia, Javad Habibi, Annayya R. Aroor, Michael A. Hill, Vincent G. DeMarco, Li E. Lee, Lixin Ma, Brady J. Barron, Adam Whaley-Connell, James R. Sowers
Journal: Metabolism (2017)
A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function
Authors: Stefanie Kälin, Maike Becker, Verena B. Ott, Isabelle Serr, Fabian Hosp, Mohammad M.H. Mollah, Susanne Keipert, Daniel Lamp, Francoise Rohner-Jeanrenaud, Victoria K. Flynn, Martin G. Scherm, Lucas F.R. Nascimento, Katharina Gerlach, Vanessa Popp, Sarah Dietzen, Tobias Bopp, Purna Krishnamurthy, Mark H. Kaplan, Manuel Serrano, Stephen C. Woods, Philipp Tripal, Ralf Palmisano, Martin Jastroch, Matthias Blüher, Christian Wolfrum, Benno Weigmann, Anette-Gabriele Ziegler, Matthias Mann, Matthias H. Tschöp, Carolin Daniel
Journal: Cell Metabolism (2017)
二層型ポリウレタン‐細胞外マトリックス心臓パッチはラットモデルにおける虚血性心室壁リモデリングを改善する【Powered by NICT】
Authors: D’Amore Antonio, Yoshizumi Tomo, K Luketich Samuel, T Wolf Matthew, Gu Xinzhu, Cammarata Marcello, Hoff Richard, F Badylak Stephen, R Wagner William
Journal: Biomaterials (2016)
Bevacizumab-induced hypertension: Clinical presentation and molecular understanding
Authors: Megan Li, Deanna L. Kroetz
Journal: Pharmacology & Therapeutics (2017)

Bevacizumab is a vascular endothelial growth factor-A-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of several types of cancer. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy and lead to other cardiovascular complications. The factors that contribute to interindividual variability in blood pressure response to bevacizumab treatment are not well understood. In this review, we outline research efforts to understand the mechanisms and pathophysiology of hypertension resulting from bevacizumab treatment. Moreover, we highlight current knowledge of the pharmacogenetics of bevacizumab-induced hypertension, which may be used to develop strategies to prevent or minimize this toxicity.
FDG PET/CT in 2 Cases of Renal Metastasis From Esophageal Squamous Cell Carcinoma
Authors: Qian Zhao, Aisheng Dong, Bo Yang, Yang Wang, Changjing Zuo
Journal: Clinical Nuclear Medicine (2017)

Clinically, renal metastasis from esophageal squamous cell carcinoma is uncommon. We present 2 cases of renal metastasis from esophageal squamous cell carcinoma with enhanced CT and FDG PET/CT findings. In the first case, right kidney and right renal hilum were the only known metastatic sites. In the second case, bilateral kidneys were the only known metastatic sites. All the renal metastatic tumors appeared as hypovascular and hypoattenuating masses involving both the renal cortex and medulla on enhanced CT and intense FDG uptake on FDG PET/CT.
Clinical and genetic predictors of paclitaxel neurotoxicity based on patient- versus clinician-reported incidence and severity of neurotoxicity in the ICON7 trial
Authors: S.B. Park, J.B. Kwok, R. Asher, C.K. Lee, P. Beale, F. Selle, M. Friedlander
Journal: Annals of Oncology (2017)

