tbuckley/cabot-search huggingface dataset:
OC-045 Faecal microbiota transplantation: implementing a new treatment for recurrent/refractory clostridium difficile infection using banked stool in a tertiary uk centre
Authors: KV Patel, JL Digby-Bell, RM Goel, N Henry, JD Sanderson, PM Irving, S Goldenberg
Journal: Gut (2015)

<h3>Introduction</h3> Faecal microbiota transplantation is an effective treatment for recurrent/refractory <i>Clostridium difficile</i>infection (CDI). A randomised controlled trial reported sustained response in greater than 90% of patients, with an excellent safety profile. NICE approved the treatment as of March 2014. We introduced this new service in January 2015, setting up a stool bank to treat patients with recurrent CDI. We describe the process of initiating this service. <h3>Method</h3> Stool donors are recruited from non-clinical members of hospital staff or patient selected donors. Donors must be healthy with a BMI &lt;30, not taking oral medication, not received antibiotics in the previous 3 months and not be infected or at risk of any blood-borne viruses or transmissible infectious diseases. Donors are screened for diseases including Hepatitis A, B, C, E, HIV, HTLV, syphilis, CMV, EBV, Entamoeba histolytica, Strongyloides sterocaralis, Cryptosporidium, Giardia, C.difficile, H. Pylori, Norovirus, Campylobacter, Salmonella, Shigella, E.coli O:157, MRSA and multi-drug resistant coliforms. All transplant material has a batch number allowing full traceability. After screening, donors can provide stool for transplant for up to 3 months. &gt;50 g of fresh donated stool is diluted with 250 mls 0.9% normal saline and 12.5% glycerol, filtered to remove large particles and immediately frozen at –80<sup>0</sup>C. Frozen stool can be stored for up to 6 months, offers the benefit of being available on demand, and is as effective as freshly used stool. Recipients are informed of the risks of colonoscopy and the risk of acquiring an unrecognised transmissible disease. Standard bowel preparation is given and the transplant is delivered through the endoscope channel with 75% of the donor stool placed in the caecum, and the remainder in the right colon. Alternatively, infusion can be performed via a nasoduodenal tube. <h3>Results</h3> This pathway has been successfully implemented. Procedures are performed at the end of a list to allow subsequent deep cleaning of the endoscopy room, and donor stool is available in an ice box 30 min prior to procedure. Individuals are discharged home the day after the procedure, and contacted a week later to ascertain improvement in symptoms, and at 3-months for a second assessment including laboratory testing for <i>C. difficile</i>. Preliminary experience is promising with 100% of patients achieving clinical remission within a week of a single procedure. <h3>Conclusion</h3> Introduction of a faecal transplant service for CDI is feasible. As with all new treatments safety is paramount. Thorough screening of donors, traceability of transplants and long term follow up is essential. <h3>Disclosure of interest</h3> None Declared.
TCTAP A-045 Efficacy of 3-Dimentional Optical Frequency Domain Imaging on Guide Wire Recrossing After Coronary Bifurcation Stenting
Authors: Yoshinobu Murasato, Katsuhiko Takenaka, Takahiro Mori, Masaaki Nishihara, Emiko Ejima
Journal: Journal of the American College of Cardiology (2016)
Tcf1 and Lef1 transcription factors establish CD8+ T cell identity through intrinsic HDAC activity
Authors: Shaojun Xing, Fengyin Li, Zhouhao Zeng, Yunjie Zhao, Shuyang Yu, Qiang Shan, Yalan Li, Farrah C Phillips, Peterson K Maina, Hank H Qi, Chengyu Liu, Jun Zhu, R Marshall Pope, Catherine A Musselman, Chen Zeng, Weiqun Peng, Hai-Hui Xue
Journal: Nature Immunology (2016)
TCTAP C-071 Relentless Instent Restenosis of an Old Vein Graft, a Case of Successful Recanalization of the Native Vessel via Diseased Vein Graft Using Reverse CART Technique: Where There Is a Will, There Is a Way
Authors: Umair Hayat, Nilesh Mehta, Peter Barlis
Journal: Journal of the American College of Cardiology (2016)
Use of nilotinib to induce responses with 24-month (mo) minimum follow-up in patients (pts) with chronic myeloid leukemia in blast crisis (CML-BC) resistant to or intolerant of imatinib.
Authors: F. J. Giles, H. Kantarjian, P. D. le Coutre, M. Baccarani, R. E. Blakesley, N. J. Gallagher, K. Gillis, R. A. Larson, O. G. Ottmann
Journal: Journal of Clinical Oncology (2010)

