tbuckley/cabot-search huggingface dataset:
Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care
Authors: Richard Rohr
Journal: Annals of Internal Medicine (2017)

Letters7 March 2017Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient CareRichard Rohr, MDRichard Rohr, MDFrom Broomall, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0626 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Detsky and Gropper (1) make an analogy to the athlete who loses skills after leaving the playing field. Player–coaches were once common in sports but have largely disappeared. Top athletes understand the value of a skilled observer on the sidelines who can help them improve their play. Even athletes in individual sports, who are as autonomous as any physician, place great value on their coaches and pay them out of their own pockets. The great coaches have often been undistinguished as players and are almost never superstars, but they have a skill set that differs from that ...Reference1. Detsky AS, Gropper MA. Why physician leaders of health care organizations should participate in direct patient care. Ann Intern Med. 2016;165:519-20. [PMID: 27399305]. doi:10.7326/M16-0820 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Broomall, Pennsylvania.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L16-0626. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoWhy Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care Allan S. Detsky and Michael A. Gropper Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care David S. Channin Why Physician Leaders of Health Care Organizations Should Participate in Direct Patient Care Allan S. Detsky and Michael A. Gropper Metrics 7 March 2017Volume 166, Issue 5Page: 376KeywordsConflicts of interestDisclosureHealth carePatientsSports ePublished: 7 March 2017 Issue Published: 7 March 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effects of Different Exercise Modalities on Fatigue in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Year-long Randomised Controlled Trial
Authors: Dennis R. Taaffe, Robert U. Newton, Nigel Spry, David Joseph, Suzanne K. Chambers, Robert A. Gardiner, Brad A. Wall, Prue Cormie, Kate A. Bolam, Daniel A. Galvão
Journal: European Urology (2017)

Physical exercise mitigates fatigue during androgen deprivation therapy (ADT); however, the effects of different exercise prescriptions are unknown.To determine the long-term effects of different exercise modes on fatigue in prostate cancer patients undergoing ADT.Between 2009 and 2012, 163 prostate cancer patients aged 43-90 y on ADT were randomised to exercise targeting the musculoskeletal system (impact loading+resistance training; ILRT; n=58), the cardiovascular and muscular systems (aerobic+resistance training; ART; n=54), or to usual care/delayed exercise (DEL; n=51) for 12 mo across university-affiliated exercise clinics in Australia.Supervised ILRT for 12 mo, supervised ART for 6 mo followed by a 6-mo home program, and DEL received a printed booklet on exercise information for 6 mo followed by 6-mo stationary cycling exercise.Fatigue was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 36 and vitality using the Short Form-36. Analysis of variance was used to compare outcomes for groups at 6 mo and 12 mo.Fatigue was reduced (p=0.005) in ILRT at 6 mo and 12 mo (∼5 points), and in ART (p=0.005) and DEL (p=0.022) at 12 mo. Similarly, vitality increased for all groups (p≤0.001) at 12 mo (∼4 points). Those with the highest levels of fatigue and lowest vitality improved the most with exercise (ptrend<0.001). A limitation was inclusion of mostly well-functioning individuals.Different exercise modes have comparable effects on reducing fatigue and enhancing vitality during ADT. Patients with the highest levels of fatigue and lowest vitality had the greatest benefits.We compared the effects of different exercise modes on fatigue in men on androgen deprivation therapy. All exercise programs reduced fatigue and enhanced vitality. We conclude that undertaking some form of exercise will help reduce fatigue, especially in those who are the most fatigued.
Erratum: Loss of heterozygosity in sporadic human breast carcinoma: A common region between 11q22 and 11q23.3 (Cancer Research (September 1994) 54 (4586-4589)
Authors: G. M. Hampton, A. Mannermaa, R. Winqvist, M. Alavaikko, G. Blanco, P. J. Taskinen, H. Kiviniemi, Irene Newsham, W. K. Cavenee, G. A. Evans
Journal: Cancer Research (2004)
Abstract P6-02-06: Metabolomic profiling of breast cancer and adjacent tissue
Authors: JR Santos, MM Brentanni, T Tortelli, I Dale, A Waitzberg, D Waitzberg, G Ravacci
Journal: Cancer Research (2017)