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of paclitaxel, with no reliable method to identify at-risk patients. We investigated the incidence and risk factors including genetic polymorphisms associated with the development of CIPN based on clinician and patient reporting of neuropathic symptoms.Patients and methodsRisk factors for the development of CIPN were examined in 454 patients treated with paclitaxel/carboplatin from the International Collaboration on Ovarian Neoplasms 7 (ICON7) trial. Neuropathy was graded by clinicians by standard adverse event reporting and by patients utilising OV28 questionnaire. Genetic risk factors were examined by selecting six single nucleotide polymorphisms in genes associated with microtubule function. Risk factors were assessed via dose-to-event cox regression models.ResultsGrade >2 neuropathy was reported by clinicians in 28% of patients, while 67% of patients reported 'quite a bit' or 'very much' tingling or numbness. Agreement between clinicians and patients was poor (κ = 0.236, 95% confidence interval, 0.177–0.296, P < 0.001). Older age, bevacizumab treatment and bowel resection were associated with clinician reported CIPN, while older age and volume of residual disease were associated with patient-reported neuropathy. There were no significant associations between clinician-reported neuropathy or patient-reported neuropathy and TUBB2, CEP72 or individual MAPT or GSK3B SNPs, however MAPT additive polymorphisms were associated with patient-reported neuropathy and GSK3B additive polymorphisms were associated with clinician reported CIPN.ConclusionsThere was significant discordance between patient- and clinician-reported neurotoxicity. The lack of consensus regarding optimal outcome measures and whose opinion with regard to CIPN takes precedence is a limitation in the investigation of risk factors for CIPN. Care must be taken to select and include patient-reported outcome measures in CIPN assessment to enable accurate identification of genetic and other risk factors for neuropathy.
Impact of Center Left Ventricular Assist Device Volume on Outcomes After Implantation
Authors: Jennifer A. Cowger, John M. Stulak, Palak Shah, Todd F. Dardas, Francis D. Pagani, Shannon M. Dunlay, Simon Maltais, Keith D. Aaronson, Ramesh Singh, Nahush A. Mokadam, James K. Kirklin, Christopher T. Salerno
Journal: JACC Heart Failure (2017)
FRI0690 Risk of fracture among patients with gout: a population-based cohort study
Authors: A Abdul Sultan, R Whittle, S Muller, E Roddy, C Mallen, M Blagojevic-Bucknall, T Helliwell, S Hider, Z Paskins
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout is the most common type of inflammatory arthritis, affecting 2.4% of adults in the UK and is associated with a number of co-morbidities. Our understanding of the association between gout and fracture risk is limited with previous studies offering conflicting results. <h3>Objectives</h3> To determine the risk of fracture among gout patients and assess the potential impact of urate-lowering therapy (ULT) on fracture risk. <h3>Methods</h3> Utilising primary care records from Clinical Practice Research Datalink we identified patients with gout between 1990 and 2004 who were followed up until 2015. Each gout patient was individually matched to 5 individuals without gout based on age, sex, and registered practice. Absolute rate (AR) of fracture and hazard ratios (HR) were calculated using Cox regression models. We further stratified our analysis by age, gender and ULT prescription. <h3>Results</h3> We matched 35,857 patients with incident gout to 148,407 controls. Overall, we found no increased risk of fracture among gout patients compared to controls. However, men with no evidence of ULT had higher absolute risk of fracture compared to controls (AR=39 versus 26 per 10,000 person-years) corresponding to a 23% (HR=1.23; 95% CI 1.12–1.36) increased risk. The risk was particularly high for vertebral (HR=1.50; 95% CI 1.20–1.87) and wrist fracture (HR=1.45; 95% CI 1.21–1.74). Those treated with ULT had a 12% (HR=0.88; 95% CI 0.79–0.98) lower risk of fracture. Similar findings were not observed for women. <h3>Conclusions</h3> We found higher risk of vertebral and wrist fractures among men with gout not prescribed ULT. Those prescribed ULT had lower risk of fracture compared to the general population. Further research is needed to understand the role of ULT in fracture prevention. <h3>Acknowledgements</h3> CDM is funded by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care West Midlands, the NIHR School for Primary Care Research and a NIHR Research Professorship in General Practice. TH is funded by a NIHR Clinical Lectureship in General Practice and AAS is funded by NIHR Postdoctoral Fellowship. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health <h3>Disclosure of Interest</h3> None declared
Can Rituximab be Useful for Treating SLE-Associated Immune Cytopenias ? Results from a Retrospective Multicentre Study on 62 Patients
Authors: Alexandra Serris, Zahir Amoura, Benjamin Terrier, Eric Hachulla, Nathalie Costedoat-Chalumeau, Thomas Papo, Olivier Lambotte, David Saadoun, Miguel Hie, Philippe Blanche, Corinne Haioun, Bertrand Lioger, Bertrand Godeau, Marc Michel
Journal: Blood (2016)
Outcomes of maintenance therapy with lenalidomide or bortezomib in multiple myeloma in the setting of early autologous stem cell transplantation
Authors: R Chakraborty, E Muchtar, S K Kumar, F K Buadi, D Dingli, A Dispenzieri, S R Hayman, W J Hogan, P Kapoor, M Q Lacy, N Leung, R Warsame, T Kourelis, W Gonsalves, M A Gertz
Journal: Leukemia (2017)
Exosomal miRNAs and miRNA dysregulation in cancer-associated fibroblasts
Authors: Fengming Yang, Zhiqiang Ning, Ling Ma, Weitao Liu, Chuchu Shao, Yongqian Shu, Hua Shen
Journal: Molecular Cancer (2017)

The present review aimed to assess the role of exosomal miRNAs in cancer-associated fibroblasts (CAFs), normal fibroblasts (NFs), and cancer cells. The roles of exosomal miRNAs and miRNA dysregulation in CAF formation and activation were summarized. All relevant publications were retrieved from the PubMed database, with key words such as CAFs, CAF, stromal fibroblasts, cancer-associated fibroblasts, miRNA, exosomal, exosome, and similar terms. Recent studies have revealed that CAFs, NFs, and cancer cells can secrete exosomal miRNAs to affect each other. Dysregulation of miRNAs and exosomal miRNAs influence the formation and activation of CAFs. Furthermore, miRNA dysregulation in CAFs is considered to be associated with a secretory phenotype change, tumor invasion, tumor migration and metastasis, drug resistance, and poor prognosis. Finding of exosomal miRNA secretion provides novel insights into communication among CAFs, NFs, and cancer cells. MicroRNA dysregulation is also involved in the whole processes of CAF formation and function. Dysregulation of miRNAs in CAFs can affect the secretory phenotype of the latter cells.
A phase I study of the first-in-class mitochondrial metabolism inhibitor CPI-613 in patients with advanced hematologic malignancies.
Authors: Timothy S. Pardee, Denise A. Levitan, David Duane Hurd, Leslie R. Ellis, Scott Isom, Robin Harrelson, Megan Manuel, Sarah Dralle, Susan Lyerly, Bayard L. Powell
Journal: Journal of Clinical Oncology (2013)