6510 Background: Nilotinib is a highly potent and selective BCR-ABL inhibitor with efficacy in pts with imatinib-resistant and -intolerant CML in chronic phase (CP) and accelerated phase (AP). Results from pts with CML-BC treated with nilotinib in the phase II 2101 trial are presented. Methods: Pts were treated with nilotinib 400 mg bid. Primary endpoint was confirmed hematologic response (HR). Results: 136 pts with imatinib-resistant (82%) or -intolerant (18%) CML-BC were treated with nilotinib and followed for a minimum of 24 mo. 105 pts had myeloid blast crisis (MBC) and 31 pts had lymphoid blast crisis (LBC). Baseline BCR-ABL mutations were detected in 30% of pts with MBC and 61% with LBC; T315I mutations were detected in 1% of pts with MBC and 7% with LBC. Clonal evolution was detected in 54% of all pts. Best prior response to imatinib was stable or progressive disease in 46%, with only 10% achieving prior complete HR (CHR) and 13% major cytogenetic response (MCyR). Nilotinib resulted in HR in 24% of pts with MBC and 19% with LBC. CHR occurred in 13% of pts with MBC and LBC. Responses were rapid and durable. For pts with MBC, median time to HR was 1 mo, and median duration of HR was 26 mo (range, 1.25-29.08); 60% of pts maintained HR at 24 mo. Median duration of HR was 3.6 mo for pts with LBC and no pt maintained HR at 24 mo. Nilotinib induced MCyR and CCyR in 38% and 30% of pts with MBC and 52% and 32% with LBC, respectively. In MBC pts, median time to MCyR was 1.8 mo, and median duration of MCyR was 11 mo (range, 0.03-29.08); 44% of pts maintained MCyR at 24 mo. Median duration of MCyR was 3.2 mo for pts with LBC and no pt maintained MCyR at 24 mo. Survival was 42% at 12 mo and 27% at 24 mo; 12 pts with MBC and 2 pts with LBC had transplants following nilotinib therapy. Nonhematologic adverse events were generally mild and manageable and similar to those observed in pts with CML-CP. Conclusions: Nilotinib is effective therapy in pts with imatinib-resistant or -intolerant CML-BC, generating rapid and durable responses for pts with MBC. Nilotinib exhibits a favorable safety profile in CML-BC patients. No new safety concerns were observed with 24 mo minimum follow-up. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Bristol-Myers Squibb, Novartis Novartis Bristol-Myers Squibb, Novartis Bristol-Myers Squibb, Genzyme, Novartis
Phase II study of FOLFOX plus regorafenib (REGO) in patients with unresectable or metastatic esophagogastric (EG) cancer.
Authors: Yelena Yuriy Janjigian, Geoffrey Yuyat Ku, Joanne F. Chou, Marinela Capanu, Marisa Siebel, Sree Bhavani Chalasani, Michelle S. Boyar, Zoe Goldberg, Avni Mukund Desai, David Paul Kelsen, Tooba Imtiaz, David H. Ilson
Journal: Journal of Clinical Oncology (2015)

4053 Background: REGO is a VEGFR2, FGFR2 and PDGFR small-molecule inhibitor with survival benefit in metastatic colorectal cancer. We performed a phase II trial of first-line FOLFOX+REGO in metastatic EG cancer. Methods: Patients (pts) with previously untreated metastatic EG adenocarcinoma with measurable or evaluable disease received mFOLFOX6 q14d and oral REGO 160 mg daily on days 4 to10 and 18 to 24 q28d. The primary objective was to improve historical 6-month progression-free survival (PFS) from 40% to 61% with REGO. With target accrual of 36 pts and 5% type I error rate, FOLFOX+REGO would be considered promising if ≥ 20 pts are progression free at 6 months. Tumor biomarker analysis was performed on samples using an on-site next generation sequencing (NGS) assay. Secondary endpoints included safety, partial response (PR) rate, disease control rate (DCR, PR+stable disease), exploratory biomarker analysis and overall survival. Results: Between 8/2013 -11/2014, 36 pts (10 esophageal/16 gastric/10GEJ) were accrued to this single-center study. Median age 59 and KPS 80%. Common adverse events included: Gr 2/3 hypertension (52%), Gr 2 neuropathy (39%), Gr 3/4 neutropenia (36%), Gr 2 fatigue (28%), Gr 2/3 diarrhea (17%), Gr 2 hand-foot syndrome (14%). 11 pts (31%) had one REGO dose reduction to 120mg; 5 pts (14%) were further reduced to REGO 80mg. In 27 pts with RECIST 1.1 measurable disease, the PR rate 56% (95% CI: 38%-73%). Overall DCR rate in pts with RECIST measureable and evaluable disease was 81% (95% CI: 67%-94%). 17 of 36 pts are progression-free at 6 mos, with 3 pts still on study for < 6mos. NGS of 15 tumors completed to date. 94% of tumors harbored at least one genomic alteration, TP53 mutations (73%); amplifications in KRAS (13%), EGFR (13%), CDK12 (12%), MET (7%) and FGFR2 (7%). Conclusions: mFOLFOX in combination with one-week on/one-week off REGO dosing is well tolerated. NGS is ongoing on additional samples. Updated survival, response and correlative molecular analysis data will be presented. Clinical trial information: NCT01913639.
Reversing Drug-Induced Paralysis
Authors: Rebecca Voelker
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prognosis in Childhood Epilepsy
Authors: Jean Holowach, Don L. Thurston, James O'Leary
Journal: New England Journal of Medicine (1972)