Abstract Breast cancer (BC) is the most common cause of death among women worldwide. Nowadays, research directed toward the discovery of cancer molecular characteristics has extended into various biological aspects, from early investigations of cancer genomics and proteomics to recent efforts in cancer metabolomics. We consider that breast cancer cells display significantly altered cellular processes, and thus metabolites, compared to normal cells. In this regard, the application of metabolomics towards cancer research can led to the discovery of metabolite cancer biomarkers and the identification of target therapeutics. Methods: Metabolomics signature was extracted from primary BC and adjacent tissue samples from a cohort of 182 breast cancer patients from the Institut Gustave-Roussy and Institute Curie – Paris, University of Debrecen – Hungary, and University of Tartu – Estonia. The Biocrates Life Science® company, performed the metabolomics analysis using the Absolute IDQ p180 kit. Statistical analysis was performed by MetaboAnalyst 3.0 software (p &amp;lt;0.05). Results: We observed 99 differential metabolites between breast tumor and adjacent tissues (p&amp;lt;0,05). In the tumor tissue we observed an increase of glycolysis, glutamine uptake and synthesis, glutamate production, intermediates for redox homeostasis, as well reduction in tricarboxylic acid cycle and β –oxidation impairment. Together, these pathways, favor lipogenesis with a consequent increase in saturated fatty acids and cholesterol synthesis for the formation of membranes and lipid rafts in tumors. The increase in rafts in tumors maintains proliferation signaling via membrane receptors, making them important biomarkers. Conclusion: Metabolomics analysis is useful in identifying differential metabolites between breast cancer and adjacent tissue. In this scenario, cancer cells may be dependent on some metabolites for its development, making them therapeutically valuable biomarkers. Citation Format: Santos JR, Brentanni MM, Tortelli T, Dale I, Waitzberg A, Waitzberg D, Ravacci G. Metabolomic profiling of breast cancer and adjacent tissue [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-02-06.
Prognostic Significance of PET Imaging in Relapsed or Refractory Classical Hodgkin Lymphoma Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation.
Authors: Jacob Smeltzer, Amanda F Cashen, Qin Zhang, Camille N. Abboud, John F. DiPersio, Keith Stockerl-Goldstein, Geoffrey L. Uy, Ravi Vij, Peter Westervelt, Nancy L Bartlett, Todd A Fehniger
Journal: Blood (2009)
Anti–Interleukin-31 Receptor A Antibody for Atopic Dermatitis
Authors: Thomas Ruzicka, Jon M. Hanifin, Masutaka Furue, Grazyna Pulka, Izabela Mlynarczyk, Andreas Wollenberg, Ryszard Galus, Takafumi Etoh, Ryosuke Mihara, Hiroki Yoshida, Jonathan Stewart, Kenji Kabashima
Journal: New England Journal of Medicine (2017)

Interleukin-31 may play a role in the pathobiologic mechanism of atopic dermatitis and pruritus. We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis.In this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per kilogram every 8 weeks. The primary end point was the percentage improvement from baseline in the score on the pruritus visual-analogue scale (on which a negative change indicates improvement) at week 12. Secondary end points included changes in the score on the Eczema Area and Severity Index (EASI, on which a negative change indicates improvement), and body-surface area of atopic dermatitis.Of 264 patients who underwent randomization, 216 (82%) completed the study. At week 12, among the patients who received nemolizumab every 4 weeks, changes on the pruritus visual-analogue scale were -43.7% in the 0.1-mg group, -59.8% in the 0.5-mg group, and -63.1% in the 2.0-mg group, versus -20.9% in the placebo group (P<0.01 for all comparisons). Changes on the EASI were -23.0%, -42.3%, and -40.9%, respectively, in the nemolizumab groups, versus -26.6% in the placebo group. Respective changes in body-surface area affected by atopic dermatitis were -7.5%, -20.0%, and -19.4% with nemolizumab, versus -15.7% with placebo. Among the patients receiving nemolizumab every 4 weeks, treatment discontinuations occurred in 9 of 53 patients (17%) in the 0.1-mg group, in 9 of 54 (17%) in the 0.5-mg group, and in 7 of 52 (13%) in the 2.0-mg group, versus in 9 of 53 (17%) in the placebo group.In this phase 2 trial, nemolizumab at all monthly doses significantly improved pruritus in patients with moderate-to-severe atopic dermatitis, which showed the efficacy of targeting interleukin-31 receptor A. The limited size and length of the trial preclude conclusions regarding adverse events. (Funded by Chugai Pharmaceutical; XCIMA ClinicalTrials.gov number, NCT01986933 .).
Response to PD-1 Blockade in Microsatellite Stable Metastatic Colorectal Cancer Harboring a<i>POLE</i>Mutation
Authors: Jun Gong, Chongkai Wang, Peter P. Lee, Peiguo Chu, Marwan Fakih
Journal: Journal of the National Comprehensive Cancer Network (2017)