2516^ Background: Altered metabolism is a hallmark of cancer, including hematologic malignancies. This altered metabolism is a possible therapeutic target. The lipoate derivative CPI-613 is a first in class agent that targets pyruvate dehydrogenase complex.This trial was designed to determine the maximally tolerated dose (MTD), safety, and efficacy of CPI-613 given as a single agent by IV infusion. Methods: CPI-613 was given over a 2 hour infusion on days 1 and 4 for 3 weeks every 28 days with a starting dose of 420 mg/m 2 . The dose was escalated in 6 cohorts to a final dose of 3780 mg/m 2 . Treatment could be continued if the patient experienced clinical benefit. Results: A total of 26 patients with advanced relapsed or refractory hematologic malignancies were enrolled. Patients were heavily pretreated with a median of 3 previous therapies (range 1-11). CPI-613 was well tolerated when infused over 2 hours, with no worsening of cytopenias at any dose level. After the dose was escalated to 2940 mg/m 2 the protocol was amended to a 1 hour infusion. When infused over 1 hour, 2 patients developed grade 3 renal failure. Infusion time was then returned to 2 hours and dose escalation resumed. At a dose of 3780 mg/m 2 , one patient experienced prolonged grade 3 nausea and one patient grade 3 renal failure, defining this dose as above the MTD. Renal failure resolved in all but one patient who opted for hospice care. A total of 6 patients were treated at a dose of 2940 mg/m 2 over 2 hours with no DLTs observed, establishing this as the MTD. Of the 21 patients evaluable for a response, eight achieved a response of stable disease or better for a response rate of 38%. Responses included a complete remission maintained over 27 cycles in one AML patient and clearance of marrow blasts in another, sustained partial response in both a Burkitt's and a cutaneous T cell lymphoma patient maintained over 17 and 8 cycles respectively, and stable disease in 2 multiple myeloma and 2 myelodysplasia patients. Conclusions: To our knowledge this is the first report of an agent with activity in aggressive hematological malignancies that is not myelosuppressive. The therapeutic index appears high suggesting CPI-613 should be further studied in phase II trials. Clinical trial information: NCT01034475.
Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters
Authors: Wolfgang Winnicki, Harald Herkner, Matthias Lorenz, Ammon Handisurya, Željko Kikić, Bernhard Bielesz, Benjamin Schairer, Thomas Reiter, Farsad Eskandary, Gere Sunder-Plassmann, Guerkan Sengoelge
Journal: Kidney International (2017)
in vivo指向進化により同定されたペプチドCC12の低侵襲眼内送達への非侵襲による抗血管新生【Powered by NICT】
Authors: Chen Chong, Liu Kun, Xu Yupeng, Zhang Pengwei, Suo Yan, Lu Yi, Zhang Wenyuan, Su Li, Gu Qing, Wang Huamao, Gu Jianren, Li Zonghai, Xu Xun
Journal: Biomaterials (2017)
Minimally invasive and targeted therapeutic cell delivery to the skin using microneedle devices
Authors: B. Gualeni, S.A. Coulman, D. Shah, P.F. Eng, H. Ashraf, P. Vescovo, G.J. Blayney, L.-D. Piveteau, O.J. Guy, J.C. Birchall
Journal: British Journal of Dermatology (2017)

Translation of cell therapies to the clinic is accompanied by numerous challenges, including controlled and targeted delivery of the cells to their site of action, without compromising cell viability and functionality.To explore the use of hollow microneedle devices (to date only used for the delivery of drugs and vaccines into the skin and for the extraction of biological fluids) to deliver cells into skin in a minimally invasive, user-friendly and targeted fashion.Melanocyte, keratinocyte and mixed epidermal cell suspensions were passed through various types of microneedles and subsequently delivered into the skin.Cell viability and functionality are maintained after injection through hollow microneedles with a bore size ≥ 75 μm. Healthy cells are delivered into the skin at clinically relevant depths.Hollow microneedles provide an innovative and minimally invasive method for delivering functional cells into the skin. Microneedle cell delivery represents a potential new treatment option for cell therapy approaches including skin repigmentation, wound repair, scar and burn remodelling, immune therapies and cancer vaccines.
Adiponectin Improves Endothelial Redox State in Human Atherosclerosis by Phosphorylating eNOS and Improving Its Enzymatic Coupling
Authors: M Margaritis, A Antonopoulos, S Reilly, R Sayeed, M Petrou, R De Silva, C Bakogiannis, B Casadei, K M Channon, C Antoniades
Journal: Circulation (2012)