Abstract One hundred and forty-eight epileptic children, seizure free for four years on anticonvulsant medication, were followed for five to 12 years after drug withdrawal to determine the frequency of relapse and to discern any prognostic criteria. Seizures recurred in 36 (24 per cent). There was no relation of relapse to sex, race, heredity, puberty or seizure frequency. With an early age at onset of epilepsy and prompt seizure control the recurrence rate was 13 per cent. It was at least twice as high in cases with a late onset, prolonged duration and neurologic, psychologic or electroencephalographic abnormalities. Relapse rates were lowest in grandmal attacks (8 per cent), febrile seizures (12 per cent) and petit-mal epilepsy (12 per cent). In psychomotor attacks the relapse rate was 25 per cent. The highest rate was in children with jacksonian seizures (53 per cent) and multiple seizure types (40 per cent). In a large percentage of selected cases these data support a favorable outcome after drug with...
Abstract A43: Opposing roles of the 19S regulatory- and 20S core-proteasomal subunits in controlling sensitivity of multiple myeloma cells to proteasome inhibition.
Authors: Diego Acosta-Alvear, Martin Kampmann, Min Y. Cho, Thomas Wild, Chunaram Choudhary, Marc A. Shuman, Jonathan S. Weissman, Peter Walter
Journal: Clinical Cancer Research (2015)

Abstract Multiple myeloma (MM) remains a devastating incurable disease. Because of their secretory nature, MM cells heavily rely on proteostasis networks to maintain homeostasis. Indeed, paraprotein production by MM cells imposes a protein-folding burden that provides an opportunity for therapeutic intervention: because protein production in MM cells can exceed the buffering capacity of the cell for protein degradation, they are exquisitely sensitive to proteasome inhibitors. While successful, standard-of-care proteasome inhibitors, like bortezomib, remain not curative, as patients ultimately become refractory, suggesting the selection of genetic escape routes. Employing an ultra-complex shRNA library, we performed pooled shRNA screens in RPMI-8226, U-266, and JJN-3 MM cells, and in K-562 leukemia cells, and identified genes whose diminished function impact the cell's response to proteasome inhibition. Unexpectedly, we found that, contrary to knockdown of subunits in the 20S proteasome core-particle, the genetic ablation of subunits within the 19S regulatory-particle led to partial desensitization towards bortezomib. Proteome-wide analyses of in vivo ubiquitylated sites in K562 cells, in which we constitutively ablated a component of the 19S regulatory-particle, revealed potential candidate substrates that were differentially degraded in knockdown cells. We are investigating the mechanistic basis for this differential degradation to pinpoint key substrates mediating proteasome inhibitor resistance. Our results reveal potential escape routes in MM tumor cells to proteasome inhibitors, suggesting new promising targets to pre-empt resistance. Citation Format: Diego Acosta-Alvear, Martin Kampmann, Min Y. Cho, Thomas Wild, Chunaram Choudhary, Marc A. Shuman, Jonathan S. Weissman, Peter Walter. Opposing roles of the 19S regulatory- and 20S core-proteasomal subunits in controlling sensitivity of multiple myeloma cells to proteasome inhibition. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A43.
Inhibition of squamous cancer growth in a mouse model by Staphylococcal enterotoxin B-triggered Th9 cell expansion
Authors: Bei-Ping Miao, Rui-Shi Zhang, Huan-Ji Sun, Yan-Ping Yu, Tao Chen, Lin-Jing Li, Jiang-Qi Liu, Jun Liu, Hai-Qiong Yu, Min Zhang, Zhi-Gang Liu, Ping-Chang Yang
Journal: Cellular and Molecular Immunology (2015)
<i>In Vivo</i>Fluorescence Imaging of the Activity of CEA TCB, a Novel T-Cell Bispecific Antibody, Reveals Highly Specific Tumor Targeting and Fast Induction of T-Cell–Mediated Tumor Killing
Authors: Steffi Lehmann, Ramanil Perera, Hans-Peter Grimm, Johannes Sam, Sara Colombetti, Tanja Fauti, Linda Fahrni, Teilo Schaller, Anne Freimoser-Grundschober, Jörg Zielonka, Szymon Stoma, Markus Rudin, Christian Klein, Pablo Umana, Christian Gerdes, Marina Bacac
Journal: Clinical Cancer Research (2016)