Recent clinical evidence has demonstrated that microsatellite instability (MSI) or defective mismatch repair (MMR) and high tumor mutational load can predict response to the programmed cell death 1 (PD-1) receptor inhibitor pembrolizumab in metastatic colorectal cancer (mCRC). Mutations in polymerase ε (POLE), a DNA polymerase involved in DNA replication and repair, contribute to an ultramutated but microsatellite stable (MSS) phenotype in colorectal tumors that is uniquely distinct from MSI tumors. This report presents the first case in the literature describing a clinical response to pembrolizumab in an 81-year-old man with treatment-refractory mCRC characterized by an MSS phenotype and POLE mutation identified on genomic profiling by next-generation sequencing. On tumor immunostaining, a large amount of CD8-positive tumor infiltrating lymphocytes (TILs) were present, with >90% of these expressing PD-1. More than 99% of PD-L1 expression was identified on nontumor cells in the tumor microenvironment that were close to the PD-1–positive CD8 TILs. mCRC tumors harboring POLE mutations represent a hypermutated phenotype that may predict response to anti–PD-1 therapy.
Synaptic Vesicle-Recycling Machinery Components as Potential Therapeutic Targets
Authors: Ying C. Li, Ege T. Kavalali
Journal: Pharmacological Reviews (2017)

Presynaptic nerve terminals are highly specialized vesicle-trafficking machines. Neurotransmitter release from these terminals is sustained by constant local recycling of synaptic vesicles independent from the neuronal cell body. This independence places significant constraints on maintenance of synaptic protein complexes and scaffolds. Key events during the synaptic vesicle cycle—such as exocytosis and endocytosis—require formation and disassembly of protein complexes. This extremely dynamic environment poses unique challenges for proteostasis at synaptic terminals. Therefore, it is not surprising that subtle alterations in synaptic vesicle cycle-associated proteins directly or indirectly contribute to pathophysiology seen in several neurologic and psychiatric diseases. In contrast to the increasing number of examples in which presynaptic dysfunction causes neurologic symptoms or cognitive deficits associated with multiple brain disorders, synaptic vesicle-recycling machinery remains an underexplored drug target. In addition, irrespective of the involvement of presynaptic function in the disease process, presynaptic machinery may also prove to be a viable therapeutic target because subtle alterations in the neurotransmitter release may counter disease mechanisms, correct, or compensate for synaptic communication deficits without the need to interfere with postsynaptic receptor signaling. In this article, we will overview critical properties of presynaptic release machinery to help elucidate novel presynaptic avenues for the development of therapeutic strategies against neurologic and neuropsychiatric disorders.
PP82. PITUICYTOMA: WHEN SHOULD RADIOTHERAPY BE USED?
Authors: Dr Aurora Sanz-Torres
Journal: Neuro-Oncology (2017)

PURPOSE: Pituicytoma is an exceptionally rare primary nonadenomatous pituitary gland tumour arising in the neurohypophysis. Since astroglial pituitary tumours are rare and manifestations non-specific, diagnosis is usually achieved after excision. Its treatment remains uncertain and the question for the necessity of adjuvant radiotherapy remains unsettled. The aim of this poster is to report a case who underwent radiotherapy treatment upon tumour relapse and review all the available literature. METHODS: We report a case of a 68-year-old diagnosed with pituicytoma who received radiotherapy treatment upon tumour re-growth (Figure 1) and present a systematic review of the 41 papers obtained by a Medline search using the term “pituicytoma”. RESULTS: To date, 51 out of 77 reported cases of pituicytoma (table 1) were followed after surgery (median of 18 months, 3–132 months). Of 25 patients who underwent total resection, only 2 recurred. Whereas 9 of the 24 patients whose tumors were debulked showed tumour progression. Although subtotal resection is accepted as a prognostic factor, only 2 of them received adjuvant radiotherapy. The 12 patients who had documented progression were adults with a prevalence of male gender, trans-sphenoidal approach and subtotal resection. Re-resection was attempted in 7 cases, 5 received radiotherapy (one after re-operation) and 1 remains under surveillance. Follow up data after regrowth is only available for 8 of them, revealing no further progression at a median of 12 months. CONCLUSION: The role of radiotherapy remains unclear, although it seem to be effective for recurrent tumours. The therapy of choice is gross total surgical resection since subtotal removal can lead to local regrowth.
OP16. THE KETOGENIC DIET INDUCES EPIGENETIC CHANGES THAT PLAY KEY ROLES IN TUMOUR DEVELOPMENT
Authors: Ms Jessica Preston, Dr Julianna Stylianou, Ms Quingyu Zeng, Ms Sophie Glover, Dr Adrienne C Scheck, Mr Eric C Woolf, Dr Kevin O’Neill, Dr Nelofer Syed
Journal: Neuro-Oncology (2017)