CEA TCB (RG7802, RO6958688) is a novel T-cell bispecific antibody, engaging CD3ε upon binding to carcinoembryonic antigen (CEA) on tumor cells. Containing an engineered Fc region, conferring an extended blood half-life while preventing side effects due to activation of innate effector cells, CEA TCB potently induces tumor lysis in mouse tumors. Here we aimed to characterize the pharmacokinetic profile, the biodistribution, and the mode of action of CEA TCB by combining in vitro and in vivo fluorescence imaging readouts.CEA-expressing tumor cells (LS174T) and human peripheral blood mononuclear cells (PBMC) were cocultured in vitro or cografted into immunocompromised mice. Fluorescence reflectance imaging and intravital 2-photon (2P) microscopy were employed to analyze in vivo tumor targeting while in vitro confocal and intravital time-lapse imaging were used to assess the mode of action of CEA TCB.Fluorescence reflectance imaging revealed increased ratios of extravascular to vascular fluorescence signals in tumors after treatment with CEA TCB compared with control antibody, suggesting specific targeting, which was confirmed by intravital microscopy. Confocal and intravital 2P microscopy showed CEA TCB to accelerate T-cell-dependent tumor cell lysis by inducing a local increase of effector to tumor cell ratios and stable crosslinking of multiple T cells to individual tumor cells.Using optical imaging, we demonstrate specific tumor targeting and characterize the mode of CEA TCB-mediated target cell lysis in a mouse tumor model, which supports further clinical evaluation of CEA TCB. Clin Cancer Res; 22(17); 4417-27. ©2016 AACRSee related commentary by Teijeira et al., p. 4277.
TCTAP A-005 Multivessel Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction in Same Sitting - Our Experiences at Apollo Hospitals Dhaka
Authors: A.H.M. Waliul Islam, Shams Munwar, Azfar H. Bhuiyan, Shahab Uddin Talukder, A.Q.M. Reza, Tamzeed Ahmed, M.S. Alam, Intekhab Yousuf, Atique Siddique, Nighat Islam
Journal: Journal of the American College of Cardiology (2016)
Clinical features and treatment outcome of children with biphenotypic CD2+ CD19+ acute lymphoblastic leukemia: a Children's Cancer Group study.
Authors: Fatih M. Uckun, Paul Gaynon, Harland Sather, Diane Arthur, Michael Trigg, David Tubergen, James Nachman, Peter Steinherz, Martha G. Sensel, Gregory R. Reaman
Journal: Blood (1997)
Reporting of Sex Effects by Systematic Reviews on Interventions for Depression, Diabetes, and Chronic Pain
Authors: Wei Duan-Porter, Karen M. Goldstein, Jennifer R. McDuffie, Jaime M. Hughes, Megan E.B. Clowse, Ruth S. Klap, Varsha Masilamani, Nancy M. Allen LaPointe, Avishek Nagi, Jennifer M. Gierisch, John W. Williams
Journal: Annals of Internal Medicine (2016)

Systematic reviews (SRs) have the potential to contribute uniquely to the evaluation of sex and gender differences (termed "sex effects"). This article describes the reporting of sex effects by SRs on interventions for depression, type 2 diabetes mellitus, and chronic pain conditions (chronic low back pain, knee osteoarthritis, and fibromyalgia). It includes SRs published since 1 October 2009 that evaluate medications, behavioral interventions, exercise, quality improvement, and some condition-specific treatments. The reporting of sex effects by primary randomized, controlled trials is also examined. Of 313 eligible SRs (86 for depression, 159 for type 2 diabetes mellitus, and 68 for chronic pain), few (n = 29) reported sex effects. Most SRs reporting sex effects used metaregression, whereas 9 SRs used subgroup analysis or individual-patient data meta-analysis. The proportion of SRs reporting the sex distribution of primary studies varied from a low of 31% (n = 8) for low back pain to a high of 68% (n = 23) for fibromyalgia. Primary randomized, controlled trials also infrequently reported sex effects, and most lacked an adequate sample size to examine them. Therefore, all SRs should report the proportion of women enrolled in primary studies and evaluate sex effects using appropriate methods whenever power is adequate.
PWE-230 The exaggerated inflammatory response to large incisional hernia and enterocutaneous fistula repair with biological mesh
Authors: J Clarke, H Thomson, A Windsor, J McCullough
Journal: Gut (2015)