The ketogenic diet induces epigenetic changes that impact on the expression of microRNAs and chromatin modifying enzymes that play key roles in tumour development. Jessica Preston1; Julianna Stylianou1, Quingyu Zeng1, Sophie Glover1, Kevin O'Neill1; Adrienne C. Scheck2; Eric C. Woolf2, Nelofer Syed1; 1 John Fulcher Molecular Neuro-Oncology Laboratory, BTRC, Imperial College, London, UK, 2 Neuro-Oncology Research, Barrow Neurological Institute, Phoenix, Arizona Glioblastoma Multiforme (GBM) is the most aggressive form of primary brain tumour, with a median survival time of just 14 months. Current therapies are relatively ineffective, and the inherent heterogeneity of these tumours reduces the efficacy of targeted therapies since the target is often not present on all tumour cells. Due to the limited effectiveness of current and novel targeted therapeutic approaches, alternative strategies are being sought out. An attractive strategy is to exploit the altered metabolism exhibited by virtually all tumour cells ie their high dependence on glucose for survival. This can be accomplished using the therapeutic ketogenic diet. The ketogenic diet (KD), is a high fat, low carbohydrate and adequate protein diet. This diet is used for the clinical management of refractory paediatric epilepsy has been shown to extend survival in a number of animal models of glioma. Furthermore, studies using the GL261-luc2 syngeneic intracranial model of malignant glioma also highlighted the ability of the KD to potentiate the effects of chemotherapy and radiotherapy. In an attempt to unravel the mechanistic basis for these observed responses, we profiled tumours from mice fed either a KD or standard diet for epigenetic changes, namely changes in the expression of microRNAs (miRNAs) by global miRNA sequencing as well as changes in the expression of chromatin modifying enzymes using the mouse epigenetic chromatin modification enzyme PCR array from Qiagen. Our results highlighted a general upregulation of microRNAs with a tumour suppressor function in tumours from animals fed a KD verses those fed a standard diet, eg. miR-138-1-5p, miR-204-5p and several members of the mmu-let-7 family. Interestingly, a number of these miRNAs have been implicated in chemotherapy and radiotherapy resistance in several cancer types, including GBM. Furthermore, we observed significant changes in chromatin modifying enzymes, namely DNMT3b, a de novo methylating enzyme and PRMT8, a protein arginine methylating enzyme in animals fed the KD. Taken together our results suggest that the KD could inhibit tumour growth and contribute to therapy sensitivity through epigenetic modifications that impact on the regulation of genes critical for tumour survival.
TGR-1202 in Combination with Ibrutinib in Patients with Relapsed or Refractory CLL or MCL: Preliminary Results of a Multicenter Phase I/Ib Study
Authors: Matthew S. Davids, Haesook T. Kim, Alyssa Nicotra, Alexandra Savell, Karen Francoeur, Jeffrey Hellman, Hari P. Miskin, Peter Sportelli, Asad Bashey, Laura Stampleman, Jens Rueter, Adam Boruchov, Jon Arnason, Caron A. Jacobson, David C. Fisher, Jennifer R. Brown
Journal: Blood (2016)
Chromosomal Abnormalities Detected by FISH in CLL May Be Influenced by Ethnic Origin: Preliminary Data from a Multicenter Study in Israel for the Israel CLL Study Group (ICLLSG).
Authors: Rosa Ruchlemer, Lev Shvidel, Andre A. Baester, Osnat Bairey, Alain Berrebi, Aaron Polliack
Journal: Blood (2007)
Decreased spermatogonial quantity in prepubertal boys with leukaemia treated with alkylating agents
Authors: M Poganitsch-Korhonen, I Masliukaite, M Nurmio, P Lähteenmäki, M van Wely, A M M van Pelt, K Jahnukainen, J-B Stukenborg
Journal: Leukemia (2017)