<h3>Introduction</h3> Biological meshes are increasingly used in the repair of complex, large incisional hernias, particularly in the context of a contaminated surgical field. In our centre it was noted that patients displayed an exaggerated and prolonged inflammatory response on post-operative blood results in comparison to other similar surgical procedures. This study aims to investigate the post-operative inflammatory response in patients undergoing placement of large biological meshes for the repair of large incisional hernias or enterocutaneous fistulae. <h3>Method</h3> Post-operative white blood cell count (WCC) and complement reactive protein (CRP) levels were recorded on the first five post-operative days for a consecutive cohort of patients following repair of large ventral or incisional hernias with or without repair of enterocutaneous fistulae. The mesh size and the presence of component separation was also recorded. Post-operative WCC and CRP data was collected for a size-matched contemporaneous, consecutive control group of patients undergoing open colorectal resections for a diagnosis of colorectal cancer. Post-operative inflammatory responses were compared. <h3>Results</h3> 41 patients underwent a large ventral hernia repair using biologic mesh, of which 16 (39.0%) underwent simultaneous repair of an enterocutaneous fistula. 27 (65.9%) underwent component separation. Post-operative CRP was significantly higher in patients in the hernia group on the third (188 vs. 133) and fourth (188 vs. 117) post-operative days (p &lt; 0.01). There was no significant difference in WCC on either day. The CRP response was not significantly different between groups by the fifth post-operative day. Repair of enterocutaneous fistulae was associated with significantly increased CRP levels on the third and fourth post-operative day when compared to hernia repair alone. There was a positive correlation between mesh area (mean area = 183cm<sup>2</sup>) and CRP level on the third post-operative day (Pearson’s r = 0.42). <h3>Conclusion</h3> Patients undergoing large ventral hernia repairs using biological mesh display an exaggerated and prolonged inflammatory response in comparison to open colorectal cancer resections. The inflammatory response is no different between groups by the fifth post-operative day. This data suggests that an exaggerated inflammatory response should be expected in such procedures and that normalisation of inflammatory markers ought to be expected by the fifth post-operative day. <h3>Disclosure of interest</h3> None Declared.
Replication of DNA After Binding of the Carcinogen 7,12-Dimethylbenz [&lt;italic&gt;a&lt;/italic&gt;] anthracene
Authors: Richard R. Bates, Sol del Ande Eaton, David L. Morgan, Stuart H. Yuspa
Journal: JNCI Journal of the National Cancer Institute (1970)

To determine whether DNA, to which a carcinogenic polycyclic hydrocarbon is bound, can replicate, cell cultures of mouse skin were incubated with 7,12-dimethylbenz[a]anthracene-3H (3H-DMBA). The 3H-DMBA was then removed from the culture medium and 5-bromodeoxyuridine (BUDR) in thymine-free medium was added either immediately or after an intervening period in normal medium. Isopyknic centrifugation of DNA from these cells separated the DNA into two distinct bands. The heavy, BUDR-containing band, replicating after removal of DMBA from the medium, had approximately half as much bound DMBA as the lighter band of DNA which had not replicated. Separation of the two strands of BUDR-containing DNA by isopyknic centrifugation in an alkaline gradient demonstrated that most of the DMBA was bound to the parent strand and little or none to the newly synthesized strand. Thus a major portion of the binding of DMBA to DNA is to a single strand, and DNA to which DMBA is bound can replicate.
Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia
Authors: Ferran Nadeu, Julio Delgado, Cristina Royo, Tycho Baumann, Tatjana Stankovic, Magda Pinyol, Pedro Jares, Alba Navarro, David Martín-García, Sílvia Beà, Itziar Salaverria, Ceri Oldreive, Marta Aymerich, Helena Suárez-Cisneros, Maria Rozman, Neus Villamor, Dolors Colomer, Armando López-Guillermo, Marcos González, Miguel Alcoceba, Maria José Terol, Enrique Colado, Xose S. Puente, Carlos López-Otín, Anna Enjuanes, Elías Campo
Journal: Blood (2016)