Decreased spermatogonial quantity in prepubertal
An oral microjet vaccination system elicits antibody production in rabbits
Authors: Kiana Aran, Marc Chooljian, Jacobo Paredes, Mohammad Rafi, Kunwoo Lee, Allison Y. Kim, Jeanny An, Jennifer F. Yau, Helen Chum, Irina Conboy, Niren Murthy, Dorian Liepmann
Journal: Science Translational Medicine (2017)

Noninvasive immunization technologies have the potential to revolutionize global health by providing easy-to-administer vaccines at low cost, enabling mass immunizations during pandemics. Existing technologies such as transdermal microneedles are costly, deliver drugs slowly, and cannot generate mucosal immunity, which is important for optimal immunity against pathogens. We present a needle-free microjet immunization device termed MucoJet, which is a three-dimensional microelectromechanical systems-based drug delivery technology. MucoJet is administered orally, placed adjacent to the buccal tissue within the oral cavity, and uses a self-contained gas-generating chemical reaction within its two-compartment plastic housing to produce a high-pressure liquid jet of vaccine. We show that the vaccine jet ejected from the MucoJet device is capable of penetrating the buccal mucosal layer in silico, in porcine buccal tissue ex vivo, and in rabbits in vivo. Rabbits treated with ovalbumin by MucoJet delivery have antibody titers of anti-ovalbumin immunoglobulins G and A in blood serum and buccal tissue, respectively, that are three orders of magnitude higher than rabbits receiving free ovalbumin delivered topically by a dropper in the buccal region. MucoJet has the potential to accelerate the development of noninvasive oral vaccines, given its ability to elicit antibody production that is detectable locally in the buccal tissue and systemically via the circulation.
Abstract IA26: Conditionally Reprogrammed Cells (CRCs): A simple, two-component cell system for basic and clinical cancer research
Authors: Richard Schlegel
Journal: Clinical Cancer Research (2016)

Abstract Conditional reprogramming (CR) is a new cell biology technique that allows for the rapid and efficient outgrowth of matched normal and tumor epithelial tissue from patient samples. This approach combines the use of a ROCK inhibitor and irradiated feeder cells to induce and select for stem-like cells from adult tissues. While normal CR cells can be maintained for prolonged periods in vitro (in most cases they are conditionally immortalized), they retain their potential to differentiate normally when returned to an appropriate in vivo or in vitro environmental niche. Tumor cells can also be readily established in culture, although they can exhibit reduced dependence upon feeder cells and ROCK inhibitor for continued proliferation. The high efficiency of this system makes it feasible to establish cell cultures from rare tumor specimens. Minor modifications of the CR method also allow for the outgrowth of neuroendocrine and mesenchyme-like cells, possibly including cells that have undergone epithelial/mesenchymal transition. Biobanking using the CR method is now standardly applied in our pathology department in order to generate a renewable resource of patient samples for scientific investigation. The greatest challenge for routine application of this method is the selection of tumor cells from surgical biopsy specimens. Since both normal and tumor cells proliferate under these conditions, it is critical to evaluate the histologic composition of the biopsies and to validate the outgrowth of tumor cells using molecular biomarkers. Modified growth conditions are being developed to facilitate the selective outgrowth of tumor cells from mixed normal/tumor samples. This cell culture system has been used to identify new therapies for rare tumors (1) and characterize patient biopsies (2), and is now being applied broadly in new NCI initiatives for second-generation cancer cell models. 1. N Engl J Med 367:1220, 2012 2. Science 346:1480, 2014 Citation Format: Richard Schlegel. Conditionally Reprogrammed Cells (CRCs): A simple, two-component cell system for basic and clinical cancer research. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA26.
Thymic NF-κB-inducing kinase regulates CD4+ T cell-elicited liver injury and fibrosis in mice
Authors: Hong Shen, Liang Sheng, Yi Xiong, Yeung-Hyen Kim, Lin Jiang, Zheng Chen, Yong Liu, Kalyani Pyaram, Cheong-Hee Chang, Liangyou Rui
Journal: Journal of Hepatology (2017)